First-line Therapy For Treatment Research Articles

Zenker’s Per-Oral Endoscopic Myotomy (Z-POEM): The Ideal First Line Therapy for Treatment of Zenker’s Diverticulum

Zenker's diverticulum is a mucosal herniation at the pharyngoesophageal junction. While open surgical myotomy is the conventional treatment, robust evidence on third-space flexible endoscopic myotomy is lacking. We assessed safety, effectiveness and patient-reported outcomes of per-oral endoscopic myotomy (Z-POEM) in the largest reported single-centre experience with this technique. Retrospective cohort study was performed of consecutive patients undergoing Z-POEM in a tertiary hospital thoracic surgery practice from 2018-2024. Data collected included demographics, comorbidities, clinical and radiographic (pre/post-operative esophagram) outcomes, and validated patient-reported quality-of-life outcomes (Dakkak and Eckardt scores). Descriptive analyses were used to describe the population, outcomes, and complications. Aggregate and individual-patient symptom trajectories were charted over time. Fifty-seven patients (57.9% female, n=33) with a mean age of 74 years underwent Z-POEM. Median diverticulum size was 2 cm (IQR 2-3). All patients reported subjective symptom improvement and showed complete resolution of obstructed barium flow on postoperative esophagrams. At median follow-up of 9 months, all Z-POEM patients reported clinically-important improvements in objective symptom scores, with symptom trajectories showing rapid and durable improvement up to 5 years postoperatively. Four patients (7%) experienced complications. Majority of the cohort (66.7%) was unsuitable for rigid stapled myotomy, mainly due to short diverticulum or limited neck/mouth movement. No patients required repeat myotomy. We demonstrate significant and sustained relief of patient-reported outcomes/symptoms following Z-POEM, including for small diverticuli, with low complication rates. Its safety and versatility has made it the new standard of care locally; Z-POEM can be adopted by third-space endoscopy-trained thoracic surgeons.

Anlotinib plus penpulimab plus chemo-less therapy in first-line treatment for persistent, recurrent, or metastatic cervical cancer: A single-arm, phase II study (ALTN-AK105-II-06)

Anlotinib plus penpulimab plus chemo-less therapy in first-line treatment for persistent, recurrent, or metastatic cervical cancer: A single-arm, phase II study (ALTN-AK105-II-06)

1755P Multimodal therapy in first line treatment of very high risk Ewing sarcoma patients: Results of the French prospective multicenter COMBINAIR3 phase II trial

1755P Multimodal therapy in first line treatment of very high risk Ewing sarcoma patients: Results of the French prospective multicenter COMBINAIR3 phase II trial

761P Anti-angiogenic therapy in first-line treatment of low-grade serous ovarian cancer: Exploratory meta-analysis of the prospective AGO-OVAR 11/12/16 studies

761P Anti-angiogenic therapy in first-line treatment of low-grade serous ovarian cancer: Exploratory meta-analysis of the prospective AGO-OVAR 11/12/16 studies

Comparison of efficacy and safety of PD-1/PD-L1 combination therapy in first-line treatment of advanced NSCLC: an updated systematic review and network meta-analysis.

