Joshi, Utsav

Acute myeloid leukemia (AML) is an aggressive hematologic malignancy characterized by the clonal proliferation of myeloid precursors and rapid progression. Historically consisting of intensive chemotherapy, AML management has evolved significantly due to advances in molecular diagnostics and risk stratification. This review discusses current therapeutic paradigms in AML, emphasizing the growing role of personalized medicine across age and risk groups. For younger, fit patients, intensive regimens such as the “7 + 3” protocol remain the standard, often enhanced by targeted agents like FMS-like tyrosine kinase 3 (FLT3) and IDH inhibitors. Older or unfit individuals benefit from low-intensity treatments such as hypomethylating agents combined with venetoclax, now considered a frontline standard of care. The use of liposomal chemotherapy (CPX-351), measurable residual disease (MRD) monitoring, and maintenance therapy further refine post-remission strategies. Emerging therapies, including menin inhibitors, antibody–drug conjugates, and immunotherapies like CAR-T cells and vaccines, offer additional options, especially in relapsed/refractory settings. This comprehensive review outlines the current landscape and future directions in AML therapy, emphasizing the transition toward individualized, mutation-driven treatment strategies.

Background : Metastatic lung carcinoids (MLCs) represent a rare subset of lung cancers with distinct histologic subtypes. Survival outcomes and prognostic factors have not been well-studied in the real-world setting. This study investigates the impact of various treatments, including chemotherapy, hormonal therapy, and no treatment, on the overall survival (OS) of patients with typical and atypical MLC. Methods: Patients with MLC between 2010 and 2020 were included from the National Cancer Database based on histologic codes ICD-O-3 8240/3 and 8249/3. Kaplan–Meier curves and multivariate Cox proportional hazard regression were used to compare OS and evaluate prognostic factors. Results: The median age at diagnosis was 68 and 69 years for atypical and typical MLC, respectively. The 3-year OS for the atypical MLC cohort was 22.11%, and for typical MLC was 41.94% ( P < 0.001). In the atypical MLC cohort, chemotherapy showed a nonsignificant benefit in OS (hazard ratio [HR], 0.89; 95% confidence interval [CI], 0.73–1.05; P = 0.21), whereas hormonal therapy was associated with significantly improved OS (HR, 0.72; 95% CI, 0.52–0.98; P =0.04). However, in the typical MLC cohort, chemotherapy was associated with adverse OS (HR, 2.15; 95% CI, 1.85–2.49; P < 0.0001), and hormonal treatment showed better, albeit nonsignificant OS (HR, 0.84; 95% CI, 0.67–1.05; P = 0.13). Conclusion: There is a notable difference in survival outcomes between typical and atypical MLC based on the treatment strategies. While hormonal therapy shows improvement in the OS, the effectiveness of chemotherapy varies depending on the histologic subtype. These findings emphasize the necessity for personalized therapeutic approaches based on the specific characteristics of MLC, ultimately contributing to improved patient outcomes in this challenging oncologic group. Further research is warranted to validate and expand upon these observations.

Abstract Purpose: Triple-negative invasive lobular carcinoma (TN-ILC) of breast cancer is a rare disease and the clinical outcomes and prognostic factors are not well-defined. Methods: Women with stage I-III TN-ILC or triple-negative invasive ductal carcinoma (TN-IDC) of the breast undergoing mastectomy or breast-conserving surgery between 2010 and 2018 in the National Cancer Database were included. Kaplan-Meier curves and multivariate Cox proportional hazard regression were used to compare overall survival (OS) and evaluate prognostic factors. Multivariate logistic regression was performed to analyze the factors associated with pathological response to neoadjuvant chemotherapy. Results: The median age at diagnosis for women with TN-ILC was 67 years compared to 58 years in TN-IDC (p<0.001). There was no significant difference in the OS between TN-ILC and TN-IDC in multivariate analysis (HR 0.96, p=0.44). Black race and higher TNM stage were associated with worse OS, whereas receipt of chemotherapy or radiation was associated with better OS in TN-ILC. Among women with TN-ILC receiving neoadjuvant chemotherapy, the 5-year OS was 77.3% in women with a complete pathological response (pCR) compared to 39.8% in women without any response. The odds of achieving pCR following neoadjuvant chemotherapy were significantly lower in women with TN-ILC compared to TN-IDC (OR 0.53, p<0.001). Conclusion: Women with TN-ILC are older at diagnosis but have similar OS compared to TN-IDC after adjusting for tumor and demographic characteristics. Administration of chemotherapy was associated with improved OS in TN-ILC, but women with TN-ILC were less likely to achieve complete response to neoadjuvant therapy compared to TN-IDC.

