Abstract 3832: Fluid-overload associated large B-cell lymphoma and determinants of outcomes: Analysis of a pooled database

Fluid-Overload Associated Large B-Cell Lymphoma Clinicopathologic Features and Determinants of Outcomes: Analysis of a Pooled Database

Background B-cell lymphoma with MYC, BCL2, and/or BCL6 rearrangements are classified as double/triple- hit lymphoma (DTHL). They usually, but not always, tend to be high-grade aggressive B-cell lymphoma with worse prognosis. Despite this classification, DTHL remains a heterogeneous group with varied molecular profiles, biological behavior, and prognosis. Therefore, we conducted this pooled database analysis to identify the prognostic factors, clinicopathological characteristics, and therapeutic strategies influencing survival in this rare disease. Methods To study the demographic characteristics, molecular and immunohistochemical signatures, therapeutic interventions, survival, and prognostic factors, we compiled a pooled database of 161 cases that fit the diagnostic criteria for DTHL. Kaplan-Meier survival curves were constructed. Cox proportional hazards model and Log-rank tests were used to assess the influence of demographic and clinicopathologic factors on overall survival (OS) and disease-free survival (DFS). Results A compiled a dataset of 161 patients with confirmed DTHL. The median age was 62 with F:M of 1.08. The median duration of symptoms before diagnosis was 2 months. DTHL involved the lymph nodes (41%), bone marrow (31%), bone (14%), CNS (5%), skin (4%), liver (3%), and spleen (2%). Constitutional symptoms were reported in 20%. The cohort consisted of primary (50%), secondary/transformed (16%), and follicular DTHL. The median OS and DFS of the cohort were 69 and 27 months, respectively. Bone marrow and extra-lymphatic organ involvement were associated with worse DFS and non-significant numerically worse OS. LDH>500 (p=0.006), PAX5-negative (p=0.01), CD79a-negative (p=0.02), and Ki67>80% (p<0.0001) were associated with worse OS. Similarly, CD5+, CD10+, and MUM1+ had worse OS, but did not reach statistical significance. Follicular DTHL was associated with the best median OS and DFS followed by primary then secondary/transformed in decreasing order. Advanced stage and high IPI were also associated with worse non-significant numerical OS. Age and sex did not impact OS. Compared to no treatment, chemotherapy and stem cell transplant had incrementally superior median OS (3 vs. 55 vs. NR months, p=0.008). Frontline intensive chemotherapy yielded similar DFS and OS to CHOP-like regimens. Patients who attained CR as their best response also had a superior median OS (p<0.0001). Conclusion This study presents clinicopathologic data from a cohort of patients with primary, secondary, and follicular DTHL. It identifies the type of DTHL, IHC profile, LDH levels, type of therapy, and quality of response to treatment as critical determinants of OS. Citation Format: Philip A. Haddad, Supriya Gupta, Ankita Gupta, Christopher Graham. Clinicopathologic determinants of survival in double/triple hit lymphoma: Analysis of a pooled database [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3831.

Double/Triple Hit Lymphoma Descriptors and Clinicopathologic Determinants of Survival: Analysis of a Pooled Database

Mast Cell Leukemia Descriptors and Clinicopathologic Determinants of Survival: Analysis of a Pooled Database

Blastic Plasmacytoid Dendritic Cell Neoplasm Descriptors and Clinicopathologic Determinants of Survival: Analysis of a Pooled Database

Acute Erythroid Leukemia Clinicopathologic Determinants of Survival: Analysis of a Pooled Database

Clinicopathologic Determinants of Survival in Hemophagocytic Lymphohistiocytosis: Analysis of a Real-World Database

Plasmablastic Lymphoma Descriptors and Clinicopathologic Determinants of Survival: Analysis of a Pooled Database

Primary Cutaneous Diffuse Large B-Cell Lymphoma-Leg Type Descriptors and Clinicopathologic Determinants of Survival: Analysis of a Pooled Database