The use of immune checkpoint inhibitors has led to an increase in randomized controlled trials exploring various first-line combination treatment regimens. With the introduction of new PD-1/PD-L1 inhibitors, there are now more clinical options available. For the first time, the AK105 monoclonal antibody Penpulimab, developed in China, was included. The AK105-302 Phase III trial studied the efficacy and safety of Penpulimab combined with chemotherapy in patients with advanced or metastatic squamous NSCLC. To determine the optimal treatment options, we conducted an updated network meta-analysis to compare the effectiveness and safety of these regimens. The system retrieves data from Chinese and English electronic databases, Clinical Trials, and the gov Clinical Trial Registration website up to September 6, 2023. The study indirectly compared the efficacy and safety of PD-1/PD-L1 combination regimens, including overall survival (OS), progression-free survival (PFS), objective response rate (ORR), all-grade adverse events, and above-grade III adverse events. Subgroup analyses were conducted based on programmed death ligand 1 (PD-L1) level, histological type, ECOG score, sex, and smoking history. Nineteen RCTS were included, with a total of ten thousand eight hundred patients. Penpulimab plus chemotherapy (Pen + CT) provided the best OS (HR = 0.55, 95% CI 0.38-0.81) for PD-L1 patients with non-selective advanced NSCLC. Except Nivolumab plus Ipilimumab (Niv + Ipi), other PD-1/PD-L1 combination therapies significantly extended PFS compared with CT, and Nivolumab plus Bevacizumab combined with chemotherapy (Niv + Bev + CT) (HR = 0.43, 95% CI 0.26-0.74) provided the best PFS benefit and was comparable to Pen + CT (HR = 1.0) for PFS prolongation. For ORR, except Niv + Ipi, all the other regimens significantly improved ORR compared with CT. In terms of safety, except Tor + CT, the incidence of any-grade AEs or grade ≥ 3 adverse events may be higher than those of chemotherapy. The subgroup analysis revealed that for patients with PD-L1 levels below 1%, treatment with Tor + CT resulted in the best progression-free survival (HR = 0.47, 95% CI 0.25-0.86). For patients with PD-L1 levels of 1% or higher, Sintilimab plus chemotherapy (Sin + CT) (HR = 0.56, 95% CI 0.31-0.99) and Camrelizumab plus chemotherapy (Cam + CT) (HR = 0.43, 95% CI 0.28-0.64) were associated with the best overall survival and progression-free survival, respectively. For patients with SqNSCLC, combined immunotherapy may provide greater survival benefits. For patients with Non-sqNSCLC, Niv + Bev + CT and Tor + CT were associated with optimal PFS and OS, respectively. Cam + CT provided the best PFS in male patients with a history of smoking and an ECOG score of 0. In both female and non-smoking patient subgroups, Pem + CT was associated with the best PFS and OS benefits. For patients with advanced non-selective PD-L1 NSCLC, two effective regimens are Pen + CT and Niv + Bev + CT, which rank first in OS and PFS among all patients. Cam + CT and Tor + CT have advantages for OS in patients with SqNSCLC and Non-sqNSCLC, respectively. Niv + Ipi + CT provided the best OS benefit for patients with an ECOG score of 0, while Pem + CT may be the most effective treatment for patients with an ECOG score of 1. Pem + CT has a better effect on female patients and non-smokers. Sin + CT was found to be the most effective treatment for male patients and the smoking subgroup, while Cam + CT was found to be the most effective for PFS. In addition, Tor + CT was associated with the best PFS for patients with negative PD-L1 expression. Pem + CT was found to significantly improve both PFS and OS compared to CT alone. For patients with positive PD-L1 expression, Sin + CT and Cam + CT were found to be optimal for OS and PFS, respectively. It is important to note that, with the exception of Tor + CT, the toxicity of the other combinations was higher than that of CT alone.

A Network Meta-analysis of the Efficacy of Drug Therapy in First-line Treatment of Advanced Hepatocellular Carcinoma.

Systemic therapy is mainly recommended for advanced hepatocellular carcinoma (HCC). Considering the variety of treatments available for HCC, there is a need to understand their relative benefits and risks, especially for the newly approved combination of immune checkpoint inhibitors and vascular endothelial growth factor inhibitors represented by atezolizumab in combination with bevacizumab. A reticulated meta-analysis was used to evaluate the efficacy and safety of atezolizumab-bevacizumab combination therapy compared with other first-line systemic therapies for the treatment of patients advanced HCC. PubMed, The Cochrane Library, Web of Science, and Embase databases were searched from the time of library construction to 01 December 2022, and the data were extracted and analyzed using Stata16.0 for Meta-analysis. The data were extracted separately, and a meta-analysis was performed using the software Stata16.0. 16 clinical studies with 8,779 subjects were identified from 13,417 records and were used to build the evidence network for all trials. TThe combination therapy of atezolizumab and bevacizumab has the advantage of prolonging the OS of patients when treating advanced HCC [HR=5.71, 95%CI (4.30, 7.12), p<0.05] Also, the combination therapy has the advantage of prolonging the patient's progression free survival [HR=1.60, 95%CI (0.89, 2.49), p<0.05]. Atezolizumab-bevacizumab combination therapy can improve clinical outcomes such as OS and PFS in patients with advanced HCC.

Efficacy and safety analysis of immune checkpoint inhibitor rechallenge therapy in locally advanced and advanced non-small cell lung cancer: a retrospective study.

Immune checkpoint inhibitors (ICIs) have dramatically changed the first-line treatment pattern of non-small cell lung cancer (NSCLC) without driver gene alterations. However, the optimal choice for second-line treatment after initial treatment with ICIs is unclear. This study aimed to clarify the efficacy and safety of ICI rechallenge therapy in locally advanced and advanced NSCLC. We retrospectively analyzed the histories of 224 patients with locally advanced or advanced NSCLC treated with programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors alone or in combination with chemotherapy and/or antiangiogenic therapy in first-line treatment. Progression-free survival 2 (PFS2) was the time from the first defined progress disease (PD) to the second disease progression or death. Efficacy evaluation was performed directly in accordance with RECIST v1.1 criteria. Adverse events (AEs) were graded following the National Cancer Institute Common Terminology Criteria for Adverse Events v5.0. Survival data were estimated using the Kaplan-Meier method or Cox survival regression model and compared using the log-rank test in overall cohort and other subgroups. There were no significant differences in objective response rate (ORR) and median PFS2 (mPFS2) between the ICI rechallenge group and non-rechallenge group (ORR: 10.3% vs. 15.3%, P=0.308; mPFS2: 5.33 vs. 4.40 months, P=0.715). And the ICI rechallenge group showed no new safety signals compared with non-rechallenge group. In ICI rechallenge group, patients resistant to first-line immunotherapy had a lower ORR and shorter PFS2 compared with those who responded to initial ICIs treatment (ORR: 7.0% vs. 17.6%, P=0.038; mPFS2: 3.68 vs. 5.91 months, P=0.014). No significant difference in mPFS2 was observed among different second-line treatment groups (P=0.362). Radiotherapy in second-line treatment and ICI rechallenge therapy were not the main factors affecting PFS2. ICI rechallenge therapy beyond disease progression did not improve clinical outcomes in patients with NSCLC, but no new safety signals emerged. However, patients with favorable response to initial ICIs treatment still showed significant efficacy of subsequent ICI rechallenge therapy.

