Phase II trial of a novel chemotherapy regimen CVEP (cyclophosphamide, vinblastine, etoposide and prednisolone) for acquired immunodeficiency syndrome (AIDS)-associated lymphomas.

Management of acquired immunodeficiency syndrome (AIDS)-related diffuse large B-cell (DLBCL) and plasmablastic lymphomas (PBL) poses significant challenges. The evidence supports use of dose-adjusted EPOCH (etoposide, prednisone, vincristine, cyclophosphamide and doxorubicin) with or without rituximab as first-line therapy. The need for central venous access, growth factors and significant toxicities limits its use in resource-constrained settings. To address these challenges, we have developed a novel regimen, CVEP (cyclophosphamide, vinblastine, etoposide, and prednisolone) based on the pharmacodynamic principles of dose-adjusted EPOCH. This single-centre phase II study evaluated the efficacy and safety of CVEP regimen in patients with de novo systemic AIDS-related DLBCL and PBL. The primary objective was complete response (CR) rates as assessed by positron emission tomography-computed tomography. The secondary objectives were incidence of Grade 3/4 toxicities, toxicities requiring hospitalisation, and disease-free survival. From May 2011 to February 2017, 42 patients were enrolled. At the end of therapy the CR rates were 69% (29/42) in the intention-to-treat population and 80.5% (29/36) in evaluable patients. At a median follow-up of 69 months, the 5-year disease-free survival was 65.3%. Out of 217 cycles administered, febrile neutropenia occurred in 19.3% and hospitalisation was required in 18.3% of cycles. There were two treatment-related deaths. The CVEP regimen is an active and safe regimen for AIDS-related DLBCL and PBL.

Human Immunodeficiency Virus Associated Plasmablastic Lymphoma Involving Bones and Peritoneum in a 4-Year-old Child.

In children with underlying Human Immunodeficiency virus infection and AIDS, hematolymphoid cancers, especially non-hodgkin lymphomas are common. Plasmablastic lymphoma is one such non-hodgkin lymphomas arising from the head and neck region (especially sinonasal) but extremely rare. We describe the clinical course in a 4-year-old boy who presented with a solitary bony swelling of the right knee joint, which on diagnostic work-up turned out to be plasmablastic lymphoma. With combination chemotherapy, intrathecal chemotherapy, and early institution ofHighly active anti-retroviral therapy, the child continues to be in remission.

Phyllodes Tumor as a Secondary Neoplasm in Survivors of Childhood Cancer: A Tertiary Care Cancer Centre Experience.

Secondary neoplasms (SNs) are being increasingly identified in long-term survivors of childhood cancer. Phyllodes tumor (PT) form a distinctly uncommon SN. We report a series of 6 female childhood cancer survivors who developed PT as SN. The median age at primary diagnosis was 13 years. Their primary tumors were bone sarcoma (4) and acute leukemia (2), and all were treated with chemotherapy, predominantly with alkylating agents and/or anthracyclines. None had received direct radiotherapy to the chest wall. Subsequently, PT were detected after a median interval of 7.5 years, with 2 patients developing bilateral and malignant PT. The series highlights a rare SN in childhood cancer survivors, underscoring the importance of regular long-term follow-up.

Clinicopathologic Profile and Treatment Outcomes of Children With Diffuse Large B-cell Lymphomas: Experience From a Tertiary Cancer Center in India.

Clinicopathologic profile and outcome of 15 children (15 years or above) with diffuse large B-cell lymphoma treated with MCP-842 protocol are reported. Eleven of 15 presented with advanced (stage-III/IV) disease. Post-2 cycles of chemotherapy, complete metabolic and morphologic response was documented in 10 (66%) and rest 5 (33%) with partial response achieved complete metabolic remission by end of treatment. At a median follow-up of 44 months (range: 16 to 79 mo), the 3-year event-free survival and overall-survival were 77.1%±11.7% and 85.7%±9.4%, respectively. Though majority of our patients had advanced disease, outcome on MCP-842 protocol was satisfactory.

Clinical outcomes and prognostic factors in children with B-cell lymphoblastic lymphoma (LBL) treated according to on modified BFM-90 protocol: Experience from a Tertiary cancer care center in India.

