Affecting Treatment Response Research Articles

Sex differences in pancreatic cancer

This review article discusses the currently available evidence on the importance of biological and social sex in pancreatic cancer in the context of the operative, perioperative and multimodal treatment. In pancreatic cancer there are gender differences with respect to the incidence, treatment response and prognosis. Sex significantly influences both innate and adaptive immune responses, thereby affecting treatment response and survival rates. Women are less likely to receive systemic treatment and tend to wait longer for surgery but have better perioperative outcomes after pancreatic resection. Overall, female pancreatic cancer patients seem to have longer survival under treatment; however, they report asubjectively lower quality of life and higher disease burden.

Can the efficacy of a medical treatment be predicted based on the type of idiopathic premature ventricular contraction?

BackgroundPremature ventricular contractions (PVCs) are common arrhythmias with diverse clinical implications. This retrospective study aimed to evaluate the efficacy of medical treatments using various clinical, imaging, and electrocardiographic parameters in patients with idiopathic PVCs. MethodsA total of 1051 patients with idiopathic PVCs were retrospectively analyzed. Patients were categorized into three groups based on treatment response: beta-blocker (BB) responders (479 patients), calcium-channel blocker (CCB) responders (335 patients), and class 1c antiarrhythmic (AA) responders (237 patients). Clinical, imaging, and electrocardiographic data were collected and analyzed to assess the factors influencing treatment response. ResultsAge, left ventricular ejection fraction (LVEF), PVC QRS duration, CI variability, and multiple PVC morphologies were identified as significant factors affecting treatment response. Older age and lower LVEF were associated with better response to BB treatment, whereas CCB responders showed narrower QRS complexes. BB responders also exhibited higher CI variability, possibly linked to automaticity mechanisms. Moreover, the BB responder group had a higher frequency of multiple PVC morphologies. ConclusionThese findings emphasize the importance of tailored treatment approaches based on individual patient characteristics.

Periodontal Osseous Defects: A Treatment-Oriented Classification to Guide Regenerative Treatment Planning.

Periodontal bony defects are classified into 'supraosseous' ('suprabony') or 'infraosseous' ('infrabony') according to the location of the base of the defect compared to the coronal part of the residual alveolar crest. Infraosseous defects are generally considered more challenging to treat and are thought to be associated with a higher risk of periodontal progression. The emergence and advancement of periodontal regenerative procedures have improved the clinician's ability to manage infraosseous defects. However, limitations still exist. This paper reviews the definitions of periodontal osseous defects and provides a new classification framework for infraosseous defects, relating them to the chances of success of regenerative procedures and therefore to their treatment planning options. Infraosseous defects are hereby divided into intrabony and inter-root defects. Factors affecting treatment response, such as number of walls, depth and extension into buccal and lingual surfaces are added to the classification framework.

Role of the Triglyceride-Glucose Index as a Predictor of Therapeutic Response to Tadalafil in Patients With Erectile Dysfunction.

The triglyceride-glucose (TyG) index is an easily calculable indicator of endothelial dysfunction. We aimed to evaluate the effect of the TyG index on treatment response in patients using tadalafil for the treatment of erectile dysfunction (ED). The data of patients who used tadalafil for ED in our urology clinic between January 2018 and January 2023 were reviewed. The patients completed the 5-item International Index of Erectile Function (IIEF-5) questionnaire before treatment and in the 3rd month of treatment. Response to tadalafil treatment was accepted as an increase in IIEF category. Patients were divided into 2 groups according to treatment response. Factors affecting response to treatment were evaluated with a multivariate analysis. Of the 134 patients included in the study, 99 (73.3%) responded to tadalafil treatment. Mean age and body mass index (BMI) of the patient group responding to treatment were significantly lower than in the untreated group. The rates of diabetes mellitus (DM) and metabolic syndrome (MetS) were significantly lower in the group responding to treatment. Fasting glucose, triglyceride and total cholesterol values were significantly lower in the group responding to treatment than in the treatment-resistant group. The TyG index was 130.0 (102.0-180.0) in the group responding to treatment and 245.0 (182.0-320.0) in the treatment-resistant group (p=0.001). In the multivariate analysis, age, BMI, DM, MetS, and TyG index were affecting treatment response. A high TyG index negatively affects the response to treatment in patients using tadalafil for ED. In addition, age, BMI, presence of DM and MetS are other factors affecting the response to treatment.

