Cancers, Volume 16, Issue 8 (April-2 2024) – 168 articles

Purpose: This study sought to investigate changes in quality of life (QoL) and symptom burden among palliative care patients undergoing one week of inpatient care in a specialized palliative care unit (PCU). The patient population was stratified into two groups, with one group pretreated from pre-admission palliative care (PC) provided by an outpatient multidisciplinary PC team, while the other group did not receive such support prior to admission. Although the average duration of treatment at a PCU in Germany is 1–2 weeks, the question also arises as to whether a significant improvement in symptom burden and QoL can be expected after just one week of PC in a PCU. Methods: PC patients with various cancer entities were prospectively included in a non-randomized study. Patients in group 1 received outpatient specialized PC prior to admission, while patients in group 2 did not. Over an 8-month period, we gathered data from one academic cancer center, utilizing the EORTC QLQ-C30, one of the most widely used patient-reported outcome (PRO) instruments to assess health-related QoL in cancer patients. Patients completed the QLQ-C30 at T0 (admission or one day later) and T1 (one week later), enabling the assessment of potential changes in their QoL and symptom burden over time. Results: A total of 103 patients (51.5% male) were enrolled (group 1: 42%, group 2: 58%). At T0, there were no significant differences regarding QLQ-C30 scores between groups 1 and 2, except from global health/QoL (group 1 mean 20.7, group 2 mean 25.6, p = 0.026). Over the course of one week several significant and clinically relevant changes were found: Emotional functioning demonstrated an uplift in both groups (group 1: mean 41.5 IQR 33 vs. 53.1 IQR 50, p = 0.014, group 2: mean 48.2 IQR 46 vs. 56.8 IQR 58, p = 0.029), as did the global health status (group 1: M 20.7 IQR 17 vs. 36.2 IQR 33, p < 0.001, group 2: M 25.6 IQR 25 vs. 35.3 IQR 33, p < 0.001). Nausea and vomiting showed a reduction (group 1: M 29.9 IQR 17 vs. 6.8 IQR 0, p < 0.001, group 2: M 22.6 IQR 17 vs. 8.2 IQR 0, p < 0.001), along with a notable decline in pain (group 1: M 67.4 IQR 67 vs. 25.3 IQR 17, p < 0.001, group 2: M 73.1 IQR 83 vs. 29.7 IQR 17, p < 0.001). A decrease was observed in insomnia (group 1: M 63.6 IQR 67 vs. 27.6 IQR 33, p < 0.001, group 2: M 60.1 IQR 67 vs. 27.6 IQR 33, p < 0.001). There were no significant differences between groups 1 and 2 in the extent of improvement in the various symptom scales from T0 to T1. Conclusion: The findings of our study demonstrate that QoL and several symptoms prevalent in cancer patients cared for in the PCU experienced significant enhancement over the span of just one week. Both groups, patients receiving specialized outpatient PC prior to admission and those without, equally benefited from inpatient PC. All mentioned changes from T0 to T1 are considered not only significant but clinically relevant. Full article

Gastric cancer (GC) ranks third in terms of cancer-related deaths and is the fifth most commonly diagnosed type of cancer. Its risk factors include Helicobacter pylori infection, Epstein–Barr virus infection, the consumption of broiled and charbroiled animal meats, salt-preserved and smoke-enhanced foods, alcohol drinking, tobacco smoking, exposure to ionizing radiation, and positive family history. The limited effectiveness of conventional therapies and the widespread risk factors of GC encourage the search for new methods of treatment and prevention. In the quest for cheap and commonly available medications, numerous studies focus on herbal medicine, traditional brews, and spices. In this review, we outline the potential use of spices, including turmeric, ginger, garlic, black cumin, chili pepper, saffron, black pepper, rosemary, galangal, coriander, wasabi, cinnamon, oregano, cardamom, fenugreek, caraway, clove, dill, thyme, Piper sarmentosum, basil, as well as the compounds they contain, in the prevention and treatment of GC. We present the potential molecular mechanisms responsible for the effectivity of a given seasoning substance and their impact on GC cells. We discuss their potential effects on proliferation, apoptosis, and migration. For most of the spices discussed, we also outline the unavailability and side effects of their use. Full article