Pediatric B-cell lymphoblastic lymphoma (LBL) is a rare entity, and appropriate treatment for pediatric B-cell LBL is not well defined. While intensive ALL type regimens achieve long term survival of 90% across Western co-operative group trials, published data from Asian studies on long term outcomes are scarce. We retrospectively analyzed the data of pediatric B-cell LBL patients treated between January 2010 and December 2017 on a uniform protocol (modified BFM 90). Kaplan-Meier method was used to estimate the survival and Cox regression models to identify prognostic factors. Of 21 patients who received treatment on the modified BFM-90 protocol, 17(81%) were alive in remission, 3(14%) had relapse, and 1(4%) had treatment-related mortality (TRM) while in remission. Two of 3 relapsed patients subsequently expired. With a median follow-up of 66 months (range 6-114), 5-year event free survival (EFS) and overall survival (OS) were 80% (95% CI:71-89%) and 91% (95% CI:85-97%), respectively. While delayed presentation from symptom onset (p=0.030), and partial response at early (D35) interim assessment (p=0.025) had inferior EFS, patients with elevated baseline LDH had a worse OS (p=0.037). Outcomes of pediatric B-cell LBL patients treated on a modified BFM-90 protocol at a single center in India were excellent. In our study, higher disease burden manifested by elevated baseline LDH and delayed presentation (≥3months) and partial interim response portend poorer survival.Supplemental data for this article is available online at https://doi.org/10.1080/08880018.2021.2005725.

Noncanonical pS727 post translational modification dictates major STAT3 activation and downstream functions in breast cancer.

Activation of STAT3 via Y705-phosphorylation is well documented across multiple cancer types and thus forms the basis of canonical pathway to judge STAT3 activation. Recently, important roles of two other post translational modification (PTM) sites, i.e. S727-phosphorylation and K685-acetylation, leading to STAT3 activation are reported. However, their critical mode of function in controlling STAT3 dimerization and signaling, independent of canonical activation remains elusive. Therefore, to understand the functional relevance of each STAT3 PTMs in breast cancer (BC), cell models are developed by stable overexpression of PTM-site specific point mutants, i.e. Y705F, S727A or K685R, in a 3'UTR-STAT3 knockdown BC cell background. Results using this model system reveal novel findings showing that phosphorylation at S727 can lead to STAT3 activation independent of phosphoY705. We also demonstrate that loss of pS727 or K685ac significantly affects functional phenotypes such as cell survival and proliferation as well as downstream transcriptional activity (Twist 1, Socs3, c-Myc, Bcl-1 and Mcl-1) of STAT3. Thereafter, by utilizing a BRET biosensor for measuring STAT3 phosphorylation in live cells, a crucial role of pS727 in dictating STAT3 activation and homodimerization formation is uncovered. Further by performing retrospective IHC analysis of total and phospho-forms of STAT3 in a cohort of 76 triple negative breast cancer (TNBC) patient samples, a significant dominant expression of phosphoS727 over phosphoY705 PTM (p < 0.001) is found in STAT3 positive cases. We also focus on validating known STAT3 inhibitor molecules for their action against both pY705 and pS727 activation. This study for the first time demonstrates that an anti-helminth drug compound, Niclosamide, is capable of inactivating both phospho-PTM sites on STAT3 and exhibits excellent anticancer efficacy in preclinical TNBC tumour model.

Increased toxicities in children with Burkitt lymphoma treated with rituximab: Experience from a tertiary cancer center in India.