A Retrospective Case-Control Study on the Differences in the Effectiveness of Theta-Burst Stimulation Therapy for Depression with and without Antidepressant Medication.

Transcranial magnetic stimulation (TMS) therapy has few side effects and comparable therapeutic effects to antidepressant treatment, but few studies have introduced TMS therapy as an initial treatment for MDD. The objective of this study was to retrospectively compare the clinical outcomes between 50 MDD patients without antidepressants (i.e., TMS monotherapy) and 50 MDD patients with antidepressants plus TMS therapy, matched for age, sex, and depression severity. The presence or absence of antidepressant therapy in first-line treatment was determined via a detailed interview by psychiatrists. The study design was a retrospective observational case-control study using the TMS registry data. The key inclusion criteria were adult patients who met the diagnosis of MDD and received 20-30 sessions of intermittent theta-burst stimulation (iTBS) therapy to the left dorsolateral prefrontal cortex (DLPFC). In this study, the Montgomery-Åsberg Depression Rating Scale (MADRS) was used as the primary outcome measure. No significant group differences existed in the baseline MADRS total score between the unmedicated and medicated patient groups. Following TMS therapy, no significant group differences in response rate, remission rate, or relative total score change in the MADRS were observed. The main limitations were the retrospective design and the use of registry data as a source. Our findings suggest that TMS monotherapy may be as effective as TMS add-on therapy to antidepressants when used as the first-line therapy for MDD, but randomized controlled trials are needed.

Selective adjuvant radiation therapy for distant lymph node metastasis in patients with stage 4B epithelial ovarian cancer: a case series

Although the efficacy of surgery followed by taxane- and platinum-based systemic chemotherapy has been clearly demonstrated in the standard first-line treatment of epithelial ovarian cancer, the role of radiation therapy for distant lymph node metastasis in patients with epithelial ovarian cancer is not well-established due to a lack of reported studies. We identified four patients who underwent selective adjuvant radiation therapy for neck and para-aortic lymph node lesions after primary debulking surgery between 2020 and 2022, followed by platinum-based chemotherapy for stage 4B high-grade serous ovarian cancer. Through a retrospective review of medical records, we analyzed patient clinicopathologic features, treatment course, and imaging findings. The median age was 49.25 years (range, 46–54 years). All patients had the International Federation of Gynecology and Obstetrics stage 4B disease. Following primary debulking surgery, all patients received weekly paclitaxel-carboplatin chemotherapy and maintenance treatment with poly(ADP-ribose) polymerase (PARP) inhibitors. All patients received selective adjuvant radiation therapy for neck and para-aortic lymph node metastasis before PARP inhibitor maintenance. The median follow-up time was 36.75 months (range, 19–45 months). All patients achieved a complete response. None of the patients experienced disease recurrence or died during the follow-up period. The management of distant lymph node metastasis in patients with epithelial ovarian cancer remains a matter of debate. Selective adjuvant radiation therapy in first-line treatment for ovarian cancer appears to be a feasible approach with maintenance therapy for stage 4B epithelial ovarian cancer.

Role of proton pump inhibitors dosage and duration in Helicobacter pylori eradication treatment: Results from the European Registry on H. pylori management.

