Benefit In Terms Of Survival Research Articles

Four-year overall survival follow-up and dynamic EBV titer analysis of toripalimab versus placebo in combination with gemcitabine and cisplatin as first-line treatment for recurrent or metastatic nasopharyngeal carcinoma (r/m NPC).

6039 Background: In October 2023, the US FDA approved toripalimab in combination with Gemcitabine-Cisplatin (GP) as first-line treatment for recurrent or metastatic (r/m) NPC based on the results of JUPITER-02 study (NCT03581786). Here we report the results of four-year overall survival (OS) follow-up and dynamic EBV DNA copy number and its correlation with clinical outcome. Methods: Patients with r/m NPC (n=289) were randomized (1:1) to receive toripalimab 240 mg (n=146) or placebo (n=143) in combination with GP once every 3 weeks (Q3W) for up to 6 cycles, followed by monotherapy with toripalimab or placebo until disease progression, intolerable toxicity, or completion of 2 years of treatment. Stratification factors were ECOG performance score (0 vs. 1) and extent of disease (recurrent vs.primary metastatic). The primary endpoint was progression free survival by an independent review committee. Secondary endpoints included OS and safety. Exploratory endpoints included dynamic blood EBV DNA copy number and its correlation with clinical efficacy. Results: By the cutoff date of January 9, 2024, 50 months after the last patient was enrolled, 150 deaths were recorded. Compared with the results from the final OS analysis, consistent survival improvement was observed for toripalimab over placebo: HR=0.61 (95% CI: 0.44-0.85), nominal p=0.0027. The median OS was not yet reached in the toripalimab arm and was 33.7 months in the placebo arm. The 5-year OS rates were 52.0% in the toripalimab arm, and 33.9% in the placebo arm. Among patients with detectable baseline EBV DNA copy number and at least one EBV result after study treatment, significantly more patients from the toripalimab arm had EBV DNA copy number decreased to undetectable level than those in the placebo arm, 96.3% vs. 84.5%, p= 0.004. In addition, significantly less patients experienced EBV DNA copy number rebound in the toripalimab arm than in the placebo arm after the initial reduction, 36.5% vs, 57.4%, p=0.002. The median time from the lowest EBV DNA copy number to the rebound was 20.5 vs. 6.0 months in the toripalimab and placebo arms respectively. The rebound also preceded investigator-assessed disease progression by a median of 1.9 months in the toripalimab arm. Conclusions: The combination of toripalimab and chemotherapy showed long term survival benefit than chemotherapy alone with a 5-year OS rate at 52%. EBV DNA copy number might be used to monitor clinical response and predict disease progression. Clinical trial information: NCT03581786 .

Sub-lobar resection versus lobectomy for challenging intraoperative frozen sections in lung adenocarcinoma within 3 cm

ObjectivesIntraoperative frozen section (FS) analysis is pivotal in guiding surgical interventions for early-stage lung adenocarcinoma. However, the challenge arises when distinguishing between Minimally Invasive Adenocarcinoma (MIA) and Invasive Adenocarcinoma (IAC) poses diagnostic difficulties. This study investigates the prognosis and clinicopathological characteristics of patients encountering this diagnostic challenge. MethodsWe conducted a retrospective analysis of 7,082 intraoperative FSs from early-stage lung adenocarcinoma cases. The cases with pulmonary nodules within 3cm and diagnosed as indeterminate FSs were included. We analyzed baseline data, computed tomography (CT) findings, and pathological characteristics. Prognostic data were obtained from patients with confirmed IAC diagnoses through final pathological examination. ResultsOut of 7,082 FSs, 551 cases presented challenges in distinguishing between MIA and IAC. Upon final pathological examination, 233 cases were identified as IAC, while 314 were classified as MIA. The median invasive pathological size in the IAC group was larger than that in the MIA group (0.6cm vs 0.3cm). 131 cases (56.2%) with IAC underwent lobectomy, while 102 cases (43.8%) underwent sub-lobar resection.Among the MIA cases, 220 cases (69.8%) underwent sub-lobar resection, while 95 cases (30.2%) underwent lobectomy. No recurrence and disease specific death was observed during the follow-up period, regardless of surgical strategy. ConclusionsIndeterminate intraoperative FSs, posing diagnostic challenges in distinguishing between MIA and IAC. Sub-lobar resection presented the same long term survival benefit compared with the lobectomy for indeterminate lung adenocarcinoma within 3cm during intraoperative FSs.

