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Simple Summary: Febrile neutropenia is associated with high mortality, and the administration of anti-pseudomonal agents is required. Traditionally, combination therapy with aminoglycosides was weakly recommended in the guidelines, but recently, with the emergence of resistant bacteria, there has been increasing hope for combination antimicrobial therapy. The purpose of this systematic review, based on RCTs published up to 2023, is to examine how much more effective combination therapy with beta-lactams and aminoglycosides is compared to monotherapy with beta-lactams. We performed a systematic review of studies that compared beta-lactams vs. beta-lactams plus aminoglycosides for the treatment of febrile neutropenia in cancer patients. Method: We searched CENTRAL, MEDLINE, and Embase for studies published up to October 2023, and randomized controlled trials (RCTs) that compared anti-Pseudomonas aeruginosa beta-lactam monotherapy with any combination of an anti-Pseudomonas aeruginosa beta-lactam and an aminoglycoside were included. Result: The all-cause mortality rate of combination therapy showed no significant differences compared with that of monotherapy (RR 0.99, 95% CI 0.84 to 1.16, high certainty of evidence). Infection-related mortality rates showed that combination therapy had a small positive impact compared with the intervention with monotherapy (RR 0.83, 95% CI 0.66 to 1.05, high certainty of evidence). Regarding treatment failure, combination therapy showed no significant differences compared with monotherapy (RR 0.99, 95% CI 0.94 to 1.03, low certainty of evidence). In the sensitivity analysis, the treatment failure data published between 2010 and 2019 showed better outcomes in the same beta-lactam group (RR 1.10 [95% CI, 1.01–1.19]). Renal failure was more frequent with combination therapy of any daily dosing regimen (RR 0.46, 95% CI 0.36 to 0.60, high certainty of evidence). Conclusion: We found combining aminoglycosides with a narrow-spectrum beta-lactam did not spare the use of broad-spectrum antibiotics. Few studies included antibiotic-resistant bacteria and a detailed investigation of aminoglycoside serum levels, and studies that combined the same beta-lactams showed only a minimal impact with the combination therapy. In the future, studies that include the profile of antibiotic-resistant bacteria and the monitoring of serum aminoglycoside levels will be required. [ABSTRACT FROM AUTHOR]

Simple Summary: The relationship between head and neck cancer and heart attack is a complex area of medical research that has potential implications for patient care and outcomes. This study aimed to assess the risk of developing heart disease attributable to head and neck cancer. In this study, we examined the association between head and neck cancer and the risk of heart attack using a database of 1,025,340 South Korean patients. There were no associations between the development of a heart attack in head and neck cancer survivors who did not receive radiation or chemotherapy. Our results consistently indicated a negligible long-term increase in the risk of developing a heart attack after a head and neck cancer diagnosis. Enhanced screening protocols for cancer detection have increased survival in patients with head and neck cancer (HNC), which highlights the need to address the sequelae of therapy-induced cardiovascular complications. This study was conducted to assess the incidence and risk of acute myocardial infarction (AMI) in patients with HNC who have not undergone radiation or chemotherapy using a comprehensive, population-based cohort dataset. A total of 2976 individuals without cancer and 744 individuals with HNC were matched using the propensity score method. The findings indicated that the occurrence rates of AMI were comparable between the HNC (2.19) and non-cancer groups (2.39). Cox regression analysis did not demonstrate a significant increase in the risk of AMI in patients with HNC (hazard ratio: 0.93, 95% confidence interval: 0.50–1.73). No increased risk of AMI was observed in the HNC group compared to the non-cancer group, regardless of the time since the HNC diagnosis. Subgroup analyses showed no notable differences in the AMI risk between the groups when considering sex, age, comorbidities, and cancer type. This study showed that patients with HNC who have not been treated with radiation or chemotherapy did not exhibit an increased incidence or risk of AMI compared to individuals without cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: Radiation-associated sarcomas pose a significant clinical challenge due to their complexity, aggressiveness, and poor prognosis. Our retrospective study is one of the largest descriptions of radiation-associated sarcomas, aiming to shed light on their clinicopathologic characteristics and highlight treatment approaches. Our research found a significant association between high radiation-associated sarcoma histologic grade and inferior clinical outcomes. We also found that localized radiation-associated sarcoma patients who underwent margin-negative resections lived significantly longer than their counterparts. Our analysis thus confirms the paramount role of tumor grade and the central importance of margin-negative oncologic resection in determining clinical outcomes for radiation-associated sarcomas. Radiation-associated sarcomas (RASs) are rare tumors with limited contemporary data to inform prognostication and management. We sought to identify the clinical presentation, patterns of care, and prognostic factors of RASs. RAS patients treated at a single institution from 2015 to 2021 were retrospectively reviewed for clinicopathologic variables, treatment strategies, and outcomes. Thirty-eight patients were identified with a median follow-up of 30.5 months. The median age at RAS diagnosis was 68.4 years (27.9–85.4), with a median latency from index radiotherapy (RT) of 9.1 years (3.7–46.3). RAS histologies included angiosarcoma (26%), undifferentiated pleomorphic sarcoma (21%), and osteosarcoma (18%). Most were high-grade (76%). Genomic profiling revealed low tumor mutational burden, frequent inactivating TP53 mutations (44%), CDKN2A deletions (26%), and MYC amplifications (22%), particularly in breast angiosarcomas. Of 38 patients, 33 presented with localized disease, 26 of whom were treated with curative intent. Overall, the median progression-free survival (PFS) was 9.5 months (1.4–34.7), and the overall survival (OS) was 11.1 months (0.6–31.6). Patients with localized vs. metastatic RASs had a longer PFS (HR, 3.0 [1.1–8.5]; p = 0.03) and OS (HR, 3.0 [1.04–8.68]; p = 0.03). Among localized RAS patients, high grade was associated with shorter OS (HR, 4.6 [1.04–20.30]; p = 0.03) and resection with longer OS (mean 58.8 vs. 6.1 months, HR, 0.1 [0.03–0.28]; p < 0.001). Among patients undergoing resection, negative margins were associated with improved OS (mean 71.0 vs. 15.5 months, HR, 5.1 [1.4–18.2]; p = 0.006). Patients with localized disease, particularly those undergoing R0 resection, demonstrated significantly better outcomes. Novel strategies are urgently needed to improve treatment outcomes in this challenging group of diseases. [ABSTRACT FROM AUTHOR]

Simple Summary: The selection of radiation dose/fractionation schemes for limited-stage small cell lung cancer (LS-SCLC) is highly controversial. It mainly involves the impact of total biologically effective dose, overall treatment time, and fractionation dose on survival and toxicity. This article comprehensively analyzes current relevant research and discusses the advantages and disadvantages of conventional-dose/fractionation radiotherapy (ConvTRT), hyperfractionated radiotherapy (HyperTRT), hypofractionated radiotherapy (HypoTRT), and stereotactic body radiotherapy (SBRT), in order to find the most suitable dose fractionation scheme and provide reference for clinical practice. Regardless of the radiotherapy modality, controlling the radiotherapy time to around 3 weeks is beneficial for improving survival and local control rates while reducing toxicity reactions. ConvTRT with a high total prescription dose is not recommended, because a prolonged radiotherapy time may reduce the tumor control probability of some rapidly proliferating tumor cells. In balancing acute reactions, late reactions, and treatment outcomes (local control or overall survival), the advantages of HyperTRT over HypoTRT still exist. For the radical radiotherapy regimen recommended by current guidelines (45 Gy/30 fractions), we suggest moderately increasing the fractionation dose and total dose, which may further improve prognosis. To explore the most suitable dosage regimen for limited-stage small cell lung cancer (LS-SCLC) and provide references for clinical selection, strict inclusion criteria were applied, and studies were screened from Pubmed, Embase, and Web of Science. Subsequently, data on two-year overall survival rates and dosage regimens were collected, and scatter plots were constructed to provide a comprehensive perspective. The survival benefits of various dosage regimens were evaluated, and a linear quadratic equation was utilized to fit the relationship between the biologically effective dose (BED10) and the two-year overall survival rate. Among the five randomized controlled trials, the two-year overall survival rate of ConvTRT regimens with BED10 > 60 Gy (rough value) was only at or below the median of all ConvTRT regimens or all included study regimens, indicating that increasing the number and total dose of ConvTRT does not necessarily lead to better prognosis. In the exploration of HypoTRT regimens, there was a linear positive correlation between BED10 and the two-year overall survival rate (p < 0.0001), while the exploration of HyperTRT regimens was relatively limited, with the majority focused on the 45 Gy/30 F regimen. However, the current 45 Gy/30 F regimen is not sufficient to control LS-SCLC, resulting in a high local recurrence rate. High-dose ConvTRT regimens have long treatment durations and may induce tumor regrowth which may cause reduced efficacy. Under reasonable toxicity reactions, HyperTRT or HypoTRT with higher radiotherapy doses is recommended for treating LS-SCLC. [ABSTRACT FROM AUTHOR]

Simple Summary: Corticosteroid use for the treatment of immune related adverse events (irAEs) after immune checkpoint inhibitor (ICI) use comes with concerns of side effects and the potential abrogation of antitumor immunity. Relatedly, the impact of steroid-sparing immunosuppressive agents (SSIAs) for treatment of irAEs on tumor outcomes is not well known, and current literature on this topic is limited by study design and issues around immortal time bias. This retrospective case-control study accounts for immortal time bias via strategic statistical methodology. Our results suggest that SSIAs used for irAE treatment may not negatively impact cancer outcomes in malignant melanoma and non-small cell lung cancer. For patients with melanoma, our results demonstrated better progression free survival for patients treated with infliximab compared to patients treated with corticosteroid monotherapy for irAEs. This study supports the safety for utilizing SSIAs for irAE treatment in patients receiving immune checkpoint inhibitors. Our study also encourages accounting for immortal time bias in the design of other observational studies in this space to accurately convey results and draw clinically meaningful conclusions. Background: The effects of steroid-sparing immunosuppressive agents (SSIAs), used for the treatment of immune-related adverse events (irAEs), on immune checkpoint inhibitor (ICI) antitumor activity is not well known. We compared tumor outcomes of patients who received corticosteroid monotherapy (CS) versus a corticosteroid plus SSIA (CS-SSIA) for irAE treatment, using statistical methods to address immortal time bias. Methods: We conducted a retrospective case-control study on patients ≥ 18 years with melanoma or non-small-cell lung cancer (NSCLC) treated with ≥1 ICI at a quaternary care center between 1 January 2016 and 11 January 2021. Patients were divided into two cohorts: CS or CS-SSIA. We used propensity score nearest-neighbor matching to match on tumor type, stage, and prior lines of therapy. Primary outcomes were progression-free survival (PFS) and overall survival (OS). Secondary outcomes included the time from the start of the irAE treatment to the irAE resolution. Hazard ratios (HRs) for PFS and OS were calculated using the Cox proportional hazard regression method with both (1) the time to the steroid and SSIA as time-varying covariates and (2) a binary exposure classification not accounting for the time to the treatment. Results: A total of 167 patients were included after matching (132 in the CS cohort and 35 in the CS-SSIA cohort). Sixty-six percent of all the patients had melanoma. The most common irAEs requiring treatment were gastroenterocolitis and hepatitis. In an adjusted analysis not accounting for immortal time bias, there were no significant differences in PFS (HR 0.75, 95% CI [0.46–1.23]) or OS (HR 0.82, 95% CI [0.46–1.47]). In analyses using a time-varying treatment indicator, there was a trend toward improved PFS in patients treated with SSIAs (HR 0.54, CI 0.26–1.10). There was no difference in OS (HR 1.11, CI 0.55–2.23). Patients with melanoma who specifically received infliximab had improved PFS compared to patients with CS only, after adjusting for immortal time bias (HR 0.32, CI 0.24–0.43). Conclusions: The use of SSIAs with CS did not have worse outcomes than CS monotherapy. In melanoma, our findings showed improved PFS for the use of infliximab versus steroid monotherapy for irAEs. Large, prospective, randomized controlled trials are needed to confirm these findings and guide the optimal treatment of irAEs. [ABSTRACT FROM AUTHOR]

Simple Summary: Allogeneic hematopoietic stem cell transplantation (allo-HCT) remains an effective treatment modality in many hematological malignancies. Few studies directly compare rabbit anti-thymocyte globulin (r-ATG) formulations Thymoglobuline (ATG-T) and Grafalon (ATG-G). Our retrospective analysis compared the outcomes in 87 adult allo-HCT patients receiving ATG-T or ATG-G. No significant differences were found in acute graft-versus-host disease (aGvHD) incidence. However, chronic GvHD (cGvHD) was less common with ATG-T (7.5% vs. 38.3%, p = 0.001). ATG-T patients had higher cytomegalovirus (CMV) reactivation rates (70% vs. 31.9%, p < 0.001) and a shorter time to CMV (<61 days, 77.8% vs. 33.3%, p = 0.008), but were mostly asymptomatic (85.7% vs. 43.8%, p = 0.005). Overall survival (OS) and relapse-free survival (RFS) at 5 and 3 years, respectively, showed no significant differences between ATG-T and ATG-G (32.0% vs. 40.3%, p = 0.423; 66.7% vs. 60.4%, p = 0.544). Despite notable advancements in immunotherapy in the past decades, allogeneic hematopoietic stem cell transplantation (allo-HCT) remains a promising, potentially curative treatment modality. Only a limited number of studies have performed a direct comparison of two prevalent rabbit anti-thymocyte globulin (r-ATG) formulations—specifically, Thymoglobuline (ATG-T, formerly Genzyme) and Grafalon (ATG-G, formerly Fresenius). The primary objective of our retrospective analysis was to compare the outcomes of adult patients undergoing matched or mismatched unrelated donor (MUD/MMUD) allo-HCT, with a graft-versus-host disease (GvHD) prophylaxis based on either ATG-T or ATG-G. A total of 87 patients who had undergone allo-HCT between 2012 and 2022 were included. We observed no significant differences between ATG-T and ATG-G concerning the occurrence of acute graft-versus-host disease (aGvHD), regardless of its severity. Conversely, chronic graft-versus-host disease (cGvHD) occurred less frequently in the ATG-T group compared to the ATG-G group (7.5% vs. 38.3%, p = 0.001). The negative impact of ATG-G on cGvHD was confirmed by multivariate analysis (HR 8.12, 95% CI 2.06–32.0, p = 0.003). Patients treated with ATG-T manifested a higher incidence of cytomegalovirus (CMV) reactivations (70% vs. 31.9%, p < 0.001), with a shorter time between transplant and CMV (<61 days, 77.8% vs. 33.3%, p = 0.008) and a higher median CMV copy number (1000 vs. 0, p = 0.004). Notably, despite a higher occurrence of CMV reactivations in the ATG-T cohort, most patients were asymptomatic compared to ATG-G (85.7% vs. 43.8%, p = 0.005). By multivariate analysis, only aGvHD had an influence on CMV reactivations (HR 0.18, 95% CI 0.04–0.75, p = 0.019). Finally, we observed no significant differences in terms of 5-year overall survival (OS) and 3-year relapse-free survival (RFS) while comparing ATG-T and ATG-G (32.0% vs. 40.3%, p = 0.423; 66.7% vs. 60.4%, p = 0.544, respectively). [ABSTRACT FROM AUTHOR]