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. Full article

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. Full article

Patients with aggressive cancer, e.g., gastrointestinal cancer, are prone (≥50% chance) to developing cancer cachexia (CC). Little is known about the effects of CC on the biomechanical function of muscle. A promising prevention strategy was found in the form of a multi-modal therapy combining mild resistance exercise (e.g., whole-body electro-myostimulation, WB-EMS) and a protein-rich diet. In a previous study of ours, this was effective in counteracting the loss of muscle mass, yet a systematic and comprehensive assessment of active and passive single muscle fibre functions was so far absent. This pilot study investigated the biomechanical function of single muscle fibres (rectus abdominis) from the biopsies of conventionally treated (pre-)cachectic cancer ((pre-)CC) patients (m = 9), those receiving the multi-modal therapy comprising WB-EMS training and protein-rich nutrition (m = 3), and a control group (m = 5). Our findings not only align with previous findings showing the absolute force loss in CC that is accelerated by atrophy but also speak in favour of a different, potentially energy- and Ca²⁺-homeostasis-related effect that compromises muscle contraction (F ~0.9 mN vs. F ~0.6 mN in control patients). However, myofibrillar Ca²⁺ sensitivity and the quality of contraction were unaltered (pCa50: 5.6–5.8). Single fibres from the (pre-)CC patients receiving WB-EMS training and protein supplementation were significantly more compliant (p < 0.001 at ≥130% of resting length L₀). Those fibres displayed a similar softness to the ones from the control patients (axial compliance ~15 m/N at ≥130% L₀), while single fibres from the patients with (developing) cachexia were significantly stiffer (axial compliance ~7 m/N, p < 0.001 at ≥130% L₀). Adjuvant multi-modal therapy (WB-EMS training and nutritional support) contributes to maintaining the axial compliance of single fibres and potentially improves the quality of life for patients at risk of developing CC. Full article

Background: We estimated metastatic-death risk when the treatment of small choroidal melanomas is deferred until growth is observed. Methods: In 24 patients with choroidal melanoma (median diameter 5.85 mm), the exponential growth rate estimated by a mixed-effects model was 4.3% per year. Using the Liverpool Uveal Melanoma Prognosticator Online v.3 (LUMPO3), we measured changes in 15-year metastatic and non-metastatic death risks according to whether the tumor is treated immediately or after observing growth 4 or 12 months later, considering age, sex, and metastasis predictors. Results: In 40-year-old females with 10 mm, disomy 3 and monosomy 3 choroidal melanomas (prevalence 16%), the 15-year absolute risks of metastatic death are 4.2% and 76.6%, respectively, increasing after a 4-month delay by 0.0% and 0.2% and by 3.0% and 2.3% with tumor growth rates of 5.0% and 20.0%, respectively. With 12-month delays, these risks increase by 0.0% and 0.5% and by 1.0% and 7.1%, respectively. Increases in metastatic-death risk are less with smaller tumors and with a higher risk of non-metastatic death. Conclusions: Deferring treatment of choroidal melanomas until documentation of growth may delay iatrogenic visual loss by months or years and is associated with minimal increase in metastatic mortality, at least with small tumors with usual growth rates of up to 40% per year. Full article

SARS-CoV-2 and blood-borne viral coinfections are well reported. Nevertheless, little is known regarding the seroprevalence of SARS-CoV-2 and coinfection with blood-borne viruses in hematologic malignancy patients in Ethiopia. We aimed to assess the seroprevalence of SARS-CoV-2 and associated infections with hepatitis B and other viruses among adolescent and adult acute leukemia patients at Tikur Anbessa Specialized Hospital, Addis Ababa, Ethiopia. A cross-sectional study was conducted from July 2020 to June 2021. Blood samples were tested for the presence of anti-SARS-CoV-2, HBV, HCV, and HIV with ELISA kits and occult hepatitis B infection with a real-time polymerase chain reaction assay. Out of a total 110 cases, the SARS-CoV-2 seroprevalence was 35.5%. The prevalence showed a significant increment from July 2020 to the end of June 2021 (p = 0.015). In 22.7% and 2.7% of leukemia cases, HBV and HIV, respectively, were detected. No HCV was identified. The rate of SARS-CoV-2 coinfection with HBV and HIV was 28% (11/39) and 2.6% (1/39), respectively; however, there was no statistically significant association between SARS-CoV-2 seropositivity with HBV and HIV (p > 0.05). There is a need for viral screening in leukemia cases to monitor infections and inform management. Full article