BACKGROUND: Even though rituximab has emerged as standard of care for the management of high-risk pediatric Burkitt lymphoma (BL), its safety in children from the low-middle-income countries (LMICs) remains to be proven. We herein report our experience of using rituximab in children with BL. METHODS: All patients diagnosed with BL between January 2015 and December 2017 were treated in a risk-stratified manner with either the modified MCP-842 or modified LMB protocol. Patients with poor response to MCP-842 were switched to the LMB-salvage regimen. In addition, rituximab was given to selected high-risk patients. RESULT: Forty-two (49.4%) of 85 patients with BL received rituximab. The incidence of febrile neutropenia (90.5% vs 67.4%; P = 0.02), pneumonia (38.1% vs 11.6%; P = 0.005), intensive care unit admissions (54.5% vs 17.6%; P = 0.002), and toxic deaths (26.2% vs 9.3%; P = 0.04) was higher among BL patients who received rituximab. Pneumonia was fatal in 11 of 16 (69%) patients who received rituximab. On multivariate analysis, rituximab continued to be significantly associated with toxic deaths ( OR: 11.45 [95% CI: 1.87-70.07; P = 0.008]). The addition of rituximab to intensive chemotherapy resulted in an inferior one-year event-free survival (49.4% ± 8.1% vs 79.3% ± 6.5%; P = 0.025) and one-year overall survival (63.1% ± 8.5% vs 91.8% ± 4.5%; P = 0.007) with no improvement in one-year relapse-free survival (78.3% ± 7.3% vs 83.9% ± 6.0%; P = 0.817). CONCLUSION: Rituximab was associated with increased toxicities and toxic deaths in our patients. The potential immunomodulatory effect of rituximab and increased susceptibility to infections in patients from LMICs have to be carefully considered while choosing this drug in the treatment of BL in resource-constrained settings.

Clinical profile and outcome of classical Hodgkin lymphoma treated with a risk-adapted approach in a tertiary cancer center in India.

BACKGROUND: Classical Hodgkin lymphoma (cHL) has excellent survival rates, but late effects are an issue and dictate modern approaches. We analyzed the clinical profile and outcome of cHL treated on a risk-adapted approach aimed at reducing late effects while improving historical outcomes at our center. PROCEDURE: Children (≤15 years) consecutively treated for cHL from January 2013 through December 2016 were retrospectively analyzed. 18 FDG-PET-CT-based staging and response assessment was done after two cycles for early response (ERA) and end of chemotherapy (late-response assessment [LRA]) if not in complete response (CR; Deauville < 4) at ERA. Stages IA/IB/IIA were low risk (LR) and received two cycles of ABVD (adriamycin/bleomycin/vinblastine/dacarbazine). Stages IAX/IBX/IIAX/IIB/IIIA were intermediate risk (IR), and stages IIBE/IIBX/IIIAE/IIIAX/IIIB/IVA/IVB were high risk (HR). Both received two cycles of OEPA (oncocristine/etoposide/prednisolone/adriamycin). Those in ERA-CR received two cycles of ABVD if LR, and two and four cycles of COPDac (cyclophosphamide/oncocristine/prednisolone/dacarbazine), respectively, for IR and HR. Involved-field radiotherapy (IFRT) was given to bulky sites and ERA < CR. Those at LRA < CR (Deauville < 3) or progression at any stage received salvage regimens. RESULTS: In the study period, 126 patients were identified who received the above protocol. There were 12 LR, and 114 advanced staged Hodgkin lymphoma (AHL) (18, IR; 96, HR) of which 91 (79.8%) had bulky sites. Eight (66.6%) LR and 93 (83%) AHL patients achieved ERA-CRs. IFRT was given to 4 (33.3%) LR patients with ERA < CR, and 92 (80.7%) of AHL (91 bulky sites; 1 ERA < CR). At a median follow-up of 31 months (range, 17-62), three-year event-free survival (EFS) and overall survival (OS) were both 100% for LR, and 94.4% (95% CI, 66.0%-99.2%) for IR, whereas for HR it was 90.3% (95% CI, 82.2%-94.8%) and 92.6% (95% CI, 85.2%-96.4%), respectively. CONCLUSIONS: Children with HL have favorable outcomes with manageable toxicities when treated on a risk-stratified and adapted approach. A high proportion of AHL have bulky disease necessitating IFRT, a concern that will have to be factored in future strategies.

Triple Negative Breast Cancer: Expression of Folate Receptor Alpha in Indian population.