Abstract 4083: Pre-clinical development of IAMA-005, a long-acting cytokine fusion of modified IL-2 and IFN-α

Abstract In 1990s, both IL-2 and IFN-α were approved as the first two immunotherapies for metastatic melanoma and renal cell carcinoma; IFN-α was also approved for hairy cell leukemia. Although the response rates are relatively low, along ~25%, those who responded have long term survival benefits. However, the severe toxicity especially in high dose prohibited their broad use in oncology. Recently, there have been tremendous interests in modifying these two cytokines in the efforts to reduce the toxicity and enhance the activity. One such effort is to enhance the binding of IL-2 to the intermediate affinity β/γ receptors, which are expressed and function on CD8 T cells and NK cells. Another effort is to reduce the binding of IL-2 to high affinity α/β/γ receptors which mostly expressed on Treg and stimulate the growth of Treg cells, which suppress immune responses. Recently, whether it’s better to target intermediate affinity or high affinity for cancer therapy has become controversial with some studies showing that high affinity receptor engagements are required for robust anti-tumor activity while others favoring intermediate affinity receptor engagement for better efficacy; However, the clinical comparison is still lacking to be sure which approach is better. Here we have developed a long-acting novel IL-2-Fc-IFN-α fusion molecule termed IAMA-005 that has mutations to reduce the toxicity effects of IL-2 and IFN-α. We have characterized this molecule preclinically both in vitro and in vivo. IAMA-005 has demonstrated a potent tumor cell killing activities in numerous cancer cell lines including BT-474, SK-OV-3, NCI-N87, OE19, HCC-1954, MDA-MB-231, MDA-MB-468. When combined with IAMA-004 (a Her2-CD47-CD16 tri-specific antibody) in vitro, the tumor cell killing activities were dramatically increased. In addition, IAMA-005 was also tested in patient-derived Ex-Vivo fluids (one malignant pleural effusion and one malignant asities) and demonstrated excellent tumor cell killing efficacies. In addition, the killing activities of IAMA-005 could be attributed to the specific part of the fusion molecule because of the TME immune cell compositions. The in vivo assays to demonstrate efficacy and safety are ongoing and will be presented in the poster. These results suggest that this fusion cytokine molecule may be used in monotherapy in certain indications and an excellent complementary therapeutic to antibody targeted therapies or immunotherapies when used in combination. Citation Format: Liming Liu, Zhen Han, Yang Fan, Qi Pan. Pre-clinical development of IAMA-005, a long-acting cytokine fusion of modified IL-2 and IFN-α [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4083.

Host plant-mediation of viral transmission and its consequences for a native butterfly.

Pathogens play a key role in insect population dynamics, contributing to short-term fluctuations in abundance as well as long-term demographic trends. Two key factors that influence the effects of entomopathogens on herbivorous insect populations are modes of pathogen transmission and larval host plants. In this study, we examined tritrophic interactions between a sequestering specialist lepidopteran, Euphydryas phaeton, and a viral pathogen, Junonia coenia densovirus, on its native host plant, Chelone glabra, and a novel host plant, Plantago lanceolata, to explore whether host plant mediates viral transmission, survival, and viral loads. A two-factor factorial experiment was conducted in the laboratory with natal larval clusters randomly assigned to either the native or novel host plant and crossed with either uninoculated controls or viral inoculation (20% of individuals in the cluster inoculated). Diapausing clusters were overwintered in the laboratory and checked weekly for mortality. At the end of diapause, all surviving individuals were reared to adulthood to estimate survivorship. All individuals were screened to quantify viral loads, and estimate horizontal transmission postmortem. To test for vertical transmission, adults were mated, and the progeny were screened for viral presence. Within virus-treated groups, we found evidence for both horizontal and vertical transmission. Larval clusters reared on the native host plant had slightly higher horizontal transmission. Survival probability was lower in clusters feeding on the native host plant, with inoculated groups reared on the native host plant experiencing complete mortality. Viral loads did not differ by the host plant, although viral loads decreased with increased sequestration of secondary compounds on both host plants. Our results indicate that the use of a novel host plant may confer fitness benefits in terms of survival and reduced viral transmission when larvae feeding on it are infected with this pathogen, supporting hypotheses of potential evolutionary advantages of a host range expansion in the context of tritrophic interactions.

Differences in Treatment Outcomes According to the Insertion Method Used in Extracorporeal Cardiopulmonary Resuscitation: A Single-Center Experience.