Abstract BACKGROUND: The OncotypeDX assay analyzes the expression of 21 genes, including HER2 and Grb7, to assess the predictive effect of chemotherapy in breast cancer recurrence among women with early-stage estrogen-receptor (ER) positive/HER2-negative breast cancer. In this study, we evaluate the distribution of recurrence score from the OncotypeDX assay based on the HER2 expression status by immunohistochemistry (IHC). METHODOLOGY: Utilizing the National Cancer Database, we identified adult women with a diagnosis of stage I – III ER+/HER2- invasive ductal carcinoma of the breast between the years 2010 and 2018. Recurrence scores were classified into low (&lt; 11), intermediate (11-26), and high risk (&gt;26); and the distribution of these recurrence scores cross-tabulated with different IHC scores of HER2 expression (0, 1+, and 2+) by IHC. Women with an IHC score of 2+ had to be negative for HER2 gene amplification by FISH. Multivariate logistic regression model adjusting for age, race, origin, progesterone receptor status, grade, and cancer stage was used to assess the odds of receiving a high OncotypeDx Score (≥26). RESULT: Among 198,931 women with ER+/HER2 negative breast cancer, 59,632 (30.0%) had HER2 IHC score of 0, 102,170 (51.4%) had IHC score of 1+, and 37,129 (18.6%) women were with IHC score of 2+. The median age at diagnosis of breast cancer among all three categories of HER2 expression was 59 years. The median recurrence score for women with IHC scores of 0,1+, and 2+ was 15, 15, and 16 respectively (p &lt; 0.001). A higher proportion of women with HER2 IHC score of 2+ had a high recurrence score compared to women with an IHC score of 0 (15.2% vs. 13%, p &lt; 0.001). In multivariate analysis, compared to women with HER2 IHC score of 0, women with HER2 IHC score of 2+/FISH negative were observed to have higher Odds (OR: 1.16; 95% CI: 1.11 – 1.20, p &lt; 0.001) of receiving high recurrence score. There was no significant difference in the odds of receiving a high recurrence score between women with IHC 0+ and 1+(OR: 0.99; 95% CI: 0.96 – 1.03, p 0.82). CONCLUSION: Women with a HER2 IHC score of 2+ were observed to have a higher odds of receiving high-risk recurrence scores as compared to women with IHC score of 0. This needs to be further correlated with the response to chemotherapy and the risk of recurrence. Citation Format: Anish Shah, Pravash Budhathoki, Suman Gaire, Utsav Joshi, Siddhartha Yadav. Influence of HER2 expression status in the distribution of recurrence score from the OncotypeDx assay among women with early-stage estrogen-receptor-positive/HER2-negative breast cancer [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 P6-01-41.

Abstract Background: HER2-positive invasive lobular carcinoma (ILC) of the breast is a rare entity. Treatment decisions for HER2-positive lobular breast cancer are often extrapolated from the HER2-positive ductal subtype of breast cancer but the clinical outcomes and prognostic factors are not well defined. Methodology: Women with a diagnosis of stage I to III HER2-positive ILC or invasive ductal carcinoma (IDC) of the breast between 2010 and 2018 were identified from the National Cancer Database. Baseline characteristics were compared between ILC and IDC using Chi-square test for categorical variables and the Mann-Whitney U test for continuous variables. Five-year overall survival (OS) was estimated by the Kaplan Meir method. Multivariate cox proportional hazards regression model including age, race, ethnicity, Charleston Deyo score, grade, TNM stage, and treatment modalities such as type of surgery, chemotherapy, and radiation was used to identify factors associated with OS in HER2-positive ILC. In a subset of patients receiving neoadjuvant chemotherapy, the odds of achieving a complete pathological response were compared between women with ILC and IDC in a multivariate logistic regression model adjusting for age, race, ethnicity, Charleston Deyo score, grade, and clinical stage. Results: A total of 4,197 women with HER2-positive ILC and 116,984 women with HER2-positive IDC were included in the final analysis. The median age at diagnosis was 63 years for women with HER2-positive ILC and 56 years for women with HER2-positive IDC (p&lt; 0.001). The five-year OS among women with HER2-positive ILC was 93.1%, 90.8%,and 78.8% in TNM stages I, II, and III respectively. In multivariate analysis, a significant difference in difference in overall survival was not observed between women with HER2 positive ILC and IDC (Hazard Ratio [HR]: 1.0, 95% Confidence Interval [CI]: 0.9 - 1.1, p=0.55). Among women receiving neoadjuvant chemotherapy, a complete pathological response was observed in 31.7% of women with HER2-positive ILC and 42.7% of HER2-positive IDC. In multivariate analysis, there was no difference in odds of achieving a complete pathological response to neoadjuvant chemotherapy between HER2-positive ILC and IDC (Odds Ratio [OR]: 0.8, 95%CI: 0.7 - 1.0, p=0.12). Higher odds of complete pathological response in HER2-positive ILC were observed for women with estrogen-receptor negative (OR: 2.0, 95% CI: 1.1- 3.8), p= 0.02) and progesterone-receptor negative (OR 2.4, 95%CI: 1.5- 3.7), p&lt; 0.001) tumors. The five-year OS for women with a complete pathological response, partial response, and no response after neoadjuvant chemotherapy in HER2-positive ILC were 89.6%, 84.9%, and 77.3% respectively (p=0.01). Conclusion: This study demonstrates that HER2-positive ILC has comparable clinical outcomes to HER2-positive IDC and response to neoadjuvant chemotherapy correlates with OS in HER2-positive ILC. These findings lend support to the current practice of treating HER2-positive ILC and IDC in a similar manner. Citation Format: Suman Gaire, Pravash Budhathoki, Utsav Joshi, Anish Shah, Grace M. Choong, Siddhartha Yadav. Clinical outcomes of loco-regional HER2-positive invasive lobular carcinoma of the breast [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 P4-06-04.