Simple Summary: Treosulfan and melphalan (TreoMel)-based high-dose chemotherapy (HDCT) has been successfully used as a conditioning regimen in acute myeloid leukemia (AML) patients undergoing autologous stem cell transplantation (ASCT). However, despite intensive first-line induction treatment and upfront consolidation with HDCT and ASCT, AML relapse rates are still high, and further efforts are needed to improve patient outcomes. In this study, we investigated how increased doses of melphalan impact the safety of HDCT with TreoMel and patient outcomes. A total of 51 AML patients were included in the analysis: 31 (60.8%) received standard-dose treosulfan combined with melphalan 140 mg/m2 (TreoMel 140) and 20 (39.2%) received melphalan 200 mg/m2 (TreoMel 200). There were no statistically significant differences in relapse (0.45 vs. 0.30, p = 0.381) and mortality rates (0.42 vs. 0.15, p = 0.064) between the melphalan 140 mg/m2 and 200 mg/m2 cohorts, nor for PFS (HR: 0.81, 95% CI: 0.29–2.28, p = 0.70) or OS (HR: 0.70, 95% CI: 0.19–2.57, p = 0.59) for the TreoMel 140 vs. TreoMel 200 cohorts. The side effect profile was comparable between both patient groups. Our results show that a higher melphalan dose is well tolerated. No significant differences for patient outcomes could be observed, possibly due to the relatively small patient cohort and short follow-up. Longer follow-up and prospective randomized studies would be required to confirm the safety profile and clinical benefit. (1) Background: Treosulfan and melphalan (TreoMel)-based high-dose chemotherapy (HDCT) has shown promising safety and efficacy as a conditioning regimen for acute myeloid leukemia (AML) patients undergoing autologous stem cell transplantation (ASCT). However, despite intensive first-line induction treatment and upfront consolidation with HDCT and ASCT, AML relapse rates are still high, and further efforts are needed to improve patient outcomes. The aim of this study was to compare two melphalan dose schedules in regard to the safety of TreoMel HDCT and patient outcomes. (2) Methods: We retrospectively analyzed the safety and efficacy of two melphalan dose schedules combined with standard-dose treosulfan in AML patients undergoing HDCT and ASCT at the University Hospital of Bern, Switzerland, between August 2019 and August 2023. Patients received treosulfan 42 g/m2 combined with either melphalan 140 mg/m2 (TreoMel 140) or melphalan 200 mg/m2 (TreoMel 200). Co-primary endpoints were progression-free survival (PFS), overall survival (OS), as well as safety profile. (3) Results: We included a total of 51 AML patients: 31 (60.8%) received TreoMel 140 and 20 (39.2%) TreoMel 200. The patients' basal characteristics were comparable between both cohorts. No significant differences in the duration of hospitalization or the adverse event profile were identified. There were no statistically significant differences in relapse (0.45 vs. 0.30, p = 0.381) and mortality rates (0.42 vs. 0.15, p = 0.064) between the melphalan 140 mg/m2 and 200 mg/m2 cohorts, nor for PFS (HR: 0.81, 95% CI: 0.29–2.28, p = 0.70) or OS (HR: 0.70, 95% CI: 0.19–2.57, p = 0.59) for the TreoMel 140 vs. TreoMel 200 cohort. (4) Conclusions: A higher dose of melphalan (TreoMel 200) was well tolerated overall. No statistically significant differences for patient outcomes could be observed, possibly due to the relatively small patient cohort and the short follow-up. A longer follow-up and prospective randomized studies would be required to confirm the safety profile and clinical benefit. [ABSTRACT FROM AUTHOR]

Simple Summary: Prostate cancer is a commonly diagnosed cancer in men with varying outcomes following treatment. This study focuses on a specific feature observed in some prostate cancers called a histologically overt stromal response (HOST-response), which involves changes in the tissue surrounding the cancer cells. Our research used data from patients who had undergone surgery for prostate cancer to explore how this stromal response impacted their recovery without the cancer returning. We found that the presence of a HOST-response is linked to a higher chance of the cancer coming back sooner. These findings suggest that monitoring for this feature could help identify patients who might benefit from additional treatments after surgery, which could potentially improve their outcomes. The results of this study could guide future clinical trials aiming to refine treatment strategies for prostate cancer patients exhibiting a HOST-response. Purpose: Given the variable clinical course of prostate cancer and the limitations of current prognostic factors, this study was conducted to investigate the impact of a histologically overt stromal response (HOST-response) to prostate cancer on clinical outcomes after radical prostatectomy. Methods: This retrospective analysis utilized The Cancer Genome Atlas (TCGA) to evaluate data from individuals with a confirmed diagnosis of prostate cancer who underwent radical prostatectomy and had available pathology slides. These slides were assessed for the presence of a HOST-response, similar to desmoplasia. The primary endpoint was progression-free survival (PFS). A multivariable competing risk regression analysis was used to assess whether a significant association existed between HOST-response and PFS, adjusting for known prostate cancer prognostic factors. Results: Among the 348 patients analyzed, 166 (47.70%) demonstrated a HOST-response. After a median follow-up of 37.87 months (IQR: 21.20, 65.50), the presence of a HOST-response was significantly associated with a shorter PFS (SDHR, 2.10; 95% CI, 1.26 to 3.50; p = 0.004), after adjusting for covariates. Conclusions: HOST-response in prostate cancer patients treated with radical prostatectomy is significantly associated with reduced PFS, suggesting a potential benefit from adjuvant therapy and highlighting the need for further investigation in a prospective randomized clinical trial. [ABSTRACT FROM AUTHOR]

Simple Summary: Keyhole surgery has replaced open surgery as the gold standard of care in the surgical treatment of cancer of the womb. Previous reviews comparing keyhole and open surgery exclusively analysed data from randomised control trials. We present a comprehensive review using randomised and non-randomised trials to compare keyhole surgery and open surgery. This review investigates benefits, complications and long-term outcomes in terms of survival after treatment of cancer of the womb, and it shows that keyhole surgery lessened blood loss and the length of hospital stay compared to open surgery. Among the keyhole methods, robotic surgery decreased some complications while rendering the return of cancer less likely. Background: Total hysterectomy with bilateral salpingo-oophorectomy via minimally invasive surgery (MIS) has emerged as the standard of care for early-stage endometrial cancer (EC). Prior systematic reviews and meta-analyses have focused on outcomes reported solely from randomised controlled trials (RCTs), overlooking valuable data from non-randomised studies. This inaugural systematic review and network meta-analysis comprehensively compares clinical and oncological outcomes between MIS and open surgery for early-stage EC, incorporating evidence from randomised and non-randomised studies. Methods: This study was prospectively registered on PROSPERO (CRD42020186959). All original research of any experimental design reporting clinical and oncological outcomes of surgical treatment for endometrial cancer was included. Study selection was restricted to English-language peer-reviewed journal articles published 1 January 1995–31 December 2021. A Bayesian network meta-analysis was conducted. Results: A total of 99 studies were included in the network meta-analysis, comprising 181,716 women and 14 outcomes. Compared with open surgery, laparoscopic and robotic-assisted surgery demonstrated reduced blood loss and length of hospital stay but increased operating time. Compared with laparoscopic surgery, robotic-assisted surgery was associated with a significant reduction in ileus (OR = 0.40, 95% CrI: 0.17–0.87) and total intra-operative complications (OR = 0.38, 95% CrI: 0.17–0.75) as well as a higher disease-free survival (OR = 2.45, 95% CrI: 1.04–6.34). Conclusions: For treating early endometrial cancer, minimal-access surgery via robotic-assisted or laparoscopic techniques appears safer and more efficacious than open surgery. Robotic-assisted surgery is associated with fewer complications and favourable oncological outcomes. [ABSTRACT FROM AUTHOR]

Simple Summary: This position paper aims to address specific clinical questions regarding the use of cyclin-dependent kinase 4/6 inhibitors in elderly patients with early or advanced breast cancer. Its objectives are to delineate the current state of knowledge regarding the efficacy of these treatments in the elderly population and their tolerance profile, including the impact on quality of life, with a particular focus on the frailest subgroups, and to attempt to define the optimal treatment strategy for elderly and fragile patients (dosage and therapeutic sequence). Background: Breast cancer (BC) incidence increases with age, particularly in HR-positive/HER2-negative subtypes. Cyclin-dependent kinase 4 and 6 inhibitors (CDK 4/6is) alongside endocrine therapy (ET) have emerged as promising treatments for HR-positive/HER2-negative advanced and early BC. However, their efficacy, safety, and impact on quality of life (QoL) in older and frail patients remain underexplored. Methods: This position paper assesses the existing literature from 2015 to 2024, focusing on CDK4/6is use in patients aged 65 years and older with HR-positive/HER2-negative BC. Results: Our analysis methodically addresses critical questions regarding the utilization of CDK4/6is in the elderly BC patient population, organizing findings from the metastatic and adjuvant settings. In the metastatic setting, CDK4/6is significantly improve progression-free survival (PFS), paralleling benefits observed in younger patients, and suggest potential overall survival (OS) benefits, warranting further investigation. Despite an increased incidence of grade ≥ 3 adverse events (AEs), such as neutropenia and asthenia, CDK4/6is present a markedly lower toxicity profile compared to traditional chemotherapy, with manageable side effects. QoL analysis indicates that integrating CDK4/6is into treatment regimens does not significantly impact elderly BC patients' daily life and symptom management. Special attention is given to frail subgroups, and personalized approaches are recommended to balance efficacy and adverse effects, such as starting with ET alone and introducing CDK4/6is upon progression in patients with a low disease burden. Transitioning to the adjuvant setting, early results, particularly with abemaciclib, indicate positive effects on disease-free survival (DFS), emphasizing the need for continued analysis to validate these findings and assess long-term implications. However, data on older patients are insufficient to conclude whether they truly benefit from this treatment. Conclusion: Overall, CDK4/6is present a favorable benefit-risk profile in older BC patients, at least in advanced BC; however, further research is warranted to optimize treatment strategies and improve outcomes in this population [ABSTRACT FROM AUTHOR]

Simple Summary: Angiosarcoma is a rare type of soft tissue sarcoma with a progressive and unpredictable disease course. Currently, surgery is the only well-defined treatment option. Adjuvant oncological treatment remains inconclusive. In effort to provide evidence for improved management and follow-up, the purpose of this study was to assess treatment outcomes and identify prognostic factors. We identified a nation-wide cohort of 154 patients with complete follow-up. Adjuvant oncological treatment did not benefit overall survival, risk of metastasis, or recurrence. Cutaneous tumors, surgery, and negative margin showed improved overall survival, yet without reducing the risk of recurrence and metastasis, resulting in a grave overall survival rate. Angiosarcoma is a rare aggressive and understudied soft tissue sarcoma with pending evidence-based treatment guidelines due to varying study cohorts and inconsistent outcome measures. Surgery with wide resection is currently considered to be the cornerstone in management. In a population-based cohort identified from Danish National Health Registers between 2000 and 2017, this study aimed to define prognostic factors in patients with newly diagnosed soft tissue angiosarcoma. Kaplan–Meier survival analysis demonstrated 5-year overall survival of 28%. Competing risk analysis demonstrated cumulative incidence of local recurrence of 30% and metastasis of 43%. Multivariable Cox models among 154 included patients demonstrated age above 60 years and metastasis to be independently associated with worse overall survival. Cutaneous tumors, surgery, and negative resection margin were independently associated with improved overall survival. Adjuvant oncological treatment did not improve overall survival, risk of metastasis, or recurrence. Negative margin was not associated with lower risk of recurrence and metastasis. We conclude that, despite demonstrated improved survival after surgery with wide resection, overall survival remains poor. [ABSTRACT FROM AUTHOR]

Simple Summary: Despite the promising evidence of the Royal Marsden Hospital (RMH) score as a readily available prognostic biomarker in patients with cancer, the wide scale implementation in clinical practice as well as the true benefit in clinical decision-making is lacking. Therefore, we systematically reviewed the available evidence on the association between the RMH score and prognosis in patients with cancer. This comprehensive meta-analysis, encompassing over a hundred thousand patients, revealed a negative association between a higher RMH score and survival in cancer patients. The available evidence demonstrates that the RMH score is not only a selective biomarker for patients enrolled in clinical trials, but also a useful prognostic biomarker in a real-world setting. Future research should aim to validate and refine this score, ensuring its optimal application in clinical practice and decision-making. Background: Cancer remains a leading cause of death globally, necessitating the identification of prognostic biomarkers to guide treatment decisions. The Royal Marsden Hospital (RMH) score, based on readily available blood tests and clinical features, has emerged as a prognostic tool, although its performance across variable clinical scenarios is not thoroughly delineated. Therefore, we aimed to systematically assess the association between RMH score and survival in cancer patients. Methods: We conducted a systematic literature search across Pubmed, Scopus, and Web of Science databases for studies published up to 15 February 2024. We performed a meta-analysis with the generic inverse variance method with a random-effects model and reported hazard ratios (HR) with 95% confidence intervals (CI). Results: Nineteen studies encompassing 127,230 patients were included. A higher RMH score was significantly associated with worse overall survival (OS) (HR: 2.09, 95% CI: 1.87–2.33, p < 0.001) and progression-free survival (PFS) (HR: 1.80, 95% CI: 1.48–2.18, p < 0.001). This association was consistent across various subgroups, including study population (clinical trial vs. real-world cohort), geographic region, and tumor type. Conclusion: This meta-analysis, including over a hundred thousand patients, demonstrates a negative association between a higher RMH score and survival in cancer patients. The RMH score holds promise as a readily available prognostic tool across diverse cancer types and clinical settings. Future research should focus on validating and refining this score to aid clinical decision-making. [ABSTRACT FROM AUTHOR]