Venoarterial extracorporeal membrane oxygenation (ECMO) is a key treatment method used with patients in cardiac arrest who do not respond to medical treatment. A critical step in initiating therapy is the insertion of ECMO cannulas. Peripheral ECMO cannulation methods have been preferred for extracorporeal cardiopulmonary resuscitation (ECPR). Patients who underwent ECPR at Daegu Catholic University Medical Center between January 2017 and May 2023 were included in this study. We analyzed the impact of 2 different peripheral cannulation strategies (surgical cutdown vs. percutaneous cannulation) on various factors, including survival rate. Among the 99 patients included in this study, 66 underwent surgical cutdown, and 33 underwent percutaneous insertion. The survival to discharge rates were 36.4% for the surgical cutdown group and 30.3% for the percutaneous group (p=0.708). The ECMO insertion times were 21.3 minutes for the surgical cutdown group and 10.3 minutes for the percutaneous group (p<0.001). The factors associated with overall mortality included a shorter low-flow time (hazard ratio [HR], 1.045; 95% confidence interval [CI], 1.019-1.071; p=0.001) and whether return of spontaneous circulation was achieved (HR, 0.317; 95% CI, 0.127-0.787; p=0.013). Low-flow time was defined as the time from the start of cardiopulmonary resuscitation to the completion of ECMO cannula insertion. No statistically significant difference in in-hospital mortality was observed between the surgical and percutaneous groups. However, regardless of the chosen cannulation strategy, reducing ECMO cannulation time was beneficial, as a shorter low-flow time was associated with significant benefits in terms of survival.

Propensity score analysis demonstrates no long term survival benefit from contemporary endovascular aneurysm repair compared to open in Aotearoa New Zealand.

Current guidelines for AAA management are based on landmark trials comparing EVAR and open aneurysm repair (OAR) conducted more than 20 years ago. Important advancements have been made in peri-operative care but the impact of EVAR and OAR on long-term patient survival has not been well reported using contemporary data. The objective of this study was to compare the short and long-term outcomes of OAR and EVAR in the recent era. This retrospective observational study included all patients undergoing intact AAA repair in NZ from 1st of January 2011 until 31st of December 2019. Data was collected from national administrative and clinical vascular databases and matched using unique identifiers. Time-to-event survival analyses was conducted using cox proportional hazard models to adjust for confounders and propensity score matching were used. Two thousand two hundred and ninety-seven patients had an intact AAA repair with a median (IQR) age of 75 (69-80) years; 494 (21.2%) patients were females and 1206 (53%) underwent EVAR. The 30-day mortality for OAR and EVAR was 4.8% and 1.2%. The median (IQR) follow up was 5.2 (2.3-9.2) years. After propensity matching for co-variates, the study cohort consisted of 835 patients in each matched group. Patients undergoing EVAR had a higher overall mortality (HR 1.48 (95% CI: 1.26-1.74) after adjusting for confounders compared to OAR. Analysis of survival following EVAR and OAR in the current era demonstrates that patients that underwent EVAR had a lower 30-day mortality. However, in the long-term after adjusting for confounders OAR had a better overall survival.

Real World Experience of FLT3-Inhibitor Post-Transplant Maintenance with Sorafenib Demonstrating Superior Overall- and Relapse Free Survival Following Allogeneic Hematopoietic Stem Cell Transplantation in FLT3-ITD Mutated Acute Myeloid Leukemia

