Improvement In Survival Research Articles

New systemic treatment options for advanced cholangiocarcinoma.

Cholangiocarcinoma (CCA) is a rare and aggressive cancer, mostly diagnosed at advanced or metastatic stage, at which point systemic treatment represents the only therapeutic option. Chemotherapy has been the backbone of advanced CCA treatment. More recently, immunotherapy has changed the therapeutic landscape, as immune checkpoint inhibitors (ICIs) have yielded the first improvement in survival and currently, the addition of either durvalumab or pembrolizumab to standard of care cisplatin plus gemcitabine represents the new first-line treatment option. However, the use of immunotherapy in subsequent lines has not demonstrated its efficacy and therefore, it is not approved, except for pembrolizumab in the selected microsatellite instability-high (MSI-H) population. In addition, advances in comprehensive genomic profiling have led to the identification of targetable genetic alterations, such as isocitrate dehydrogenase 1 (IDH1), fibroblast growth factor receptor 2 (FGFR2), human epidermal growth factor receptor 2 (HER2), proto-oncogene B-Raf (BRAF), neurotrophic tropomyosin receptor kinase (NTRK), rearranged during transfection (RET), Kirsten rat sarcoma virus (KRAS), and mouse double minute 2 homolog (MDM2), thus favoring the development of a precision medicine approach in previously treated patients. Despite these advances, the use of molecularly driven agents is limited to a subgroup of patients. This review aims to provide an overview of the newly approved systemic therapies, the ongoing studies, and future research challenges in advanced CCA management.

Salivary Microbiome Relates to Neoadjuvant Immunotherapy Response in OSCC.

Most patients diagnosed with oral squamous cell carcinoma (OSCC) present with locally advanced stages, which are typically associated with poor outcomes. Although immunotherapy offers potential improvements in patient survival, its efficacy is hampered by low response rates. The microbiome is widely involved in tumor immunity and may play a role in immunotherapy. This study aimed to investigate the potential association between the oral (salivary) microbiome and immunotherapy response in patients with OSCC. Salivary metagenome sequencing was performed on 47 patients with OSCC undergoing neoadjuvant immunotherapy (NAIT) in a clinical trial (NCT04649476). Patients were divided into responders and nonresponders based on their pathological responses. The results showed that the species richness of the salivary microbiome was lower in the nonresponders before NAIT than in the responders. Differential analysis revealed that nonresponders exhibited a lower relative abundance of 34 bacterial species and a higher relative abundance of 4 bacterial species. Notably, low levels of Eubacterium infirmum, Actinobaculum, and Selenomas (EAS) in the saliva may be associated with the nonresponse of patients with OSCC to NAIT. A nomogram based on EAS was developed and validated to determine the efficacy of NAIT. The area under the curve for the training cohort was 0.81 (95% confidence interval, 0.66 to 0.81). Quantitative polymerase chain reaction confirmed that low levels of salivary EAS effectively identified nonresponders to NAIT. Furthermore, the low abundance of salivary EAS was closely correlated with a low density of intratumoral CD4+, CD14+, CD68+, and FOXP3+ cells. Metabolic functional annotation revealed numerous biosynthetic processes associated with EAS that were more active in responders. In summary, this study provides valuable data resources for the salivary microbiome and reveals that nonresponders have different salivary microbiome profiles than responders do before NAIT. Low salivary EAS levels can serve as potential biomarkers for distinguishing nonresponders from responders.

Bevacizumab Erlotinib Switch Maintenance in Chemo-Responsive Advanced Gallbladder and Cholangiocarcinoma (BEER BTC): A Multicenter, Open-Label, Randomized, Phase II Trial.

