Treatment Outcomes In Patients Research Articles

Impact of GABA pathway genes expression on first-line treatment outcomes in patients (pts) with metastatic colorectal cancer (mCRC): Data from CALGB/SWOG 80405 (Alliance).

Impact of GABA pathway genes expression on first-line treatment outcomes in patients (pts) with metastatic colorectal cancer (mCRC): Data from CALGB/SWOG 80405 (Alliance).

Molecularly matched therapies identified by comprehensive genomic profiling before the first-line setting to provide alternative treatment outcomes in patients with solid tumors: 1-year follow-up of the prospective FIRST-Dx study.

3137 Background: Comprehensive genomic profiling (CGP) test by next-generation sequencing has been reimbursed in Japan since 2019. However, only 9.4% of patients (pts) had received molecularly-matched treatment because CGP test in Japan is only indicated after standard of care (SoC). To determine the clinical utility of a CGP test (FoundationOne CDx) in the first-line setting for pts with advanced solid tumors, we previously reported the results of the FIRST-Dx study, in which the molecular tumor board identified molecular-based recommended therapy (MBRT) for 61% of pts (105/172) (Matsubara J, et al. JAMA Netw Open 2023). In this 1-year follow-up of the FIRST-Dx study, we investigated the clinical benefits provided by the upfront CGP test. Methods: The FIRST-Dx study was a multi-institutional, prospective study in 6 hospitals in Japan. Chemotherapy-naïve adult pts with advanced solid tumor (GI, Lung, Breast, GYN, Melanoma) and ECOG performance status of 0-1 were enrolled. This follow-up study was planned for 3 years and an interim analysis was prespecified at 1 year after the final patient enrollment in the FIRST-Dx study. Primary endpoint was overall survival (OS). Secondary endpoints were the proportion of pts who received MBRT, overall response rate, progression-free survival (PFS), and a PFS ratio (PFS on MBRT/PFS on prior therapy). Results: Data from 172 pts with a median follow-up of 15.1 months were available. Median OS was not reached (95% CI: 18.4 months to not reached). Thirty-nine pts (22.7%) had received MBRT. The total number of pts treated with MBRT were 21 in 1st-line, 20 in 2nd-line, 4 in 3rd-line, and 1 in 4th-line, respectively. Overall response rate was 56.3% [95% CI: 29.9-80.2%] in 1st-line MBRT group vs 42.3% [95% CI: 33.9-51.1%] in 1st-line SoC (N=137), and 26.3% [95% CI: 9.1-51.2%] in 2nd-line MBRT group vs 17.1% [95% CI: 9.7-27.0%] in 2nd-line SoC (N=82), respectively. Median PFS was 12.9 months [95% CI: 7.4 months to not reached] in 1st-line MBRT group vs 11.3 months [95% CI: 8.6-14.1 months] in 1st-line SoC, and 6.9 months [95% CI: 2.8 months to not reached] in 2nd-line MBRT group vs 5.7 months [95% CI: 3.7-7.4 months] in 2nd-line SoC, respectively. Regarding the PFS ratio of 2nd-line MBRT (N=15) (PFS on MBRT in 2nd-line/PFS on 1st-line therapy), median PFS ratio was 1.0 (range: 0.1-14.6) and 4 pts (27%) had the PFS ratio of >1.3, indicating that MBRT might be effective in changing the clinical outcome (Von Hoff DD, et al. J Clin Oncol 2010). Conclusions: We showed that MBRT identified by CGP test before the first-line setting provides better treatment outcomes than SoC in pts with solid tumors early in their disease course. Our data suggested that the timing of CGP test in Japan for pts with advanced solid tumors should be indicated before starting SoC. Clinical trial information: jRCT1050220041 .

The role of determining HER2neu status in patients with gastric cancer.