Introduction Acute myeloid leukemia (AML) with FLT3-internal tandem duplication (ITD) is known to have a significantly high risk of relapse even with allogeneic stem cell transplantation (HCT), for which post-transplant maintenance therapy with FLT3 inhibitors (FLT3i) has been applied. Although there is a randomized trial comparing Sorafenib maintenance vs no treatment, real world experience is still limited. Despite the increased use of FTL3i maintenance in clinical practice, the optimal dose and duration of post-transplant Sorafenib maintenance remains uncertain. Accordingly, we performed a retrospective chart review to analyze the survival benefit with Sorafenib maintenance, dose tolerability and the impact of FLT3-ITD allele frequency (AF) at initial diagnosis of AML on treatment outcomes in the context of post-HCT Sorafenib maintenance. Patients and method We conducted a retrospective study including 69 patients who received an allogeneic HCT from 2019 to 2023 for AML with FLT3-ITD, of which 24 patients received Sorafenib as post-HCT maintenance therapy. Primary endpoint was relapse-free survival (RFS). The use of Sorafenib maintenance treatment was treated as a time-dependent covariate and Mantel-Byar test (MBT) was conducted to compare outcomes between Sorafenib maintenance group vs others, which will avoid immortal bias. FLT3-ITD allele frequency (AF) was assessed by molecular PCR test, and the cutoff was determined using a binary recursive partitioning method with AF of 54.6% as a cutoff. Results Out of 69 patients, 61 (88%) were in CR1 vs 8 (12%) in CR2 prior to HCT. Sorafenib was started in 24 patients (35%) at a median of 95 days post-HCT with a dose of 200mg every other day (n=2), 200mg once daily (n=17) or 200mg twice daily (n=5). The most common maintenance dose was 200mg once daily (n=9), followed by 200mg twice daily (n=6), 200mg every other day (n=5), and 400mg twice daily (n=1). The median Sorafenib maintenance duration was 15 months (1-53 months) at the last follow-up. There were no relapses in the patients who completed 2 years of Sorafenib maintenance. Sorafenib was discontinued in 6 patients, due to relapse (n=2), death of unrelated cause (n=1), GVHD (n=1), pneumonitis (n=1) and recurrent hypoglycemia (n=1). Adverse events requiring Sorafenib dose reduction included, GI intolerance (n=7), skin rash (n=7), thrombocytopenia (n=4), transaminitis (n=3), neuropathy (n=3), GVHD (n=2) and pneumonitis (n=2). The median follow-up duration for all the patients was 27 months (5-51) following HCT, or 13 months (1.3-48) following Sorafenib maintenance. Using Kaplan-Meier test, the 2-year RFS in patients on Sorafenib maintenance was 84.5% vs 40.5% for no Sorafenib (p=0.00049). The 2-year OS was 88.2% vs 53.9% (p=0.0043), respectively. The CIR was 9.8% vs 39.9% (p=0.00634), while the NRM was 5.6% vs 19.7% (p =0.122), respectively. In the MBT, Sorafenib maintenance was found to reduce the mortality risk by 62.5% (HR 0.375 (0.109-1.29], p=0.120) and reduced the relapse/mortality risk by 71.2% (HR 0.288 [0.084-0.984], p=0.047). With respect to FLT3-ITD AF, the group with higher AF showed extremely higher HR for RFS compared to those with lower FLT-ITD (HR 29.37 [3.007-286.8], p=0.0036). When evaluating RFS and OS with combined risk incorporating the use of Sorafenib and FLT3-ITD AF, we have 4 subgroups (figure 1). In patients with a lower AF, the RFS was 87.7% vs 56.8% in the Sorafenib (n=20), vs no Sorafenib group (n=31), respectively. In patients with a higher AF, the RFS was 66.7% vs 0.0% in the Sorafenib (n=3), vs no Sorafenib group (n=8; p=0.0009), respectively. In a multivariate analysis, we confirmed the 2-year RFS for patients who had a high FLT3-ITD and received Sorafenib maintenance was statistically significant when compared to no Sorafenib maintenance. Conclusion Sorafenib maintenance post-transplant in FLT3-ITD mutated AML patients significantly improves the OS and RFS. Sorafenib maintenance is tolerable with 200mg twice daily or lower in most patients. Reduced doses of Sorafenib improve tolerability, with no significant impact on increased risk of relapse. Higher AF group of FLT3-ITD at initial diagnosis defined by ≥54.6% using PCR, was associated with significantly increased risk of relapse even after HCT. Sorafenib maintenance seems to provide survival benefit in terms of RFS, particularly in the patients with higher AF FLT3-ITD.

Long-term outcomes of neo-adjuvant chemotherapy on borderline resectable oral cavity cancers: Real-world data of 3266 patients and implications for clinical practice

BackgroundNeo-adjuvant chemotherapy (NACT) followed by response assessment is the standard treatment algorithm for locally advanced oral cavity squamous cell carcinomas (OCSCC) in the Indian subcontinent. The 3-drug NACT regimen (Docetaxel-Cisplatin-5-FU) has shown improvement in overall survival over 2-drug regimen (Docetaxel-Cisplatin) in a phase-3 randomised study. We have analysed the 10-year outcomes with this treatment algorithm. MethodsThis was an institutional review board approved retrospective analysis of a prospectively collected dataset of borderline resectable OCSCC patients who underwent NACT. Patients who became resectable after NACT underwent surgery followed by appropriate adjuvant therapy. Patients who were unresectable received definitive chemoradiation (CTRT), palliative chemotherapy, radiotherapy or best supportive care based on general condition. ResultsA total of 3266 patients were included. The most common subsite was buccal mucosa and the most frequent indication was peri-tumoral edema upto zygoma. More than 2-drugs NACT was offered to 32.9% patients. Overall, 32.5% patients had a response to NACT. A total of 1358 patients were offered curative treatment, of which 929 (32%) underwent surgery and the rest underwent definitive chemo-radiation (14.8%). Patients who received more than 2-drugs NACT versus those who received 2-drugs had a 10-years OS of 21% vs 5.1% (p < 0.001). Patients who underwent surgery versus those who did not had a 10-year OS of 21.8% vs 4.1% (p < 0.001). Patients who achieved pCR had a 5-year OS of 45.3% vs 13.3% for those who did not (p < 0.001). ConclusionNACT leads to long term survival benefit in patients of borderline resectable oral cavity cancer.

OGC P57 Are Cervical Lymph Node Dissections in Oesophageal Cancer Patients Undergoing Oesophagectomy Beneficial?