Patients with chemotherapy-responsive advanced biliary tract cancers (BTCs) are usually observed after 6 months of gemcitabine-based therapy. There is limited prospective evidence for maintenance strategies after chemotherapy. This investigator-initiated, open-label, randomized, integrated phase II-III study enrolled adult patients with advanced BTC from two cancer centers in India. Patients with histologically confirmed advanced biliary tract adenocarcinoma who had at least disease stabilization after 6 months of gemcitabine-based chemotherapy were randomly assigned (1:1) to either active surveillance or switch maintenance, which was a combination of bevacizumab 5 mg/kg intravenous once every 21 days plus erlotinib 100 mg once daily. Both arms were continued until disease progression, unacceptable toxicity, or patient decision to withdraw. The primary end point of the phase II component of the trial was investigator-evaluated progression-free survival. This trial is registered with Clinical Trials Registry of India (CTRI/2019/05/019323I). From May 2021 to November 2022, 98 patients were randomly assigned to active surveillance (n = 49) or bevacizumab-erlotinib (n = 49). A majority of patients had gallbladder cancer (80%). The median follow-up was 13.4 months. The median progression-free survival was 3.1 months (95% CI, 2.47 to 3.64) in the active surveillance group versus 5.3 months (95% CI, 3.53 to 7.04) in the bevacizumab-erlotinib group (hazard ratio, 0.51 [95% CI, 0.33 to 0·74]; P = .0013). The most common grade 3 class-specific adverse events associated with bevacizumab-erlotinib were acneiform rash 1 (2%) and oral stomatitis 1 (2%) with erlotinib and bleeding 1 (2%) with bevacizumab. The combination of bevacizumab and erlotinib as switch maintenance improves progression-free survival with an acceptable safety profile compared with active surveillance in patients with advanced BTCs in this phase II study. The trial moves on to the phase III component to evaluate improvement in overall survival.

Optimal candidates and surrogate endpoints for HAIC versus Sorafenib in hepatocellular carcinoma: an updated systematic review and meta-analysis.

Hepatic artery infusion chemotherapy (HAIC) has been a long-standing intervention for hepatocellular carcinoma (HCC). Despite positive clinical outcomes, its inclusion in guidelines remains limited due to a lack of evidence-based support. This study aims to identify optimal target populations for HAIC and validate associations between intermediate endpoints with overall survival (OS). Following PRISMA guidelines, a comprehensive search was conducted in PubMed, Embase, Cochrane Library, and Web of Science. The primary search strategy was based on medical subject headings terms (MeSH) using "Hepatic arterial infusion chemotherapy", "HAIC", "Sorafenib", "Nexavar", "hepatocellular carcinoma", "HCC", "Liver cancer", combined with free text words. Data extraction, quality assessment, and analysis were performed according to pre-registered protocol. A total of 26 studies, 6456 HCC patients were included for analysis (HAIC, n=2648; Sorafenib, n=3808). Pooled outcomes revealed that Sorafenib demonstrated better OS only in patients who were refractory to trans-arterial chemoembolization (TACE) (HR=1.32,95%CI [1.01-1.73]), in other subgroups or overall HCC population HAIC consistently outperformed Sorafenib in patients' survival. Radiologically, higher response rates in the HAIC group does not necessarily translate into survival improvement, but the hazard ratios (HRs) of 1y-OS (R2=0.41, P=0.0044) and 1y-progression free survival (1y-PFS) (R2=0.77, P=0.0002) strongly correlated with the patients OS. Meanwhile, larger tumour size (HR=1.86,95%CI [1.12-3.1, 95%), heavier tumour burden (HR=2.32, 95%CI [1.33-4.02), existence of MVI or EHS (HR=1.65,95%CI[1.36-2]; HR=1.60,95%CI[1.19-2.14]), and AFP >400ng/mL (HR=1.52, 95%CI [1.20-1.92]) were identified as independent risk factors for OS, while HAIC treatment (HR=0.54, 95%CI[0.35-0.82]) and lower BCLC stage (HR=0.44, 95%CI[0.28-0.69]) were potential protective factors for HCC patients. HAIC monotherapy appears noninferior to Sorafenib in HCC treatment, with potential benefits in specific subgroups. The robust correlation between 1y-OS/1y-PFS and OS, alongside identified risk and protective factors from the present study, offers valuable insights for designing future large prospective studies in this field.

Trends in Presentation, Management, and Survival of Women With Breast Cancer in a Multiethnic, Middle-Income Asian Setting.