Management of Helicobacter pylori (H. pylori) infection requires co-treatment with proton pump inhibitors (PPIs) and the use of antibiotics to achieve successful eradication. To evaluate the role of dosage of PPIs and the duration of therapy in the effectiveness of H. pylori eradication treatments based on the 'European Registry on Helicobacter pylori management' (Hp-EuReg). Hp-EuReg is a multicentre, prospective, non-interventionist, international registry on the routine clinical practice of H. pylori management by European gastroenterologists. All infected adult patients were systematically registered from 2013 to 2022. Overall, 36,579 patients from five countries with more than 1000 patients were analysed. Optimal (≥90%) first-line-modified intention-to-treat effectiveness was achieved with the following treatments: (1) 14-day therapies with clarithromycin-amoxicillin-bismuth and metronidazole-tetracycline-bismuth, both independently of the PPI dose prescribed; (2) All 10-day (except 10-day standard triple therapy) and 14-day therapies with high-dose PPIs; and (3) 10-day quadruple therapies with clarithromycin-amoxicillin-bismuth, metronidazole-tetracycline-bismuth, and clarithromycin-amoxicillin-metronidazole (sequential), all with standard-dose PPIs. In first-line treatment, optimal effectiveness was obtained with high-dose PPIs in all 14-day treatments, in 10- and 14-day bismuth quadruple therapies and in 10-day sequential with standard-dose PPIs. Optimal second-line effectiveness was achieved with (1) metronidazole-tetracycline-bismuth quadruple therapy for 14- and 10days with standard and high-dose PPIs, respectively; and (2) levofloxacin-amoxicillin triple therapy for 14days with high-dose PPIs. None of the 7-day therapies in both treatment lines achieved optimal effectiveness. We recommend, in first-line treatment, the use of high-dose PPIs in 14-day triple therapy and in 10-or 14-day quadruple concomitant therapy in first-line treatment, while standard-dose PPIs would be sufficient in 10-day bismuth quadruple therapies. On the other hand, in second-line treatment, high-dose PPIs would be more beneficial in 14-day triple therapy with levofloxacin and amoxicillin or in 10-day bismuth quadruple therapy either as a three-in-one single capsule or in the traditional scheme.

Real-World Patient Characteristics, Treatment Patterns, and Outcomes in Patients with Chronic Lymphocytic Leukemia/Small Lymphocytic Leukemia in China: A Retrospective Analysis Using a Real-World Database

Background: Innovation in chronic lymphocytic leukemia/small lymphocytic leukemia (CLL/SLL) has yield tremendous progresses and new treatment options recently. However, real-world treatment patterns, healthcare utilization and costs associated with CLL/SLL are not well studies in middle-income countries such as China. Because CLL/SLL predominantly affects older adults, this study aimed to evaluate baseline characteristics, treatment patterns, healthcare resource utilization (HCRU), costs, and survival in a representative sample of patients from Tianjin city who newly diagnosed with CLL/SLL. Methods: This retrospective study used integrated regional electronic healthcare records from 2004 to 2022. The sample included patients newly diagnosed with CLL/SLL with continuous healthcare encounters (index date = first CLL/SLL diagnosis date). Outcomes included treatment patterns, all-cause and CLL/SLL-related HRU and costs, and overall survival in the frontline and relapsed/refractory settings. Results: We identified 3665 patients meeting the inclusion/exclusion criteria. Overall, patients with CLL/SLL were 62 years of age at index date, 1409 (38.5%) were female, and 910 (24.8%) had insurance coverage. Patients had an average CCI of 1.6 (SD:2.0) during baseline, and the most common comorbid conditions were hypertension (8.9%), pulmonary infection (7.8%) and diabetes (5.9%). 1500 (41.0%) of patients had been exposed to CLL/SLL-directed treatment, with 856(57.0%), 343(22.9%) and 301(20.0%) of patients exposed to chemotherapy, immunochemotherapy and targeted therapy in first-line treatment, respectively. Among the subgroup of patients received targeted therapy, 335 (74.4%), 98 (21.8%) ,5 (1.1%) ,4 (0.9%) and 8 (1.8%) used ibrutinib, zanubrutinib, orelabrutinib, venetoclax, and lenalidomide. 15 (0.4%) and 2 (0.05%) patients received stem cell transplantation and CAR-T, respectively. In terms of HCRU, 2434of patients (66.4%) had a hospitalization due to any cause, 1769 (48.4%) of which were CLL/SLL-related. Emergency department and outpatient service use increased over the study period. Mean per person per month (PPPM) use for inpatient, outpatient and ED visits were 0.53, 0.30 and 0.59, respectively. Mean total PPPM healthcare costs were $ 3125.0 (inpatient), $ 488.1 (outpatient), $ 87.6 (ED), and $ 1085.8 (medication). Median OS from initial diagnosis or 1L treatment initiation were not achieved. The 1-year and 3-year survival rate was 95.1% and 88.5 % from 1L treatment initiation, 97.6 % and 92.8% from the initial diagnosis. Conclusions: In this real-world study using regional healthcare data, we observed distinct demographic, clinical and tumor-related characteristics. Patients were diverse in terms of age, insurance status and healthcare resource utilization. As newer therapies continue to accumulate, future studies should examine how unmet needs in patients with CLL/SLL can be addressed to ensure better access to novel treatment.