Simple Summary: Deleterious LKB1 inactivation in KRAS-driven lung adenocarcinomas (LUACs) has been studied thoroughly; however, LKB1 inactivation is not limited in adenocarcinomatous histology, nor in KRAS mutational status. We investigated LKB1 loss by IHC in 188 metastatic and 60 non-metastatic tumors from patients with operable non-small cell lung cancer (NSCLC) of various histologies and its correlation with cell cycle targets, EMT inducers, antitumor immunity response regulators, cell adhesion molecules and KRAS co-mutations. LKB1 loss was associated with STING loss irrespective of KRAS status both overall and in lung adenocarcinomas (LUACs) and, importantly, also in the metastatic setting. Concurrent LKB1 loss and β-catenin loss of membranous expression correlated with a significant decrease in median overall survival and increased risk of death. The expression status of LKB1 in association with STING and β-catenin membranous expression status could be used as stratification factors for patients with operable NSCLC in the procedure of precision medicine in lung cancer. To investigate the incidence and prognostically significant correlations and cooperations of LKB1 loss of expression in non-small cell lung cancer (NSCLC), surgical specimens from 188 metastatic and 60 non-metastatic operable stage I-IIIA NSCLC patients were analyzed to evaluate their expression of LKB1 and pAMPK proteins in relation to various processes. The investigated factors included antitumor immunity response regulators STING and PD-L1; pro-angiogenic, EMT and cell cycle targets, as well as metastasis-related (VEGFC, PDGFRα, PDGFRβ, p53, p16, Cyclin D1, ZEB1, CD24) targets; and cell adhesion (β-catenin) molecules. The protein expression levels were evaluated via immunohistochemistry; the RNA levels of LKB1 and NEDD9 were evaluated via PCR, while KRAS exon 2 and BRAFV600E mutations were evaluated by Sanger sequencing. Overall, loss of LKB1 protein expression was observed in 21% (51/248) patients and correlated significantly with histotype (p < 0.001), KRAS mutations (p < 0.001), KC status (concomitant KRAS mutation and p16 downregulation) (p < 0.001), STING loss (p < 0.001), and high CD24 expression (p < 0.001). STING loss also correlated significantly with loss of LKB1 expression in the metastatic setting both overall (p = 0.014) and in lung adenocarcinomas (LUACs) (p = 0.005). Additionally, LKB1 loss correlated significantly with a lack of or low β-catenin membranous expression exclusively in LUACs, both independently of the metastatic status (p = 0.019) and in the metastatic setting (p = 0.007). Patients with tumors yielding LKB1 loss and concomitant nonexistent or low β-catenin membrane expression experienced significantly inferior median overall survival of 20.50 vs. 52.99 months; p < 0.001 as well as significantly greater risk of death (HR: 3.32, 95% c.i.: 1.71–6.43; p <0.001). Our findings underscore the impact of the synergy of LKB1 with STING and β-catenin in NSCLC, in prognosis. [ABSTRACT FROM AUTHOR]

Simple Summary: Pleural mesothelioma (PM) is characterized by its poor prognosis due to late-stage diagnosis, limited effective treatment options and the lack of biomarkers for treatment decision. The role of macroscopic radical surgery has therefore been questioned. Thus, there is an urgent need for predictive biomarkers aiding clinicians in tailoring more personalized and effective therapeutic strategies. Besides validating the prognostic role of Ki67 expression in tumor samples in 70 PM patients from two different centers with detailed clinical characteristics, here we suggest for the first time Ki67 as a biomarker to predict the patient's benefit from lung-sparing surgery within multimodality therapy in epithelioid mesothelioma. Pleural mesothelioma (PM), linked to asbestos-induced inflammation, carries a poor prognosis. Therapy ranges from therapy limitation to aggressive multimodality treatment. Given the uncertainty about treatment benefits for patients, this study aimed to assess the role of Ki67 as a prognostic and predictive parameter in PM. Ki67 was measured in the specimens of 70 PM patients (17 female, 53 male) from two centers and correlated to overall survival (OS) and therapy outcome. The median OS was 16.1 months. The level of Ki67 expression was divided into low (≤15%) and high (>15%). A low value of Ki67 expression was associated with a longer OS (Ki67 ≤ 15%: 31.2 (95% CI 6.5–55.8) months vs. Ki67 > 15%: 11.1 (95% CI 7.7–14.6) months, p = 0.012). The 5-year survival represents 22% in the low Ki67 expression group, in contrast to 5% in the high Ki67 expression group. We found a significant interaction term of Ki67 with multimodality treatment (p = 0.031) translating to an OS of 48.1 months in the low expression Ki67 group compared to 24.3 months in the high Ki67 expression group when receiving surgery within multimodality therapy. Therefore, Ki67 stands out as a validated prognostic and, most importantly, novel predictive biomarker for treatment benefits, particularly regarding surgery within multimodality therapy. [ABSTRACT FROM AUTHOR]

Simple Summary: This study aims to describe the factors associated with poor mobilization in patients undergoing autologous peripheral blood stem cell harvest. Poor mobilization was observed in 30.5% of the patients included in the investigation. While older age, myelotoxic agents, and low platelet counts were associated with poor mobilization in patients with hematologic diseases, a history of radiation therapy to the spine and pelvic region was associated with mobilization failure in patients with non-hematologic diseases. In patients who received plerixafor, 14.2% suffered from mobilization failure, with differences in hemoglobin, platelet counts, and mobilization regimens noted between the poor and good mobilization groups. Identifying potential risk factors for poor mobilization in specific groups of patients will aid in planning therapy and ensuring successful transplantation in those requiring hematopoietic stem cell transplants. Peripheral blood stem cell transplantation (PBSCT) is an important therapeutic measure for both hematologic and non-hematologic diseases. For PBSCT to be successful, sufficient CD34+ cells need to be mobilized and harvested. Although risk factors associated with poor mobilization in patients with hematologic diseases have been reported, studies of patients with non-hematologic diseases and those receiving plerixafor are rare. To identify factors associated with poor mobilization, data from autologous PBSC harvest (PBSCH) in 491 patients were retrospectively collected and analyzed. A multivariate analysis revealed that in patients with a hematologic disease, an age older than 60 years (odds ratio [OR] 1.655, 95% confidence interval [CI] 1.049–2.611, p = 0.008), the use of myelotoxic agents (OR 4.384, 95% CI 2.681–7.168, p < 0.001), and a low platelet count (OR 2.106, 95% CI 1.205–3.682, p = 0.009) were associated with poor mobilization. In patients with non-hematologic diseases, a history of radiation on the pelvis/spine was the sole associated factor (OR 12.200, 95% CI 1.934–76.956, p = 0.008). Among the group of patients who received plerixafor, poor mobilization was observed in 19 patients (19/134, 14.2%) and a difference in the mobilization regimen was noted among the good mobilization group. These results show that the risk factors for poor mobilization in patients with non-hematologic diseases and those receiving plerixafor differ from those in patients with hematologic diseases; as such, non-hematologic patients require special consideration to enable successful PBSCH. [ABSTRACT FROM AUTHOR]

Simple Summary: Although several techniques exist for reconstructing partial hypopharyngeal defects following a total laryngectomy, no international consensus has been reached to date. As a result, there currently are large differences between institutions with regard to the flap types used to perform these reconstructions. The aim of this systematic review and meta-analysis was to examine the complication rates and functional results of commonly used reconstructive techniques for hypopharyngeal defects. Pectoralis major myofascial flaps showed promising results compared to free-flap reconstructions, with similar rates of fistulas, strictures and flap failure. In contrast, pectoralis major myocutaneous flaps had a significantly higher fistula rate (34%) in comparison to other flap types (range: 7–17%), whereas no differences were observed for strictures, flap failure or oral intake. Free flaps and pectoralis major myofascial flaps should be considered the preferred methods for the reconstruction of partial hypopharyngeal defects following total laryngectomy. Background: Various operative techniques exist to reconstruct partial hypopharyngeal defects following total laryngectomy. The current study aimed to investigate and compare complications and functional results following commonly used reconstructive techniques. Methods: A systematic review and meta-analysis were performed using studies that investigated outcomes after the reconstruction of a partial hypopharyngeal defect. The outcomes of interest were fistulas, strictures, flap failure, swallowing function and postoperative speech. Results: Of the 4035 studies identified, 23 were included in this review. Four common reconstructive techniques were reported, with a total of 794 patients: (1) pectoralis major myocutaneous and (2) myofascial flap, (3) anterolateral thigh free flap and (4) radial forearm free flap. Fistulas occurred significantly more often than pectoralis major myocutaneous flaps (34%, 95% CI 23–47%) compared with other flaps (p < 0.001). No significant differences in the rates of strictures or flap failure were observed. Pectoralis major myofascial flaps were non-inferior to free-flap reconstructions. Insufficient data were available to assess speech results between flap types. Conclusion: Pectoralis myocutaneous flaps should not be the preferred method of reconstruction for most patients, considering their significantly higher rate of fistulas. In contrast, pectoralis major myofascial flaps yield promising results compared to free-flap reconstructions, warranting further investigation. [ABSTRACT FROM AUTHOR]

Simple Summary: Pembrolizumab monotherapy remains the first-line standard of care for patients with metastatic NSCLC and a PD-L1 tumor proportion score ≥ 50%. However, although other real-world studies have been published, long-term follow-up data on progression-free survival, overall survival, treatment response, and safety in a large cohort of patients are still lacking. We evaluated these outcomes in a cohort of 880 patients treated with first-line pembrolizumab monotherapy in 16 Italian centers. We also analyzed the prognostic impact of variables such as age, sex, histology, PD-L1 expression, ECOG, habitual smoking, and the presence of brain metastases. Median PFS and OS were 8.6 and 25.5 months, respectively, consistent with the results of Keynote-024. According to univariate analysis, it was determined that PD-L1 expression, ECOG, and habitual smoking had an impact on PFS, while age, sex, ECOG, histology, and habitual smoking had an impact on OS. However, results from univariate analysis should be considered with caution. Results from the phase III Keynote-024 clinical trial established pembrolizumab monotherapy as the first-line standard of care for patients with metastatic NSCLC who have PD-L1 expression ≥ 50%, EGFR, and ALK wild-type tumors. However, given the differences between patients treated in routine clinical practice and those treated in a clinical trial, real-world data are needed to confirm the treatment benefit in standard practice. Given the lack of data on large cohorts of patients with long follow-ups, we designed an observational retrospective study of patients with metastatic NSCLC who were treated with pembrolizumab, starting from its reimbursement eligibility until December 2020. The primary endpoints were PFS and OS, determined using the Kaplan–Meier method. Response and safety were also evaluated. We followed 880 patients (median follow-up: 35.1 months) until February 2022. Median PFS and OS were 8.6 months (95% CI: 7.6–10.0) and 25.5 months (95% CI: 21.8–31.6), respectively. We also found that ECOG PS, PD-L1 expression, and habitual smoking were prognostic factors for PFS, while age, sex, ECOG PS, habitual smoking and histology had an impact on OS. Multivariable analysis confirms the prognostic role of PD-L1 for PFS and of ECOG for both PFS and OS. 39.9% of patients reported an adverse event, but only 6.3% of patients discontinued therapy due to toxicity. Our results suggest a long-term benefit of pembrolizumab in the first-line setting, as well as a safety profile consistent with the results of Keynote-024. Many collected variables appear to influence clinical outcome, but results from these exploratory unadjusted analyses should be interpreted with caution. [ABSTRACT FROM AUTHOR]

Simple Summary: Metastatic triple-negative breast cancer is an aggressive cancer with an average survival of 8 to 13 months. However, survival varies significantly among patients. We studied a large group of women in the National Cancer Database to better understand these survival differences. We found that the key factors influencing survival were comorbidity score (overall health status), histology (cancer subtype), number of metastatic sites (extent of cancer spread), and whether or not they received chemotherapy or immunotherapy. Our study's findings can help better predict survival based on an individual's specific factors and guide treatment strategies. Background: Metastatic triple-negative breast cancer (TNBC) is aggressive with poor median overall survival (OS) ranging from 8 to 13 months. There exists considerable heterogeneity in survival at the individual patient level. To better understand the survival heterogeneity and improve risk stratification, our study aims to identify the factors influencing survival, utilizing a large patient sample from the National Cancer Database (NCDB). Methods: Women diagnosed with metastatic TNBC from 2010 to 2020 in the NCDB were included. Demographic, clinicopathological, and treatment data and overall survival (OS) outcomes were collected. Kaplan–Meier curves were used to estimate OS. The log-rank test was used to identify OS differences between groups for each variable in the univariate analysis. For the multivariate analysis, the Cox proportional hazard model with backward elimination was used to identify factors affecting OS. Adjusted hazard ratios and 95% confidence intervals are presented. Results: In this sample, 2273 women had a median overall survival of 13.6 months. Factors associated with statistically significantly worse OS included older age, higher comorbidity scores, specific histologies, higher number of metastatic sites, presence of liver or other site metastases in those with only one metastatic site (excluding brain metastases), presence of cranial and extra-cranial metastases, lack of chemotherapy, lack of immunotherapy, lack of surgery to distant sites, lack of radiation to distant sites, and receipt of palliative treatment to alleviate symptoms. In the multivariate analysis, comorbidity score, histology, number of metastatic sites, immunotherapy, and chemotherapy had a statistically significant effect on OS. Conclusions: Through NCDB analysis, we have identified prognostic factors for metastatic TNBC. These findings will help individualize prognostication at diagnosis, optimize treatment strategies, and facilitate patient stratification in future clinical trials. [ABSTRACT FROM AUTHOR]