e16067 Background: Over the past two decades, gastric cancer has continued to maintain a leading position in both incidence and mortality rates among all malignant neoplasms in the Republic of Kazakhstan. Recent data indicate that amplification or overexpression of the HER2 gene is detected in 7-34% of gastric cancer cases, significantly impacting treatment outcomes. Studying a specific group of patients with HER2 overexpression in gastric cancer is of great interest in clinical oncology. Research aim: To examine the long-term treatment outcomes in patients with gastric cancer depending on the status and level of HER-2 expression in real clinical practice. Methods: Analysis was conducted on 172 formalin-fixed paraffin-embedded samples of gastric adenocarcinoma and gastroesophageal junction carcinoma, subjected to immunohistochemical examination to determine HER2 protein expression. Patients' ages ranged from 18 to 85 years, with a mean age of 61.7 years; among them, 106 (61.6%) were male and 66 (38.4%) were female. Of the 172 patients, 64 (37.2%) had primary tumors located at the gastroesophageal junction, while 108 (62.8%) had tumors located in the body of the stomach. Based on differentiation grade, the majority were G3-100 (50%), G2-91 (45%), G1-9 (5%). HER2 testing was performed on the Ventana BenchMark Ultra platform using the HER2 (4B5) antibody. Results: HER2 overexpression was detected in 26 (15.1%) of the 172 patients. Patients with HER2 2+ non-amplified were 6 (3.5%), HER2 2+ amplified were 8 (4.6%), HER2 1+ was detected in 19 (11%) cases, and HER2 0 was found in 121 (80.9%) cases. Long-term results revealed statistically significant differences, notably the highest overall survival rate in patients with HER-2 overexpression compared to HER-2 low and absence of HER-2. The HER2 3 (+FISH/SISH) variant was significantly more prevalent in 84.6% compared to HER2 0 in 52%, and HER2 1 in 48%, p < 0.05. Comparison of Her2 status using the chi-square method in groups revealed probable differences concerning tumor localization, with a criterion value of 0.034; morphological form (criterion value = 5.83); and differentiation grade (criterion value = 10.05). Conclusions: These results underscore the importance of further HER2 research in gastric cancer and gastroesophageal junction carcinoma for the development of personalized therapeutic strategies.

Clinical characteristics and treatment outcomes of advanced penile squamous cell carcinoma: Real-world evidence from a tertiary cancer center in Brazil.

e17025 Background: Penile cancer is a rare disease worldwide. However, Brazil has an annual incidence of 1.5 cases per 100,000 inhabitants, representing 2% of male cancers. This study aims to evaluate clinical characteristics and treatment outcomes of patients (pts) with advanced penile squamous cell carcinoma (SCC) in a large tertiary cancer center in Brazil. Methods: We performed a retrospective database analysis of pts with advanced penile squamous cell carcinoma (SCC) treated at Instituto do Cancer do Estado de Sao Paulo between January 2008 and October 2023. Medical records were reviewed for demographic, clinicopathological features and treatment outcomes data. Cumulative survival probabilities were computed using the Kaplan-Meier method. Prognostic factors associated with survival were evaluated through univariate analyses, using the Cox regression model. Results: We identified 91 pts with advanced penile SCC eligible for analysis. Median age was 62 years (IQR 44.5-64.5), most were married (53.8%), diagnosed with stage T3/T4 (60.4%), and N2/N3 (64.9%) SCC. At diagnosis, 65% were classified as stage IV (T4, N3, or M1 disease). De novo metastasis occurred in 35% pts. Neoadjuvant chemotherapy was given to 30.8%, mainly ITP regimen containing paclitaxel, ifosfamide, and cisplatin (46.4%). First-line palliative chemotherapy was given to 50.5%, being carboplatin and paclitaxel the predominant choice (47.8%). Disease progression occurred in 54% pts, after a median follow-up of 21.8 months. At the last follow-up, 61.5% had nodal disease. Most common sites of metastasis were lung (50.5%) and liver (19.8%). Overall survival (OS) was 12.9 months (95% CI 9.8 - 18.3). Prognostic factors significantly correlated with OS were ECOG 0-1 (HR 0.40, 95% CI 0.21 - 0.74, p=0.003) and complete response post-chemotherapy (HR 0.14; 95% CI 0.02 - 0.80, p=0.02). No association with survival was found for region/state of origin, distance from patient’s home to the hospital, marital status, education level, and age. Conclusions: Advanced penile squamous cell carcinoma (SCC) presents significant challenges in Brazil, with high rates of advanced disease at diagnosis. OS correlated with complete response to chemotherapy and performance status.

The treatment outcomes of patients with BRAFV600E–mutated metastatic colorectal cancer (mCRC): The Polish retrospective cohort study.

The treatment outcomes of patients with <i>BRAF^V600E</i>–mutated metastatic colorectal cancer (mCRC): The Polish retrospective cohort study.

Treatment outcomes for patients with Ga68-PSMA-PET prostate cancer (PC) with or without conventional imaging correlates.

Treatment outcomes for patients with Ga68-PSMA-PET prostate cancer (PC) with or without conventional imaging correlates.