Granular data on breast cancer (BC) are pertinent for surveillance, planning, and monitoring of cancer care delivery. We determined the trends in clinical presentation, management, and survival of women with BC in a multiethnic middle-income Asian setting over 15 years. Data of 7,478 Malaysian women newly diagnosed with invasive BC between 2005 and 2019 from three hospital-based cancer registries were included. Trends in demographic, tumor, and treatment characteristics were compared across period 1 (P1): 2005-2009, period 2 (P2): 2010-2014, and period 3 (P3): 2015-2019. Overall survival and net survival were determined. More women in P3 than P1 were older than 60 years at diagnosis. Only a marginal increase in proportion of women with stage I disease was observed (23.7% v 27.2% in P1 and P3, respectively, P = .004). Nonetheless, patients were increasingly presenting with smaller tumors, fewer axillary node involvement, well-differentiated tumors, and hormone receptor expression in recent times. Proportion of women with human epidermal growth factor receptor 2 (HER2)-overexpressed tumors significantly decreased. Among indicated patients, receipt of anticancer therapies was somewhat similar over the calendar periods, except for neoadjuvant chemotherapy and anti-HER2 therapy, where increases in administration were noted. Significant improvements in survival were observed over the 15 years, particularly for HER2-overexpressed BCs. Although the improvements in BC survival that we have observed validate ongoing cancer control efforts and treatment advances, study findings suggest that more could be done for earlier detection and improved access to effective therapies in our settings.

Survival improvements in esophageal and gastric cancers in the Nordic countries favor younger patients.

Esophageal cancer (EC) and gastric cancer (GC) are fatal cancers with a relatively late age of onset. Age is a negative risk factor for survival in many cancers and our aim was to analyze age-specific survival in EC and GC using the recently updated NORDCAN database. NORDCAN data originate from the Danish, Finnish, Norwegian, and Swedish nationwide cancer registries covering years 1972 through 2021 inviting for comparison of 50-year survival trends between the countries. Relative 1- and 5-year survival and 5/1-year conditional survival (i.e., survival in those who were alive in Year 1 to survive additional 4 years) were analyzed. Survival in EC showed large gains for patients below age 80 years, 5-year survival in Norwegian men reaching 30% and in women over 30% but for 80-89 year old survival remained at 10%. In contrast, hardly any gain was seen among the 80-89 year patients for 1-year survival and small gains in 5 year and 5/1-year survival. Survival gaps between age-groups increased over time. For GC there was also a clear age-related negative survival gradient but the survival gaps between the age groups did not widen over time; Norwegian male and female 5-year survival for 80-89 year old was about 20%. The age-specific survival difference in GC arose in Year 1 and did not essentially increase in 5-year survival. While there were differences in survival improvements between the countries, poor survival of the 80-89 year old patients was shared by all of them. To conclude, survival has improved steadily in younger GC and EC patients in most Nordic countries. While the 80-89 year old population accounts for nearly a quarter of all patients and their poor survival depressed overall survival, which can therefore be increased further by improving diagnostics, treatment and care of elderly EC and GC patients.

The worldwide survival rate of total hip arthroplasties is improving: a systematic comparative analysis using worldwide hip arthroplasty registers.

The aim of this study was to evaluate the development of the worldwide survival rate of primary total hip arthroplasty (THA). The hypothesis was that survival improved over the last decade in worldwide arthroplasty registers. THA registers were screened in 2022 and compared between different countries with respect to the number of primary implantations per inhabitant, age, fixation type, and survival rate, and compared to similar data from 2009. The data from these reports were analyzed in terms of number, age distribution, and procedure type of primary THAs. Survival curves and a comparative analysis with respect to the development over time were calculated. We identified nine hip arthroplasty registers that contained sufficient data to be included. A large variation was found in the annual number of primary THA implantations per inhabitant, with more than the factor 4 for all age groups across regions. The procedure type varied strongly as well, e.g. in Sweden, 50% were cemented THAs, whereas in Emilia-Romagna (Italy), 96% of THAs were implanted cementless. We found an improved survival rate of 5%, with 90% of survival after 15 years in the cohorts from 2021 compared to 85% in the cohorts from 2009. The present study revealed a significant improvement in the survival of THA in worldwide arthroplasty registers within different countries and regions over the period of one decade. We believe that it is safe to state that the success of THA is still rising with respect to this main outcome.