Simple Summary: Lockdowns and health service disruptions during the COVID-19 pandemic led to concerns about a potential decrease in essential health screenings, even after the pandemic. It is crucial to understand how the pandemic affected women's participation in breast cancer screenings in Japan and whether getting the COVID-19 vaccine influenced their participation rates. We analyzed data from over 6110 women aged 40 to 74 years from a large online survey conducted in 2021 and 2022. Our findings showed that the number of women getting screened for breast cancer did not decrease after the pandemic. Moreover, women who were vaccinated against COVID-19 were more likely to attend their screenings compared to those who were not vaccinated. This result aligns with the observation that vaccinated individuals tend to be more proactive about their health. There is limited information on whether the COVID-19 pandemic was associated with decreased breast cancer screening uptake and if COVID-19 vaccination was associated with an increase in screening uptake. Our study explored the uptake of breast cancer screening in Japan after the COVID-19 pandemic and assessed its association with the COVID-19 vaccination. We analyzed data from the Japan COVID-19 and Society Internet Survey (JACSIS), a web-based prospective cohort survey, and we included 6110 women without cancer history who were aged 40 to 74 years that participated in the 2012 and 2022 surveys. We examined the regular breast cancer screening uptake before and after the pandemic and employed a multivariable Poisson regression model to seek any association between COVID-19 vaccination and screening uptake. Of 6110, 38.2% regularly participated in screening before the pandemic and 46.9% did so after the pandemic. Individuals unvaccinated due to health reasons (incidence rate ratio (IRR) = 0.47, 95% CI: 0.29–0.77, p = 0.003) and for other reasons (IRR = 0.73, 95% CI: 0.62–0.86, p < 0.001) were less likely to undergo screening compared to fully vaccinated individuals. There was no long-term decrease in breast cancer screening uptake after the pandemic in Japan. Vaccination was linked to increased uptake, but there was no dose relationship. [ABSTRACT FROM AUTHOR]

Simple Summary: Richter transformation (RT) is characterized by the transformation of CCL in the aggressive lymphoma variant with a significant worsening in prognosis. Initial reports about a substantial impact of 2-deoxy-2-[18F]-fluoro-D-glucose positron emission tomography/computed tomography (2-[18F]FDG PET/CT) in predicting RT are available in the literature. Using data from 15 published studies, including 1593 CLL patients, we demonstrated that 2-[18F]FDG uptake expressed as the maximum standardized uptake value (SUVmax) has a high negative predictive value. Richter transformation is a rare phenomenon characterized by the transformation of cell chronic lymphocytic leukemia (CLL) into a more aggressive lymphoma variant. The early identification of CLLs with a high risk of RT is fundamental. In this field, 2-deoxy-2-[18F]-fluoro-D-glucose positron emission tomography/computed tomography (2-[18F]FDG PET/CT) has been shown to be a non-invasive and promising tool, but apparently, unclear data seem to be present in the literature. This systematic review and bivariate meta-analysis aimed to investigate the diagnostic performance of 2-[18F]FDG PET/CT and its parameters in predicting RT. Between 2006 and 2024, 15 studies were published on this topic, including 1593 CLL patients. Among semiquantitative variables, SUVmax was the most investigated, and the best threshold derived for detecting RT was five. With this cut-off value, a pooled sensitivity of 86.8% (95% CI: 78.5–93.3), a pooled specificity of 48.1% (95% CI: 27–69.9), a pooled negative predictive value of 90.5% (95% CI: 88.4–92.4), a pooled negative likelihood ratio of 0.35 (95% CI: 0.17–0.70), a pooled positive likelihood ratio of 1.8 (95% CI: 1.3–2.4), and a pooled diagnostic odds ratio of 6.7 (3.5–12.5) were obtained. With a higher cut-off (SUVmax = 10), the specificity increased while the sensitivity reduced. The other metabolic features, like metabolic tumor volume, total lesion glycolysis, and radiomic features, were only marginally investigated with controversial evidence. [ABSTRACT FROM AUTHOR]

Simple Summary: Sex differences in cancer are well-established. However, less is known about sex differences in the diagnosis of brain metastasis and outcomes among patients with advanced melanoma. Using the nationwide Flatiron Health electronic health record-derived de-identified database, this study showed that males had greater odds of brain metastasis, and poorer real-world overall survival compared to females among those with brain metastasis, while there were no sex differences in clinical outcomes for those with advanced melanoma without brain metastasis. Sex differences in cancer are well-established. However, less is known about sex differences in diagnosis of brain metastasis and outcomes among patients with advanced melanoma. Using a United States nationwide electronic health record-derived de-identified database, we evaluated patients diagnosed with advanced melanoma from 1 January 2011–30 July 2022 who received an oncologist-defined rule-based first line of therapy (n = 7969, 33% female according to EHR, 35% w/documentation of brain metastases). The odds of documented brain metastasis diagnosis were calculated using multivariable logistic regression adjusted for age, practice type, diagnosis period (pre/post-2017), ECOG performance status, anatomic site of melanoma, group stage, documentation of non-brain metastases prior to first-line of treatment, and BRAF positive status. Real-world overall survival (rwOS) and progression-free survival (rwPFS) starting from first-line initiation were assessed by sex, accounting for brain metastasis diagnosis as a time-varying covariate using the Cox proportional hazards model, with the same adjustments as the logistic model, excluding group stage, while also adjusting for race, socioeconomic status, and insurance status. Adjusted analysis revealed males with advanced melanoma were 22% more likely to receive a brain metastasis diagnosis compared to females (adjusted odds ratio [aOR]: 1.22, 95% confidence interval [CI]: 1.09, 1.36). Males with brain metastases had worse rwOS (aHR: 1.15, 95% CI: 1.04, 1.28) but not worse rwPFS (adjusted hazard ratio [aHR]: 1.04, 95% CI: 0.95, 1.14) following first-line treatment initiation. Among patients with advanced melanoma who were not diagnosed with brain metastases, survival was not different by sex (rwOS aHR: 1.06 [95% CI: 0.97, 1.16], rwPFS aHR: 1.02 [95% CI: 0.94, 1.1]). This study showed that males had greater odds of brain metastasis and, among those with brain metastasis, poorer rwOS compared to females, while there were no sex differences in clinical outcomes for those with advanced melanoma without brain metastasis. [ABSTRACT FROM AUTHOR]

Simple Summary: Head and neck cancer is associated with significant morbidity. Shoulder and neck dysfunction, weight loss, and declines in muscular strength and physical functioning are commonly seen following cancer therapies. This pragmatic randomized controlled trial involved sixty-one individuals with cancer in the head and neck region who had completed their cancer treatment. The primary aim was to assess the effectiveness of the addition of lower-body resistance exercise training to a physiotherapeutic shoulder and neck exercise protocol on fatigue-related quality of life. Findings support the benefit of the combined intervention for fatigue-related quality of life, six-minute walk test distance, upper- and lower-body muscular strength, and physical activity level. The continued improvement in treatment effect over the one-year follow-up period suggests promise from this interdisciplinary approach to bridge individuals with head and neck cancer from rehabilitation care to general exercise and physical activity. Background: Established barriers to general exercise and physical activity among individuals with head and neck cancer include dry mouth, difficulty eating, weight loss, fear of injury, comorbidities, and treatment-related symptoms of pain and fatigue. Methods/Design: A 12-week pragmatic randomized controlled trial was conducted followed by an optional supported exercise transition phase. Eligible participants were individuals with head and neck cancers who had undergone surgery and/or radiation therapy to lymph node regions in the neck. Participants were randomized to a comparison group involving a shoulder and neck physiotherapeutic exercise protocol, or to a combined experimental group comprising the shoulder and neck physiotherapeutic exercise protocol and lower-body resistance exercise training. The primary outcome of this study was fatigue-related quality of life. Results: Sixty-one participants enrolled, 59 (97%) completed the randomized trial phase, 55 (90%) completed the 24-week follow-up, and 52 (85%) completed the one-year follow-up. Statistically significant between-group differences were found in favor of the combined experimental group for the fatigue-related quality of life, fitness outcomes, and overall physical activity. Paired comparisons confirmed significant within-group improvements for both groups from baseline to one-year follow-up across most outcomes. Discussion: A group-based combined physiotherapeutic and lower-body resistance exercise program was feasible and effective. Findings are limited to individuals who had undergone a surgical neck dissection procedure. Given the complexity of head and neck cancer, further pragmatic interdisciplinary research is warranted. [ABSTRACT FROM AUTHOR]

Simple Summary: Newly diagnosed type 2 diabetes mellitus is associated with a higher risk of cancer, possibly in young individuals with diabetes. While the incidence of cancer is mildly decreasing in the background population, it does not decrease in patients with type 2 diabetes. In non-diabetic persons, certain types of cancer also occur in young age, while the 60–69-year-old group dominates for cancer cases in patients with type 2 diabetes. The majority of the new cancer cases is recognized within 6 months after the diagnosis of diabetes. This may call for increased cancer surveillance in patients with newly diagnosed type 2 diabetes mellitus. (1) Background: Patients with type 2 diabetes mellitus (T2DM) are at higher risk of cancer but how these two diseases associate is still debated. The goal of this study was the assessment of the overall incidence of cancer among patients with newly diagnosed T2DM in Hungary. (2) Methods: A nationwide, retrospective, longitudinal study was performed using a Hungarian database. After exclusion of cases of age < 18 years, with gestational diabetes, with polycystic ovary syndrome, and with type 1 and prevalent type 2 diabetes mellitus, the incident T2DM (approx. 50,000 cases yearly) and for comparison, the diabetes-free Hungarian adult population (approx. 7,000,000 cases yearly) was included in the study. The primary endpoints were the overall and site-specific incidence and annual percentage change of the incidence of cancer in both populations. (3) Results: The overall incidence of cancer in patients amounted to 29.4/1000 and 6.6/1000 with or without T2DM, respectively, and the OR (95%CI) of cancer of the T2DM group was 4.32 (4.14–4.53), p < 0.0001. The risk of having cancer was age dependent. The incidence of cancer was declining in the non-diabetic but was unchanged in the T2DM population. The average lag time of diagnosing cancer after the detection of T2DM was 3.86 months. (4) Conclusions: Incident T2DM is associated with a significantly higher overall risk of incident cancer, with a reverse correlation of age. Newly registered T2DM patients were suggested to be screened for cancer within 6 months. [ABSTRACT FROM AUTHOR]

Simple Summary: In this prospective cohort study of metastatic melanoma patients receiving immune checkpoint inhibitors, we identified a serum chemokine CCL20 increase at baseline with a significantly impaired progression-free and overall survival and as an independent negative prognostic factor for PFS and OS in univariate as well as in multivariate analysis. CCL20 may represent a novel blood biomarker for the prediction of prognosis in advanced melanoma under immunotherapy with a special emphasis on progression. Background: Immune checkpoint inhibition has revolutionized melanoma therapy, but many patients show primary or secondary resistance. Biomarkers are, therefore, urgently required to predict response prior to the initiation of therapy and to monitor disease progression. Methods: In this prospective study, we analyzed the serum C-C motif chemokine ligand 20 (CCL20) concentration using an enzyme-linked immunosorbent assay. Blood was obtained at baseline before the initiation of immunotherapy with anti-PD-1 monotherapy or Nivolumab and Ipilimumab in advanced melanoma patients (stages III and IV) enrolled at the University Medical Center Hamburg-Eppendorf. The CCL20 levels were correlated with clinico-pathological parameters and disease-related outcomes. Results: An increased C-C motif chemokine ligand 20 (CCL20) concentration (≥0.34 pg/mL) at baseline was associated with a significantly impaired progression-free survival (PFS) in the high-CCL20 group (3 months (95% CI: 2–6 months) vs. 11 months (95% CI: 6–26 months)) (p = 0.0033) and could be identified as an independent negative prognostic factor for PFS in univariate (Hazard Ratio (HR): 1.98, 95% CI 1.25–3.12, p = 0.004) and multivariate (HR: 1.99, 95% CI 1.21–3.29, p = 0.007) Cox regression analysis, which was associated with a higher risk than S100 (HR: 1.74). Moreover, high CCL20 levels were associated with impaired overall survival (median OS not reached for low-CCL20 group, p = 0.042) with an HR of 1.85 (95% CI 1.02–3.37, p = 0.043) in univariate analysis similar to the established prognostic marker S100 (HR: 1.99, 95% CI: 1.02–3.88, p = 0.043). Conclusions: CCL20 may represent a novel blood-based biomarker for the prediction of resistance to immunotherapy that can be used in combination with established strong clinical predictors (e.g., ECOG performance score) and laboratory markers (e.g., S100) in advanced melanoma patients. Future prospective randomized trials are needed to establish CCL20 as a liquid biopsy-based biomarker in advanced melanoma. [ABSTRACT FROM AUTHOR]

Simple Summary: We aimed to investigate potential prognostic markers for enfortumab vedotin therapy in Asian patients with advanced or metastatic urothelial carcinoma. We retrospectively enrolled 61 Japanese patients treated with enfortumab vedotin therapy and analyzed overall survival, adverse events, and potential prognostic markers. Enrolled patients (38 men, 23 women; median age 74 [IQR: 68–79] years) had bladder cancer (26 patients) or upper-tract urothelial carcinoma (35 patients). Our study provides real-world data showing that enfortumab vedotin prolonged survival in Asian patients similar to the EV-301 trial. Additionally, the C-reactive protein level might be considered a prognostic marker of enfortumab vedotin therapy in such patients. Background: In the EV-301 trial, enfortumab vedotin prolonged survival in patients with locally advanced or metastatic urothelial carcinoma previously treated with platinum-based therapy and programmed cell death 1/programmed death-ligand 1 inhibitor. However, real-world Asian data are limited, and potential prognostic markers are non-existent. We aimed to investigate potential prognostic markers for enfortumab vedotin therapy in Asian patients. Methods: We retrospectively enrolled 61 Japanese patients treated with enfortumab vedotin therapy at our hospital and affiliated hospitals between January 2019 and September 2023. Results: Enrolled patients (38 men, 23 women; median age 74 [IQR: 68–79] years) had bladder cancer (26 patients) or upper-tract urothelial carcinoma (35 patients). Fifty-four patients reported adverse events (grade >3 in 12). Skin disorders, pruritus, and neuropathy were common adverse effects. The median overall survival was 17.1 months (95% confidence interval: 10.0–not applicable). In multivariate analysis, the C-reactive protein level was an independent marker predicting favorable overall survival with enfortumab vedotin. Patient characteristics did not differ between C-reactive protein-high and -low groups. Conclusions: Our study provides real-world data showing that enfortumab vedotin prolonged survival in Asian patients similar to the EV-301 trial. Additionally, the C-reactive protein level might be considered a prognostic marker of enfortumab vedotin therapy in such patients. [ABSTRACT FROM AUTHOR]