Abstract Background Cervical lymph node dissection in patients undergoing oesophagectomy can be indicated when there is suspicion of involved cervical nodes, although there is controversy around the benefits of this additional procedure on the prognosis of these patients. This study aims to assess the consequences and survival after cervical lymph node dissection, and to weigh the risks and benefits of this procedure. Methods This retrospective study included seven patients with oesophageal squamous cell carcinoma (SCC), and one with oesophageal adenocarcinoma who underwent cervical lymph node dissection in addition to oesophagectomy at the Churchill Hospital. There was a male to female ratio of 1:3, and all had neoadjuvant chemotherapy and were staged with PET-CT. PET staging scan results were compared pre and post neo-adjuvant therapy (NAT) to assess nodal involvement. Final histopathology was also recorded. Results All patients had evidence of cervical nodal involvement on PET scan, two of whom developed nodal involvement only after NAT. Only two patients had neck node involvement on histopathology: one had SCC and showed good response to NAT; the other had undifferentiated carcinoma and showed new para-tracheal node involvement after NAT, later developing supraclavicular node recurrence. Two cases were complicated by recurrent laryngeal nerve (RLN) injury, one with bilateral and one with partial vocal cord palsy. There was a 5-year survival rate of 62.5%, with non-survivors uniquely having recurrent disease. Conclusions Lymph node dissection alongside oesophagectomy achieved good 5-year survival in this small cohort, but with a significant risk of RLN injury. Further studies investigating the proportion of metastatic neck nodes found on dissection, long term survival benefits and cancer reoccurrence are required.

Abstract 12344: Effect of Valved versus Non-Valved Conduits in Norwood Procedure on Ventricular Size and Function in Stage I Palliation for Hypoplastic Left Heart Syndrome

Background: Mortality in the interstage period remains high in hypoplastic left heart syndrome (HLHS) after introduction of the right ventricle (RV) to pulmonary artery conduit to the Norwood procedure. Prior studies have not shown long term survival benefit with conduits, possibly due to regurgitation and volume load, which may cause decreased RV function. Valved conduits (VC) were introduced more recently to address these limitations. Hypothesis: The goal of the study was to assess differences in RV size and function during the interstage period between patients undergoing Norwood procedure with valved versus non-valved conduits (NVC). We hypothesized that patients with VC would have smaller increases in RV size and improved function compared to those with NVC. Methods: Twenty-five consecutive neonates with HLHS who underwent Norwood procedure with VC were compared to 25 consecutive neonates who underwent Norwood with NVC from 2013 and 2022. Primary outcomes were RV size measured by end diastolic area (EDA) on 4-chamber images and function measured by RV fractional area change and global longitudinal strain. Results: Most patients with VC (96%) did not develop more than mild conduit regurgitation. There was no difference in EDA increase one month post op between groups, but there was a significantly smaller increase in EDA pre-Glenn compared to baseline in the VC group (Table 1). Functional measures were not significantly different during follow up. There was no difference in interstage cardiac events or mortality. Conclusions: Patients with VC at time of Norwood had smaller increases in ventricular size compared to those with NVC, but there were no differences in functional parameters during follow up. It is possible decreased volume load will have a beneficial long term effect on the immature myocardium of infants with HLHS. Larger studies are needed to further examine the hemodynamic benefits of VC in the interstage period and throughout the stages of palliation.

Indications for Cardiac Catheterization and Percutaneous Coronary Intervention in Patients with Resuscitated Out-of-Hospital Cardiac Arrest.

The role of emergent cardiac catheterization after resuscitated out-of-hospital cardiac arrest (OHCA) has evolved based on recent randomized evidence. This review aims to discuss the latest evidence and current indications for emergent coronary angiography (CAG) and mechanical circulatory support (MCS) use following OHCA. In contrast to previous observational data, recent RCTs evaluating early CAG in resuscitated OHCA patients without ST elevation have uniformly demonstrated a lack of benefit in terms of survival or neurological outcome. There is currently no randomized evidence supporting MCS use specifically in patients with resuscitated OHCA and cardiogenic shock. Urgent CAG should be considered in all patients with ST elevation, recurrent electrical or hemodynamic instability, those who are awake following resuscitated OHCA, and those receiving extracorporeal cardiopulmonary resuscitation (ECPR). Recent evidence suggests that CAG may be safely delayed in hemodynamically stable patients without ST-segment elevation following resuscitated OHCA.

Comparison between regular additional endobiliary radiofrequency ablation and photodynamic therapy in patients with advanced extrahepatic cholangiocarcinoma under systemic chemotherapy.