Background: Primary Cutaneous Diffuse Large B-cell Lymphoma-Leg Type (PCDLBCL-LT) is a rare but non-indolent subtype of B-cell lymphoma. While most PCDLBCL-LT starts over the lower extremities, some cases may present at other cutaneous sites. The determinants of survival outcomes in this disease are not very well defined. Therefore, we conducted this pooled database analysis to identify the prognostic factors, clinicopathological characteristics, and therapeutic strategies that influence survival in this disease. Methods: To study the demographic characteristics, molecular and immunohistochemical signatures, therapeutic interventions, survival, and prognostic factors, we compiled a pooled database of 122 cases that fit the diagnostic criteria for PCDLBCL-LT. Kaplan-Meier survival curves were constructed. Cox proportional hazards model and Log-rank tests were used to assess the influence of demographic and clinicopathologic factors on overall survival (OS) and disease-free survival (DFS). Results: A total of 122 patients with confirmed PCDLBCL-LT were identified. The median age was 76. There was a male preponderance with M:F of 2.4. Seventy-three percent involved the extremities. The median duration of symptoms before diagnosis was 3.5 months. Involvement of lymph nodes, bone marrow, bone, and CNS occurred in 11%, 3%, 4%, and 3%, respectively. Constitutional symptoms were reported in 5%. The median OS and DFS of the whole group were 39 and 32 months, respectively. Patients younger than 70 had better median DFS (NR vs. 24 months, p=0.02) with a non-significant better median OS. Lymphadenopathy (45 vs. 18 months, p=0.006) and stage T3 compared to T1/T2 (16 vs 41 months, p=0.006) were associated with worse OS. Sex, constitutional symptoms, IHC phenotype, extra-lymphatic/extra-cutaneous organ involvement, and histologic cutaneous patterns did not impact OS. Compared to no treatment, chemotherapy, XRT+/-surgery, and stem cell transplant had numerically better OS without reaching statistical significance (5 vs. 39 vs. 41 vs. NR months, p=0.15). Patients who attained CR as their best response also had a superior median OS compared to responses less than CR and none (61 vs. 23 vs. 11 months, p<0.0001). Conclusion: This study presents updated clinicopathologic data from a large, pooled cohort of patients with PCDLBCL-LT. It identifies age, lymph node involvement, T stage, type of therapy, and quality of response to treatment as critical determinants of OS. Citation Format: Philip A. Haddad, Millicent Amankwah. Primary cutaneous diffuse large B-cell lymphoma-leg type and clinicopathologic determinants of survival: Analysis of a pooled database [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3833.

Background Histiocytic sarcoma (HS) is an aggressive, rare malignant neoplasm of cells with histiocytic differentiation. It can occur de novo or develop in the context of other malignant disorders. HS can present as disseminated or localized lesions in the skin, lymphatics, gastrointestinal tract, central nervous system, or other organs. Little is known about factors that impact HS clinical outcomes. We conducted this pooled database analysis to delineate key clinicopathological characteristics, prognostic indicators, and treatment modalities that affect survival in this rare histiocytic entity. Methods To study the demographic characteristics, molecular and immunohistochemical signatures, therapeutic interventions, survival, and prognostic factors, we compiled a pooled database of 146 cases of HS. Kaplan-Meier survival curves were constructed. Cox proportional hazards model and Log-rank tests were used to assess the influence of demographic and clinicopathologic factors on overall survival (OS). Results A total of 146 patients with confirmed HS were identified. The median age was 52, with bimodal peaks between 14-28 and 56-70 years. There was a male preponderance with M:F of 1.3. Primary sites of involvement were CNS (21%), GI(16%), soft tissues (12%), H&N and bones (9% each), skin (8%), liver (7%), spleen (5%), lung (4%), and breast (1%). Lymphadenopathy and bone marrow (BM) were involved in 21% and 42%, respectively. Constitutional symptoms were present in 6%. The median size of the HS tumor was 4.45cm. The median OS of the whole group was 16 months. Age younger than 55 had better median OS (NR vs. 6 months, p=0.038). The primary site of involvement also impacted the median OS, where soft tissues and visceral disease had longer OS than those with CNS and spleno-lymphatic disease (60 vs. 7 vs. 6 months, p=0.03). Stage 1 disease had better median OS than stages 2-4 (p=0.06). Furthermore, unifocal had better median OS than multifocal/multicentric disease (60 vs. 9 months, p=0.007). The presence of inflammatory background positively impacted OS (p=0.01). Compared to no treatment, localized therapies such as surgery (S) and radiation therapy (RT), and systemic combination chemotherapy (CT) were statistically superior, with a median OS of 1, 204, and 21 months, respectively (p=0.003). With HS not amenable to complete resection, CT and CT+S were superior to RT+S (15 vs. 60 vs. 7 months, p=0.008). While BM involvement and size >10 cm were associated with worse OS, the latter did not reach statistical significance. There was no difference in median OS with respect to sex. Conclusion This study presents updated clinicopathologic data from a pooled cohort of patients with HS. It identifies age, the primary site of the disease, stage and extent of the disease, the inflammatory background status, and treatment approach as key determinants of OS. Citation Format: Dinesh Keerty, Philip A. Haddad. Histiocytic sarcoma descriptors and clinicopathologic determinants of survival: Analysis of a pooled database. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6749.