Simple Summary: Melanoma is the most common primary intra-ocular cancer in adults. In case of suspected extra-ocular tumoral involvement, patients may be required to undergo computed tomography (CT) and magnetic resonance imaging (MRI). Positron emission tomography (PET) with 18F-Fluorodeoxyglucose (18F-FDG) is another imaging modality that can be used in uveal melanoma assessment. Although comprehensive systematic reviews and meta-analyses were published on the role of 18F-FDG PET imaging in cutaneous melanoma, there is no ample evidence regarding its value in uveal melanoma patients. Thus, in this systematic review and meta-analysis, we tried to investigate the existing literature and provide a comprehensive study on the diagnostic and prognostic values of 18F-FDG PET in uveal melanoma. In this systematic review and meta-analysis (PRISMA-compliant), we tried to investigate diagnostic and prognostic values of 18F-FDG PET in uveal melanoma. A systematic search was conducted on the main medical literature databases to include studies that evaluated 18F-FDG PET as the imaging modality to evaluate patients with uveal melanoma. Overall, 27 studies were included. Twelve had data about the detection rate of 18F-FDG PET in primary intra-ocular tumours. The pooled sensitivity was 45% (95%CI: 41–50%). Furthermore, studies showed that the larger the primary tumour, the higher its uptake. Among the included studies, 13 assessed 18F-FDG PET in detecting metastasis. The pooled sensitivity and specificity were 96% (95%CI: 81–99%) and 100% (95%CI: 94–100%), respectively. Regarding liver metastasis, they were 95% (95%CI: 79–99%) and 100% (95%CI: 91–100%), respectively. Noteworthy, the level of 18F-FDG uptake was a strong predictor of patient survival. Lastly, 18F-FDG PET could characterise lesions from the histopathology perspective, distinguishing high-risk from low-risk diseases. Overall, although not reliable in detecting primary intra-ocular tumours, 18F-FDG PET is highly accurate for diagnosing metastatic uveal melanomas. It can also be a highly valuable modality in terms of patient prognostication. Thus, 18F-FDG PET can be recommended in patients diagnosed with uveal melanoma to enhance decision-making and patient management. [ABSTRACT FROM AUTHOR]

Simple Summary: Compared to socioeconomically affluent areas, lower breast cancer incidence and similar or higher mortality have been reported in deprived areas. We provide a possible explanation to this paradox, by estimating and comparing incidence by stage at diagnosis between different levels of area-based socioeconomic deprivation in France. As deprivation increased, all-stages and early (stage I and stage II) invasive breast cancer incidence significantly decreased, while advanced (stage III–IV) breast cancer incidence significantly increased. In this study, we assessed the influence of area-based socioeconomic deprivation on the incidence of invasive breast cancer (BC) in France, according to stage at diagnosis. All women from six mainland French departments, aged 15+ years, and diagnosed with a primary invasive breast carcinoma between 2008 and 2015 were included (n = 33,298). Area-based socioeconomic deprivation was determined using the French version of the European Deprivation Index. Age-standardized incidence rates (ASIR) by socioeconomic deprivation and stage at diagnosis were compared estimating incidence rate ratios (IRRs) adjusted for age at diagnosis and rurality of residence. Compared to the most affluent areas, significantly lower IRRs were found in the most deprived areas for all-stages (0.85, 95% CI 0.81–0.89), stage I (0.77, 95% CI 0.72–0.82), and stage II (0.84, 95% CI 0.78–0.90). On the contrary, for stages III–IV, significantly higher IRRs (1.18, 95% CI 1.08–1.29) were found in the most deprived areas. These findings provide a possible explanation to similar or higher mortality rates, despite overall lower incidence rates, observed in women living in more deprived areas when compared to their affluent counterparts. Socioeconomic inequalities in access to healthcare services, including screening, could be plausible explanations for this phenomenon, underlying the need for further research. [ABSTRACT FROM AUTHOR]

Simple Summary: We aimed to identify risk factors and evaluate the accuracy of existing risk stratifications developed for non-muscle-invasive bladder cancer (NMIBC) regarding their ability to predict high-grade recurrence and progression. We included 171 NMIBC patients treated with TURBT and adjuvant BCG, of whom 73 experienced recurrence (42.7%), and 29 developed progression (17%). Available risk models (EORTC/ CUETO/ EAU) demonstrated limited accuracy in predicting high-grade recurrence-free (RFS) and progression-free survival (PFS). Multivariable analysis identified independent predictors for high-grade RFS, including T1HG tumor at repeat TURBT, tumor multiplicity, previous history of high-grade NMIBC, and EORTC2006 progression risk score. In conclusion, the available risk models lack accuracy in predicting high-grade RFS and PFS in BCG-treated NMIBC, suggesting potential improvement with the inclusion of additional risk factors. The currently available EORTC, CUETO and EAU2021 risk stratifications were originally developed to predict recurrence and progression in non-muscle-invasive bladder cancer (NMIBC). However, they have not been validated to differentiate between high-grade (HG) and low-grade (LG) recurrence-free survival (RFS), which are distinct events with specific implications. We aimed to evaluate the accuracy of available risk models and identify additional risk factors for HG RFS and PFS among NMIBC patients treated with Bacillus Calmette–Guérin (BCG). We retrospectively included 171 patients who underwent transurethral resection of the bladder tumor (TURBT), of whom 73 patients (42.7%) experienced recurrence and 29 (17%) developed progression. Initially, there were 21 low-grade and 52 high-grade recurrences. EORTC2006, EORTC2016 and CUETO recurrence scoring systems lacked accuracy in the prediction of HG RFS (C-index 0.63/0.55/0.59, respectively). EAU2021 risk stratification, EORTC2006, EORTC2016, and CUETO progression scoring systems demonstrated low to moderate accuracy (C-index 0.59/0.68/0.65/0.65) in the prediction of PFS. In the multivariable analysis, T1HG at repeat TURBT (HR = 3.17 p < 0.01), tumor multiplicity (HR = 2.07 p < 0.05), previous history of HG NMIBC (HR = 2.37 p = 0.06) and EORTC2006 progression risk score (HR = 1.1 p < 0.01) were independent predictors for HG RFS. To conclude, available risk models lack accuracy in predicting HG RFS and PFS in -NMIBC patients treated with BCG. [ABSTRACT FROM AUTHOR]

Simple Summary: Our study aimed to delineate the variables associated with the link between chronic periodontitis and hematologic cancers. The hazard ratio for hematologic cancers in patients with chronic periodontitis was also evaluated. Comprehensive statistical analyses revealed a 1.25-fold risk of hematologic cancers in the chronic periodontitis group. Factors such as being male and having hypertension were identified as increased risk factors for hematologic cancers. This nuanced exploration, including a subtype analysis for leukemia and lymphoma, contributes valuable insights into the complex relationship between chronic periodontitis and specific hematologic cancer subtypes. These findings could enhance our understanding of potential cancer risk factors in Taiwan. Background: Chronic periodontitis, an inflammation-related disorder affecting global populations, has been revealed to be linked to diverse cancers. Numerous epidemiological studies have not shown a link between chronic periodontitis and blood cancers in Taiwan. Methods: This study included 601,628 patients, diagnosed with newly chronic periodontitis by the ICD-9-CM classification, who were enrolled from 2001 to 2021 in the National Health Insurance Research Database (NHIRD) in Taiwan. In this study, we employed comprehensive statistical analyses to investigate the association between chronic periodontitis and hematologic cancers. Initially, we calculated incidence density and used a Poisson regression to analyze relative risk. Subsequently, we compared the cumulative incidence of hematological cancer in both chronic and non-chronic periodontitis groups using the Kaplan–Meier method. Results: The results revealed a significantly lower cumulative incidence of hematologic cancer in individuals with non-chronic periodontitis over a 12-year follow-up period. To further explore the risk factors, a Cox proportional hazard regression analysis was conducted. Being male (adjusted hazard ratio [aHR] = 1.21, 95% CI: 1.04 to 1.42; p = 0.014) and having hypertension (aHR = 1.34, 95% CI: 1.06 to 1.69; p = 0.015) were demonstrated to be associated with an increased risk of hematologic cancers, respectively. In addition, in a subtype multivariate analysis for categorizing hematologic cancers into lymphoma and leukemia, the aHR for leukemia was 1.48 (95% CI: 1.13 to 1.93; p = 0.004) and aHR for lymphoma was 1.15 (95% CI: 0.96 to 1.37; p = 0.140). Conclusions: This study found that being male and having hypertension were the significant risk factors for hematological malignancies. Moreover, the association between chronic periodontitis and specific subtypes of hematologic cancers was confirmed. [ABSTRACT FROM AUTHOR]

Simple Summary: There are publications on the use of Imiquimod in cervical intraepithelial neoplasia (CIN) and HPV clearance; however, the literature is not consistent about its efficacy. Moreover, in cervical precancers, surgical solutions are widely accepted therapies, despite their association with increased obstetrical complications, such as miscarriage and preterm birth. Therefore, a conservative solution is needed. Topical Imiquimod reduced CIN and enhanced HPV clearance, though surgical intervention conization was found to be more effective than Imiquimod treatment. Side effects were common, though mostly mild. Topical Imiquimod could be a valuable therapeutic option for CIN patients, especially for women who have future pregnancy desires. Imiquimod should be incorporated into guidelines as evidence shows it is effective and safe. Introduction: Topical Imiquimod is an immune response modifier approved for the off-label use of vulvar intraepithelial neoplasia. We conducted this systematic review and meta-analysis to investigate the efficacy and safety of Imiquimod in treating cervical intraepithelial neoplasia (CIN) and human papillomavirus (HPV)-positive patients. Methods: The study was prospectively registered (CRD420222870) and involved a comprehensive systematic search of five medical databases on 10 October 2022. We included articles that assessed the use of Imiquimod in cervical dysplasia and HPV-positive patients. Pooled proportions, risk ratios (RRs), and corresponding 95% confidence intervals (CIs) were calculated using a random effects model to generate summary estimates. Statistical heterogeneity was assessed using I2 tested by the Cochran Q tests. Results: Eight articles reported on 398 patients who received Imiquimod out of 672 patients. Among CIN-2–3 patients, we observed a pooled regression rate of 61% (CI: 0.46–0.75; I2: 77%). When compared, Imiquimod was inferior to conization (RR: 0.62; CI: 0.42–0.92; I2: 64%). The HPV clearance rate in women who completed Imiquimod treatment was 60% (CI: 0.31–0.81; I2: 57%). The majority of side effects reported were mild to moderate in severity. Conclusions: Our findings indicate that topical Imiquimod is safe and effective in reducing cervical intraepithelial neoplasia and promoting HPV clearance. However, it was found to be inferior compared to conization. Imiquimod could be considered a potential medication for high-grade CIN patients and should be incorporated into guidelines for treating cervical dysplasia. [ABSTRACT FROM AUTHOR]

Simple Summary: Immunotherapy with PD-1/PD-L1 inhibitors has been shown to significantly improve the survival rates of non-small-cell lung cancer (NSCLC) patients in advanced or metastasised stages. In the present real-world data study, we examined patients with advanced or metastasised NSCLC and compared overall survival between a control group receiving a PD-1/PD-L1 inhibitor therapy and the combinatorial group receiving PD-1/PD-L1 inhibitors plus add-on Viscum album L. Our findings revealed that patients in the combinatorial group lived seven months longer in comparison to the control group (p < 0.001). Furthermore, in patients with a PD-L1-positive tumour that received first-line anti-PD-1/PD-L1 therapy, the adjusted hazard of death was reduced by 56% through the addition of Viscum album L. (p < 0.001). Our findings imply that the addition of Viscum album L. to PD-1/PD-L1 inhibitors is associated with improved survival in patients with advanced or metastasised NSCLC. A limitation of this study is the observational and non-randomised study design; prospective randomised trials are warranted. Immunotherapy with PD-1/PD-L1 inhibitors has significantly improved the survival rates of patients with metastatic non-small-cell lung cancer (NSCLC). Results of a real-world data study investigating add-on VA (Viscum album L.) to chemotherapy have shown an association with the improved overall survival of patients with NSCLC. We sought to investigate whether the addition of VA to PD-1/PD-L1 inhibitors in patients with advanced or metastasised NSCLC would have an additional survival benefit. In the present real-world data study, we enrolled patients from the accredited national registry, Network Oncology, with advanced or metastasised NSCLC. The reporting of data was performed in accordance with the ESMO-GROW criteria for the optimal reporting of oncological real-world evidence (RWE) studies. Overall survival was compared between patients receiving PD-1/PD-L1 inhibitor therapy (control, CTRL group) versus the combination of anti-PD-1/PD-L1 therapy and VA (combination, COMB group). An adjusted multivariate Cox proportional hazard analysis was performed to investigate variables associated with survival. From 31 July 2015 to 9 May 2023, 415 patients with a median age of 68 years and a male/female ratio of 1.2 were treated with anti-PD-1/PD-L1 therapy with or without add-on VA. Survival analyses included 222 (53.5%) patients within the CRTL group and 193 (46.5%) in the COMB group. Patients in the COMB group revealed a median survival of 13.8 months and patients in the CRTL group a median survival of 6.8 months (adjusted hazard ratio, aHR: 0.60, 95% CI: 0.43–0.85, p = 0.004) after adjustment for age, gender, tumour stage, BMI, ECOG status, oncological treatment, and PD-L1 tumour proportion score. A reduction in the adjusted hazard of death by 56% was seen with the addition of VA (aHR 0.44, 95% CI: 0.26–0.74, p = 0.002) in patients with PD-L1-positive tumours (tumour proportion score > 1%) treated with first-line anti-PD-1/PD-L1 therapy. Our findings suggest that add-on VA correlates with improved survival in patients with advanced or metastasised NSCLC who were treated with PD-1/PD-L1 inhibitors irrespective of age, gender, tumour stage, or oncological treatment. The underlying mechanisms may include the synergistic modulation of the immune response. A limitation of this study is the observational non-randomised study design, which only allows limited conclusions to be drawn and prospective randomised trials are warranted. [ABSTRACT FROM AUTHOR]