Development of a fit-for-purpose multi-marker panel for early diagnosis of pancreatic ductal adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) suffers from lack of an effective diagnostic method, which hampers improvement in patient survival. Carbohydrate antigen 19-9 (CA19-9) is the only FDA-approved blood biomarker for PDAC, yet its clinical utility is limited due to suboptimal performance. Liquid chromatography-mass spectrometry (LC-MS) has emerged as a burgeoning technology in clinical proteomics for discovery, verification, and validation of novel biomarkers. A plethora of protein biomarker candidates for PDAC have been identified using LC-MS, yet few has successfully transitioned into clinical practice. This translational standstill is owed partly to insufficient considerations of practical needs and perspectives of clinical implementation during biomarker development pipelines, such as demonstrating analytical robustness of proposed biomarkers which is critical for transitioning from research-grade to clinical-grade assays. Moreover, throughput and cost-effectiveness of proposed assays ought to be considered concomitantly from early phases of the biomarker pipelines for enhancing widespread adoption in clinical settings. Here, we developed a fit-for-purpose multi-marker panel for PDAC diagnosis by consolidating analytically robust biomarkers as well as employing a relatively simple LC-MS protocol. In discovery phase, we comprehensively surveyed putative PDAC biomarkers from both in-house data and prior studies. In verification phase, we developed a multiple-reaction monitoring (MRM)-MS-based proteomic assay using surrogate peptides that passed stringent analytical validation tests. We adopted a high-throughput protocol including short gradient (<10 min) and simple sample preparation (no depletion or enrichment steps). Additionally, we developed our assay using serum samples, which are usually the preferred biospecimen in clinical settings. We developed predictive models based on our final panel of 12 protein biomarkers combined with CA19-9, which showed improved diagnostic performance compared to using CA19-9 alone in discriminating PDAC from non-PDAC controls including healthy individuals and patients with benign pancreatic diseases. A large-scale clinical validation is underway to demonstrate the clinical validity of our novel panel.

Further improvement of circuit survival in citrate based continuous renal replacement therapy.

Continuous renal replacement therapy (CRRT) is the most frequently used modality of renal replacement therapy (RRT) in critical care patients with acute kidney injury (AKI). Adequate CRRT delivery can be challenging, due to problems with circuit patency. To improve circuit patency, we developed a new CRRT protocol using continuous veno-venous hemodiafiltration (CVVHDF) with 3.0mmol/l regional citrate anticoagulation (CVVHDF/RCA3.0) as our first choice RRT modality. Retrospective comparison of efficacy and safety of a CVVHDF/RCA3.0 protocol with our former continuous veno-venous hemofiltration protocol with 2.2 regional citrate anticoagulation (CVVH/RCA2.2) in adult critically ill patients with AKI requiring CRRT between 25 April 2020 and 24 October 2021. In total, 56 patients (257 circuits) and 66 patients (290 circuits) were included in the CVVH/RCA2.2 and CVVHDF/RCA3.0 groups, respectively. Median circuit survival was significantly higher in patients treated with CVVHDF/RCA3.0 (39.6 (IQR 19.5-67.3) hours) compared to patients treated with CVVH/RCA2.2 (22.9 (IQR 11.3-48.6) hours) (P<.001). Higher body weight and higher convective flow were associated with a lower circuit survival. Metabolic control was similar, except for metabolic alkalosis that occurred less frequently during CVVHDF/RCA3.0 (19% of patients) compared to CVVH/RCA2.2 (46% of patients) (P=.006). CRRT circuit survival was longer with CVVHDF/RCA3.0 compared to CVVH/RCA2.2. CRRT circuit survival was negatively associated with higher body weight and higher convective flow.

Effect of neoadjuvant chemoradiation on anorectal function assessed with anorectal manometry: A systematic review and meta-analysis.