Real-World Patient Characteristics, Treatment Patterns, and Outcomes in Patients with Mantle Cell Lymphoma in China: A Retrospective Analysis Using a Real-World Database

Background: Significant advancements and novel therapeutic options have emerged in the treatment of mantle cell lymphoma (MCL) in recent years. However, there is a dearth of research on real-world treatment patterns, healthcare utilization, and costs associated with MCL in middle-income countries like China. Given that MCL predominantly affects the elderly population, this study aimed to assess the characteristics, treatment approaches, healthcare resource utilization (HCRU), costs, and survival outcomes in a representative sample of patients diagnosed with MCL in Tianjin City. Methods: This retrospective study utilized integrated regional electronic healthcare records spanning from 2004 to 2022. The sample included patients newly diagnosed with MCL who had a continuous series of healthcare encounters, with the index date set as the date of the initial MCL diagnosis. The study examined treatment patterns, all-cause and MCL-related HCRU and costs, as well as overall survival in both the initial treatment and relapsed/refractory settings. Results: The study identified 475 patients who had a confirmed diagnosis and met the specified inclusion/exclusion criteria. Overall, the patients with MCL had an average age of 58 at the index date, with 123 (25.9%) being female, and 139 (29.3%) having insurance coverage. The average Charlson Comorbidity Index (CCI) during the baseline period was 1.8 (SD:2.1), and the most prevalent comorbid conditions included hypertension (23.6%), pulmonary infection (21.9%) and diabetes (13.6%). A total of 250 (54%) patients had received treatment specific to MCL, with 57 (22.8%), 138 (55.2%), and 45 (18.0%) initiating chemotherapy, immunochemotherapy, and targeted therapy in first-line treatment, respectively. Among those who received targeted therapy,44 (50.0%), 40 (45.5%), 1 (1.1%) and 3 (3.4%) were treated with ibrutinib, zanubrutinib, orelabrutinib, and venetoclax, respectively. Additionally, 43 (9.1%) and 4 (0.8%) underwent stem cell transplantation and CAR-T therapy, respectively. Regarding HCRU, 367 patients (77.3%) experienced hospitalizations, with 328 (69.1%) of these hospitalizations related to MCL. Over the study period, the utilization of emergency department (ED) and outpatient services increased. The average monthly per person utilization rates for inpatient, outpatient, and emergency department visits were 0.62, 0.23, and 0.61, respectively. The mean total monthly healthcare costs were $9454.0 (inpatient), $895.9 (outpatient), $129.9 (ED), and $1739.0 (medication). The median overall survival (OS) from initiation of first-line (1L) treatment was 72.4 months, respectively. The 1-year and 3-year survival rates were 95.3 % and 86.9% from the initial diagnosis, and 78.6% and 71.4% from 1L treatment initiation, respectively. Conclusions: This real-world study, utilizing regional healthcare data, revealed distinctive demographic, clinical, and tumor-related characteristics among patients diagnosed with MCL. These patients demonstrated diversity in terms of age, insurance status, and healthcare resource utilization. As novel therapies continue to emerge, future investigations should address the unmet needs of patients with MCL, ensuring improved accessibility to innovative treatments.

Predictors of class IC antiarrhythmic drugs efficacy in patients with paroxysmal form of atrial fibrillation

Background. Class IC antiarrhythmic drugs (IC-AADs) are recommended as first-line therapy in treatment of lone paroxysmal atrial fibrillation (AF) along with catheter ablation of pulmonary veins. Despite previous attempts to identify predictors of IC-AADs` efficacy, the choice between IC-AADs agents is still most often carried out using empirical approach.&#x0D; Aim. To determine the predictors of IC-AADs ` efficacy in patients with paroxysmal AF in the absence of structural heart disease.&#x0D; Materials and methods. Seventy four patients (22 men, 52 women, average age 65 [57; 70] years) were treated with IC-AADs: 26 patients were prescribed lappaconitine hydrobromide (Al) (allapinin at a dosage of 75 mg/day or allaforte 50–100 mg/day), 25 patients were prescribed propafenone (P) 450–600 mg/day, 23 patients – diethylaminopropionylethoxycarbonylaminophenothiazine hydrochloride (ethacizine, E) 150 mg/day. The average frequency of AF paroxysms was 2 [0.4; 6.25] per month. Patients were divided into 2 groups depending on the effect of AADs.&#x0D; Results. Over a 12 months follow-up IC-AADs therapy was effective in 28 (37.8%) patients (Eff+ group), in the remaining 46 (62.2%) patients AF recurrences or side effects demanding AADs withdrawal were registered (Eff-group). A DC value greater or equal to 5 ms predicted the effectiveness of IC-AADs therapy with 79% sensitivity and 77% specificity (OR 12, 95% CI 3.07–49.5, p0.0001). In the Al group the deceleration capacity (DC) value greater or equal to 5.25 ms allowed predicting therapy effectiveness with 86% sensitivity and 100% specificity (OR 7, 95% CI 1.14; 43; p=0.002). In the E group, the DC index was characterized by high sensitivity (80%) and specificity (85%) for a threshold value of 5.9 ms. In case of DC above this value, the probability of E therapy efficacy increased by 22-times (OR 22, 95% CI 1.5; 314; p=0.009). In group P, the DC medians in the Eff+ and Eff- groups did not differ significantly (p=0.821). However, at low DC values (less than 4 ms) P turned out to be the most effective compared to other two IC-AADs: its effectiveness was 50%, which was significantly higher compared to E (0%) and Al (0%) (p=0.046).&#x0D; Conclusion. Estimation of the DC level before starting IC-AADs can make it easier to choose a specific drug from this group and improve treatment results: at DC above 5.2 ms, it is advisable to use Al, at DC≥6 ms – Al or E, at DC less than 4 ms – P.