The treatment outcomes of patients who failed to be randomly assigned after atezo/bev induction therapy in the Chinese TALENTop study.

e16183 Background: Hepatocellular carcinoma (HCC) patients with macrovascular invasion (MVI) are considered to be at an advanced stage of disease with limited treatment options. The combination therapy of atezolizumab (atezo) plus bevacizumab (bev) has become a global standard of care for those patients and made conversion resection possible. The Chinese TALENTop study (NCT04649489) is aiming to clarify whether hepatic resection may provide additional benefit in HCC patients with MVI responding to atezo/bev. For patients without opportunity to receive hepatic resection, subsequent treatment outcomes will be reported. Methods: Potentially resectable HCC patients with MVI and without extrahepatic metastasis are eligible for this study. Eligible patients receive 3 cycles of atezo/bev and 1 cycle of atezo as primary systemic therapy (induction phase). Patients assessed as partial response (PR) or stable disease (SD) per RECIST v1.1 and considered suitable for R0 hepatic resection are randomized in a 1:1 ratio to either Arm A, hepatic resection followed by atezo/bev for 1 year, or Arm B, continuing atezo/bev therapy. The primary endpoint is the time to treatment failure. Patients failed to be randomized will enter the survival follow-up phase. After 296 patients entered induction phase, the patient profile, subsequent treatments per local standard of care and survival of patients who failed to be randomized were analyzed. Results: From Apr 2021 to Jun 2023, 296 patients were enrolled and entered induction phase and 175 patients failed to be randomized and were followed up until Sept 2023. The main reasons for failure to be randomized were disease progression (64.6%), investigator assessment of unsuitability for R0 hepatic resection (14.3%), and others. The 175 patients were characterized with a median age of 52 (26-76), and 166 (95%) had HBV infection. Among them, 165 (94%) had combined PVTT, 24 (14%) had combined HVTT and 5 (3%) had combined IVCTT. At a median follow-up time of 10.9 months (9.7-13.1), the median overall survival (mOS) is 13.8 months (8.9-15.8), 6- and 12-month survival rate were 71% and 53%, respectively. As the result of best response during induction phase, 3 patients (1.7%) achieved PR, 92 patients (52.6%) achieved SD and 65 patients (37.1%) were PD. 123 patients (70%) received subsequent therapy. The mOS of patients received different subsequent therapies was showed below. Conclusions: This study provides data on HCC patients with MVI after receiving atezo/bev. The result shows favorable survival even in patients failed to randomization to receive conversion resection, and subsequent treatment strategy may differ survival outcomes. Clinical trial information: NCT04649489 . [Table: see text]

RWD108 Demographics, Clinical Characteristics, and Treatment Outcomes of Patients With Newly Diagnosed Multiple Myeloma in the US Across Social Determinants of Health (SDoH)

RWD108 Demographics, Clinical Characteristics, and Treatment Outcomes of Patients With Newly Diagnosed Multiple Myeloma in the US Across Social Determinants of Health (SDoH)

Prediction of colorectal cancer chemotherapy efficacy using machine learning applied to gene expression data.

e15548 Background: FOLFOX and FOLFIRI chemotherapy are considered standard first-line treatment options for colorectal cancer (CRC). However, the criteria for selecting the appropriate treatments have not been thoroughly analyzed. Here, we aim to use machine learning and genetic profiles to identify precise multi-gene panels that can predict the response to 5-Fluorouracil-based chemotherapy in colorectal cancer patients. Methods: The genetic profiling data, including drug response profiles, were retrieved from the Gene Expression Omnibus (GEO) database. These datasets were used to train and validate machine learning models. Feature selection methods, such as least absolute shrinkage and selection operator (LASSO) and variable selection from random forests (varSelRF) and various algorithms, such as Random Forest and Support Vector Machines, were applied to develop predictive models. Functional enrichment and network analyses were performed using Ingenuity Pathway Analysis (IPA). Results: This study identified relevant gene signatures at two stages of colorectal cancer: primary and metastasis using two different chemotherapy regimens, FOLFOX and FOLFIRI. The predictive models achieved an average prediction accuracy of 93% in identifying drug response outcomes across multiple chemotherapy regimens. The application of the machine learning model suggested that 28.6% of patients who failed the treatment therapy they received would benefit from the alternative treatment. Conclusions: The developed machine learning models demonstrate potential for guiding clinicians in selecting the most effective treatment options based on individual genetic profiles. With additional clinical validation, this approach could lead to improvements in treatment outcomes for patients with CRC and other cancers.