Extrahepatic cholangiocarcinoma (eCCA) remains a malignancy with a dismal prognosis. The first-line standard of care includes systemic chemotherapy (SC) and biliary drainage through stenting. Endobiliary ablative techniques, such as photodynamic therapy (ePDT) and radio-frequency ablation (eRFA), have demonstrated feasibility and favorable survival data. This study aimed to compare the oncologic outcome in patients treated with SC and concomitant eRFA or ePDT. All patients with eCCA were evaluated for study inclusion. Sixty-three patients receiving a combination of SC and at least one endobiliary treatment were retrospectively compared. Patients were stratified into three groups: SC + ePDT (n = 22), SC + eRFA (n = 28), and SC + ePDT + eRFA (n = 13). The median overall survival (OS) of the whole cohort was 14.2 months with no statistically significant difference between the three therapy groups but a trend to better survival for the group receiving ePDT as well as eRFA, during SC (ePDT + SC, 12.7 months; eRFA + SC, 13.8 months; ePDT + eRFA + SC, 20.2 months; p = 0.112). The multivariate Cox regression and subgroup analysis highlighted the beneficial effect of eRFA on OS. Overall, combined therapy was well tolerated. Only cholangitis occurred more often in the SC + eRFA group. Additional endobiliary ablative therapies in combination with SC were feasible. Both modalities, eRFA and ePDT, showed a similar benefit in terms of survival. Interestingly, patients receiving both regimes showed the best OS indicating a possible synergism between both ablative therapeutic techniques.

A model for the dissemination of circulating tumour cell clusters involving platelet recruitment and a plastic switch between cooperative and individual behaviours

BackgroundIn spite of extensive research, cancer remains a major health problem worldwide. As cancer progresses, cells acquire traits that allow them to disperse and disseminate to distant locations in the body – a process known as metastasis. While in the vasculature, these cells are referred to as circulating tumour cells (CTCs) and can manifest either as single cells or clusters of cells (i.e., CTC clusters), with the latter being the most aggressive. The increased metastatic potential of CTC clusters is generally associated with cooperative group benefits in terms of survival, including increased resistance to shear stress, anoikis, immune attacks and drugs. However, the adoption of a group phenotype poses a challenge when exiting the vasculature (extravasation) as the large size can hinder the passage through vessel walls. Despite their significant role in the metastatic process, the mechanisms through which CTC clusters extravasate remain largely unknown. Based on the observed in vivo association between CTC clusters and platelets, we hypothesized that cancer cells take advantage of the platelet-derived Transforming Growth Factor Beta 1 (TGF-β1) – a signalling factor that has been widely implicated in many aspects of cancer, to facilitate their own dissemination. To address this possibility, we evaluated the effect of exogenous TGF-β1 on an experimentally evolved non-small cell lung cancer cell line that we previously developed and used to investigate the biology of CTC clusters.ResultsWe found that exogenous TGF-β1 induced the dissociation of clusters in suspension into adherent single cells. Once adhered, cells released their own TGF-β1 and were able to individually migrate and invade in the absence of exogenous TGF-β1. Based on these findings we developed a model that involves a TGF-β1-mediated plastic switch between a cooperative phenotype and a single-celled stage that enables the extravasation of CTC clusters.ConclusionsThis model allows for the possibility that therapies can be developed against TGF-β1 signalling components and/or TGF-β1 target genes to suppress the metastatic potential of CTC clusters. Considering the negative impact that metastasis has on cancer prognosis and the lack of therapies against this process, interfering with the ability of CTC clusters to switch between cooperative and individual behaviours could provide new strategies to improve patient survival.

Novel Drugs for the Management of Diabetes Kidney Transplant Patients: A Literature Review.

The management of diabetes and renal failure is changing thanks to the appearance of new drugs such as glucagon-like peptide 1 receptor agonists (GLP1-RA) and sodium-glucose cotransporter type 2 inhibitors (SGLT2i) that have benefits in terms of survival and cardiorenal protection. Based on the potential mechanisms of GLP1-RA, kidney transplant recipients (KTRs) could benefit from their effects. However, high-quality studies are needed to demonstrate these benefits, in the transplant population, especially those related to cardiovascular benefits and renal protection. Studies with SGLT2i performed in KTRs are much less potent than in the general population and therefore no benefits in terms of patient or graft survival have been clearly demonstrated in this population to date. Additionally, the most frequently observed side effects could be potentially harmful to this population profile, including severe or recurrent urinary tract infections and impaired kidney function. However, benefits demonstrated in KTRs are in line with a known potential effects in cardiovascular and renal protection, which may be essential for the outcome of transplant recipients. Better studies are still needed to confirm the benefits of these new oral antidiabetics in the renal transplant population. Understanding the characteristics of these drugs may be critical for KTRs to be able to benefit from their effects without being damaged. This review discusses the results of the most important published studies on KTRs with GLP1-RA and SGLT2i as well as the potential beneficial effects of these drugs. Based on these results, approximate suggestions for the management of diabetes in KTRs were developed.