Simple Summary: Light-chain amyloidosis (AL) is a rare multisystem disorder. One of the most common organs involved in AL is the heart. We conducted a multi-center, retrospective analysis of 67 patients with the European 2012 modification of Mayo 2004 stage III cardiac AL. The prognosis of patients with advanced cardiac amyloidosis is poor. The median OS for the entire group was 35 months (95% CI: 7–67). The most important prognostic factors with the most significant impact on OS improvement in patients with modified Mayo stage III cardiac AL identified by multivariate Cox analysis are ECOG PS ≤ 1, NYHA FC ≤ 2, and achieving hematological response ≥ VGPR and cardiac response ≥ PR after first-line treatment. Light-chain amyloidosis (AL) is a rare multisystem disorder characterized by the deposition of misfolded amyloid fibrils derived from monoclonal immunoglobulin light chains in various organs. One of the most common organs involved in AL is the heart, with 50–70% of patients clinically symptomatic at diagnosis. We conducted a multi-center, retrospective analysis of 67 patients diagnosed between July 2012 and August 2022 with the European 2012 modification of Mayo 2004 stage III cardiac AL. The most important factors identified in the univariate Cox analysis contributing to a longer OS included Eastern Cooperative Oncology Group performance status (ECOG PS) ≤ 1, New York Heart Association functional classification (NYHA FC) ≤ 2, the use of autologous stem cell transplantation (ASCT) after induction treatment, achieving a hematological response (≥very good partial response) and cardiac (≥partial response) response after first-line treatment. The most important prognostic factors with the most significant impact on OS improvement in patients with modified Mayo stage III cardiac AL identified by multivariate Cox analysis are ECOG PS ≤ 1, NYHA FC ≤ 2, and achieving hematological response ≥ VGPR and cardiac response ≥ PR after first-line treatment. [ABSTRACT FROM AUTHOR]

Simple Summary: This retrospective study investigates the validity of lateral ventricle opening during high-grade glioma (HGG) surgery, contributing to the literature by addressing its relationship with postoperative complications in a large cohort of newly diagnosed patients with HGG. The approach of dividing patients into groups with and without lateral ventricle opening enhances the study's internal validity, allowing for a direct comparison between the two conditions. The analysis of complications, including subependymal dissemination and multifocal progression, contributes to understanding associated side effects. Furthermore, the conclusion that lateral ventricle opening does not significantly increase the risks of dissemination, hydrocephalus or cerebrospinal fluid leakage suggests practical implications for surgery. Given the importance of maximizing resection for prognosis in patients with HGG and the potential risks associated with ventricle opening, this study aimed to assess the actual increase in post-surgical complications related to lateral ventricle opening and its influence on OS and PFS. A retrospective study was conducted on newly diagnosed HGG, dividing the patients into two groups according to whether the lateral ventricle was opened (69 patients) or not opened (311 patients). PFS, OS, subependymal dissemination, distant parenchymal recurrences, the development of hydrocephalus and CSF leak were considered outcome measures. A cohort of 380 patients (154 females (40.5%) and 226 males (59.5%)) was involved in the study (median age 61 years). The PFS averaged 10.9 months (±13.3 SD), and OS averaged 16.6 months (± 16.3 SD). Among complications, subependymal dissemination was registered in 15 cases (3.9%), multifocal and multicentric progression in 56 cases (14.7%), leptomeningeal dissemination in 12 (3.2%) and hydrocephalus in 8 (2.1%). These occurrences could not be clearly justified by ventricular opening. The act of opening the lateral ventricles itself does not carry an elevated risk of dissemination, hydrocephalus or cerebrospinal fluid (CSF) leak. Therefore, if necessary, it should be pursued to achieve radical removal of the disease. [ABSTRACT FROM AUTHOR]

Simple Summary: In the era of precision medicine, translational oncology seeks to identify new, targeted therapies for tumors with rare genetic mutations. Patients receiving targeted therapy are known to have better outcomes (i.e., live longer and better) compared to those receiving non-targeted therapies. In this analysis, we retrospectively analyzed 63,873 tumor tissues to better understand the rare HRAS mutation. We found that only 0.8% of tumors are HRAS mutant, and these tumors look different at the molecular level and behave differently on a clinical level. Targeted therapies for patients with HRAS mutations, such as tipifarnib, currently exist and are being tested in various tumor types. Our study seeks to add to the limited information currently known about this rare genetic mutation. Tipifarnib is the only targeted therapy breakthrough for HRAS-mutant (HRASmt) recurrent or metastatic head and neck squamous cell carcinoma (HNSCC). The molecular profiles of HRASmt cancers are difficult to explore given the low frequency of HRASmt. This study aims to understand the molecular co-alterations, immune profiles, and clinical outcomes of 524 HRASmt solid tumors including urothelial carcinoma (UC), breast cancer (BC), non-small-cell lung cancer (NSCLC), melanoma, and HNSCC. HRASmt was most common in UC (3.0%), followed by HNSCC (2.82%), melanoma (1.05%), BC (0.45%), and NSCLC (0.44%). HRASmt was absent in Her2+ BC regardless of hormone receptor status. HRASmt was more frequently associated with squamous compared to non-squamous NSCLC (60% vs. 40% in HRASwt, p = 0.002). The tumor microenvironment (TME) of HRASmt demonstrated increased M1 macrophages in triple-negative BC (TNBC), HNSCC, squamous NSCLC, and UC; increased M2 macrophages in TNBC; and increased CD8+ T-cells in HNSCC (all p < 0.05). Finally, HRASmt was associated with shorter overall survival in HNSCC (HR: 1.564, CI: 1.16–2.11, p = 0.003) but not in the other cancer types examined. In conclusion, this study provides new insights into the unique molecular profiles of HRASmt tumors that may help to identify new targets and guide future clinical trial design. [ABSTRACT FROM AUTHOR]

Simple Summary: In this research, we explored the latest advancements in minimally invasive surgery for colon cancer, by comparing laparoscopic surgery to the robotic approach. Our goal was to determine which method has better outcomes in terms of length of surgery, hospital stay, the likelihood of conversion, rate of complications, anastomotic leaks, and the effectiveness of tumor removal by evaluating the number of lymphatic nodes harvested. The findings could help surgeons and patients make more informed decisions related to the surgical options, considering the benefits of each technique. This summary aims to give a straightforward overview of the importance of this research and how it could impact the surgical approach. Background: Minimally invasive surgery in the treatment of colon cancer has significantly advanced over the years. This systematic review and meta-analysis aimed to compare the operative outcomes of robotic and laparoscopic surgery in the treatment of colon cancer, focusing on operative time, hospital stay, conversion rates, anastomotic leak rates, and total number lymph node harvested. Methods: Following PRISMA guidelines, we conducted a systematic search across four databases up to January 2024, registering our protocol with PROSPERO (CRD42024513326). We included studies comparing robotic and laparoscopic surgeries for colon cancer, assessing operative time, hospital length of stay, and other perioperative outcomes. Risk of bias was evaluated using the JBI Critical Appraisal Checklist. Statistical analysis utilized a mix of fixed and random-effects models based on heterogeneity. Results: A total of 21 studies met the inclusion criteria, encompassing 50,771 patients, with 21.75% undergoing robotic surgery and 78.25% laparoscopic surgery. Robotic surgery was associated with longer operative times (SMD = −1.27, p < 0.00001) but shorter hospital stays (MD = 0.42, p = 0.003) compared to laparoscopic surgery. Conversion rates were significantly higher in laparoscopic procedures (OR = 2.02, p < 0.00001). No significant differences were found in anastomotic leak rates. A higher number of lymph nodes was harvested by robotic approach (MD = −0.65, p = 0.04). Publication bias was addressed through funnel plot analysis and Egger's test, indicating the presence of asymmetry (p = 0.006). Conclusions: The choice of surgical method should be individualized, considering factors such as surgeon expertise, medical facilities, and patient-specific considerations. Future research should aim to elucidate long-term outcomes to further guide the clinical decision-making. [ABSTRACT FROM AUTHOR]

Simple Summary: Cervical cancer remains the fourth leading cause of cancer-related deaths among women worldwide. The red cell distribution width (RDW) and systemic immune-inflammation index (SII) are common, well-known haematological indices. The aim of this retrospective study was to evaluate the association between pre-treatment RDW and SII, and overall survival (OS) in 249 patients treated with definitive chemoradiation therapy (CRT) for histopathologically confirmed, primary localised cervical cancer. Statistical analysis was performed using the Kaplan–Meier method, two-sided log-rank tests, and Cox proportional hazards models, with the Akaike Information Criterion (AIC) serving as a prediction error estimator. The vast majority of patients (95.2%) were diagnosed with squamous cell carcinoma (SCC) in FIGO stage III (84.7%). Patients with a low RDW (≤13.4%) and low SII (≤986.01) had a significantly longer OS (p < 0.01). The RDW remained as an independent prognostic factor in the multivariable model (p < 0.01). The RDW is a cheap and easily accessible index that could be used to improve pre-treatment prognosis assessments in patients with cervical cancer undergoing CRT. Introduction: There is growing interest in the prognostic value of routinely performed pre-treatment blood test indices, such as the RDW or SII, with the latter combining the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR). These indices were shown to be prognostic for survival in some malignancies. The purpose of this study was to evaluate the association between pre-treatment RDW and SII, and OS in patients treated with radiotherapy for primary localised cervical cancer. Material and Methods: This retrospective analysis included patients treated with definitive CRT between 2011 and 2017 for histopathologically confirmed FIGO 2018 stage IB2-IVA cervical cancer. Statistical analysis was performed using the Kaplan–Meier method, two-sided log-rank tests, and Cox proportional hazards models, with the AIC serving as a prediction error estimator. Results: The study group included 249 patients with a median age of 57.2 years and a median follow-up of 75.8 months. The majority were diagnosed with squamous cell carcinoma (237; 95.2%) and had FIGO stage III (211; 84.7%). Approximately half of the patients (116; 46.4%) had regional lymph node metastases. Patients with a low RDW (≤13.4%) and low SII (≤986.01) had a significantly longer OS (p = 0.001 and p = 0.002). The RDW remained as an independent prognostic factor in the multivariable model (high vs. low; HR = 2.04; 95% CI: 1.32–3.16; p = 0.001). Including RDW in the model decreased the Akaike Information Criterion from 1028.25 to 1018.15. Conclusions: The RDW is a cheap and widely available index that is simultaneously an independent prognostic factor for survival and could be used to improve pre-treatment prognosis assessments in patients with cervical cancer undergoing CRT. Available data encourage assessing the RDW as a prognostic factor in prospective trials to aid the identification of candidates for treatment escalation. [ABSTRACT FROM AUTHOR]

Simple Summary: Surgery is the most effective treatment for early-stage lung cancer, but it poses a heavy physical burden. Accordingly, understanding the perioperative daily life conditions of patients is important to maintain their health status and to provide appropriate treatment. We performed a prospective study to examine the socioclinical factors associated with the physical quality of life of patients who underwent surgery for lung cancer at Shonan Kamakura General Hospital, Kanagawa, Japan. In the preoperative setting, living alone and lower performance status were independently associated with worse physical quality of life. In the postoperative setting at 6 months, later smoking cessation, lower performance status, living alone, and higher comorbid burden were independently associated with worse physical quality of life. In order to maintain quality of life and provide enough treatment, perioperative management should include taking care of the patient's physical condition, lifestyle, smoking, and comorbid status. Surgery is the most effective treatment for early-stage lung cancer; however, it poses a higher physical burden than other treatment options. Therefore, understanding the perioperative course of patients is important. Using the Short Form Health Survey 36, we prospectively measured the physical quality of life of patients who underwent anatomical pulmonary resection for non-small cell lung cancer at Shonan Kamakura General Hospital, Kanagawa, Japan (n = 87). In the preoperative setting, patients who had lower performance status and lived alone had significantly worse physical quality of life scores on multivariate analysis (regression coefficient (95% confidence interval), −9.37 (−13.43–−5.32) and −10.22 (−13.74–−7.40), respectively, p < 0.0001 for both). At 6 months postoperatively, patients who stopped smoking within 1 year preoperatively (stopped smoking within 1 year vs. remote or never smokers, 41.0 ± 10.5 vs. 48.6 ± 7.2, p = 0.002), had lower performance status (0 vs. 1–2, 49.3 ± 6.6 vs. 38.6 ± 9.6, p < 0.0001), lived alone (living alone vs. living with somebody, 41.6 ± 9.7 vs. 48.1 ± 7.9, p = 0.021), and had higher comorbid burden (Charlson comorbidity index <3 vs. ≥3, 48.2 ± 6.9 vs. 39.1 ± 14.7, p = 0.003) had significantly worse physical quality of life scores on univariate analysis. More recent smoking (regression coefficient (95% confidence interval), −4.90 (−8.78–1.0), p = 0.014), lower performance status (8.90 (5.10–12.70), p < 0.0001), living alone (5.76 (1.39–10.13), p = 0.01), and higher comorbid burden (−6.94 (−11.78–−2.10), p = 0.006) were significant independent predictors of worse postoperative physical quality of life on multivariate analysis. Therefore, patients with these conditions might need additional support to maintain their physical condition after anatomical lung cancer surgery. [ABSTRACT FROM AUTHOR]