Variability patterns in dual antiplatelet therapy following endovascular repair of intracranial aneurysms: Insight into regimen heterogeneity and the need for a consensus.

This comprehensive review delves into the evolving field of neurointervention for intracranial aneurysms, exploring the critical adjunct of Dual Antiplatelet Therapy (DAPT) to endovascular coiling, stent-assisted coiling (SAC), flow-diversion stents, and flow-disruption (intrasaccular) devices. Despite growing evidence supporting the success of DAPT in reducing thromboembolic events, the lack of consensus on optimal regimens, doses, and duration is evident. Factors contributing to this variability include genetic polymorphisms affecting treatment response and ongoing debates regarding the clinical significance of hemorrhagic complications associated with DAPT. This review analyzes pre- and post-procedural antiplatelet usage across various interventions. The imperative lies in ongoing research to define optimal DAPT durations, ensuring a nuanced approach to the delicate balance between thrombosis and hemorrhage in intracranial aneurysm management.

Beneficial effects of maintaining liver function during hepatic arterial infusion chemotherapy combined with tyrosine kinase and programmed cell death protein-1 inhibitors on the outcomes of patients with unresectable hepatocellular carcinoma

Background and aimCombination therapy is the primary treatment for unresectable hepatocellular carcinoma (u-HCC). The hepatic functional reserve is also critical in the treatment of HCC. In this study, u-HCC was treated with combined hepatic arterial infusion chemotherapy (HAIC), tyrosine kinase inhibitors (TKIs), and programmed cell death protein-1 (PD-1) inhibitors to analyze the therapeutic response, progression-free survival (PFS), and safety.MethodsOne hundred sixty-two (162) patients with u-HCC were treated by combination therapy of HAIC, TKIs, and PD-1 inhibitors. PFS was assessed by Child–Pugh (CP) classification subgroups and the change in the CP score during treatment.ResultsThe median PFS was 11.7 and 5.1 months for patients with CP class A (CPA) and CP class B (CPB), respectively (p = 0.013), with respective objective response rates of 61.1 and 27.8% (p = 0.002) and conversion rates of 16 and 0% (p = 0.078). During treatment, the CP scores in patients with CPA worsened less in those with complete and partial response than in those with stable and progressive disease. In the CP score 5, patients with an unchanged CP score had longer PFS than those with a worsened score (Not reached vs. 7.9 months, p = 0.018). CPB was an independent factor negatively affecting treatment response and PFS. Patients with CPA responded better to the combination therapy and had fewer adverse events (AEs) than those with CPB.ConclusionsThus, triple therapy is more beneficial in patients with good liver function, and it is crucial to maintain liver function during treatment.

Predictors of Pharmacological Treatment Response in Children and Adolescents with Anxiety Disorders

Aim/Background: Anxiety disorders are frequently seen in children and adolescents and cause significant loss of functionality and a decrease in quality of life. This study aimed to investigate the factors affecting treatment response in children and adolescents with anxiety disorders. Methods: 340 children and adolescents aged 6-18 years who applied to child and adolescent psychiatry outpatient clinics of a university hospital between May 2018 and May 2023, diagnosed with anxiety disorder, and used only drug treatment were included in the study by retrospectively examining of the patient files. The age, gender, diagnosis, disorder severity, treatment and treatment response, comorbid disorders, physical diseases, and their treatments of the patients were recorded. Results: 116 of the patients were male, and 224 were female. While the most common diagnosis was generalized anxiety disorder (62.4%), the most frequently prescribed medication was sertraline (52.4%). Having specific phobia (p=0.026), attention-deficit hyperactivity disorder comorbidity (p=0.029) and using atypical antipsychotics (p=0.037) were negative predictors of treatment response. Other variables did not have any predictive effect on treatment response. Conclusions: Understanding the factors that influence treatment response in children and adolescents with anxiety disorders is crucial for determining the appropriate treatment and predicting the disorder's prognosis. Appropriate interventions addressing modifiable factors that have a negative impact on treatment response should be considered for treatment.

Real-world data show high efficacy of IL23 inhibitors guselkumab and risankizumab in psoriatic arthritis and difficult-to-treat areas.