Effects of lack of access to cancer medication on survival of patients with lung cancer.

e20585 Background: Lung cancer is the leading cause of cancer-related death. The treatment has evolved with the introduction of immunotherapy. During the economic crisis in Lebanon, cancer medications became unavailable forcing oncologists to adjust treatment protocols. This study aims to assess the effect of medication shortage on the progression-free survival (PFS) of lung cancer patients treated at a tertiary care center in Lebanon. Methods: A retrospective analysis of patients with metastatic NSCLC treated during the period of drug shortage (October 2021-December 2022) as compared to those treated in 2019-2020. The primary end point was progression-free survival (PFS) on first line of therapy and its association with dose density ratio (dose density given/standard dose density). Electronic medical records of 117 patients were reviewed and data of 83 eligible patients were collected and analyzed using IBM SPSS software. Results: The mean age at diagnosis was 68 years. Of the total, 63.5% were male. Additionally, 14.4% of the patients received chemotherapy, 39.7% received immunotherapy, and 42.1% received a combination of chemotherapy and immunotherapy. In total, 49 patients were eligible in the 2019/2020 category. 84% of the patients had the opportunity to receive immunotherapy. In contrast, 25 patients were eligible in the 2021/2022 category, and only 73% of them had the opportunity to receive immunotherapy. The median PFS of the 2019/2020 category was 11.2 months, compared to 5.4 months in 2021-2022 (p-value of 0.339). PFS was studied based on the dose density ratio for immunotherapy. Twenty-two patients received a full immunotherapy dose with a ratio of 1, and their PFS was 5.43 months. Twelve patients received a dose density ratio ranging from 0.01 to 0.50 and had a PFS of 10 months. Twenty-nine patients received a dose density ratio of 0.51-0.99 and had PFS of 12.8 months. Contrary to our initial expectations, we did not observe a statistically significant difference between the dose density of immunotherapy and PFS values with a p-value of 0.107. Conclusions: Despite significant shortages in immunotherapy medications, our study suggests that this has no significant detrimental effect on PFS. This unexpected discovery challenges the conventional notion that full immunotherapy doses are necessary and prompts further exploration of the complex relationship between dosage and treatment outcomes in patients.

Real-world treatment outcomes in patients with HR+ HER2- advanced breast cancer treated with CDK4/6 inhibitors and endocrine therapy.

1067 Background: The addition of cyclin-dependent kinases 4 and 6 inhibitors (CDK4/6i) to endocrine therapy (ET) improves progression-free (PFS) and overall survival (OS) in hormone receptor-positive, HER2-negative advanced breast cancer (HR+/HER2- ABC) in 1st and 2nd line setting. The international guidelines advise using 1st line CDK4/6i; however, its superiority over 2nd line use is debatable. Methods: We retrospectively analyzed clinical data of HR+/HER2- ABC pts administered palbociclib (PAL), ribociclib (RIB) or abemaciclib (ABM) added to either 1st or 2nd line ET. Results: A total of 1511 pts (PAL=507; RIB=724; ABM=280) from 11 cancer Polish centers treated between Sep 2017 and Dec 2023. Median follow-up was 29.6 (95%CI 28.2 to 30.9) months (m). Mean age was 62.6±11.9, 58.9±12.2 and 61.4±10.8 years in PAL, RIB and ABM, respectively. 815 patients (53.9%) had visceral and 1109 (73.4%) bone metastases. 1254 pts (83%) received 1st line CDK4/6i, in 841 (67%) combined with aromatase inhibitor (AI) and in 413 (33%) with fulvestrant (FUL). Second-line CDK4/6i was used in 257 pts (17%); 59 (23%) and 198 (67%) with AI and FUL, respectively. There was no difference in PFS, PFS2, and OS between three CDK4/6i in combination with AIs in 1st and 2nd line setting. Median PFS (95%CI) for 1st line AI with PAL, RIB, ABM were 29.0 (21.6-37.0), 32.0 (24.5-36.9), not reached (N/R) (21.9-N/R) m; PFS2: 37.0 (28.8-N/R), 33.0 (29.5-40.2), N/R (28.9-N/R); OS: 48.9 (42.9-N/R), 48.6 (41.9-N/R), N/R (36.7-N/R). Median PFS (95%CI) for 2nd line AI with PAL, RIB, ABM were 11.9 (9.49-N/R), 10.8 (8.27-N/R), 11.0 (6.43-N/R); PFS2: 22.7 (16.8-N/R), 32.3 (24.9-N/R), 31.0 (13.2-N/R); OS: 27.4 (24.4-N/R), 36.7 (30.1-N/R), 45.5 (29.0-N/R) (no statistical significance). In contrast, RIB+FUL was superior to PAL+FUL and ABM+FUL in both lines (Table). The safety profile was concordant with the reported data for ET + CDK4/6i. Conclusions: Identifying predictive factors of response is essential for the rational use of CDK4/6i and ET in HR+/HER2- ABC. [Table: see text]

Real-life use of delamanid: results from the European post-authorisation safety study.