Efficacy of epirubicin plus docetaxel or paclitaxel in the treatment of breast cancer

Purpose: To determine the clinical efficacy of epirubicin plus docetaxel or paclitaxel in the management of breast cancer. &#x0D; Methods: This study was a randomized controlled trial that recruited 78 patients with breast cancer treated in The First People’s Hospital of Anqing between December 2018 and March 2021. The participants were randomized to receive either epirubicin plus docetaxel (control group) or epirubicin plus paclitaxel (study group), with 39 cases in each group. Clinical outcomes, adverse events, quality of life, and prognosis of the two groups were compared. &#x0D; Results: Epirubicin plus paclitaxel produced greater efficacy than epirubicin plus docetaxel (p &lt; 0.05). The combination also exhibited a higher safety profile versus epirubicin with docetaxel, as evidenced by lower incidences of nausea and vomiting, intestinal discomfort, muscle pain, and dyspnea reactions (p &lt; 0.05). Epirubicin with paclitaxel resulted in greater improvement in quality of life in patients than epirubicin plus docetaxel (p &lt; 0.05) as well as provided more benefits in terms of survival and recurrence control than epirubicin plus docetaxel (p &lt; 0.05). &#x0D; Conclusion: Epirubicin/paclitaxel combination alleviates clinical symptoms, reduces adverse events, enhances patient prognosis, lowers the risk of postoperative recurrence, and provides superior quality of life when compared to epirubicin/docetaxel combination in breast cancer patients. Nonetheless, large-scale and better-randomized clinical trials are required to validate the findings of this study.

The 5-Year Disease-Free Survival of Third Generation Aromatase Inhibitor for Postmenopausal Women with HR-Positive HER2-Negative Non-Metastatic Breast Cancer.

Background: Several studies showed the superiority of aromatase inhibitor (AI) as first-line therapy for patients with hormone-receptor (HR)-positive breast cancer (BC). For the clinician, studies in the real world are warranted to determine treatment based on the efficacy of each drug. We compared a 5-y disease-free survival (DFS) of each AI in terms of survival benefit. Materials and Methods: We evaluated 450 medical records of postmenopausal women who were diagnosed with HR-positive HER2-negative BC (stage I - III) at Dr. Sardjito General Hospital from January to December 2019. All patients had undergone surgery and chemotherapy or radiation therapy. Moreover, study participants received anastrozole, letrozole, or exemestane for at least one year. Kaplan Meier estimation survival curve was used to analyze the survival rate. Result: Of 79 patients meeting inclusion criteria, there were 21.52% distant metastases documented. Time to disease progression of anastrozole, letrozole, and exemestane was 49 months, 58 months, and 53 months, respectively. Letrozole was found better than anastrozole (hazard ratio (HR)=4.342, 95% CI 0.95-19.95; p=0.038). Letrozole versus exemestane (HR=2.757, 95% CI 0.53-14.33; p=0,206) and anastrozole versus exemestane (HR=1.652, 95% CI 0.56-4.84; p=0.351) were found not significantly different. 5-y DFS rate of letrozole was better found (87.5%) than exemestane (73.7%) and anastrozole (61.4%). Conclusion: 5-year letrozole administration could be proposed as first-line therapy for postmenopausal women with HR-positive HER2-negative BC. A considerable subject and long-term follow-up are needed for validation.

Analysis of prognostic factors and histopathological response to neoadjuvant chemotherapy in osteosarcoma.

This study aims to examine the clinical results of patients who underwent medical and surgical treatment for osteosarcoma, to determine the overall survival (OS) and disease-free survival (DFS) rates, and to examine the effects of prognostic factors on these rates. Between January 2005 and January 2020, a total of 64 patients (38 males, 26 females; mean age: 20.9±11.5 years; range, 6 to 70 years) who received medical and surgical treatment for osteosarcoma were retrospectively analyzed. Demographic characteristics, follow-up period, tumor location and size, tumor stage and necrosis rate, metastatic disease, surgical treatments, postoperative complications, local recurrence, and metastasis were recorded. The relationship of these factors with the survival was examined. The median follow-up was 51.6 (range, 3 to 156) months. The most common tumor localization was in the distal femur with 42 (65.6%) patients and the most common histopathological subtypes were conventional osteosarcoma in 50 (78.1%) patients. The OS rates were 91.6% at one year, 65.9% at five years, and 51.6% at 10 years. With the exception of two patients who died during neoadjuvant chemotherapy, all patients underwent surgical treatment. The addition of chemotherapy + radiotherapy in the treatment did not provide any benefits in terms of survival and recurrence compared to the group that was not added, and the five-year OS rate was 79.3% compared to 20.7%, respectively. The overall 10-year survival rates were 83.9% and 37.2% in the group with a good response (≥90%) and poor response (<90%) to treatment (p=0.012). The mean survival time of three patients who presented with pathological fractures was shorter than the others (p>0.05). Surgical margin was ≤2 mm in 27 (42.2%) patients, >2 mm in 30 (46.9%) patients, and surgical margin was positive in five (7.8%) patients. The mean OS in the group with a surgical margin closure of >2 mm was 10.8±1.9 years and was longer than the other groups (p=0.047). Metastasis at the time of diagnosis, <90% tumor necrosis, a tumor size of ≥10 cm, and metastasis development were significantly associated with poor survival and were found to be independent prognostic factors. The OS rate in the patient group with Stage III-IV response after neoadjuvant chemotherapy given the cisplatin + doxorubicin protocol was found to be better than those given the European and American Osteosarcoma Studies (EURAMOS) protocol. More research is needed to determine the most optimal chemotherapy protocols in this patient population. In addition, a multidisciplinary approach in treatment is of utmost importance to improve oncological outcomes.