Light-chain (AL) amyloidosis is a rare plasma cell disorder characterized by the deposition of misfolded immunoglobulin light chains in target organs, leading to multi-organ dysfunction. Treatment approaches have historically mirrored but lagged behind those of multiple myeloma (MM). Recent advancements in MM immunotherapy are gradually being evaluated and adopted in AL amyloidosis. This review explores the current state of immunotherapeutic strategies in AL amyloidosis, including monoclonal antibodies, antibody–drug conjugates, bispecific antibodies, and chimeric antigen receptor T-cell therapy. We discuss the unique challenges and prospects of these therapies in AL amyloidosis, including the exposure of frail AL amyloidosis patients to immune-mediated toxicities such as cytokine release syndrome (CRS) and immune effector-cell-associated neurotoxicity syndrome (ICANS), as well as their efficacy in promoting rapid and deep hematologic responses. Furthermore, we highlight the need for international initiatives and compassionate programs to provide access to these promising therapies and address critical unmet needs in AL amyloidosis management. Finally, we discuss future directions, including optimizing treatment sequencing and mitigating toxicities, to improve outcomes for AL amyloidosis patients. Full article

Painful pelvic and spinal bone metastases are a considerable challenge for doctors and patients. Conventional therapies include morphine-equivalent medication (MeM) and local radiotherapy (RT), but these interventions are not always successful. More recently, hyperthermia (HT) has been applied to complement RT and MeM, and this complex approach has shown promising synergistic results. The objective of our study was to present the results of RT combined with a special kind of HT (modulated electrohyperthermia, mEHT), in which some of the thermal effect is contributed by equivalent nonthermal components, drastically reducing the necessary power and energy. This retrospective study included 61 patients divided into three groups with pelvic and spinal bone metastases to compare the effects of RT and mEHT alone and in combination (RT + mEHT). A detailed evaluation of pain intensity, measured by the brief pain inventory score, MeM use, and breakthrough pain episodes, revealed no significant differences between RT and mEHT alone; thus, these individual methods were considered equivalent. However, RT + mEHT yielded significantly better results in terms of the above parameters. Clinically, mEHT has a lower risk of adverse thermal effects, and due to its efficacy, mEHT can be used to treat RT-resistant lesions. Full article

Background: Robotic-assisted surgery is the gold standard for performing radical prostatectomy (RARP), with new robotic devices such as Hugo^TM RAS gaining prominence worldwide. Objective: We report the surgical, perioperative, and early postoperative outcomes of RARP using Hugo^TM RAS. Design, setting, and participants: Between April 2022 and October 2023, we performed 132 procedures using the Montsouris technique with a four-robotic-arm configuration in patients with biopsy-proven prostate cancer (PCa). Outcome measures: We collected intraoperative and perioperative data during hospitalization, along with follow-up data at predefined postoperative intervals of 3 and 6 months. Results and limitations: Lymphadenectomy was performed in 25 procedures, with a bilateral nerve-sparing technique in 33 and a monolateral nerve-sparing technique in 33 cases. The mean total surgery time was 242 (±57) min, the mean console time was 124 (±48) min, and the mean docking time was 10 (±2) min. We identified 17 system errors related to robotic arm failures, 9 robotic instrument breakdowns, and 8 significant conflicts between robotic arms. One post-operative complication was classified as Clavien–Dindo 3b. None of the adverse events, whether singular or combined, increased the operative time. Positive margins (pR1) were found in 54 (40.9%) histological specimens, 37 (28.0%) of which were clinically significant. At 3 and 6 months post-surgery, the PSA levels were undetectable in 94.6% and 92.1% of patients, respectively. Social urinary continence was regained in 86% after 6 months. Limitations of our study include its observational monocentric case-series design and the short follow-up data for functional and oncological outcomes. Conclusions: Our initial experience highlights the reliability of the Hugo^TM RAS system in performing RARP. Additionally, we also list problems and solutions found in our daily work. Full article