A post-authorisation safety study (PASS) on delamanid (DLM) was conducted as part of a post-approval commitment to the European Medicines Agency. The aim of this study was to evaluate the use of DLM in a real-life setting, its safety, and treatment outcomes in patients with multidrug-resistant TB (MDR-TB). This was a prospective, multicentric, non-interventional study conducted in the European Union. MDR-TB Regimen selection and patient monitoring were conducted in accordance with existing medical practices. Data on the use of DLM, related adverse events, and treatment outcomes were collected for up to 30 months after the first DLM dose. Descriptive summary statistics were used for continuous and categorical variables. Out of 86 patients, one had extrapulmonary TB. Two-thirds of the patients were treated with DLM for more than 24 weeks. The most frequent adverse drug reaction to DLM was QT interval prolongation. Resistance to DLM was detected in one patient during treatment. The treatment success rate was 77%. No new safety concerns were revealed, including in patients treated with DLM for more than 24 weeks. QT interval prolongations were well managed and did not lead to any clinically significant cardiac effects. The treatment outcomes were in line with the WHO target for Europe.

Prospective observational study of nutritional and immunological indices as predictive biomarkers of response to immune checkpoint inhibitors in non-small cell lung cancer (ICI-PREDICT study).

e20524 Background: Nutritional and immunological indices, including controlling nutritional status (CONUT) score, skeletal muscle area (SMA), and neutrophil-to-lymphocyte ratio (NLR) have been reported as predictors of response to immune checkpoint inhibitor (ICI) in non-small cell lung cancer (NSCLC). The aim of this prospective, multicenter study is to evaluate the clinical impact of pre- or early post-treatment changes in nutritional and immunological indices on treatment outcomes in patients with advanced NSCLC treated with first-line ICIs. Methods: We enrolled 301 advanced NSCLC patients treated with ICIs (monotherapy or combined with chemotherapy) as first-line therapy, without any oncogene mutations, and available data on programmed cell death-ligand 1 (PD-L1) expression (150 in training and 151 in validation cohorts) from March 2020 to November 2022. The CONUT score, SMA at the L3 level (cm2/m2), and NLR, were evaluated before treatment initiation and at the first response evaluation. Cut-off values were determined by receiver operating characteristic curves with objective response as the outcome in the training cohort. The primary endpoint was progression-free survival (PFS). For exploratory study, serum before treatment was collected to measure 15 muscle-derived cytokines (Apelin, BDNF, CX3CL1, EPO, FABP3, FSTL1, FGF21, IL-6, IL-15, Irisin, LIF, Musclin, Myostatin, OSM, and SPARC) (n = 123). Results: The median follow-up period and PFS was 17.5 (range: 7.3-39.4) and 6.9 (range: 0.1-31.5) months, respectively. In the training cohort, men (hazard ratio [HR]: 0.52, 95% confidence interval [CI]: 0.30-0.90, p = 0.0183), ΔCONUT &lt; 0 (HR: 0.59, 95% CI: 0.35-0.98, p = 0.0431), and ΔSMA &gt; −0.13 (HR: 0.56, 95% CI: 0.33-0.96, p = 0.0333) were independent predictors for PFS. In the validation cohort, PD-L1 ≥ 50% (HR: 0.54, 95% CI: 0.34-0.84, p = 0.0061), NLR &lt; 3.65 (HR: 0.47, 95% CI: 0.30-0.74, p = 0.0011), and ΔSMA &gt; −0.13 (HR: 0.61, 95% CI: 0.38-0.98, p = 0.0421) were independent predictors for PFS. In the exploratory study, multivariate analysis including muscle-derived cytokines (continuous variables) revealed that performance status = 0 (HR: 0.24, 95% CI: 0.12-0.48, p &lt; 0.0001), without baseline prednisone (≥ 10 mg/day) (HR: 0.17, 95% CI: 0.05-0.58, p = 0.0213), smoking history (HR: 0.34, 95% CI: 0.14-0.81, p = 0.0269), and FSTL1 (HR: 0.97, 95% CI: 0.93-0.99, p = 0.0185) were independent predictors of PFS. Conclusions: ΔSMA was the only factor validated as an independent predictor of PFS. The underlying biological mechanisms may be related to skeletal muscle-derived FSTL1. Clinical trial information: UMIN000040450.