The Ross Procedure in Adolescence and Beyond: Are There Still Contraindications?

The Ross procedure is an excellent operation to treat children and adults with aortic valve disease. Compared to prosthetic aortic valve replacement, it provides important clinical benefits in terms of survival, hemodynamics, freedom from valve-related complications, and durability, especially in women of childbearing age. However, the Ross procedure is a longer and technically more challenging operation. As a result, the choice of procedure should be driven by patient anatomy and clinical characteristics. This highlights the importance of concentrating care in Ross reference centers where surgical expertise and experience are present to ensure patient safety and long-term effectiveness of the operation. This manuscript reviews the major and relative contraindications to the Ross procedure.

A study to assess the effectiveness of planned teaching programme on knowledge regarding organ donation among final year diploma nursing (GNM) students in a selected college of nursing at Udupi

Background: Organ donation is the process of a person donating organs for transplant. These are given to someone with damaged organs that need to be replaced. Organ transplantation is the most preferred treatment for many of the end- stage organ disease as it increases life expectancy. Besides long –term survival benefits, organ donation also improves quality of life in many circumstances.Methodology: The research design adopted for this study was pre-experimental one group pre-test post-test design. Sixty final year diploma nursing (GNM) students were selected by convenience sampling technique. The tool used for data collection was a structured knowledge questionnaire. As an intervention, administration of planned teaching programme regarding organ donation was given. Result: The study revealed that pre-test only very few students (16.7%) had good knowledge, 36.7% had average knowledge and 46.6% had poor knowledge. In the post test all the students 100% had good knowledge. Data presented in Table 2 and Figure ranged from 6-18 and the mean score was 12.7 with 2.77. In the post ranged from 20-25 and the mean score was much higher (23.0±1.72) than the pre score. The mean difference was 10.3. The obtained ‘t’ value (t59=24.52) is higher than the table value (t59=2.00, p≤0.05). The findings are highly significant and it can be inferred that planned teaching programme regarding organ donation was highly effective in improving the knowledge of final year GNM students.

PALLIATIVE GASTRECTOMY VERSUS GASTRIC BYPASS FOR SYMPTOMATIC CLINICAL STAGE IV GASTRIC CANCER: A PROPENSITY SCORE MATCHING ANALYSIS.

Patients with clinical stage IV gastric cancer may require palliative procedures to manage complications such as obstruction. However, there is no consensus on whether performing palliative gastrectomy compared to gastric bypass brings benefits in terms of survival. To compare the overall survival of patients with distal obstructive gastric cancer undergoing palliative surgical treatment, using propensity score matching analysis. Patients who underwent palliative bypass surgery (gastrojejunostomy or partitioning) and resection between the years 2009 and 2023 were retrospectively selected. Initial and postoperative clinicopathological variables were collected. 150 patients were initially included. The derived group (n=91) presented more locally invasive disease (p<0.01), greater degree of obstruction (p<0.01), and worse clinical status (p<0.01), while the resected ones (n= 59) presented more distant metastasis (p<0.01). After matching, 35 patients remained in each group. There was no difference in the incidence of postoperative complications, but the derived group had higher 90-day mortality (p<0.01). Overall survival was 16.9 and 4.5 months for the resected and derived groups, respectively (p<0.01). After multivariate analysis, hypoalbuminemia (hazard ratio - HR=2.02, 95% confidence interval - 95%CI 1.17-3.48; p=0.01), absence of adjuvant chemotherapy (HR=5.97; 95%CI 3.03-11.7; p<0.01), and gastric bypass (HR=3,28; 95%CI 1.8-5.95; p<0.01) were associated with worse survival. Palliative gastrectomy was associated with greater survival and lower postoperative morbidity compared to gastric bypass. This may be due to better local control of the disease, with lower risks of complications and better effectiveness of chemotherapy.