763P Penpulimab + anlotinib plus chemo-less therapy in first-line treatment for persistent, recurrent, or metastatic cervical cancer: A single-arm, phase II study (ALTN-AK105-II-06)

763P Penpulimab + anlotinib plus chemo-less therapy in first-line treatment for persistent, recurrent, or metastatic cervical cancer: A single-arm, phase II study (ALTN-AK105-II-06)

Risk factors for thromboembolism during first-line treatment of patients with unresectable advanced or recurrent colorectal cancer: a retrospective short study

BackgroundWhile cancer is a risk factor for developing thromboembolism, so is the use of molecularly targeted therapies. This study aimed to determine whether thromboembolism incidence differed between vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) inhibitor use in patients with unresectable advanced or recurrent colorectal cancer, and to compare the risk of thromboembolism caused by cancer and the use of molecular targeted therapy drugs.Main bodyWe retrospectively evaluated patients with unresectable advanced or recurrent colorectal cancer who were treated with a cytotoxic anticancer drug and a VEGF or EGFR inhibitor combination between April 2016 and October 2021. Patients were compared in terms of the regimen administered, thromboembolism occurrence during the first-line treatment period, patient background, and clinical laboratory values. Of the 179 included patients, 12 of 134 (8.9%) in the VEGF-inhibitor group and 8 of 45 (17.8%) in the EGFR-inhibitor group developed thromboembolism, with no significant difference between the groups (P = 0.11). There was no significant difference in time to thromboembolism between patients in the VEGF- inhibitor group and patients in the EGFR-inhibitor group (P = 0.206). The cutoff value determined by a receiver operating characteristic analysis for the occurrence of thromboembolism was one point. Multivariate analysis using the occurrence of thromboembolism as the response variable identified at least one risk factor for thromboembolism (odds ratio = 4.17, P = 0.006, 95% confidence interval = 1.51–11.50). Molecular targeted therapies were not identified as a risk factor.ConclusionsAlthough the small sample size, there was no difference in the incidence of thromboembolism between the two molecular-targeted therapies in first-line treatment of patients with unresectable advanced or recurrent colorectal cancer. Our results suggest that risk factors for thromboembolism may be more strongly influenced by cancer itself than by the use of molecularly targeted therapies.

Cost-effectiveness of the addition of CDK4/6 inhibitors to standard endocrine therapy in first-line treatment of women with advanced HR+/HER2- breast cancer in Mexico.

To estimate the cost-effectiveness of adding a CDK4/6 inhibitor to standard endocrine therapy in the first-line setting for advanced HR+/HER2- breast cancer in postmenopausal and premenopausal women, from the perspective of the Mexican public healthcare system. We used a partitioned survival model to simulate relevant health outcomes in a synthetic cohort of patients with breast cancer derived from the PALOMA-2, MONALEESA-2, MONARCH-3 trials for postmenopausal patients, and from the MONALEESA-7 study for premenopausal patients. Effectiveness was measured in life years gained. Cost-effectiveness is reported through incremental cost-effectiveness ratios (ICER). In postmenopausal patients, palbociclib led to an increase of 1.51 life years, ribociclib of 1.58years, and abemaciclib of 1.75years, compared to letrozole alone. The ICER was 36,648 USD, 32,422 USD, and 26,888 USD, respectively. In premenopausal patients, ribociclib led to an increase of 1.82 life years when added to goserelin and endocrine therapy, with an ICER of 44,579 USD. In the cost minimization analysis, for postmenopausal patients, ribociclib was the treatment with the highest costs due to follow-up requirements. Palbociclib, ribociclib, and abemaciclib demonstrated a significant increase in effectiveness in postmenopausal patients, and ribociclib in premenopausal patients, when added to standard endocrine therapy for patients with advanced HR+/HER2- breast cancer. At the national stablished willingness to pay, only the addition of abemaciclib to standard endocrine therapy in postmenopausal women would be considered cost-effective. However, differences on results between therapies for postmenopausal patients were not statistically significant.