Resilience in Rectal Cancer Treatment: Lessons from the COVID-19 Era in Czech Republic.

The management of patients with COVID-19 infection has placed great pressure on the healthcare systems around the world. The aim of this study was to investigate the impact of the COVID-19 pandemic on the treatment outcomes of patients with rectal cancer by comparing them to those of patients with the same diagnosis in the pre-pandemic period. Retrospective data analysis of patients undergoing multimodal treatment for rectal cancer at the four university hospitals during the COVID-19 pandemic (2020-2021) and the 2-year pre-pandemic period (2018-2019). A total of 693 patients (319 in the pre-pandemic period and 374 in the pandemic period) with rectal cancer were included in the study. The demographic and clinical characteristics of patients in both study periods were comparable, as was the spectrum of surgical procedures. Palliative surgery was more common in the pandemic period (18% vs 13%, p=0.084). The proportion of patients undergoing minimally invasive surgery was higher during the COVID-19 pandemic (p=0.025). There were no statistically significant differences between the study periods in the incidence/severity of post-operative complications, 30-day mortality and length of hospital stay. The number of positive resection margins was similar (5% vs 5%). Based on these results, COVID-19 had no effect on the postoperative morbidity and mortality in patients undergoing surgery for rectal cancer. Neoadjuvant treatment was more common in the pre-pandemic period (50% vs 45%). Long-course RT was predominantly offered in the pre-pandemic period, short-course RT during the pandemic. Significantly shorter "diagnosis-surgery" intervals were observed during the pandemic (23 days vs 33 days, p=0.0002). The "surgery-adjuvant therapy" interval was similar in both analysed study periods (p=0.219). Our study showed, that despite concerns about the COVID-19 pandemic, multimodal treatment of rectal cancer was associated with unchanged postoperative morbidity rates, increased frequency of short-course neoadjuvant RT administration and shorter "diagnosis-surgery" intervals.

Oncologic outcome of response-guided axillary treatment in patients with cN1 breast cancer after primary systemic therapy.

514 Background: In breast cancer, the majority of clinically node positive (cN1) patients are treated with primary systemic treatment (PST), with increasing rates of axillary pathologic complete response (pCR). Evidence supporting tailoring axillary treatment according to the response is growing. However, it is still debatable whether ALND is beneficial in cN1 patients with residual nodal disease and if any further axillary treatment is necessary in patients achieving pCR. In this study, we present the four-year oncologic outcome of cN1 patients undergoing either axillary radiation treatment or no axillary treatment according to the ‘Marking Axillary lymph nodes with Radioactive Iodine seeds’ (MARI)-protocol. Methods: Between 2014 and 2021, we prospectively enrolled patients with node positive breast cancer and 1 - 3 involved axillary lymph nodes on FDG-PET/CT pre-PST, who were treated according to the MARI-protocol. Patients with residual disease of the MARI node (ypN1) received axillary radiotherapy (RT), while patients with a pCR of the MARI node (ypN0) received no further axillary treatment. The primary endpoint was the axillary recurrence rate. Secondary endpoints include invasive disease free survival (iDFS) and overall survival (OS), calculated using the Kaplan-Meier method. Results: Of the 367 included patients, more than half (54%, n= 198) had hormonal receptor positive (HR+)/Human Epidermal growth factor 2 negative (HER2-) breast cancer; 59 patients (16%) had HR+/HER2+; 39 patients (11%) had HR-/HER2+ and 71 patients (19%) had triple negative (TN) subtype. Median age was 49 (IQR 41 – 56) years. 231 (63%) patients who had ypN1 received RT and 136 patients (37%) who achieved ypN0 received no further axillary treatment. Median follow up was 49 (IQR 32 – 70) months. Axillary recurrence rate was 3.5% ( n= 8) in patients with ypN1 and 0.7% ( n= 1) in patients with ypN0. Most axillary recurrences ( n= 6) occurred simultaneously with distant metastases in the ypN1 group. In patients with ypN1, the iDFS was 86% and the OS 93%; in ypN0 patients, the iDFS was 93% and the OS 98%. Conclusions: Response-guided axillary treatment in patients with limited nodal disease according to the MARI protocol is associated with favorable oncologic outcome without performing ALND’s. De-escalation can therefore be considered safe. [Table: see text]

Acute Coronary Syndrome: Treatment Strategies and Outcomes in Patients Admitted to a Tertiary Care Hospital in Palestine.