This review addresses interferon (IFN) signaling in immune cells and the tumor microenvironment (TME) and examines how this affects cancer progression. The data reveal that IFNs exert dual roles in cancers, dependent on the TME, exhibiting both anti-tumor activity and promoting cancer progression. We discuss the abnormal IFN signaling induced by cancerous cells that alters immune responses to permit their survival and proliferation. Full article

Chimeric antigen receptor (CAR) T-cell therapy has become a powerful treatment option in B-cell and plasma cell malignancies, and many patients have benefited from its use. To date, six CAR T-cell products have been approved by the FDA and EMA, and many more are being developed and investigated in clinical trials. The whole field of adoptive cell transfer has experienced an unbelievable development process, and we are now at the edge of a new era of immune therapies that will have its impact beyond hematologic malignancies. Areas of interest are, e.g., solid oncology, autoimmune diseases, infectious diseases, and others. Although much has been achieved so far, there is still a huge effort needed to overcome significant challenges and difficulties. We are witnessing a rapid expansion of knowledge, induced by new biomedical technologies and CAR designs. The era of CAR T-cell therapy has just begun, and new products will widen the therapeutic landscape in the future. This review provides a comprehensive overview of the clinical applications of CAR T-cells, focusing on the approved products and emphasizing their benefits but also indicating limitations and challenges. Full article

We investigated genetic counseling and testing rates for patients with gynecologic malignancy at a tertiary care center with a large minority population. Our retrospective cohort included newly diagnosed epithelial ovarian, fallopian tube, peritoneal, or endometrial cancer patients between January 2014 and June 2022. For endometrial cancer, 373 patients were identified. A total of 207 (55%) patients were screened using mismatch repair immunohistochemistry (MMR IHC). A total of 82 (40%) had MMR deficiencies on IHC. Of these, 63 (77%) received genetic counseling. A total of 62 (98%) underwent genetic testing, and ultimately, 7 (11%) were diagnosed with Lynch syndrome (LS). The overall rate of LS was 1.9%. MMR IHC testing increased steadily, reaching 100% in 2022. For ovarian cancer, 144 patients were identified. A total of 104 (72%) patients received genetic counseling, and 99 (95%) underwent genetic testing. Rates were not influenced by race, ethnicity, insurance type, or family history of cancer. They were significantly different by cancer stage (p < 0.01). The proportion of patients who received genetic counseling increased from 47% in 2015 to 100% in 2022 (p < 0.01). Most counseling was performed by a gynecologic oncologist (93%) as opposed to a genetic counselor (6.7%). Overall, 12 (8.3%) patients were BRCA+. High rates of counseling and testing were observed with few disparities. Full article

Colorectal cancer is the third most common cancer worldwide, and the liver is the most common localization of metastatic disease. The incidence of minimally invasive liver surgery is increasing, and robotic surgery (RLR) is believed to overcome some limitations of a laparoscopic approach (LRL). We performed a systematic review and meta-analysis of operative and short-term oncologic outcomes of the laparoscopic versus robotic-assisted liver resection for colorectal liver metastases. An online search of PubMed, Embase, Scopus, and the Cochrane databases was performed. Eight studies involving 3210 patients were considered eligible for the meta-analysis. In the LRL group, a higher conversion to open rate (12.4%) was observed compared to the RLR (6.7%; p = <0.001). 30-day mortality was 0.7% for the LRL group compared to 0.5% for the RLR group (p = 0.76). Mortality in longer periods among LLR and RLR amounted to 18.2% vs. 8.0% for 1-year mortality (p = 0.07), 34.1% vs. 26.7% for 2-year mortality (p = 0.13), and 52.3% vs. 48.3% for 3-year mortality (p = 0.46). The length of hospital stay was 5.6 ± 2.5 vs. 5.8 ± 2.1 days, respectively (p = 0.47). There were no significant differences between the incidence of individual complications in the LRL and RLR groups (p = 0.78). Laparoscopic or robotic approaches for colorectal liver metastases are comparable in terms of safety and effectiveness. There are significant advantages to robotic surgery, although there is still no long-term evidence concerning overall survival, and the number of patients operated on using RLR remains small. Full article