Psoriasis and psoriatic arthritis are chronic inflammatory skin and joint diseases requiring effective therapies. Although clinical studies have shown the efficacy of IL-23 inhibitors, real-world data are limited. We conducted a single-center retrospective Greek study enrolling patients with psoriatic arthritis and moderate-to-severe plaque psoriasis being treated at our multidisciplinary psoriasis outpatient clinic. Our aim was to investigate the efficacy and safety of IL-23 inhibitors guselkumab and risankizumab. Additionally, we sought to determine the clinical characteristics affecting treatment response. Primary endpoints were the evaluation of absolute Psoriasis Area and Severity Index (aPASI) and Disease Activity Index for Psoriatic Arthritis (DAPSA) at week 24. Fifty-nine patients (55.9% male, 69.5% early onset) with a mean age of 51.7 years were included. Twenty-four patients (40.7%) had a concomitant psoriatic arthritis. Obesity was the main comorbidity (49.2%) with a mean body mass index (BMI) of 31.3 kg/m2 . Additional comorbidities were hypertension (44.1%), dyslipidemia (32.2%), and diabetes (18.6%). Only eight patients (13.6%) were naïve to previous systemic treatments, whereas 40 patients (67.8%) were bio-experienced. A statistically significant improvement of aPASI and DAPSA was demonstrated after 4, 16, and 24 weeks of treatment (P < 0.05). IL23 blockers were also efficacious in difficult-to-treat areas. Clinical outcome was affected from previous treatment with biologics. Treatment response was the same between guselkumab and risankizumab (P > 0.05). This real-world study confirms the efficacy and safety of guselkumab and risankizumab in psoriatic arthritis and psoriasis reported from clinical trials.

Immune checkpoint inhibitors combined with or without radio(chemo)therapy for locally advanced or recurrent/metastatic esophageal squamous cell carcinoma

ObjectiveThis study was designed to investigate the efficacy and prognostic factors for immune checkpoint inhibitors (ICIs) combined with or without radio(chemo)therapy and to evaluate their toxicity in patients with locally advanced or recurrent/metastatic esophageal squamous cell carcinoma (LA/RM ESCC).MethodsIn this study, 198 patients with locally advanced or recurrent/metastatic (LA/RM) ESCC who received ICIs combined with or without radiotherapy/chemotherapy in the Department of Radiotherapy of the Fourth Hospital of Hebei Medical University were retrospectively analyzed. Univariate and multivariate analyses were performed to determine the prognostic factors for overall survival (OS) and progression free survival (PFS). The factors affecting treatment response and the occurrences of treatment-related adverse events (trAEs) were analyzed.ResultsThe median OS and PFS were 30.4 months (95% confidence interval [CI] 15.1–45.7 months) and 15.3 months (95% CI 12.8–17.8 months), respectively. Univariate and multivariate analysis showed that the number of ICI cycles, the intervention of radiotherapy and dysphagia were independent factors affecting OS (Hazard ratio [HR] = 0.39, 2.043 and 0.365, respectively; P = 0.018, 0.001 and 0.032, respectively). The intervention of radiotherapy was an independent factor for PFS (hazard ratio [HR] = 18.149, P = 0.013). The median OS and PFS for patients who had complete response and partial response (Objective response, ORR) were 50.8 months (95% CI 25.8–75.7 months) and 20.5 months (95% CI 14.1–27.0), respectively, which were significantly higher than those in the non-ORR group (OSnon-ORR:17.5 months, 95% CI 14.0–21.0; χ2 = 13.881, P < 0.001; PFSnon-ORR: 12.1 months, 95% CI 10.1–14.1, χ2 = 10.676, P = 0.001). The intervention of radiotherapy could improve treatment response (χ2 = 47.725, P = 0.000). In entire study population, 83 patients (41.9%) had ≥ grade 2 trAEs.ConclusionsICIs combined with radiotherapy/chemotherapy are safe and effective in LA/RM ESCC patients. Intervention of radiotherapy, the number of immunotherapy cycles and occurrence of dysphagia affecting the overall survival of LR/RM ESCC patients. Intervention of radiotherapy was an independent prognosis factor for OS and PFS and associated with better treatment response.

Turicibacter and Acidaminococcus predict immune-related adverse events and efficacy of immune checkpoint inhibitor.