Folate Receptor Alpha (FRA) is a membrane protein expressed on the apical surface of epithelial cells. Its expression in increased in certain tumors, where it can serve as a target for therapy. Triple Negative Breast Carcinoma (TNBC) are a heterogeneous group of tumors, with limited therapy options and poor prognosis. We aimed to study the expression of FRA in TNBC. Tissue microarrays were prepared from archived paraffin blocks of 300 TNBC resection specimens. Staining for FRA immunohistochemistry was carried out using the clone 26B3.F2. Clinical and pathologic details of the patients were obtained from the electronic medical records. Chi square test was performed for correlation of clinicopathological features with FRA expression. Kaplan Meir and Cox Regression analysis were carried out to study the Disease Free Survival (DFS) and Overall Survival (OS). FRA showed positivity in 43% (129/300) of TNBCs in our study. In univariate analysis, TNBC expressing FRA had a significantly better OS compared to FRA negative tumors (p - 0.035). Also, FRA positive tumors showed a trend towards longer DFS, though this was not statistically significant. In multivariate analysis however, FRA expression did not emerge as a significant factor. To conclude, TNBCs in our study showed FRA expression and though this did not emerge as an important prognostic factor, it can represent a therapeutic target for future clinical trials.

Unfavorable presentation but comparable outcome: Presentation and outcome of children with nodular lymphocyte predominant Hodgkin lymphoma from India.

BACKGROUND: Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is an uncommon subtype of Hodgkin lymphoma (HL) with few published studies in children, entirely from North America and Europe. We analyzed clinical features and treatment outcome of pediatric NLPHL. PROCEDURE: Children less than 18 years of age diagnosed after histopathology review to have NLPHL between June 1998 and August 2016 were retrospectively analyzed. Descriptive details of clinical presentation and treatment were collected, and outcomes analyzed using Kaplan-Meier survival analysis. RESULTS: Of the 42 patients with a confirmed diagnosis of NLPHL during this period, there was complete information on 35. Median age was 11 years (range 6-16 years), male:female ratio was 4.8:1, there were 15, 11, 6, and 3 patients with Stage I, Stage II, Stage III, and Stage IV disease, respectively. Six patients had B symptoms, 10 had bulky disease, and 3 had bone marrow as well as extranodal involvement. Histology was typical NLPHL in 23 and variant in 12. Twenty-nine received chemotherapy, 10 with additional radiation, 3 patients with early stage disease received only radiotherapy and three others underwent complete node resection alone. Median follow-up was 55 months (range 7-165 months), 5 year event-free survival (EFS) was 83.3%, and overall survival 97.1%. Variant NLPHL histology was associated with higher incidence of unfavorable presentation and lower EFS. CONCLUSIONS: NLPHL in India has an excellent outcome, despite a higher incidence of unfavorable presentations such as advanced stage disease, B symptoms, and bulky disease. Variant histology is an adverse prognostic factor.

Evidence for the association of Epstein-Barr Virus in breast cancer in Indian patients using in-situ hybridization technique.

Epstein-Barr Virus (EBV) is etiologically linked to Burkitt lymphoma (BL), nasopharyngeal carcinoma, post-transplant lymphomas, Hodgkin disease, and possibly other tumors. However, the association of oncogenic EBV with breast carcinoma (BC) is still controversial and a matter of debate. We aimed to study the presence of EBV genome in BC cases in Indian patients and its association with the clinicopathological features. The formalin fixed paraffin embedded tissues from 83 women with primary invasive BC were studied for the presence of EBV by in-situ hybridization (ISH) technique for Epstein-Barr Virus Encoded RNA (EBER) with appropriate controls. Correlation of EBER-ISH positivity with clinicopathological features was performed using Fisher exact test and P<.05 was considered as significant. Eighty-three BC cases were comprised of 47 (56.5%) triple negative breast cancers (TNBC), 17 (20.5%) hormone positive and 19 (22.9%) HER2 positive cases. Of 83 cases, 25 cases (30.1%) were positive for EBER-ISH test. The positivity was restricted to the tumor cells and not seen in the surrounding breast lobules. EBER-ISH positivity was statistically associated with larger tumor size (52.6% in >5 cm tumors vs 19.3% in ≤5 cm; P=.014) and with TNBCs (21/47 [44.7%] in TNBCs vs 4/36 [11.1%] in non-TNBCs; P=.001). A possible causal association of EBV in BC cases in Indian patients is suggested by high frequency of EBER-ISH positivity noted in our study. This might have therapeutic significance because of the possible role of EBV specific cytotoxic T cells in targeting EBV associated tumor cells and can be considered as a potential targeted therapy. To the best of our knowledge, this is the first study from India to address this issue using EBER-ISH technique.