Acute coronary syndrome (ACS) is the leading cause of death worldwide despite advances in treatment and prevention measures. This study aimed to explore ACS treatment strategies (ischemia-guided vs early invasive) and risk factors among patients diagnosed with ACS in a tertiary care hospital in Palestine and to evaluate related outcomes regarding future events and standard clinical guidelines. This retrospective cohort study reviewed patient data from a Palestinian medical hospital. The study included 255 patients ≥ 18 years who were hospitalized between January 2021 and December 2021 and diagnosed with ACS. The data were analyzed using the Statistical Package for Social Science (SPSS). 71% of the participants were males. The mean age was 59.59±11.56 years. Smoking, diabetes, and hypertension were the most common risk factors. Unstable angina (UA) was the most prevalent ACS type, accounting for 43.1% (110) of cases, whereas NSTEMI accounted for 39.2% (100) and STEMI accounted for 17.6% (45) of cases. An ischemic-guided strategy approach was used in 71% (181) of the patients. Upon discharge, the most prescribed medication classes were antiplatelets (97.6%), statins (87.1%), PPIs (72.5%), and antihypertensives (71.8%). Treatment strategies were selected according to the clinical guidelines for most ACS types. ACS management in Palestine continues to evolve to overcome barriers, decrease patient mortality, and decrease hospital stay. UA and NSTEMI were the most common ACS diagnoses at admission, and the ischemic strategy was the most common modality. The findings of this study call for an increased awareness of CVD risk factors, resource availability, and adherence to clinical guidelines to improve patient outcomes and community health.

Real-world treatment patterns and clinical outcomes among patients with HR+/HER2- advanced/metastatic breast cancer receiving palbociclib in Brazil: IRIS study.

e13088 Background: Palbociclib was approved for hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2-) advanced/metastatic breast cancer (aBC/mBC) in Brazil in 2018. Worldwide studies explore palbociclib's real-world use and outcomes; however, this data is not available for Brazilian patients. IRIS Brazil study aimed to describe demographic/clinical characteristics, treatment and clinical outcomes of adult female patients who have received palbociclib as first-line treatment for HR+/HER2- aBC/mBC in private healthcare institutions in Brazil. Methods: This retrospective descriptive study included females aged 18 years or older diagnosed with HR+/HER2- aBC/mBC and those who had received palbociclib as their initial line of therapy. The study analyzed variables such as demographics, clinical characteristics, treatment history, palbociclib combinations, and clinical outcomes. Progression-free survival (PFS) and overall survival (OS) were calculated using Kaplan-Meier estimates at 6- and 12-month time points. Results: A total of 121 patients were included in the study. The mean age was 54.4 years, and 82 (67.7%) were menopausal at diagnosis. A total of 51 patients (42.1%) were treated with palbociclib + fulvestrant, while 67 (55.8%) were treated with palbociclib + aromatase inhibitors. The majority of patients (n = 79; 65.3%) did not require any dose adjustments. Among the 40 patients (33.1%) who required dose adjustments, the main reason was adverse events/toxicity (n = 36; 90%). The PFS rates at 6 and 12 months were 78% and 60%, respectively. The OS rates at 6 and 12 months were 86% and 70%, respectively. Conclusions: Results from this initial real-world assessment of clinical outcomes in Brazil suggest that Palbociclib combinations exhibit favorable effectiveness in treating HR+/HER2- aBC/mBC disease, as measured by PFS and OS rates.