Immune checkpoint inhibitors have had a major impact on cancer treatment. Gut microbiota plays a major role in the cancer microenvironment, affecting treatment response. The gut microbiota is highly individual, and varies with factors, such as age and race. Gut microbiota composition in Japanese cancer patients and the efficacy of immunotherapy remain unknown. We investigated the gut microbiota of 26 patients with solid tumors prior to immune checkpoint inhibitor monotherapy to identify bacteria involved in the efficacy of these drugs and immune-related adverse events (irAEs). The genera Prevotella and Parabacteroides were relatively common in the group showing efficacy towards the anti-PD-1 antibody treatment (effective group). The proportions of Catenibacterium (P = 0.022) and Turicibacter (P = 0.049) were significantly higher in the effective group than in the ineffective group. In addition, the proportion of Desulfovibrion (P = 0.033) was significantly higher in the ineffective group. Next, they were divided into irAE and non-irAE groups. The proportions of Turicibacter (P = 0.001) and Acidaminococcus (P = 0.001) were significantly higher in the group with irAEs than in those without, while the proportions of Blautia (P = 0.013) and the unclassified Clostridiales (P = 0.027) were significantly higher in the group without irAEs than those with. Furthermore, within the Effective group, Acidaminococcus and Turicibacter (both P = 0.001) were more abundant in the subgroup with irAEs than in those without them. In contrast, Blautia (P = 0.021) and Bilophila (P= 0.033) were statistically significantly more common in those without irAEs. Our Study suggests that the analysis of the gut microbiota may provide future predictive markers for the efficacy of cancer immunotherapy or the selection of candidates for fecal transplantation for cancer immunotherapy.

Clinically meaningful improvements in cutaneous lesions and quality of life measures in patients with atopic dermatitis with greater pruritus reductions after treatment with 60 mg nemolizumab subcutaneously every 4 weeks: subgroup analysis from a phase 3, randomized, controlled trial

BackgroundData from the Japanese phase 3 Nemolizumab-JP01 study (JapicCTI-173740) found that nemolizumab in combination with topical treatments reduced pruritus associated with atopic dermatitis inadequately controlled with current therapies.MethodsThis post-hoc analysis examined associations between improvements in pruritus (visual analog scale [VAS]) and eczema (Eczema Area and Severity Index [EASI]), and achievement of other clinically relevant endpoints including the Insomnia Severity Index (ISI), Dermatology Life Quality Index (DLQI), and Patient-Oriented Eczema Measure (POEM).ResultsPruritus VAS responders (≥50% improvement from baseline to week 16) showed greater improvements from baseline in these additional endpoints as early as week 1, compared with non-responders. Responders also had EASI improvement, and more than 80% achieved an ISI score ≤7, or had improvement in the DLQI or POEM. The percent change from baseline in VAS and EASI scores at week 16 was in favor of nemolizumab in all subgroups based on baseline characteristics. No specific factor affecting treatment response to nemolizumab was identified.ConclusionsIn this post-hoc analysis, nemolizumab-treated patients who had greater pruritus reductions also showed improvements in other eczema symptoms; pruritus alleviation appeared to be responsible for the improvements in eczema, sleep and daily life.

The association of body mass index with safety and effectiveness of first-line carboplatin-based chemotherapy in patients with metastatic non-small cell lung cancer

IntroductionCarboplatin is an anticancer drug used for treatment of various types of cancer including non-small cell lung cancer (NSCLC). Dosing is based on estimated glomerular filtration rate (GFR) using the Cockcroft-Gault formula. In overweight patients, the GFR is more likely overestimated, resulting in a potentially overdose of carboplatin affecting treatment response. This study investigated the association of body mass index (BMI) on overall survival (OS) and progression-free survival (PFS) in stage-IV NSCLC patients treated with first-line carboplatin-based chemotherapy. Secondary safety endpoints were thrombocytopenia and toxicity-related hospitalizations. Materials and methodsThis was a retrospective multicenter cohort study. Patients were categorized according to BMI<25.0 kg/m2 (normal weight and reference), 25.0-29.9 kg/m2 (overweight) or ≥30.0 kg/m2 (obese). For survival analyses adjusted hazard ratios [aHR] were calculated using multivariate Cox regression analysis. Secondary outcomes were analyzed using multivariate logistic regression providing adjusted odd ratios [aOR]. ResultsOverweight patients (n=174) had a significantly better OS (aHR=0.72, 95%-CI:0.59-0.89) and PFS (aHR=0.74, 95%-CI:0.61-0.90) compared to normal weight patients (n=268). OS nor PFS were different in obese (n=51) compared to normal weight patients. However, obesity was associated with significantly higher incidences of thrombocytopenia grade ≥3 (aOR=3.47, 95%-CI:1.75-6.90). ConclusionThis study shows a significantly longer survival for overweight compared to normal weight patients. Obese patients have an increased risk for grade ≥3 thrombocytopenia without a difference in survival following carboplatin-based chemotherapy. The implications for clinical practice are to use the Cockcroft-Gault formula with caution in patients with BMI≥30.0 kg/m2, and to verify calculated dosing of carboplatin for appropriateness.