Purpose: The study aims to examine the possible correlation between genomic alterations and preoperative olfactory function in patients with olfactory groove meningioma (OGM), due to the frequent presence of olfactory impairment. Methods: We utilised next-generation sequencing to analyse samples from 22 individuals with OGM in order to detect driver mutations. Tumour morphology was assessed using preoperative imaging, whereas olfactory function was examined using Sniffin’ Sticks. Results: In a study of 22 OGM patients, mutations were as follows: 10 with SMO/SUFU, 7 with AKT1, and 5 as wild type. Planum sphenoidale hyperostosis (PSH) was present in 75% of patients, showing significant variation by mutation (p = 0.048). Tumour volumes, averaging 25 cm³, significantly differed among groups. PSH negatively impacted olfaction, notably affecting odour threshold, discrimination, identification, and global olfactory performance score (TDI) (p values ranging from <0.001 to 0.003). Perifocal oedema was associated with lower TDI (p = 0.009) and altered threshold scores (p = 0.038). Age over 65 and female gender were linked to lower thresholds and discrimination scores (p = 0.037 and p = 0.019). Conclusion: The study highlights PSH and perifocal oedema’s significant effect on olfactory function in OGM patients but finds no link between olfactory impairment and tumour mutations, possibly due to the small sample size. This suggests that age and gender affect olfactory impairment. Additional research with a larger group of participants is needed to explore the impact of OGM driver mutations on olfactory performance. Full article

High-grade gliomas (HGGs) have a poor prognosis and are difficult to treat. This review examines the evolving landscape of endovascular therapies for HGGs. Recent advances in endovascular catheter technology and delivery methods allow for super-selective intra-arterial cerebral infusion (SSIACI) with increasing precision. This treatment modality may offer the ability to deliver anti-tumoral therapies directly to tumor regions while minimizing systemic toxicity. However, challenges persist, including blood–brain barrier (BBB) penetration, hemodynamic complexities, and drug–tumor residence time. Innovative adjunct techniques, such as focused ultrasound (FUS) and hyperosmotic disruption, may facilitate BBB disruption and enhance drug penetration. However, hemodynamic factors that limit drug residence time remain a limitation. Expanding therapeutic options beyond chemotherapy, including radiotherapy and immunobiologics, may motivate future investigations. While preclinical and clinical studies demonstrate moderate efficacy, larger randomized trials are needed to validate the clinical benefits. Additionally, future directions may involve endovascular sampling for peri-tumoral surveillance; changes in drug formulations to prolong residence time; and the exploration of non-pharmaceutical therapies, like radioembolization and photodynamic therapy. Endovascular strategies hold immense potential in reshaping HGG treatment paradigms, offering targeted and minimally invasive approaches. However, overcoming technical challenges and validating clinical efficacy remain paramount for translating these advancements into clinical care. Full article