Improvement in oncological survival for rectal cancer increases attention to anorectal dysfunction. Diagnostic questionnaires can evaluate quality of life but are subjective and dependent on patients' compliance. Anorectal manometry can objectively assess the continence mechanism and identify functional sphincter weakness and rectal compliance. Neoadjuvant chemoradiotherapy is presumed to affect anorectal function. We aim to assess anorectal function in rectal cancer patients who undergo total mesorectal excision, with or without neoadjuvant chemoradiation, using anorectal manometry measurements. MEDLINE, Embase, and Cochrane databases were searched for studies comparing perioperative anorectal manometry between neoadjuvant chemoradiation and upfront surgery for rectal cancers. Primary outcomes were resting pressure, squeeze pressure, sensory threshold volume and maximal tolerable volume. Eight studies were included in the systematic review, of which seven were included for metanalysis. 155 patients (45.3%) had neoadjuvant chemoradiation before definitive surgery, and 187 (54.6%) underwent upfront surgery. Most patients were male (238 vs. 118). The standardized mean difference of mean resting pressure, mean and maximum squeeze pressure, maximum resting pressure, sensory threshold volume, and maximal tolerable volume favored the upfront surgery group but without statistical significance. Currently available evidence on anorectal manometry protocols failed to show any statistically significant differences in functional outcomes between neoadjuvant chemoradiation and upfront surgery. Further large-scale prospective studies with standardized neoadjuvant chemoradiation and anorectal manometry protocols are needed to validate these findings.

Pegylated liposomal doxorubicin combined with trabectedin as a treatment option in uterine sarcomas: a single-institution retrospective analysis

ObjectiveThe use of conventional doxorubicin in combination with trabectedin leads to a considerable prolongation of progression-free survival in the treatment of uterine sarcomas but is associated with dose-limiting toxicities. Significant...

Preparing the Heart for a New Baby: Management of Pregnancy in Heart Transplant Recipients.

Heart transplant (HT) recipients are more frequently reaching childbearing age given improvement in median survival and outcomes after HT. Although most pregnancies in HT recipients have favorable outcomes, poor fetal outcomes and maternal complications such as hypertensive disorders of pregnancy are more common in HT recipients than in the general population. In this review, we summarize the current evidence to guide the management of pregnancy in HT recipients. Preconception counseling, focused on risk stratification and optimal timing of conception, is the first important step to optimize pregnancy outcomes. During pregnancy and in the postpartum period, frequent monitoring of graft function and immunosuppressive levels is recommended. Calcineurin inhibitors and corticosteroids should be the mainstay of treatment for both prevention and treatment of graft rejection. Delivery planning should follow usual obstetric indications, preferably with vaginal delivery at term using regional anesthesia. A multidisciplinary care team should be involved in management through all stages of pregnancy to ensure success.

Selective, Temporary Postoperative Inhibition of Lymphangiogenesis by Integrin α5β1 Blockade Improves Allograft Survival in a Murine Model of High-Risk Corneal Transplantation

Background: Corneal inflammatory hem- and lymphangiogenesis significantly increase the risk for immune rejection after subsequent allogeneic corneal transplantation. The purpose of this study was to analyze the impact of temporary selective inhibition of lymphangiogenesis after transplantation on graft survival. Methods: Allogeneic transplantation from C57BL/6 mice to BalbC mice was performed as “high-risk” keratoplasty in a prevascularized corneal host bed (suture-induced inflammatory corneal neovascularization). The treatment group received integrin α5β1-blocking small molecules (JSM6427) at the time of transplantation and for two weeks afterwards. Control mice received a vehicle solution. Grafts were evaluated weekly for graft rejection using an opacity score. At the end of the follow-up, immunohistochemical staining of corneal wholemounts for lymphatic vessels as well as CD11b+ immune cells was performed. Results: Temporary postoperative inhibition of lymphangiogenesis by JSM6427 improved the corneal graft survival significantly. At the end of the follow-up, no significant reduction in CD11b+ immunoreactive cells within the graft compared to controls was found. Conclusions: The significant improvement of corneal graft survival by the selective, temporary postoperative inhibition of lymphangiogenesis after keratoplasty using integrin antagonists shows the impact of lymphatic vessels in the early postoperative phase. Retarding lymphatic vessel ingrowth into the graft might be sufficient for the shift to immunological tolerance in the postoperative period, even after high-risk keratoplasty.