Improving accuracy of breast cancer biomarker testing in India.

There is a global mandate even in countries with low resources to improve the accuracy of testing biomarkers in breast cancer viz. oestrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2neu) given their critical impact in the management of patients. The steps taken include compulsory participation in an external quality assurance (EQA) programme, centralized testing, and regular performance audits for laboratories. This review addresses the status of ER/PR and HER2neu testing in India and possible reasons for the delay in development of guidelines and mandate for testing in the country. The chief cause of erroneous ER and PR testing in India continues to be easily correctable issues such as fixation and antigen retrieval, while for HER2neu testing, it is the use of low-cost non-validated antibodies and interpretative errors. These deficiencies can however, be rectified by (i) distributing the accountability and responsibility to surgeons and oncologist, (ii) certification of centres for testing in oncology, and (iii) initiation of a national EQA system (EQAS) programme that will help with economical solutions and identifying the centres of excellence and instill a system for reprimand of poorly performing laboratories.

Observation on frequency & clinico-pathological significance of various cytogenetic risk groups in multiple myeloma: an experience from India.

BACKGROUND & OBJECTIVES: Multiple myeloma (MM) is a plasma cell malignancy characterized by cytogenetic heterogeneity. In comparison with conventional karyotyping, fluorescence in situ hybridization (FISH) can efficiently detect various genetic changes in non-cycling plasma cells in 50-90 per cent of MM cases. The present study was undertaken in MM patients to evaluate the frequency and clinico-pathological significance of various cytogenetic abnormalities in the Indian population. METHODS: Interphase FISH was applied on purified plasma cells of 475 patients with MM using specific probes. Interphase FISH for 1q gain/1q amplification was performed on a separate group of 250 newly diagnosed MM patients. RESULTS: Low frequency of Δ13 [-13/del(13q)] (32%) and t(11;14) (5%) was observed in our 475 patients probably due to ethnic diversity. Clustering of Δ13, del(17)(p13.1) and IgH translocations in non-hyperdiploidy confirmed prognostic significance of ploidy in MM. t(4;14) and del(17)(p13.1) were high-risk groups due to correlation with high serum ß2-microglobulin, increased plasma cells and advanced disease. Hyperdiploidy and t(14;16) were associated with higher age group. In a separate group of 250 patients, 1q amplification [amp(1q)] in combination with Δ13 and/or del(17p) with t(4;14) revealed association with adverse clinico-laboratory features, which confirmed progressive role of amp(1q) with adverse prognostic impact. Amp(1q) was clustered at 1q21 and 1q25 loci. INTERPRETATION & CONCLUSIONS: Based on our findings, it appears that comprehensive analysis of various cytogenetic aberrations by interphase FISH is a powerful strategy being adapted for risk stratification of MM.

Lymphoepithelioma-like carcinoma of breast-evaluation for Epstein-Barr virus-encoded RNA, human papillomavirus, and markers of basal cell differentiation.

This is a largest series of 5 cases of lymphoepithelioma-like carcinoma (LEC) of the breast attempting to look at the expression of basal cytokeratins (CKs), human papillomavirus, and Epstein-Barr virus-encoded RNAs in these tumors. Five cases were selected after stringent evaluation of all breast carcinomas showing dense lymphoid infiltration. Histologically, all these tumors showed the typical histology except 1 tumor that showed an unusual granulomatous response. All tumors were negative for estrogen and progesterone receptors and HER2 (triple negative). Three tumors expressed CK5/6 and high-molecular-weight CK, whereas only the case with nodal metastasis expressed CK14. Analysis for in situ hybridization for Epstein-Barr virus-encoded RNAs and human papillomavirus DNA on paraffin-processed tissues was negative in all tumors. All of these patients received adjuvant therapy. One patient with tumor expressing basal marker, CK5/6, had contralateral breast malignancy after a duration of 53 months of treatment completion. The rest were disease free with the follow-up period in the range of 6 to 105 months. The lymphoepithelioma-like carcinoma of breast expressed basal CK profile that is more CK5/6 positive than CK14. Analysis of basal markers within these tumors may help in refining the definition of these tumors and in classifying them into prognostically relevant groups.