Diet-induced obesity (DIO) promotes pancreatic ductal adenocarcinoma (PDAC) in mice expressing KRasG12D in the pancreas (KC mice), but the precise mechanisms remain unclear. Here, we performed multiplex quantitative proteomic and phosphoproteomic analysis by liquid chromatography–tandem mass spectrometry and further bioinformatic and spatial analysis of pancreas tissues from control-fed versus DIO KC mice after 3, 6, and 9 months. Normal pancreatic parenchyma and associated proteins were steadily eliminated and the novel proteins, phosphoproteins, and signaling pathways associated with PDAC tumorigenesis increased until 6 months, when most males exhibited cancer, but females did not. Differentially expressed proteins and phosphoproteins induced by DIO revealed the crucial functional role of matrisomal proteins, which implies the roles of upstream regulation by TGFβ, extracellular matrix-receptor signaling to downstream PI3K-Akt-mTOR-, MAPK-, and Yap/Taz activation, and crucial effects in the tumor microenvironment such as metabolic alterations and signaling crosstalk between immune cells, cancer-associated fibroblasts (CAFs), and tumor cells. Staining tissues from KC mice localized the expression of several prognostic PDAC biomarkers and elucidated tumorigenic features, such as robust macrophage infiltration, acinar–ductal metaplasia, mucinous PanIN, distinct nonmucinous atypical flat lesions (AFLs) surrounded by smooth muscle actin-positive CAFs, invasive tumors with epithelial–mesenchymal transition arising close to AFLs, and expanding deserted areas by 9 months. We next used Nanostring GeoMX to characterize the early spatial distribution of specific immune cell subtypes in distinct normal, stromal, and PanIN areas. Taken together, these data richly contextualize DIO promotion of Kras-driven PDAC tumorigenesis and provide many novel insights into the signaling pathways and processes involved. Full article

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. Full article

Background: This study aimed to investigate the effects of tetrahydrolipstatin (orlistat) on heterotopic glioblastoma in mice by applying MRI and correlating the results with histopathology and immunochemistry. Methods: Human glioblastoma cells were injected subcutaneously into the groins of immunodeficient mice. After tumor growth of >150 mm³, the animals were assigned into a treatment group (n = 6), which received daily intraperitoneal injections of orlistat, and a control group (n = 7). MRI was performed at the time of randomization and before euthanizing the animals. Tumor volumes were calculated, and signal intensities were analyzed. The internal tumor structure was evaluated visually and with texture analysis. Western blotting and protein expression analysis were performed. Results: At histology, all tumors showed high mitotic and proliferative activity (Ki67 ≥ 10%). Reduced fatty acid synthetase expression was measured in the orlistat group (p < 0.05). Based on the results of morphologic MRI-based analysis, tumor growth remained concentric in the control group and changed to eccentric in the treatment group (p < 0.05). The largest area under the receiver operating curve of the predictors derived from the texture analysis of T2w images was for wavelet transform parameters WavEnHL_s3 and WavEnLH_s4 at 0.96 and 1.00, respectively. Conclusions: Orlistat showed effects on heterotopically implanted glioblastoma multiforme in MRI studies of mice based on morphologic and texture analysis. Full article

MYCN amplification (MNA) and disruption of tumor suppressor microRNA (TSmiR) function are key drivers of poor outcomes in neuroblastoma (NB). While MYCN and TSmiRs regulate glucose metabolism, their role in de novo fatty acid synthesis (FAS) and unsaturated FAS (UFAS) remains poorly understood. Here, we show that FAS and UFAS (U/FAS) genes FASN, ELOVL6, SCD, FADS2, and FADS1 are upregulated in high-risk (HR) NB and that their expression is associated with lower overall survival. RNA-Seq analysis of human NB cell lines revealed parallel U/FAS gene expression patterns. Consistent with this, we found that NB-related TSmiRs were predicted to target these genes extensively. We further observed that both MYC and MYCN upregulated U/FAS pathway genes while suppressing TSmiR host gene expression, suggesting a possible U/FAS regulatory network between MYCN and TSmiRs in NB. NB cells are high in de novo synthesized omega 9 (ω9) unsaturated fatty acids and low in both ω6 and ω3, suggesting a means for NB to limit cell-autonomous immune stimulation and reactive oxygen species (ROS)-driven apoptosis from ω6 and ω3 unsaturated fatty acid derivatives, respectively. We propose a model in which MYCN and TSmiRs regulate U/FAS and play an important role in NB pathology, with implications for other MYC family-driven cancers. Full article