The prognostic effect of pretreatment 18F-FDG PET/CT metabolic parameters in locally advanced Esophageal Squamous Cell Carcinoma treated with definitive chemoradiotherapy

IntroductionIn this study, we aimed to examine the relation between pre-treatment 18F-FDG PET/CT metabolic parameters [(including the maximum standard uptake value (SUVmax), metabolic tumor volume (MTV), and tumor lesion glycolysis (TLG)] and treatment response and survival in locally-advanced Esophageal Squamous Cell Cancer (ESCC) treated with definitive chemoradiotherapy (dCRT). MethodsA total 76 patients with locally-advanced ESCC who received dCRT between June 2015 and December 2019 were included in this retrospective study. Patients were divided into two groups as complete response (CR) or non-complete response (Non-CR) according to response to treatment. AUC was obtained as 0.749 (p < 0.001) in the ROC curve drawn by MTV for the CR. The MTV value was ≤12 cm3, with 72.1% sensitivity and 73.0% specificity. ResultsOf the 76 patients, 38 (50%) were male and 38 (50%) were female. The median age was 62 (39–84) years. The treatment response in 35 (46%) patients was CR. MTV value was >12cm3 in 41(54%) patients. Median follow-up time was 14.5 months. In patients with MTV>12cm3, median progression-free survival(mPFS) and median overall survival(mOS) were 9 months and 11 months, respectively, whereas mPFS and OS could not be reached in those with MTV≤12 cm3 (p < 0.001 and p < 0.001, respectively). In patients with non-CR, mPFS and mOS were 8 months and 9 months, respectively, whereas mPFS and OS could not be reached in patients with CR (p < 0.001 and p < 0.001, respectively). In multivariate analysis, age (odds ratio [OR], 1.07), ECOG PS (OR, 11.1), and MTV (OR, 4.73) were found to be the factors affecting treatment response. ConclusionIn our study, treatment response and MTV were found to be the factors associated with survival in patients treated with dCRT, showing the pre-treatment MTV value as a predictor of treatment response.

Efficacy of Direct Acting Anti-Viral Agents in Patients Infected with Chronic Hepatitis C Virus: A Single Center Experience

Background: Hepatitis virus C (HCV) infection is affecting millions of people globally with an estimated prevalence in Pakistan ranging from 4.5 to 8%. Advent of oral direct acting antiviral agents (DAAs) in combination therapy has made possible the treatment of decompensated cirrhosis secondary to hepatitis C (HCV) infection. Therefore, this study focused to evaluate safety and efficacy of direct antiviral agents (DAAs) in compensated and decompensated cirrhotic patients.&#x0D; Materials and Methods: This cross sectional study was conducted in the Department of Hepatogastroenterology, Sindh Institute of Urology and Transplantation (SIUT) Karachi, from 1st September 2017 to 30th June 2018. Patients diagnosed with HCV, presenting in outpatient department were enrolled. All patients received Daclatasavir, Sofosbuvir and Ribavirin combination. Patient without cirrhosis and with cirrhosis received treatment for 12 and 24 weeks, respectively. End of treatment response was taken as primary end point. Statistical analysis was performed by SPSS version 20.0.&#x0D; Results: Out of 180 patients, 88(48.9%) were male and 92(51.1%) were female, with mean age of 44.59±11.29 years. Majority had genotype 3 i.e., 145(80.6%). In this study population, 97(53.9%) patients were non-cirrhotic and received 3 months treatment while 83(46.1%) cirrhotic patient got 6 months treatment. Post- stratification observed that young patients have better treatment response rate than older individuals (p-=0.031) On the other hand, statistical insignificant association was observed between end of treatment response with regards to gender, duration of treatment, history of hepatic encephalopathy and ascites.&#x0D; Conclusion: This study concluded that treatment with direct antiviral agents of Hepatitis C virus related chronic liver disease is effectual and has shown equivalent response in cirrhotic and non-cirrhotic patients. Age is an important factor affecting treatment response i.e, better response achieved in patient with less than 45 years.