A retrospective study of correlation of morphologic patterns, MIB1 proliferation index, and survival analysis in 134 cases of plasmacytoma.

Plasmacytoma classified into solitary plasmacytoma of bone (SPB) and extramedullary plasmacytoma (EMP) is characterized by infiltrate of plasma cells of diverse maturity and by their monoclonal immunoglobulin products. Both SPB and EMP represent different groups of neoplasm in terms of location, tumor progression, and overall survival rate. There is a need for features that indicate likelihood of myeloma in patients with plasmacytoma without other manifestations. This study was an attempt to study the morphologic patterns of plasmacytoma (SPB and EMP), MIB1 proliferation index, and correlation of these with clinicopathologic features and survival of the patients. The study group comprised of 134 cases of plasmacytoma (88 SPB and 46 EMP) over duration of 8 years and were graded as per Bartl's histologic grading system. Commonest site was vertebral body in SPB (36%) and upper aerodigestive tract in EMP (48%). On serum electrophoresis, overall M band was detected in 41% cases. Both SPB and EMP on histology revealed similar morphologic features. MIB1 proliferation index ranged from less than 1% to 80%. It was slightly higher in EMP in comparison with SPB (P value = .002). Seventy percent of cases, which progressed to multiple myeloma (MM) showed MIB1 labeling index more than 10%; however, it was not statistically significant in predicting the disease progression. With the median follow-up of 19 months (range, 1-99 months), 10 SPB had disease progression of which 7 converted to MM, and 3 developed EMP, with a median interval of 21 months (range, 8-75 months) for the development of MM and 3 months (range, 3-9 months) for the progression to EMP. Five-year survival for EMP varied by site, with poorest survival in brain/central nervous system EMP as compared with EMP at other sites. To conclude, grade and MIB1 proliferation index help in predicting aggressive course in plasmacytoma.

Validation of Dual-Color Dual In Situ Hybridization for HER2/neu Gene in Breast Cancer.

CONTEXT.­: Human epidermal growth factor (HER2/neu) gene amplification, a poor prognostic factor in invasive breast cancer, has shown substantial utility as a predictive marker, with significantly improved survival following anti-HER2 therapies like trastuzumab. Dual-color dual in situ hybridization (D-DISH), a recently introduced fully automated assay for HER2/neu evaluation on light microscopy, has several advantages over fluorescence in situ hybridization (FISH). OBJECTIVE.­: To standardize and validate the D-DISH assay using FISH as the gold standard and assess interobserver reproducibility in interpreting the D-DISH assay. DESIGN.­: D-DISH was performed using the latest HER2 Dual ISH DNA Probe Cocktail assay (Ventana Medical Systems Inc, Tucson, Arizona) in 148 cases of invasive breast cancer. The same block was used for performing immunohistochemistry by Ventana PATHWAY anti-HER2/neu (4B5) antibody and FISH assay by ZytoLight SPEC ERBB2/CEN17 Dual Color Probe. D-DISH was separately interpreted by 4 pathologists blinded to FISH results. RESULTS.­: Concordance of 98.65% and a Cohen κ value of 0.97 were observed between FISH and D-DISH. Intraclass correlation coefficient (0.93-0.97) and κ values (0.98-1.0) for interobserver reproducibility showed almost perfect agreement by D-DISH. Interobserver reproducibility was also evaluated for genomic heterogeneity, HER2 group categorization, and polysomy (κ values 0.42-0.74, 0.89-0.93, and 0.98-1.0, respectively). CONCLUSIONS.­: We successfully validated the latest version of D-DISH assay as a substitute for FISH in predicting HER2 gene status with significant interobserver reproducibility, concluding that this D-DISH assay may be introduced in routine diagnostic services as a reflex test to ascertain HER2 gene status.