Pancreatic ductal adenocarcinoma (PDAC), one of the deadliest cancers, presents significant challenges in diagnosis and treatment due to its aggressive, metastatic nature and lack of early detection methods. A key obstacle in PDAC treatment is the highly complex tumor environment characterized by dense stroma surrounding the tumor, which hinders effective drug delivery. Nanotechnology can offer innovative solutions to these challenges, particularly in creating novel drug delivery systems for existing anticancer drugs for PDAC, such as gemcitabine and paclitaxel. By using customization methods such as incorporating conjugated targeting ligands, tumor-penetrating peptides, and therapeutic nucleic acids, these nanoparticle-based systems enhance drug solubility, extend circulation time, improve tumor targeting, and control drug release, thereby minimizing side effects and toxicity in healthy tissues. Moreover, nanoparticles have also shown potential in precise diagnostic methods for PDAC. This literature review will delve into targeted mechanisms, pathways, and approaches in treating pancreatic cancer. Additional emphasis is placed on the study of nanoparticle-based delivery systems, with a brief mention of those in clinical trials. Overall, the overview illustrates the significant advances in nanomedicine, underscoring its role in transcending the constraints of conventional PDAC therapies and diagnostics. Full article

Bladder cancer (BC) diagnosis is reliant on cystoscopy, an invasive procedure associated with urinary tract infections. This has sparked interest in identifying noninvasive biomarkers in body fluids such as blood and urine. A source of biomarkers in these biofluids are extracellular vesicles (EVs), nanosized vesicles that contain a wide array of molecular cargo, including small noncoding RNA such as transfer RNA-derived fragments (tRF) and microRNA. Here, we performed small-RNA next-generation sequencing from EVs from urine and serum, as well as from serum supernatant. RNA was extracted from 15 non-cancer patients (NCPs) with benign findings in cystoscopy and 41 patients with non-muscle invasive BC. Urine and serum were collected before transurethral resection of bladder tumors (TUR-b) and at routine post-surgery check-ups. We compared levels of tRFs in pre-surgery samples to samples from NCPs and post-surgery check-ups. To further verify our findings, samples from 10 patients with stage T1 disease were resequenced. When comparing tRF expression in urine EVs between T1 stage BC patients and NCPs, 14 differentially expressed tRFs (DEtRFs) were identified. In serum supernatant, six DEtRFs were identified among stage T1 patients when comparing pre-surgery to post-surgery samples and four DEtRFs were found when comparing pre-surgery samples to NCPs. By performing a blast search, we found that sequences of DEtRFs aligned with genomic sequences pertaining to processes relevant to cancer development, such as enhancers, regulatory elements and CpG islands. Our findings display a number of tRFs that may hold potential as biomarkers for the diagnosis and recurrence-free survival of BC. Full article

Cytoreductive surgery (CRS) combined with hyperthermic intrathoracic chemoperfusion (HITOC) is a promising treatment strategy for pleural mesothelioma (PM). The aim of this study was to evaluate the impacts of this multimodal approach in combination with systemic treatment on disease-free survival (DFS) and overall survival (OS). In this retrospective multicenter study, clinical data from patients after CRS and HITOC for PM at four high-volume thoracic surgery departments in Germany were analyzed. A total of 260 patients with MPM (220 epithelioid, 40 non-epithelioid) underwent CRS and HITOC as part of a multimodal treatment approach. HITOC was administered with cisplatin alone (58.5%) or cisplatin and doxorubicin (41.5%). In addition, 52.1% of patients received neoadjuvant and/or adjuvant chemotherapy. The median follow-up was 48 months (IQR = 38 to 58 months). In-hospital mortality was 3.5%. Both the resection status (macroscopic complete vs. incomplete resection) and histologic subtype (epithelioid vs. non-epithelioid) had significant impacts on DFS and OS. In addition, adjuvant chemotherapy (neoadjuvant/adjuvant) significantly increased DFS (p = 0.003). CRS and HITOC within a multimodal treatment approach had positive impacts on the survival of patients with epithelioid PM after macroscopic complete resection. The addition of chemotherapy significantly prolonged the time to tumor recurrence or progression. Full article