e23536 Background: Embryonal rhabdomyosarcoma (ERS) refers to malignant soft tissue tumors with phenotypical, histological features of primitive skeletal muscle. ERS commonly involves the head and neck region and genitourinary system. Genitourinary embryonal rhabdomyosarcoma (GUERS) is considered an entity similar to other ERS based on Intergroup Rhabdomyosarcoma Study Group (IRSG) with non-prostate GUERS considered low risk. This study seeks to define other high-risk subtypes in this population. Methods: To study the demographic and molecular characteristics, therapeutic interventions, survival, and prognostic factors, we compiled a pooled database of 137 cases of GUERS. Kaplan-Meier survival curves, Cox proportional-hazards model and Log-rank tests were used to assess the influence of demographic and clinicopathologic factors on overall survival (OS) and disease-free survival (DFS). Results: 137 patients with confirmed GUERS were identified: median age was 16 and F:M ratio of 1.6. Female reproductive organs (49%), renal and urinary tract (24%), male reproductive organs (23%), and abdomino-pelvis (4%) were involved. Lymph node involvement and metastasis occurred in 11% and 13%, respectively. Staging consisted of stage I (65%), stage II (15%), stage III (8%), and stage IV (12%). Rhabdomyosarcoma clinical groups were mostly IA (41%), IIIA (31%) and IV (13%). Risk groups consisted of low (71%), intermediate (17%), and high (13%). Median OS and DFS were 96 and 42 months, respectively. The primary site of involvement impacted OS, with urinary tract organ involvement having the best median OS, compared to female reproductive organs, male reproductive organs, and abdomino-pelvis involvement (p = 0.01). While primary pelvic disease (p = 0.03), prostate (p = 0.008), and lymph node involvement (p = 0.001) were associated with worse OS, cervix/vaginal involvement tended to have better OS (p = 0.06). Constitutional symptoms (p = 0.0007), obstruction (p = 0.047) and metastases (p = 0.02) were associated with worse OS. Clinical staging system (p = 0.0008), risk groupings (p = 0.06) correlated with OS, but not clinical groupings (p = 0.26). GUERS with vimentin+, CD99- and SMA+ had worse survival (only the latter was statistically significant). Compared to no treatment, RT, CT+/-RT, S+CT+RT were superior with mOS of 2, 6, NR, 96 months, respectively (p < 0.0001). Achieving CR had superior OS (p < 0.0001). OS was not impacted by age, sex, or extent of surgery. Conclusions: Genitourinary embryonal rhabdomyosarcoma is a distinct clinical entity with outcomes worse than other forms of ERS defined by the Clinical Groups of IRSG. Prostate, primary pelvic and obstructive symptoms have worse OS compared to bladder and cervical involvement and we propose their inclusion in the current Clinical Group. This study presents updated clinicopathologic data from a pooled cohort of patients with GUERS.