Sequence of Contact X-ray Brachytherapy (CXB) and External Beam Radiation (EBRT) in organ-preserving treatment for small rectal cancer

Background and purposeExternal Beam Radiotherapy (EBRT) followed by Contact X-ray Brachytherapy (CXB) and vice versa are viable alternatives to surgery for selected rectal cancer patients who have small tumours (≤3 cm). However, the optimal sequence of treatment needs to be established. We compared two approaches using Propensity Score (PS) matching and inverse probability treatment weighting (IPTW) analyses to investigate whether the sequence of treatment affected patient outcomes. Materials and methodsThis retrospective analysis (2008–2019) included patients with rectal adenocarcinoma (cT1-3,N0-1,M0, grade 1–2, size ≤ 3 cm) who received both EBRT and CXB, irrespective of treatment sequence. PS matching and IPTW were conducted to balance covariate standardised mean differences between groups. Oncological outcomes and rate of post-treatment rectal bleeding were assessed. ResultsFollowing PS matching and IPTW analyses from 251 eligible patients; 103 starting with EBRT (median follow-up: 37 [IQR:18–56] months) and 148 with CXB (median follow-up: 32 [IQR:16–54] months, a significant improvement in 3-year overall survival (77% vs 85%, p = 0.02, [HR:0.58 (95% CI:0.37–0.91)]) and a higher risk of post-treatment rectal bleeding (grade 1 (26%) and grade 2 (6%)) were found in patients who started with CXB (p = 0.08). No significant differences were observed in local regrowth (18% vs 12%, p = 0.47), distant relapse (10% vs 6%, p = 0.53), 3-year organ preservation rates (70% vs 75%, p = 0.20, [HR:0.66 (95% CI: 0.35–1.26)]), or disease-free survival (78% vs 82%, p = 0.17, [HR: 0.47 (95% CI: 0.16–1.38)]) ConclusionIn patients with rectal cancer (≤3 cm), commencing with CXB rather than EBRT, was associated with improved overall survival, but had a higher risk of G1/2 rectal bleeding. No statistically significant differences were observed in other oncological outcomes.

A multifaceted role of bisphosphonates from palliative care to anti-cancer therapy in solid tumors.

Bisphosphonates (P-C-Ps) also called diphosphonates are the structural analogs of naturally occurring pyrophosphates. Bisphosphonates are traditionally used and shown to provide long-term success in the treatment and prevention of osteoporosis and other bone loss pathologies. Furthermore, bisphosphonates are gaining popularity in the present era of cancer therapeutics and prevention. The usage of bisphosphonates as adjuvant or neoadjuvant therapy, either as a single agent or combined with other chemotherapy, has been studied in different solid tumors. This review aims to present the various roles of bisphosphonates in solid tumors. Articles in MEDLINE/PubMed and the National Institutes of Health Clinical Trials Registry (http://www. Clinicaltrials.gov) between 1 January 2011 and 1 February 2022 were extracted using MeSH terms "bisphosphonates/diphosphosphonates and mechanism," "bisphosphonates and breast cancer," "bisphosphonates and prostate cancer," "bisphosphonates and lung cancer," "bisphosphonates and cancer risk," and "bisphosphonates and adverse events." Manual searches of some major oncology journals were also conducted. This review article focuses on the antitumor activity of bisphosphonates, safety profile, and the role of bisphosphonates as preventive, neoadjuvant, and adjuvant chemotherapy. A significant improvement in overall survival and cancer-specific survival and recurrence-free survival with the usage of bisphosphonates is noted in breast cancer patients, particularly in post-menopausal women. Though great progress has been achieved in over 20 years, further research is needed to identify the subgroup of patients that are most likely to benefit from adjuvant bisphosphonate therapy and to determine regimens with greater efficacy and better safety profile.