Direct oral anticoagulant (DOACs) prescribing practices of members of the Society of Gynecologic Oncology and American Society of Clinical Oncology

BackgroundCancer associated venous thromboembolism (VTE) is associated with significant morbidity and mortality. Direct oral anticoagulants (DOACs) have emerged as alternatives to injectable medications for both thromboprophylaxis and treatment of VTE. Several recent clinical trials have demonstrated safety and efficacy of DOACs in high risk patients receiving systemic chemotherapy as well as postoperative prophylaxis after surgery for gynecologic cancer. Major consensus guidelines from multiple organizations support the use of DOACs for these indications but prescription practices are not well characterized. MethodsA survey study was sent concurrently to members of the Society of Gynecologic Oncology (SGO) and American Society of Clinical Oncology (ASCO) Research Survey Pool between May and June of 2021. The study was designed to assess DOAC prescription practices amongst members of these societies who routinely prescribe chemotherapy. Bivariate analyses comparing responses from ASCO participants and SGO participants were compared using chi-squared and Fisher exact tests. ResultsA total of 103 physicians were included in the ASCO group and 139 in the SGO group. A majority of participants in both groups reported familiarity with prescribing DOACs (99% of ASCO and 96% of SGO respondents). ASCO respondents were more likely to consider DOACs as first line therapy for treatment of cancer-associated VTE than SGO members (82% vs 63%, p < 0.01) and SGO members were more likely to consider low molecular weight heparin (LMWH) the standard of care treatment (66% vs 25% p < 0.01). Most respondents in both groups (75%) felt DOACs were equally safe and effective compared to LMWH but more ASCO members felt DOACs were cost effective (70% vs 49%, p < 0.01). More SGO respondents reported having prescribed prophylactic anticoagulation during chemotherapy than ASCO members (53% vs 35%, p < 0.01). ConclusionASCO respondents were more likely to prescribe DOACs for both treatment and prophylaxis of cancer-associated VTE than SGO members. However, SGO members were more likely to prescribe prophylactic anticoagulation to high risk patients initiating chemotherapy compared to ASCO members.

Abstract P4-01-19: Real World Statistics on CDK4/6 Inhibitor Use in Metastatic Hormone Receptor Positive and HER2-Negative Breast Cancer with a Focus on Age

Abstract Background: Combining CDK 4/6 inhibitors with hormone directed therapy using aromatase inhibitors (AI) or selective estrogen receptor down-regulators (SERD) is considered first line therapy for treatment of hormone receptor positive (HR+) human epidermal receptor 2 negative (HER2-) metastatic breast cancer (mBC). Here we aim to evaluate first line CDK 4/6 inhibitor practice patterns both nationally and locally (Wisconsin) in HR+ HER2- mBC patients and evaluate age as a potential factor impacting practice patterns. Methods: A retrospective analysis was performed utilizing IQVIA Anonymized Patient Longitudinal Data. The data base captures 60-85% of cancer patients across all 50 states in the United States and relies on diagnostic coding used in service or treatment claim filing. Patients queried were greater than 18 years old and were identified by a code indicating CDK4/6 inhibitor therapy or a combination of codes indicating mBC, HR+ status and HER- status. First line treatment was categorized as CDK4/6 inhibitor combination therapy, AI monotherapy, SERD, selective estrogen receptor modulator (SERM) monotherapy, chemotherapy, or other. Patients were further filtered by year, location, practice type (academic vs community), and age. Results: A total of 313,978 patients with mBC receiving first-line therapy were identified nationally between 2015 and 2021. The proportion of patients on first line CDK4/6 inhibitor combination therapy nationally significantly improved from 20% in 2015 (N=27,063) when palbociclib was first approved, to 53% in 2021 (N=54,023) (Table 1.) In 2021, first line use of CDK 4/6 inhibitor combination therapy was higher at 59% both in WI and our institution Froedtert Hospital and the Medical College of Wisconsin Cancer Center (Table 2.) At our center in 2021, the use of first line CDK4/6 inhibitor combination therapy in patients greater than age 65 was significantly lower at 35% (N=39) compared to patients less than 65 at 75% (N=64.) Further delineating the age groups at our center (Table 3,) use of CDK4/6 inhibitor combination therapy in patients aged 70-79 was 35% (N=20) and fell to 20% in patients greater than 80 in age (N=8.) Conclusion: Despite significant improvement in long-term outcomes with first line CDK4/6 inhibitor combination therapy in HR+ HER2- mBC patients, overall national usage is suboptimal. At our center, this was particularly apparent in patients older than 70. Identifying barriers to optimal use is critical to improve utilization of this important and effective class of drugs. National Percentages of HR+ HER2- mBC Patients Stratified by First Line Treatment Between 2015-2021 HR+ HER2- mBC patients Nationally treated with first line therapy (N=313,978.) National and Local Percentages of HR+ HER2- mBC Patients Stratified by First Line Treatment in 2021 HR+ HER2- mBC patients treated with first line therapy in 2021 Nationally (N=54,026,) in Wisconsin (N=694,) and at Froedtert Hospital and the Medical College of Wisconsin Cancer Center (N=103.) Local Percentages HR+ HER2+ mBC Patients Stratified by First Line Treatment and Age Group HR+ HER2- mBC patients treated with first line therapy in 2021 at Froedtert Hospital and the Medical College of Wisconsin Cancer Center (N=103.) Citation Format: Kathleen Monahan, Sailaja Kamaraju, Yee Chung Cheng, Janet Retseck, Deepika Sriram, John Burfeind, Christopher Chitambar, Lubna N. Chaudhary. Real World Statistics on CDK4/6 Inhibitor Use in Metastatic Hormone Receptor Positive and HER2-Negative Breast Cancer with a Focus on Age [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-01-19.