e20045 Background: Hepatoid adenocarcinoma of the lung (HAL) is a rare and aggressive subtype of thoracic cancer characterized by morphological similarities to hepatocellular carcinoma, including alpha-fetoprotein (AFP) production. Due to its rarity, there is a limited understanding of its clinical behavior and optimal management strategies. This exploratory analysis aims to evaluate an HAL database to identify demographic patterns, therapeutic approaches, and prognostic factors in this rare cancer. Methods: To study the demographic characteristics, molecular and immunohistochemical signatures, therapeutic interventions, prognostic factors, and survival, we compiled a pooled database of cases that satisfy the diagnostic criteria for HAL. Kaplan-Meier survival curves were constructed. Cox proportional hazards model and Log-rank tests were used to assess the influence of demographic and clinicopathologic factors on overall survival (OS). Results: A total of 104 patients with confirmed HAL were identified. The median age was 63, with a male preponderance (M:F 8). Eighty-seven percent were smokers. The median tumor size was 6cm, and the median AFP level was 5820 ng/ml, with 28% of the cases being non-secretors. The two most commonly involved primary sites were the right upper lobe (38%) and the left upper lobe (23%). Eleven percent presented with stage I, 15% with stage II, 33% with stage III, and 41% with stage IV. CNS metastases were diagnosed in 40%. ALK and EGFR mutations were present in 4% each, dMMR in 7%, KRAS mutations in 11%, and PD-L1>1% in 21%. The median OS and DFS of the cohort were 15 and 12 months, respectively. Ki67 of <50% was associated with better OS (p=0.0006). Early stages (I&II) had a superior median OS to advanced stages (NR vs. 12 months, p=0.0004). In the early stages, surgical resection (S) was associated with superior OS (p=0.02). In stage III, S, radiation (RT), and combined modalities (CM) were superior to chemotherapy (CT) alone (p=0.06). In stage IV, compared to no treatment, S, RT, CT, and CM were statistically superior with a median OS of 0.5, 2, 3, 12, and NR months, respectively (p<0.0001). Incorporating immune checkpoint inhibitors into the treatment of advanced HAL was associated with better median OS at 36 months (p=0.07). While Size>10cm, AFP non-secretors, and CNS metastases had numerically worse OS, they did not reach statistical significance. Age, sex, primary site, and smoking status did not impact OS. Conclusions: This pooled analysis highlights tumor stage, Ki67 index, and treatment modality as key prognostic factors. Surgical resection and combined treatment strategies significantly improve survival in early and advanced disease, respectively, while immune checkpoint inhibitors show promise in advanced stages. These findings underscore the need for tailored therapeutic approaches and further research to optimize outcomes for this rare malignancy.

e23537 Background: Embryonal rhabdomyosarcoma (ERS) is a soft tissue sarcoma of skeletal muscle with mesenchymal precursor cells that involve the genitourinary system or head and neck. Currently, head and neck embryonal rhabdomyosarcoma (HNERS) is considered a similar entity to other ERS subtypes by the Intergroup Rhabdomyosarcoma Study Group (IRSG), with only parameningeal disease being considered as high risk. We seek to identify other higher risk phenotypes in this population. Methods: To study the demographic, molecular and IHC characteristics, therapeutic interventions, survival, and prognostic factors, we compiled a pooled database of 101 cases of HNERS. Kaplan-Meier survival curves, Cox proportional-hazards model and Log-rank tests were used to assess the influence of demographic and clinicopathologic factors on overall survival (OS). Results: 101 patients with confirmed HNERS were identified: median age of 6.5 years, male predominance with M:F ratio of 1.7. While R0 was achieved in 44%, surgical R1 and R2 were feasible in 13% and 44% of the cases. HNERS involved the following anatomic sites: Parameningeal (49%), Skull (40%), Maxilla (39%), Nasopharynx (34%), Ears (25%), Oropharynx (17%), Nervous system (16%), Larynx (14%), Mandible (12%), Internal Jugular (7%), Orbit and Carotids (6% each), Tongue (3%), and thyroid (2%). Lymph nodes, and bone marrow were involved in 11% and 2%, respectively. Metastases occurred in 4%. The stage distribution consisted of stage I (41%), stage II (34%), stage III (19%), and stage IV (6%). Clinical groups comprised: IA(23%), IB(4%), IIA(8%), IIB(3%), IIIA(45%), IIIB(12%), and IVA(4%). Risk groups consisted of low (53%), intermediate (41%), and high (6%). The cohort’s median DFS was 240 months whereas the median OS was not reached. OS was negatively affected by parameningeal (p = 0.01), nasopharyngeal (p = 0.02), ear (p = 0.02), nerve (p = 0.0001), bone (p = 0.002), and LN (p = 0.0004) involvement. The presence of metastases was associated with worse OS (p = 0.0001). The IRSG staging system (p < 0.0001), the risk groupings (p = 0.0001), and the clinical groupings (p = 0.06) correlated with OS, though the latter did not reach statistical significance. Compared to no treatment, localized therapies such as surgery and radiation therapy, and combination chemotherapy had statistically significant improvement in OS (p = 0.027). Achieving CR was associated with superior OS (p < 0.0001). OS wasn't impacted by age, sex, extent of surgery, IHC, BM involvement or other head and neck anatomic site involvement. Conclusions: Embryonal Rhabdomyosarcoma of the Head and Neck is a distinct clinical subtype of ERS not fully defined by IRSG clinical groups when compared to other types of embryonal rhabdomyosarcoma. Parameningeal, nasopharyngeal, ear involvement had poor OS and should be considered as a clinical grouping. This study presents updated data from a pooled cohort of patients with HNERS.

Acute Megakaryocytic Leukemia Clinicopathologic Determinants of Survival: Analysis of a Pooled Database