Combined Organ Transplantation in Patients with Advanced Liver Disease.

Transplantation of the liver in combination with other organs is an increasingly performed procedure. Over the years, continuous improvement in survival could be realized through careful patient selection and refined organ preservation techniques, in spite of the challenges posed by aging recipients and donors, as well as the increased use of steatotic liver grafts. Herein, we revisit the epidemiology, allocation policies in different transplant zones, indications, and outcomes with regard to simultaneous organ transplants involving the liver, that is combined heart-liver, liver-lung, liver-kidney, and multivisceral transplantation. We address challenges surrounding combined organ transplantation such as equity, utility, and logistics of dual organ implantation, but also advantages that come along with combined transplantation, thereby focusing on molecular mechanisms underlying immunoprotection provided by the liver to the other allografts. In addition, the current standing and knowledge of machine perfusion in combined organ transplantation, mostly based on center experience, will be reviewed. Notwithstanding all the technical advances, shortage of organs, and the lack of universal eligibility criteria for certain multi-organ combinations are hurdles that need to be tackled in the future.

Recent Updates in the Diagnosis and Management of Kidney Diseases in Multiple Myeloma

Multiple myeloma (MM) represents a difficult-to-treat plasma cell malignancy and the second most common hematologic malignancy in adults, significantly impacting kidney function. The spectrum of kidney involvement in MM is broad, encompassing electrolyte imbalances, tubular injury, and even rare glomerular diseases. The evolution of MM treatment modalities has led to notable improvements in the long-term survival of patients experiencing kidney-related complications. Over the past decade, groundbreaking therapeutic agents have emerged, including proteasome inhibitors, immunomodulatory drugs, anti-CD38 monoclonal antibodies, selective inhibitors of nuclear export, and antibody-drug conjugates. These novel therapies have revolutionized the landscape of MM management, offering new hope for patients and challenging the traditional treatment paradigms. This comprehensive review explores recent advances in the diagnosis and management of MM, emphasizing the pivotal role of these innovative therapeutic agents in improving patient outcomes. We delve into the intricacies of diagnosing MM, highlighting the significance of early detection and precise diagnostic tools. We elucidate the evolving treatment strategies, emphasizing the mechanisms of action and clinical efficacy of the latest agents. This manuscript provides valuable insights into the ever-evolving field of MM management, shedding light on the remarkable progress achieved in enhancing the prognosis and quality of life of MM patients.

Impact of hyperthermic intraperitoneal chemotherapy on gastric cancer survival: Peritoneal metastasis and cytology perspectives.

Gastric cancer presenting with peritoneal metastasis is notably associated with diminished survival prospects. The use of cytoreductive surgery in conjunction with hyperthermic intraperitoneal chemotherapy (HIPEC) has been shown to increase survival rates in these patients. Despite these advancements, debates persist regarding the magnitude of survival improvement attributed to this treatment modality. The present investigation examined survival outcomes following HIPEC in individuals diagnosed with gastric cancer and peritoneal metastasis, and it took a comparative analysis of patients exhibiting positive and negative cytological findings. To compare the impact of HIPEC on survival in gastric cancer patients with peritoneal metastasis and positive or negative cytology. Between April 2013 and March 2020, 84 patients with advanced gastric cancer treated at our institution were categorized into three cohorts: HIPEC (20 patients with peritoneal metastasis), cytology-positive (23 patients without peritoneal nodules but with positive wash cytology), and cytology-negative (41 patients with advanced gastric cancer, no peritoneal nodules, and negative wash cytology). The HIPEC cohort underwent gastrectomy with HIPEC, while the cytology-positive and cytology-negative groups received gastrectomy alone. The demographic, pathological, and survival data of the groups were compared. The HIPEC cohort-predominantly younger females-exhibited relatively extended surgical durations and high blood loss. Nevertheless, the complication rates were consistent across all three groups. Median survival in the HIPEC group was 20.00 ± 4.89 months, with 1-year, 2-year, and 3-year overall survival rates of 73.90%, 28.70%, and 9.60%, respectively. These figures paralleled the survival rates of the cytology-positive group (52.20% at 1 year, 28.50% at 2 years, and 19.00% at 3 years). Notably, 47% of patients experienced peritoneal recurrence. HIPEC may offer a modest improvement in short-term survival for patients with gastric cancer and peritoneal metastasis, mirroring the outcomes in cytology-positive patients. However, peritoneal recurrence remained high.