Simple Summary: Radiomics is the extraction of high-dimensional quantitative features from medical images. These features have shown potential to provide diagnostic and prognostic information in various oncological settings, but their reproducibility and stability can be affected by multiple physiological and technical factors. In this study, we assessed the effect of contrast agent timing on radiomics features using dynamic contrast-enhanced CT or MRI in prostate and lung cancers, whereby multiple images are acquired with a high temporal resolution after contrast agent application. We observed that a substantial number of radiomics features are contrast perfusion dependent and prone to bias. Therefore, when using contrast-enhanced scans for radiomics studies, patient-specific perfusion timing (e.g., test bolus protocol) should be applied. Background: The reproducibility of radiomics features extracted from CT and MRI examinations depends on several physiological and technical factors. The aim was to evaluate the impact of contrast agent timing on the stability of radiomics features using dynamic contrast-enhanced perfusion CT (dceCT) or MRI (dceMRI) in prostate and lung cancers. Methods: Radiomics features were extracted from dceCT or dceMRI images in patients with biopsy-proven peripheral prostate cancer (pzPC) or biopsy-proven non-small cell lung cancer (NSCLC), respectively. Features that showed significant differences between contrast phases were identified using linear mixed models. An L2-penalized logistic regression classifier was used to predict class labels for pzPC and unaffected prostate regions-of-interest (ROIs). Results: Nine pzPC and 28 NSCLC patients, who were imaged with dceCT and/or dceMRI, were included in this study. After normalizing for individual enhancement patterns by defining seven individual phases based on a reference vessel, 19, 467 and 128 out of 1204 CT features showed significant temporal dynamics in healthy prostate parenchyma, prostate tumors and lung tumors, respectively. CT radiomics-based classification accuracy of healthy and tumor ROIs was highly dependent on contrast agent phase. For dceMRI, 899 and 1027 out of 1118 features were significantly dependent on time after contrast agent injection for prostate and lung tumors. Conclusions: CT and MRI radiomics features in both prostate and lung tumors are significantly affected by interindividual differences in contrast agent dynamics. [ABSTRACT FROM AUTHOR]

Simple Summary: Proton pump inhibitors (PPIs) are very commonly prescribed drugs in gastroenterology. The present study evaluated a potential association between PPI intake and a subsequent diagnosis of liver cancer in Germany. We observed that long-term PPI intake in women as well as in patients < 60 years might be associated with an increased risk of liver cancer. These findings support current efforts to reduce the inappropriate use of PPIs in clinical routine. Background: Proton pump inhibitors (PPIs) are among the most commonly prescribed drugs in gastroenterology. Although PPIs are mostly well tolerated, long-term PPI intake has been linked with diabetes mellitus, osteoporosis and infectious disease. In the present study, we evaluated a potential association between PPI intake and a subsequent diagnosis of liver cancer in a large real-world cohort of outpatients in Germany. Methods: A total of 1766 patients with liver cancer, as well as 8830 propensity-score-matched controls, were identified from the Disease Analyzer database (IQVIA). The outcome of the study was the association between PPI use and a subsequent diagnosis of liver cancer, which was evaluated using multivariable logistic regression analyses. Results: Overall, 42.9% of the liver cancer patients and 39.0% of the controls received at least one PPI prescription before the index date. PPI prescriptions at any time before the index date were associated with an increased risk of subsequent liver cancer (OR: 1.18; 95% CI: 1.06–1.31). The positive association was observed in all age groups, as well as in women and men, but only in women (OR: 1.30; 95% 1.09–1.55) did it reach the predefined level of significance (p < 0.01). When considering the duration of PPI therapy, only PPI therapy for at least two years was significantly associated with an increased risk of liver cancer (OR: 1.28; 95% 1.09–1.50). In an analysis stratified by age and sex, this association was strongest in the age group < 60 years (OR: 1.99; 95% 1.21–3.26). Conclusions: Our data suggest that long-term PPI intake in women as well as in patients < 60 years might be associated with an increased risk of liver cancer. These findings support current efforts to reduce the inappropriate use of PPIs in routine clinical practice and to link PPI prescribing to a clear medical indication. [ABSTRACT FROM AUTHOR]

Simple Summary: The two major histological subtypes of breast cancer are ductal and lobular cancers. Histology impacts the biological behavior of breast cancer, so it is imperative to study its influence on the overall survival of breast cancer patients. The existing literature reports conflicting conclusions regarding the impact that histology might have on survival, so we aimed to study a large sample of patient data obtained from the National Cancer Database to determine if histology and several other clinical factors have an impact on the survival of early-stage breast cancer patients who have T1–T2 tumors, are clinically node-negative and have no metastatic activity. These results may help clinicians better understand the behaviors of different subtypes of breast cancer and will help them take a more tailored approach to breast cancer treatment. Histology is an important predictor of the behavior of breast cancer. We aim to study the impact of histology on the overall survival (OS) of breast cancer patients. We studied 11,085 breast cancer patients diagnosed with T1–T2 tumors, clinically node-negative and non-metastatic, from 2004 to 2019 included in the National Cancer Database. Kaplan–Meier curves, log-rank tests and Cox regression models were used to study the impact of histology and other variables on OS. In our patient population, 8678 (78.28%) had ductal cancer (IDC), while 2407 (21.71%) had lobular cancer (ILC). ILC patients were significantly more likely to be older, Caucasian, have a lower grade at diagnosis and be hormone receptor-positive compared to IDC patients. There was no statistically significant difference in the 5-year OS of early stage ductal (16.8%) and lobular cancer patients (16.7%) (p = 0.200). Patients of Hispanic and African American origin had worse OS rates compared to non-Hispanic and Caucasian patients, respectively. For node-positive disease, HER2+ tumors and triple-negative tumors, chemotherapy had a positive influence on OS (HR 0.85, 95% CI 0.77–0.93, p = 0.0012). Histology did not have a significant impact on the 5-year OS of early stage breast cancer patients. [ABSTRACT FROM AUTHOR]

Simple Summary: HCC is the most common malignant primary hepatic tumor, which can be treated by various therapies including surgery, ablation, or transarterial methods such as cTACE. Each of these treatments has its own indications depending on the stage of the disease. cTACE is mostly performed in patients with intermediate stage HCC. This large retrospective single-center study shows the long-term results including survival and prognostic factors of patients with HCC treated by TACE in different treatment settings over 20 years. The aim of this study was to retrospectively evaluate the effects of conventional transarterial chemoembolization (cTACE) for the treatment of hepatocellular carcinoma over 20 years regarding overall survival (OS) and prognostic factors for OS. During the period from 1996 to 2016, 836 patients with HCC were treated with cTACE. Data evaluation was performed on the basis of pre- and postinterventional MRI and CT scans. Survival analysis was performed by Kaplan–Meier estimator; prognostic factors were determined by the use of Cox regression analysis. Overall, 4084 (mean 4.89 TACE sessions/patient) procedures were assessed. Median OS was 700 days (99% CI, 632.8–767.2). Depending on the indication, patients treated with a neoadjuvant intention showed the best OS (1229 days, 99% CI 983.8–1474.2) followed by curative intention (787 days, 99% CI 696.3–877.7), and then palliative intention (360 days, 99% CI 328.4–391.6). Portal vein thrombosis (HR 2.19, CI 1.63–2.96, and p < 0.01) and Child–Pugh class B or worse (HR 1.44, CI 1.11–1.86, and p < 0.001) were significantly associated with shorter OS. Patients with HCC benefit from TACE after careful patient selection. Portal vein thrombosis and Child–Pugh class B or worse are significantly unfavorable prognostic factors for patients' survival. [ABSTRACT FROM AUTHOR]

Simple Summary: Non-smallcell lung cancer patients frequently develop brain metastases. Most patients are treated with radiotherapy, but the potential benefit from radiotherapy in patients with poor performance status is uncertain. Consequently, the risk of futile treatment is high. This study provides knowledge to improve the treatment decision-making process. We report a prospective study of 294 patients treated with radiotherapy for brain metastases in 2017–2021, focusing on the correlation between performance status and survival. Our data support that patients with ECOG performance status 3–4 should not be offered radiotherapy, as they are likely to have very short expected survival. Also, if not candidates for surgery or stereotactic radiotherapy, patients with ECOG 2 have an expected survival equal to those with ECOG 3–4, especially if extra-cranial metastases are uncontrolled. Therefore, these patients should be offered the best supportive care rather than WBRT to improve symptoms and preserve quality of life near the end of life. Up to 40% of non-smallcell lung cancer (NSCLC) patients develop brain metastases (BMs). The potential benefits of radiotherapy (RT) in patients with poor performance status (PS) are questionable, with considerable risk for futile treatment. We analyzed overall survival after initial radiotherapy in NSCLC patients with BMs, focusing on the relationship between PS and survival after RT. This study reports a prospective observational study including consecutive 294 NSCLC patients with first-time BMs. Overall survival (OS) was calculated from the start of RT to death or last follow-up (1 June 2023). Overall, in the 294 included patients (median age 69 years), the median OS was 4.6 months; 2.5 months after WBRT (n = 141), and 7.5 months after SRT (n = 153). After WBRT, mOS was equally poor for patients with ECOG 2 (1.9 months) and ECOG 3–4 (1.2 months). After SRT, mOS for patients with ECOG 2 was 4.1 months; for ECOG 3 patients, mOS was 4 1.6 months. For NSCLC patients with ECOG 2 diagnosed with BMs who are not candidates for surgery or SRT, WBRT should be questioned due to short survival. [ABSTRACT FROM AUTHOR]

Simple Summary: After esophageal resection for cancer, severe postoperative complications (SPCs) have been reported in up to 20% of patients. These are associated with prolonged hospital stay, augmented costs, need for supplementary treatments, and increased 90-day mortality. The global effect of SPCs on long-term survival after esophagectomy is discussed, whereas, in the current literature, it is not frequently covered. The present systematic review and individual patient data meta-analysis suggests a statistically significant detrimental effect of SPCs on 5-year overall survival in patients undergoing curative esophagectomy for cancer. Also, a clinical trend toward reduced 5-year cancer specific survival and disease-free survival was perceived. Background. Severe postoperative complications (SPCs) may occur after curative esophagectomy for cancer and are associated with prolonged hospital stay, augmented costs, and increased in-hospital mortality. However, the effect of SPCs on survival after esophagectomy is uncertain. Aim. To assess the impact of severe postoperative complications (SPCs) on long-term survival following curative esophagectomy for cancer, we conducted a systematic search of PubMed, MEDLINE, Scopus, and Web of Science databases up to December 2023. The included studies examined the relationship between SPCs and survival outcomes, defining SPCs as Clavien–Dindo grade > 3. The primary outcome measure was long-term overall survival (OS). We used restricted mean survival time difference (RMSTD) and 95% confidence intervals (CIs) to calculate pooled effect sizes. Additionally, we applied the GRADE methodology to evaluate the certainty of the evidence. Results. Ten studies (2181 patients) were included. SPCs were reported in 651 (29.8%) patients. The RMSTD overall survival analysis shows that at 60-month follow-up, patients experiencing SPCs lived for 8.6 months (95% Cis −12.5, −4.7; p < 0.001) less, on average, compared with no-SPC patients. No differences were found for 60-month follow-up disease-free survival (−4.6 months, 95% CIs −11.9, 1.9; p = 0.17) and cancer-specific survival (−6.8 months, 95% CIs −11.9, 1.7; p = 0.21). The GRADE certainty of this evidence ranged from low to very low. Conclusions. This study suggests a statistically significant detrimental effect of SPCs on OS in patients undergoing curative esophagectomy for cancer. Also, a clinical trend toward reduced CSS and DFS was perceived. [ABSTRACT FROM AUTHOR]

Simple Summary: The timely diagnosis and surgical treatment of skin squamous cell carcinomas is crucial for patient outcomes. However, interruptions to health care services, such as a pandemic, natural disaster, or war, can affect patients' willingness to seek medical assistance. We investigated the impact of the delayed diagnosis of squamous cell carcinomas of the skin by comparing patient and carcinoma characteristics before (2018–2019) and after (2021–2022) the second wave of the COVID-19 pandemic. We found that patients were less likely to seek medical assistance, and when they did, carcinomas were more advanced. To curb the spread of the virus, types of surgery changed. Background: The delayed diagnosis of skin tumors is associated with a worsened prognosis. The impact of the interruption of clinical and surgical health services during the COVID-19 pandemic lockdowns has been documented among many pathologies. The impact of delayed diagnoses on patients with cutaneous squamous cell carcinomas (cSCCs) is poorly defined. Objective: To compare patient and lesion characteristics and the surgical management of excised cSCCs prior to the pandemic shutdown of services (2018–2019) with the phase following the pandemic's second wave (2021–2022). Methods: An observational, single-center, cross-sectional study of 416 surgically excised cSCCs over the course of two years was performed. Only patients with histologically confirmed cSCC were enrolled. Data collection included patient demographics and lesion characteristics, time to surgery, surgical approach, and histological data. Results: More cSCC lesions were excised prior to the interruption of services (n = 312 vs. n = 186). Lesions were significantly larger (1.7 ± 1.2 vs. 2.1 ± 1.5 cm; p = 0.006) and more invasive (52% vs. 89%; p < 0.001), in the period 2021–2022. Surgical reconstructive techniques were significantly different (p = 0.001). Metastatic involvement was confirmed in three subjects (one in 2018–2019 and two in 2021–2022). There were no significant differences in the time to surgery or patient characteristics. Multivariable regression analysis identified a 4.7-times higher risk of tumor invasion (OR 4.69, 95%CI 2.55–8.16, p < 0.001), a two-times higher chance of dermo-epidermal grafts (OR 2.06, 95%CI 1.09–3.88, p = 0.025), and a 3.2-times higher risk of positive surgical margins (OR 3.21, 95%CI 1.44–7.17, p = 0.004). Conclusions: Diagnostic delays of cutaneous SCCs associated with reduced patient access to clinical and diagnostic services are associated with a 4.7-times increased risk of more severe invasion, a three-times increased risk of positive surgical margins, and a significant impact on surgical management, compared to the pre-pandemic period. Comparable patient cohort characteristics and time to surgery remained unchanged. [ABSTRACT FROM AUTHOR]