The curative treatment of multiple solid tumors, including head and neck squamous cell carcinoma (HNSCC), utilizes radiation. The outcomes for HPV/p16-negative HNSCC are significantly worse than HPV/p16-positive tumors, with increased radiation resistance leading to worse locoregional recurrence (LRR) and ultimately death. This study analyzed the relationship between immune function and outcomes following radiation in HPV/p16-negative tumors to identify mechanisms of radiation resistance and prognostic immune biomarkers. A discovery cohort of 94 patients with HNSCC treated uniformly with surgery and adjuvant radiation and a validation cohort of 97 similarly treated patients were utilized. Tumor immune infiltrates were derived from RNAseq gene expression. The immune cell types significantly associated with outcomes in the discovery cohort were examined in the independent validation cohort. A positive association between high Th2 infiltration and LRR was identified in the discovery cohort and validated in the validation cohort. Tumor mutations in CREBBP/EP300 and CASP8 were significantly associated with Th2 infiltration. A pathway analysis of genes correlated with Th2 cells revealed the potential repression of the antitumor immune response and the activation of BRCA1-associated DNA damage repair in multiple cohorts. The Th2 infiltrates were enriched in the HPV/p16-negative HNSCC tumors and associated with LRR and mutations in CASP8, CREBBP/EP300, and pathways previously shown to impact the response to radiation. Full article

Theranostics define diagnostic evaluations directing patient-specific therapeutic decisions. Molecular theranostics involves genomic, transcriptomic, proteomic, metabolomic and finally phenonic definitions thyroid cancer differentiation. It is the functional differentiation that determines the sensitivity and accuracy of RAI imaging as well as the effectiveness of RAI treatment. Total thyroidectomy is performed to empower an anticipated RAI treatment. A preoperative determination of the genomic and transcriptomic profile of the tumor is a strong predictor of response to therapeutic interventions. This article discusses the oncopathophysiologic basis of the theranostic risk stratification approach. Full article

In HPV-associated carcinomas, some examples of cancer-related genes altered by viral insertion and corresponding to potential therapeutic targets have been described, but no quantitative assessment of these events, including poorly recurrent targets, has been reported to date. To document these occurrences, we built and analyzed a database comprised of 1455 cases, including HPV genotypes and tumor localizations. Host DNA sequences targeted by viral integration were classified as “non-recurrent” (one single reported case; 838 loci), “weakly recurrent” (two reported cases; 82 loci), and highly recurrent (≥3 cases; 43 loci). Whereas the overall rate of cancer-related target genes was 3.3% in the Gencode database, this rate increased to 6.5% in “non-recurrent”, 11.4% in “weakly recurrent”, and 40.1% in “highly recurrent” genes targeted by integration (p = 4.9 × 10⁻⁴). This rate was also significantly higher in tumors associated with high-risk HPV16/18/45 than other genotypes. Among the genes targeted by HPV insertion, 30.2% corresponded to direct or indirect druggable targets, a rate rising to 50% in “highly recurrent” targets. Using data from the literature and the DepMap 23Q4 release database, we found that genes targeted by viral insertion could be new candidates potentially involved in HPV-associated oncogenesis. A more systematic characterization of HPV/host fusion DNA sequences in HPV-associated cancers should provide a better knowledge of HPV-driven carcinogenesis and favor the development of personalize patient treatments. Full article

Breast cancer affected more than 2.3 million women in 2022 and is the most diagnosed cancer among women worldwide. The incidence rates are greater in developed regions and are significantly higher among women with higher education and socioeconomic status. Therefore, it is reasonable to assume that the way women live their lives may impact their risk of being diagnosed with breast cancer. This systematic review aimed to identify what is known about the causes and risk factors of breast cancer, excluding genetic causes. A comprehensive systematic search identified 2387 systematic reviews, 122 were included and six overall themes identified. In our “top list” with the 36 most important findings, a study of breast density had the highest effect size for increasing the risk of breast cancer, and a high sex-hormone-binding globulin level was the most protective factor. Many of the included studies investigating the same topics had conflicting results. The conclusion from this evidence synthesis reveals a lack of consensus of factors associated with the causes and risk of breast cancer. These findings suggest that recommendations about lifestyle and breast cancer should be made with caution. Full article