PI3K inhibitors in hematology: When one door closes….

The phosphatidylinositol 3-kinase (PI3K) signaling pathway regulates key cellular processes and is one of the most aberrantly activated pathways in cancer. The class I PI3K catalytic subunits p110g and p110d are highly enriched in leukocytes, providing additional rationale for targeting these PI3Ks in hematologic malignancies. In 2014, the PI3Kd inhibitor idelalisib was the first of four PI3K inhibitors to receive regulatory approval for relapsed B-cell malignancies. This was followed by approvals of the pan-class I inhibitor copanlisib (2017), the dual PI3Kg/d inhibitor duvelisib (2018), and the PI3Kd and casein kinase-1e inhibitor umbralisib (2021). Copanlisib and umbralisib received accelerated approvals, while idelalisib and duvelisib received initial accelerated approvals followed by full approvals. The accelerated approvals were based on overall response rates, however follow-up studies showed increased risk of death and serious side effects. Furthermore, the confirmatory trial with copanlisib failed to show an improvement in progression free survival when compared to chemoimmunotherapy. These developments led to black box warnings for idelalisib and duvelisib, and withdrawal of copanlisib and umbralisib from the market by their manufacturers. Given the uncertain future of this drug class, additional manufacturers terminated ongoing phase III trials with novel PI3K inhibitors. Here, we review the development and current status of PI3K inhibitors in hematology, limitations to their use, and our perspective on whether there is a future for PI3K inhibitors in hematology.

Impact of cancer diagnosis on life expectancy by area-level socioeconomic groups in New South Wales, Australia: a population-based study.

Improvement in cancer survival over recent decades has not been accompanied by a narrowing of socioeconomic disparities. This study aimed to quantify the loss of life expectancy (LOLE) resulting from a cancer diagnosis and examine disparities in LOLE based on area-level socioeconomic status (SES). Data were collected for all people between 50 and 89 years of age who were diagnosed with cancer, registered in the NSW Cancer Registry between 2001 and 2019, and underwent mortality follow-up evaluations until December 2020. Flexible parametric survival models were fitted to estimate the LOLE by gender and area-level SES for 12 common cancers. Of 422,680 people with cancer, 24% and 18% lived in the most and least disadvantaged areas, respectively. Patients from the most disadvantaged areas had a significantly greater average LOLE than patients from the least disadvantaged areas for cancers with high survival rates, including prostate [2.9 years (95% CI: 2.5-3.2 years) vs. 1.6 years (95% CI: 1.3-1.9 years)] and breast cancer [1.6 years (95% CI: 1.4-1.8 years) vs. 1.2 years (95% CI: 1.0-1.4 years)]. The highest average LOLE occurred in males residing in the most disadvantaged areas with pancreatic [16.5 years (95% CI: 16.1-16.8 years) vs. 16.2 years (95% CI: 15.7-16.7 years)] and liver cancer [15.5 years (95% CI: 15.0-16.0 years) vs. 14.7 years (95% CI: 14.0-15.5 years)]. Females residing in the least disadvantaged areas with thyroid cancer [0.9 years (95% CI: 0.4-1.4 years) vs. 0.6 years (95% CI: 0.2-1.0 years)] or melanoma [0.9 years (95% CI: 0.8-1.1 years) vs. 0.7 years (95% CI: 0.5-0.8 years)] had the lowest average LOLE. Patients from the most disadvantaged areas had the highest LOLE with SES-based differences greatest for patients diagnosed with cancer at an early stage or cancers with higher survival rates, suggesting the need to prioritise early detection and reduce treatment-related barriers and survivorship challenges to improve life expectancy.