Simple Summary: Colorectal cancer is one of the most frequent malignant diseases in the world. The question of whether to remove the primary tumor in asymptomatic synchronous metastatic colorectal cancer or keep the tumor intact is still controversial. The operation before the necessary systemic chemotherapy has many pros and cons. For those patients who are candidates for metastasectomy, the removal of the primary tumor is inevitable. We conducted a retrospective data analysis of 449 patients treated in six years. The study showed clear evidence that removing the primary tumor results in fewer primary-tumor-related complications (bleeding, obstruction) and significantly improves overall survival. The delay of systemic therapy due to the operation did not show any undesired consequences. We strongly think that for those who are suitable for any kind of manipulation of the primary tumor (removal or irradiation of the rectal cancer), this is undoubtedly advantageous. Aim: The complex medical care of synchronous metastatic colorectal (smCRC) patients requires prudent multidisciplinary planning and treatments due to various challenges caused by the primary tumor and its metastases. The role of primary tumor resection (PTR) is currently uncertain; strong arguments exist for and against it. We aimed to define its effect and find its best place in our therapeutic methodology. Method: We performed retrospective data analysis to investigate the clinical course of 449 smCRC patients, considering treatment modalities and the location of the primary tumor and comparing the clinical results of the patients with or without PTR between 1 January 2013 and 31 December 2018 at the Institute of Oncotherapy of the University of Pécs. Results: A total of 63.5% of the 449 smCRC patients had PTR. Comparing their data to those whose primary tumor remained intact (IPT), we observed significant differences in median progression-free survival with first-line chemotherapy (mPFS1) (301 vs. 259 days; p < 0.0001; 1 y PFS 39.2% vs. 26.6%; OR 0.56 (95% CI 0.36–0.87)) and median overall survival (mOS) (760 vs. 495 days; p < 0.0001; 2 y OS 52.4 vs. 26.9%; OR 0.33 (95% CI 0.33–0.53)), respectively. However, in the PTR group, the average ECOG performance status was significantly better (0.98 vs. 1.1; p = 0.0456), and the use of molecularly targeted agents (MTA) (45.3 vs. 28.7%; p = 0.0005) and rate of metastasis ablation (MA) (21.8 vs. 1.2%; p < 0.0001) were also higher, which might explain the difference partially. Excluding the patients receiving MTA and MA from the comparison, the effect of PTR remained evident, as the mOS differences in the reduced PTR subgroup compared to the reduced IPT subgroup were still strongly significant (675 vs. 459 days; p = 0.0009; 2 y OS 45.9 vs. 24.1%; OR 0.37 (95% CI 0.18–0.79). Further subgroup analysis revealed that the site of the primary tumor also had a major impact on the outcome considering only the IPT patients; shorter mOS was observed in the extrapelvic IPT subgroup in contrast with the intrapelvic IPT group (422 vs. 584 days; p = 0.0026; 2 y OS 18.2 vs. 35.9%; OR 0.39 (95% CI 0.18–0.89)). Finally, as a remarkable finding, it should be emphasized that there were no differences in OS between the smCRC PTR subgroup and metachronous mCRC patients (mOS 760 vs. 710 days, p = 0.7504, 2 y OS OR 0.85 (95% CI 0.58–1.26)). Conclusions: The role of PTR in smCRC is still not professionally justified. Our survey found that most patients had benefited from PTR. Nevertheless, further prospective trials are needed to clarify the optimal treatment sequence of smCRC patients and understand this cancer disease's inherent biology. [ABSTRACT FROM AUTHOR]

Simple Summary: In this study, we investigated the effectiveness of different imaging techniques, including CT, PET–CT, MRI, and USG, in detecting extracapsular spread (ECS) in advanced Head and Neck Cancer (HNC). The presence of tumor cells beyond lymph nodes, known as extracapsular spread (ECS), worsens the condition. This research compares different imaging techniques like CT, MRI, PET–CT, and USG to detect ECS before surgery. The findings show that while MRI and PET–CT are more sensitive than CT in spotting ECS, all methods have similar accuracy in correctly identifying it. This suggests the need to refine the criteria used in imaging to better diagnose ECS in HNC, which could significantly impact how this cancer is treated in the future. Background: Extracapsular spread (ECS) is the extension of cancer cells beyond the lymph node capsule and is a significant prognostic factor in head and neck cancers. This meta-analysis compared the diagnostic accuracy of CT, MRI, PET, and USG in detecting ECS in head and neck cancers. Methodology: The authors conducted a systematic review and meta-analysis of studies that compared the diagnostic accuracy of CT, MRI, PET, and USG in detecting ECS in head and neck cancers. They included studies that were published between 1990 and December 2023 and that used histopathology as the reference standard for ECS. Results: The pooled sensitivity and specificity of CT scan were 0.63 (95% CI = 0.53–0.73) and 0.85 (95% CI = 0.74–0.91), respectively. The pooled sensitivity and specificity of MRI were 0.83 (95% CI = 0.71–0.90) and 0.85 (95% CI = 0.73–0.92), respectively. The pooled sensitivity and specificity of PET were 0.80 (95% CI = 0.74–0.85) and 0.93 (95% CI = 0.92–0.94), respectively. The pooled sensitivity and specificity of USG were 0.80 (95% CI = 0.68–0.88) and 0.84 (95% CI = 0.74–0.91), respectively. MRI had significantly higher sensitivity than CT scan (p-0.05). The specificity of CT and MRI was not significantly different (p-0.99). PET scan had the highest specificity among all imaging modalities. Conclusion: MRI is the most accurate imaging modality for detecting ECS in head and neck cancers. CT scan is a reasonable alternative, but PET scan may be considered when high specificity is required. USG may not add any further benefit in detecting ECS. [ABSTRACT FROM AUTHOR]

Simple Summary: Patients with small kidney cancers who undergo tumor resection, can experience incomplete tumor tissue removal. This is termed "positive surgical margin" (PSM) and is of interest in terms of the risk for cancer recurrence and survival outcomes. In this study, we investigated outcomes in 523 patients, of which 48 patients had PSM after tumor resection. We found positive margin rates to be lower in robot-assisted tumor resection compared to traditional methods (5.5% vs. 12.2%). Patients with a PSM had higher rates of recurrence during follow-up compared to patients with negative margins (23% vs. 9.3%), highlighting the impact of surgical approach in preventing PSM and thereby influencing the risk of cancer recurrence. However, the presence of PSM did not affect patient survival. Background: Partial nephrectomy (PN) is the preferred treatment for small, localized kidney tumors. Incomplete resection resulting in positive surgical margins (PSM) can occur after PN. The impact of PSM on the risk of recurrence and survival outcomes is not fully understood. We aimed to explore the relationship between PSM, the risk of recurrence and impact on survival after PN in a large multicenter cohort from Denmark. Methods: This was a retrospective cohort study including patients who underwent PN for renal cell carcinoma (RCC) at three departments in Denmark between 2010 and 2016. Data including pathological features, surgical techniques, and patient follow-up was retrieved from electronic medical health records and national databases. We used a combination of descriptive statistics, comparative analysis (comparisons were carried out by Mann–Whitney Test, independent Student's t-test, or Pearson's chi-Square Test), univariate and multivariate logistic regression analyses, and survival analysis methods. Results: A total of 523 patients were included, of which 48 (9.1%) had a PSM. Recurrence was observed in 55 patients (10.5%). Median follow-up time was 75 months. We found a lower incidence of PSM with robot-assisted PN (p = 0.01) compared to open or laparoscopic PN. PSM was associated with a higher risk of recurrence compared to negative margins in univariate analysis, but not multivariate analysis. However, the study was underpowered to describe this association with other risk factors. Overall survival did not differ between patients with PSM and negative margins. Conclusions: Our study presents further evidence on the negative impact of PSM on recurrence after PN for RCC, highlighting the importance of achieving NSM, thus potentially improving clinical outcomes. A surgical approach was found to be the only predictive factor influencing the risk of PSMs, with a reduced risk observed with robot-assisted laparoscopy. [ABSTRACT FROM AUTHOR]

Simple Summary: This study explored a potentially significant player in the spread of metastatic cancer: "hybrid cells" (HCs) combining features of both epithelial (common in tissues) and immune cells (such as macrophages). HCs were found in more than one type of tumor (THC) and showed a unique transcriptional profile including the activation of functional pathways, potentially explaining their mobility, dissemination into circulation, and metastatic progression. Normal healthy tissue also showed hybrid cells (NHC), but they were rare and could be easily distinguished from THCs based on their gene expression profile. The study also developed a way to identify HCs in large datasets generated at the single-cell level, paving the way for further research on their function and as potential therapeutic targets. Metastatic cancer is a leading cause of death in cancer patients worldwide. While circulating hybrid cells (CHCs) are implicated in metastatic spread, studies documenting their tissue origin remain sparse, with limited candidate approaches using one–two markers. Utilizing high-throughput single-cell and spatial transcriptomics, we identified tumor hybrid cells (THCs) co-expressing epithelial and macrophage markers and expressing a distinct transcriptome. Rarely, normal tissue showed these cells (NHCs), but their transcriptome was easily distinguishable from THCs. THCs with unique transcriptomes were observed in breast and colon cancers, suggesting this to be a generalizable phenomenon across cancer types. This study establishes a framework for HC identification in large datasets, providing compelling evidence for their tissue residence and offering comprehensive transcriptomic characterization. Furthermore, it sheds light on their differential function and identifies pathways that could explain their newly acquired invasive capabilities. THCs should be considered as potential therapeutic targets. [ABSTRACT FROM AUTHOR]

Simple Summary: Cancer is implicated in multiple pathways that increase thrombogenicity, and lung cancer patients have a 20% higher risk of venous thromboembolism in comparison to the general population. Venous thromboembolic disease (VTE) in cancer patients, which includes deep vein thrombosis (DVT) and pulmonary embolism (PE), can lead to the delay of cancer treatment and, thus, result in increased mortality, morbidity, and burden on healthcare resources. Factors contributing to thrombotic burden are related to cancer, patients, treatment, and laboratory findings. Thromboprophylaxis during active lung cancer treatment with adequate anticoagulation might improve outcomes. Thromboprophylaxis with low molecular weight heparin (LMWH) is the standard of care, but due to the vast heterogeneity of lung cancer patients, there is no consensus on the optimal dose and duration of the treatment. Background: The aim of this study was to record and assess the efficacy and safety ofthromboprophylaxis with an intermediate dose of Tinzaparin in lung cancer patients with high thrombotic risk. Methods: This was a non-interventional, single-arm, prospective cohort study of lung cancer patients who received thromboprophylaxis with Tinzaparin 10.000 Anti-Xa IU in 0.5 mL, OD, used in current clinical practice. Enrolled ambulatory patients signed informed consent. Anti-Xa levels were tested. Results: In total, 140 patients were included in the study, of which 81.4% were males. The histology of the tumor was mainly adenocarcinoma. Lung cancer patients with high thrombotic risk based on tumor, patient, treatment, and laboratory-related factors were enrolled. Only one patient experienced a thrombotic event (0.7%), and 10 patients had bleeding events (7.1%), including only one major event. Anti-Xa levels measured at 10 days and 3 months did not differ significantly between patients who developed hemorrhagic events and those who did not (p = 0.26 and p = 0.32, respectively). Conclusion: Thromboprophylaxis with an intermediate Tinzaparin dose in high thrombotic-risk lung cancer patients is a safe and effective choice for the prevention of VTE. [ABSTRACT FROM AUTHOR]

Simple Summary: SETD2, a histone methyltransferase and epigenetic modifier, and SETD2 protein expression were explored in a prostate cancer non-surgical cohort of 202 cases. Notably, SETD2 showed higher intensity in advanced and castrate-resistant disease compared to incidental cases. Moreover, elevated SETD2 expression is significantly associated with poorer prognosis, lower overall survival (OS), and decreased cancer-specific survival (CSS). High-risk SETD2 combined with PTEN loss or ERG positivity improved the prognostication for these outcomes. Additionally, the TCPA protein database and TCGA PRAD GSEA implicated SETD2 in pathways linked to tumor progression, chemoresistance, and adverse prognosis, including the AMPK, cAMP, and PI3K-Akt signaling pathways. SET-domain containing 2 (SETD2) is a histone methyltransferase and an epigenetic modifier with oncogenic functionality. In the current study, we investigated the potential prognostic role of SETD2 in prostate cancer. A cohort of 202 patients' samples was assembled on tissue microarrays (TMAs) containing incidental, advanced, and castrate-resistant CRPCa cases. Our data showed significant elevated SETD2 expression in advanced and castrate-resistant disease (CRPCa) compared to incidental cases (2.53 ± 0.58 and 2.21 ± 0.63 vs. 1.9 ± 0.68; p < 0.001, respectively). Interestingly, the mean intensity of SETD2 expression in deceased vs. alive patients was also significantly different (2.31 ± 0.66 vs. 2 ± 0.68; p = 0.003, respectively). Overall, high SETD2 expression was found to be considered high risk and was significantly associated with poor prognosis and worse overall survival (OS) (HR 1.80; 95% CI: 1.28–2.53, p = 0.001) and lower cause specific survival (CSS) (HR 3.14; 95% CI: 1.94–5.08, p < 0.0001). Moreover, combining high-intensity SETD2 with PTEN loss resulted in lower OS (HR 2.12; 95% CI: 1.22–3.69, p = 0.008) and unfavorable CSS (HR 3.74; 95% CI: 1.67–8.34, p = 0.001). Additionally, high SETD2 intensity with ERG positive expression showed worse prognosis for both OS (HR 1.99, 95% CI 0.87–4.59; p = 0.015) and CSS (HR 2.14, 95% CI 0.98–4.68, p = 0.058). We also investigated the protein expression database TCPA, and our results showed that high SETD2 expression is associated with a poor prognosis. Finally, we performed TCGA PRAD gene set enrichment analysis (GSEA) data for SETD2 overexpression, and our data revealed a potential association with pathways involved in tumor progression such as the AMPK signaling pathway, the cAMP signaling pathway, and the PI3K-Akt signaling pathway, which are potentially associated with tumor progression, chemoresistance, and a poor prognosis. [ABSTRACT FROM AUTHOR]