A single-center analysis of visual outcomes and associated factors after intravenous methylprednisolone treatment for dysthyroid optic neuropathy

BackgroundDysthyroid optic neuropathy (DON) is a serious threatening vision loss in Graves’ ophthalmopathy (GO). Although the European Group on Graves’ Ophthalmopathy (EUGOGO) recommend intravenous methylprednisolone therapy for first line treatment, some characteristics predicting the response are still inconclusive.AimTo study the efficacy of intravenous pulse methylprednisolone (IVMP) in treating dysthyroid optic neuropathy (DON) and to identify factors predicting poor response to the treatment.MethodsAll patients diagnosed with DON between January 2010 and December 2021 at Rajavithi Hospital, Thailand, receiving IVMP 1 g/ day for 3 consecutive days were analyzed. The efficacy at 1 week and 3, 6, 12-months in terms of improvement of best corrected visual acuity (BCVA) and proptosis were compiled.ResultsOf the entire 57 DON cases that received IVMP, 50.9% gained at least 0.2 Logarithm of the Minimum Angle of Resolution (logMAR) at 1 week, and the improvement from initial to 1-week BCVA was 0.63 ± 0.63 logMAR (p < 0.001) and the decrease in proptosis was 1.8 ± 1.36 mm (p < 0.001). The remaining 23 orbits underwent orbital decompression and were excluded from the long-term efficacy analysis. In the last 12-months’ follow-up time, there was an improvement of BCVA (0.53 ± 0.47 logMAR) and proptosis (0.59 ± 0.66 mm) (both p < 0.001). At last visit, there was an improvement of BCVA (0.2 logMAR) and proptosis (2 mm) in 76.5, and 5.9% respectively. Significant predictive factors of poor treatment response were age ≥ 55 years (odds ratio [OR]: 8.28, 95% confidence interval [CI]: 1.368–50.121, p = 0.021); longer onset duration before treatment (OR: 5.10, 95%CI: 1.061–24.501, p = 0.042); and proptosis at baseline (OR: 9.31, 95%CI: 1.872–46.280, p = 0.006). The strongest risk factor for predicting poor response to IVMP was poor initial visual acuity (OR: 10.26, 95%CI: 1.363–77.234, p = 0.024).ConclusionsIVMP is effective for both short- and long-term treatment to improve visual acuity greater than proptosis. Older age, longer disease duration, poor initial visual acuity, and proptotic orbits were identified as risk factors for predicting poor response to IVMP treatment in Thai population. DON patients having those risk factors should be suspected, and treated early with IVMP to preserve their future vision.

Management of pediatric ureterolithiasis in the emergency room: A single institution review and new management pathway

Urolithiasis is an increasingly common condition seen in children with an annual incidence of 2-3% in children under 18, and up to 10% in adolescents. Treatment of stones varies including observation, IV hydration, pain management, medical expulsive therapy (MET), or surgery. Though well-studied and often used in adults, MET (alpha-adrenergic antagonists to facilitate passage of ureteral stones), is not routinely prescribed in pediatric patients. The goals of this study were to review a quaternary children's hospital's emergency room frequency of MET utilization for ureterolithiasis as well as evaluate the clinical outcomes of children who were prescribed MET compared to those treated with pain control alone. A retrospective review was performed of children 2 months to 18 years with ureterolithiasis who presented to a quaternary children's hospital ED from 2011 to 2017. The primary outcome was the frequency of MET prescribed. Secondary outcomes included the following comparisons in patients who received MET and analgesics with those who received analgesics alone: hospital admission rate, length of hospitalization, emergency room re-presentation rate, surgical intervention, spontaneous stone passage, urology consultation, how the urology consult affected MET utilization, referral to outpatient urology and nephrology clinics, and CT utilization in the ED. Comparisons were performed utilizing Fischer's exact and t-tests. 139 patients were included with a mean age of 14 years (SD 4.14), 42% male. There was no difference between age, gender, stone size, return to the ED, serum creatinine, or length of hospitalization (if admitted) between patients who were and were not placed on MET. The rate of stone passage was significantly higher for those placed on MET (45%) versus not (20%)(p=0.0022). Urology was consulted for 93% of the cases where children were prescribed MET, compared with only 52% of cases where MET was not prescribed (p = <0.0001). In our experience MET was significantly underutilized in patients where urology was not involved. This is similar to a study by Itano etal. which found urology consultation in the ED significantly increased use of tamsulosin for ureterolithiasis in adults. Children with ureterolithiasis placed on MET had a significantly higher rate of stone passage compared to children managed by pain control alone. Given the benefits of MET to increase the rate of spontaneous stone passage it may be considered first line therapy for treatment of children with ureterolithiasis.