Prolonged progression-free survival achieved by octreotide LAR plus transarterial embolization in low-to-intermediate grade neuroendocrine tumor liver metastases with high hepatic tumor burden.

ObjectiveTo evaluate the efficacy and outcome of transarterial embolization (TAE) plus octreotide long‐acting repeatable (LAR) on patients with low‐to‐intermediate neuroendocrine tumor liver metastases (NETLM).MethodsOne hundred and sixteen patients with G1/G2 NETLM treated with TAE plus octreotide LAR at the First Affiliated Hospital, Sun Yat‐sen University between January 12, 2016 and September 24, 2020 were reviewed. Radiological response was evaluated according to response evaluation criterion in solid tumor version 1.1. Overall progression‐free survival (PFS) was assessed. Intrahepatic and extrahepatic PFS were evaluated in the whole cohort and in patients with the extrahepatic disease (EHD), respectively. Factors affecting treatment response and overall PFS were analyzed using the logistic regression model and Cox proportional hazard model. Adverse events were recorded and evaluated according to Common Terminology Criteria for Adverse Events 5.0.ResultsThe median overall PFS of the whole cohort was 13.6 months. For the patients with EHD, the median intrahepatic PFS and extrahepatic PFS were 13.6 and 26.1 months, respectively. The median overall PFS of patients with hepatic tumor burden (HTB) <10%, 10%–25%, 25%–50%, and >50% were 25.2, 13.6, 11.2, and 12.3 months, respectively. Ki67 >10%, HTB >50%, and bone metastasis were independently associated with overall PFS. The objective response rate was 78.4%. In patients with HTB 25%–50% and >50%, responders (complete response or partial response) had significant prolonged PFS compared with nonresponders (stable disease or progression disease). Ki67 >10%, bone metastasis, and clear tumor margin were independently associated with response to TAE. The most frequent adverse events that occurred after TAE were postembolization syndrome, and no treatment‐associated death occurred during the perioperative period.ConclusionTransarterial embolization plus octreotide LAR can significantly prolong the PFS of neuroendocrine tumor liver metastases, especially with high HTB over 50%. Selected patients with HTB >25% (ki67 ≤10%, absence of bone metastasis, clear tumor margin) could derive prognostic advantage from the combined treatment.

Could Antinuclear Antibody Positivity Be a Factor Affecting Treatment Response in Immune Thrombocytopenia Patients on Eltrombopag?

Objective:Eltrombopag remains a prominent option in the treatment of steroid-dependent or steroid-refractory immune thrombocytopenia (ITP) patients. Unfortunately, not all patients respond to eltrombopag. Antinuclear antibody (ANA) positivity can be seen at rates of up to 30% in ITP patients. Despite being widely used, more markers to predict the response to eltrombopag are still needed. In the present study, we aimed to show the association between ANA positivity and eltrombopag response in ITP patients.Materials and Methods:Patients who were diagnosed with ITP in the Trakya University Faculty of Medicine’s Department of Hematology and who underwent eltrombopag treatment due to their resistance to steroids and other treatments were included in our study. ANA measurement was performed by indirect fluorescent antibody method and titers of 1:160 and above were considered positive. ANA measurements were made before starting eltrombopag.Results:Forty-five patients were included in our study, 33 being women and 12 men. The mean age of the patients was 45.73 years. There were 14 patients with ANA positivity and 31 patients were found to be ANA-negative. Response rates were higher in ANA-negative patients compared to ANA-positive patients in the 1st and 6th months of eltrombopag treatment (p<0.05).Conclusion:ANA positivity in ITP may indicate unresponsiveness to eltrombopag treatment, a finding that should be further supported by prospective studies involving more patients.

Association Between Race/Ethnicity and Survival in Women With Advanced Ovarian Cancer.