Predictive Value of Preoperative ICG-R15 Testing in Post-hepatectomy Liver Failure Following Major Liver Resection: Indian Experience.

Surgical resection stands as the preeminent therapeutic approach for both primary hepatocellular carcinoma and metastatic liver malignancies. Its efficacy is contingent upon the attainment of a comprehensive excision while ensuring a sufficient future liver remnant (FLR). However, post-hepatectomy liver failure (PHLF) remains a significant challenge, particularly in patients with preexisting liver disease. The present study aims to investigate the predictive value of the preoperative indocyanine green retention test at 15 min (ICG-R15) in identifying patients at risk of PHLF following major liver resection. This retrospective review focused on patients who underwent the ICG-R15 test before major liver resection between August 2021 and January 2023. All patients underwent standard preoperative evaluation and staging. Patients with primary or metastatic liver cancer planned for major resection and undergoing ICG-R15 were included in the study. Patients with elevated serum bilirubin (> 3 mg/dl) and those not undergoing liver resection or minor liver resection (< 3 segments) were excluded from the study. PHLF was defined by the International Study Group of Liver Surgery (ISGLS) criteria. Follow-up was performed to identify 90-day morbidity. Using univariate and multivariate logistic regression analyses, we confirmed independent risk parameters that predicted postoperative major complications and severe PHLF. The study included 72 patients who underwent preoperative ICG-R15 testing prior to major liver resection. PHLF occurred in 28 patients (38.9%), with 24 patients (33.3%) classified as severity score B and 3 patients (4.16%) had severity score C. Univariate analysis revealed future liver remnant (FLR), ICG-R15, and blood transfusion as predictors of PHLF. Multivariate analysis confirmed FLR (p = 0.019) and ICG-R15 (p = 0.032) as significant predictors. Receiver operating characteristic curve analysis yielded an area under the curve of 0.642 for ICG-R15 in predicting PHLF. An optimal cut-point of 7.5 was determined. Our study highlights the importance of preoperative risk assessment of liver function evaluation using the ICG-R15 test, to predict the risk of PHLF following liver resection. Implementing appropriate interventions, especially in patients with borderline FLR, can improve surgical outcomes and enhance patient safety. Further research and prospective studies are essential to refine risk prediction models and improve rates of PHLF after liver resections.

A Retrospective Cohort Study to Evaluate the Outcomes of HIV-Associated High-Grade B-Cell Non-Hodgkin Lymphoma (NHL) Treated with Dose Adjusted EPOCH (+/-R) Regimen.

High-grade B-cell NHL's are more common in seropositive patients. They are biologically different from their seronegative counterparts. We report our analysis on our cohort of patients who were treated with DA-EPOCH(+/-R). We retrospectively analyzed treatment-naïve HIV-associated High-grade B-cell NHL patients (aged ≥ 18) treated with DA-EPOCH(+/-R) regimen from 2011 to 2015. Descriptive statistics were summarized with median and range; survival outcomes were analyzed with Kaplan-Meier method. The cohort comprised of 40 patients [DLBCL(19), Burkitt's Lymphoma(16), High-grade B-Cell Lymphoma-Unclassifiable(09), and Plasmablastic Lymphoma(01)] and the median CD4 + T cell count was 202/mm3. CNS prophylaxis was administered with intrathecal methotrexate to 90% of patients. With a median follow-up of 72 months, an estimated 5-year OS was 82.5%, and 5-PFS was 77.5%. There were 9 deaths, and 9 patients had progression. At least 4 cycles of chemotherapy were administered to 35 (93%) patients, with 28 (70%) receiving 6 cycles. Grade 3-4 toxicities were seen in 33 (83%) patients- febrile neutropenia (65%) being the most common followed by mucositis (25%) and peripheral neuropathy (13%). There was no difference in survival based on IPI, CD 4 + T cell count, CDI, or duration of HIV. DA-EPOCH(+/-R) is a highly effective regimen in seropositive high-grade B-cell lymphoma, even in the presence of adverse features. Supplementary Information: The online version contains supplementary material available at 10.1007/s12288-023-01652-3.