Circulating tumor DNA for recurrence monitoring following resection for pancreas adenocarcinoma.

e16365 Background: Detecting early recurrence among patients with resected pancreatic cancer may facilitate earlier treatment and better outcomes for patients with resected pancreatic ductal adenocarcinoma (PDAC). Circulating tumor DNA (ctDNA) has shown promise as a tumor-specific biomarker for PDAC but has not yet entered routine clinical use. This study aims to conduct analytical and clinical validation of Signatera ctDNA profiling to predict recurrence in patients with PDAC. Methods: A retrospective IRB-approved protocol evaluating the use of Signatera ctDNA testing among patients who underwent resection at Northwell Health during 2019-2023. The utility of ctDNA status to predict PDAC recurrence during follow-up was assessed using cox regression. Results: There were 91 ctDNA tests among 24 patients. With a median follow-up of 15 months, recurrence was observed in 38% (9/24) of patients and 8 patients died. Among patients with recurrence, most of them had positive ctDNA before showing signs of recurrence on the imaging (6/9, 66.7%) with mean lead time of 116 days, while 2 of them had positive ctDNA after recurrence and one patient never had positive ctDNA. At the time of recurrence, eight patients had elevated CA19-9, while two patients with normal CA19-9 had positive ctDNA. The median recurrence-free survival (RFS) was 23 months (95% CI, 11-not reached). Patients with detectable preoperative ctDNA had significantly decreased median RFS (14 months; 7 of 10 (70%) recurred) when compared with patients negative for ctDNA [not reached; 2/14 (14.3%) recurred; P= 0.005). In multivariable Cox model after adjusting for potential risk factors, detection of ctDNA was associated with RFS. (table). Conclusions: Signatera ctDNA profiling identified relapse earlier than imaging for most patients. These results suggest the potential for a prospective trial evaluating early treatment interventions in this deadly disease to improve survival rates. [Table: see text]

Symptom Profiles and Intensive Treatment Outcomes in Sexual Minority and Heterosexual Patients With OCD

Sexual minority (SM) individuals appear to be at greater risk for obsessive-compulsive disorder (OCD). Despite this, little is known about OCD presentation and treatment outcomes among SM individuals. Although some research has suggested that SM individuals may be more likely to endorse intrusive thoughts related to violence/sex/religion compared to heterosexual individuals, extant literature has neglected to examine potential differences across different SM groups, a notable limitation given the apparent differences in the types of minority stress that each group experiences and the unique health disparities affecting each group. The current study sought to address these gaps by examining potential differences in OCD symptom severity, presentation, and treatment outcomes using analysis of variance and profile analysis in a clinical sample of 1,502 cisgender patients diagnosed with OCD enrolled in intensive OCD treatment (87.5% heterosexual, 6.6% bisexual, 4.7% lesbian or gay, and 1.1% questioning). Replicating previous research, neither OCD severity nor treatment outcomes differed by sexual orientation, and findings extended previous research that no differences across SM groups were observed, either. However, contrary to previous research, there was also no evidence for unique profiles of OCD symptoms across sexual orientation groups, and questioning individuals reported significantly less severe symmetry symptoms compared to heterosexual and bisexual individuals. Findings are encouraging in that they suggest that cisgender bisexual, lesbian or gay, and questioning individuals with OCD can still benefit significantly and to the same degree as their cisgender heterosexual peers in intensive OCD treatment. Potential explanations for conflicting findings regarding symptom profiles are discussed.

Effectiveness of narrowband ultraviolet B monotherapy versus combination therapy with systemic agents in patients with early-stage mycosis fungoides and the association with plaque lesions.

Narrowband ultraviolet B (NB-UVB) has been recommended as first-line therapy for early-stage mycosis fungoides (MF) in international guidelines. NB-UVB can be used as monotherapy or part of a multimodality treatment regimen. There is limited evidence on the effectiveness and optimal patients of NB-UVB in combination with systemic therapies in MF. We aimed to assess the effectiveness of the combination versus NB-UVB monotherapy in early-stage MF and if plaque lesion status was related to these effects. This observational cohort study included 247 early-stage MF patients who had received NB-UVB combined with systemic therapies vs. NB-UVB monotherapy from 2009 to 2021. The primary outcome was partial or complete response. Overall response rate and median time to response were calculated. Hazard ratios (HRs) were estimated using the Cox model. In 139 plaque-stage patients, the response rate for combination therapy group was higher than that of monotherapy group (79.0%vs. 54.3%, p=0.006). The adjusted HR for combination therapy compared with NB-UVB monotherapy was 3.11 (95% CI 1.72-5.63). The combination therapy group also showed shorter time to response (4vs. 6 months, p=0.002). In 108 patch-stage patients, the response rate and time to response in two treatment groups showed no significant difference. There was therefore an observed interaction with patients' plaque lesion status for the effect size of NB-UVB combination therapy. No serious adverse events were observed. Adding systemic treatments to NB-UVB did not improve the treatment outcome of patch-stage patients, but it surpassed NB-UVB monotherapy for early-stage patients with plaques.