IntroductionOvarian cancer is the fifth-leading cause of cancer-related mortality in US women. There are survival disparities between non-Hispanic black (NHB) and non-Hispanic white (NHW) women. We assessed if insurance status or extent of disease modified the effect of race/ethnicity on survival for ovarian cancer.MethodsA historical cohort was assembled using the 2007-2015 National Cancer Institute’s Surveillance, Epidemiology, and End Result (SEER) dataset. Adult NHB and NHW (>18 years) diagnosed with regional and distant ovarian cancer were included. The outcome was five-year cause-specific mortality. Multivariable Cox regression models were fitted, including race by the extent of disease and race by insurance status interaction terms.ResultsFor each significant interaction, separate Cox models were fitted. In total 8,043 women were included. The insurance status/race interaction was not statistically significant, but the extent of disease modified the effect of race on survival. NHB survival was lower in regional disease (adjusted hazard ratio (HR) =1.6; 95% confidence interval (CI) 1.1-2.4), while there was no difference in survival between women with distant disease (adjusted HR =1.0; 95%CI 0.9-1.2).ConclusionsOvarian cancer mortality is similar between NHB and NHW women with the distant disease but higher in NHB women with regional disease. Further research should clarify whether this difference is due to access to quality cancer treatment or other factors affecting treatment response.

Bone Marrow Levels of PARP1 mRNA Predict Response to Treatment with 5-Azacytidine in Patients with Myelodysplastic Syndrome

IntroductionPoly [ADP-ribose] polymerase 1 (PARP1) is the major member of a family of nuclear enzymes that participate in DNA repair and gene transcription, by recruiting various proteins involved in DNA repair to sites of DNA damage. PARP1 overexpression has been correlated to poor treatment response in children with acute lymphoblastic leukemia, while PARP1-driven apoptosis is important in patients with chronic lymphocytic leukemia. Moreover, PARP1 inhibitors have been tested in vitro in lymphoid malignancies, acute myeloid leukemia, myelodysplastic syndrome (MDS) and acute promyelocytic leukemia.We have recently shown that bone marrow PARP1 mRNA levels correlate to the prognosis of patients with MDS (Diamantopoulos et al. Blood Cancer 2017). Moreover, PARP1 has been related to hypermethylation through DNA methyltransferase-1 (DNMT1) gene upregulation and protein activation (Zampieri et al. PLoS One. 2009). This correlation with DNA methylation is very important, since hypermethylation is a major event in the pathogenesis of high risk MDS, and hypomethylating agents, such as 5-azacytidine, are the most effective available treatment option for patients with higher risk MDS.AimBased on the relation of PARP1 with hypermethylation, we investigated the correlation of bone marrow PARP1 mRNA levels of patients with MDS with treatment response to 5-azacytidine.MethodsBone marrow samples were collected from patients with MDS at diagnosis. Only samples from patients that were eventually treated with 5-azacytidine were selected for analysis. RNA extraction and reverse transcription were performed using standard protocols. Primers for PARP1 and beta-actin were designed using the primer3 software (University of Massachusetts, USA) and a SYBR green based real-time PCR was performed on a CFX96 RT-PCR system (Bio-Rad Laboratories, Hercules, CA, USA). PARP1 mRNA levels were expressed as a PARP1/beta-actin ratio. IBM SPSS statistics, version 23.0 (IBM Corporation, North Castle, NY, USA) was used for the analysis of the results.ResultsSixty-seven patients diagnosed with MDS per the WHO 2008 classification and treated with 5-azacytdine were included in the study. The basic characteristics of the patients are shown in Table 1. The median follow-up of the patients was 25.8 (2.6-117.0) months. Response to treatment with 5-azacytidine per the International Working Group (IWG) criteria is shown in Table 1. The median PARP1 mRNA level was 0.0793 (range (0.0000424 - 3.43). Response to treatment differed between patients with high and low PARP1 mRNA levels (Independent samples Kruskal-Wallis test, 2-sided p=0.009). More precisely, the median level of PARP1 mRNA was 4 times higher in responders (partial response, complete response, hematologic improvement) than in non-responders (failure and stable disease), Independent samples Mann-Whitney U test, 2-sided p=0.006. We found no correlation of any other of the studied factors (MDS type, IPSS, IPSS-R, WPSS, karyotype risk, number of cytopenias, marrow blast percentage, hemoglobin level, neutrophil and platelet count, dose reduction of 5-azacytidine) to response to treatment in this cohort of patients. Although there was no correlation of PARP1 mRNA levels with overall survival, survival of patients after 5-azacytidine treatment tended to be longer in patients with higher PARP1 mRNA levels (38.7 versus 19.8 months, log rank test, p=0.136).DiscussionWe found that patients with MDS and high PARP1 mRNA levels have a better response to treatment with 5-azacytidine. This correlation has a theoretical basis, since upregulation of PARP1 is correlated to DNA hypermethylation, and hypomethylating agents may be more effective in cells with higher methylation levels. Moreover, in our cohort of patients, PARP1 level was the only factor affecting treatment response, although this response was not translated into a survival benefit.PAPR1 is the only biological factor and one of very few identified factors to predict response to treatment with hypomethylating agents - low hemoglobin and platelet count were found to be an independent factor of poor response to hypomethylating agents (Jung et al. Oncotarget 2016), and absence of aberrant myeloid progenitor cells were found to predict response to treatment (Alhan et al. Cytometry B Clin Cytom 2014). A possible synergy between PARP1 inhibitors and hypomethylating agents in MDS should be further investigated. [Display omitted] DisclosuresVassilakopoulos:Amgen: Consultancy, Honoraria, Research Funding; Roche: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Research Funding; Celgene/GenesisPharma: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding.

Aflibercept Treatment Results and Association with Baseline Characteristics in Cases of Newly Diagnosed Neovascular Age-Related Macular Degeneration

Objectives:To evaluate functional and anatomical responses to intravitreal aflibercept (IVA) treatment in newly diagnosed and untreated neovascular age-related macular degeneration (nvAMD) cases and to investigate the effect of baseline lesion characteristics on anatomical responses.Materials and Methods:This prospective, cross-sectional study included a series of 139 eyes of 133 patients that were diagnosed with active nvAMD and had not been treated. All eyes were subjected to complete ophthalmological examination, spectral-domain optical coherence tomography and fluorescein angiography, and 42 eyes also underwent indocyanine green angiography. IVA treatment was performed using a “treat and extend” regimen after 3 injections at 4-6 weeks intervals. Anatomical and functional responses at 4 weeks after the last injection were evaluated in eyes that completed 3 injections and the subgroup of eyes that completed 6 IVA injections. The effect of baseline lesion characteristics on IVA treatment results was also investigated.Results:All 139 eyes included in the study received 3 IVA injections (group 1) and 62 received 6 IVA injections. Both groups showed statistically significant improvement in best-corrected visual acuity (p<0.001 for both). The rate of complete response was 54.6% and 58.0% in groups 1 and 2, respectively. In group 1, the presence of pigment epithelial detachment (PED) and serous PED were identified as negative initial factors (p=0.043, p=0.005, respectively). However, none of the baseline characteristics were significantly associated with anatomical response in group 2.Conclusion:In our study, it was determined that successful anatomical and functional results were achieved with 3 and 6 doses of IVA in eyes with newly-diagnosed and untreated nvAMD. Among baseline characteristics, the presence of PED and serous PED in particular were found to be factors affecting treatment response negatively.

Influence of serum inflammatory cytokines on cytochrome P450 drug metabolising activity during breast cancer chemotherapy: a patient feasibility study

Individual response to chemotherapy in patients with breast cancer is variable. Obesity and exercise are associated with better and worse outcomes, respectively, and it is known that both impact the systemic cytokine milieu. Cytochrome P450 (CYP) enzymes are responsible for the metabolism of many chemotherapy agents, and CYP enzyme activity has been shown to be modified by inflammatory cytokines in vitro and in vivo. Cytokine-associated changes in CYP metabolism may alter chemotherapy exposure, potentially affecting treatment response and patient survival. Therefore, better understanding of these biological relationships is required. This exploratory single arm open label trial investigated changes in in vivo CYP activity in twelve women treated for stage II or III breast cancer, and demonstrated for the first time the feasibility and safety of utilising the Inje phenotyping cocktail to measure CYP activity in cancer patients receiving chemotherapy. Relative CYP activity varied between participants, particularly for CYP2C9 and CYP2D6, and changes in serum concentrations of the inflammatory cytokine monocyte chemoattractant protein 1 inversely correlated to CYP3A4 activity during chemotherapy. Future use of phenotyping cocktails in a clinical oncology setting may help guide drug dosing and improve chemotherapy outcomes.Clinical Trial Registration: Trial was retrospectively registered to the Australia New Zealand Clinical Trial Registry (ANZCTR). ACTRN12620000832976, 21 Aug 2020, https://www.anzctr.org.au/ACTRN12620000832976.aspx.