Initial Experiences in Adolescents and Young Adults with T-Cell Acute Lymphoblastic Leukemia/Lymphoma Treated with the Modified BFM 2002 Protocol in a Resource-Constrained Setting.

Prutha Jinwala T-cell acute lymphoblastic leukemia/lymphoblastic lymphoma (T-ALL/LBL) in adolescents and young adults (AYAs) is a clinically aggressive malignancy and life-threatening at diagnosis. Intensive chemotherapy protocols, inspired by the Berlin-Frankfurt-Münster (BFM) regimen, along with central nervous system (CNS) prophylaxis, have achieved a 75 to 85% 5-year disease-free survival rate. However, in cases of marrow and CNS relapses, second-line chemotherapy is usually ineffective. This study aimed to assess the safety and efficacy of the BFM 2002 protocol and to correlate clinical profiles and prognostic factors with survival outcomes in AYA T-ALL/LBL patients. We retrospectively analyzed data from T-ALL/LBL patients treated at the Department of Medical Oncology, Sri Aurobindo Institute of Medical Sciences (SAIMS), Indore, between 2018 and 2021. Twenty-one patients aged 15 to 29 years were studied for their clinical course and laboratory parameters over 36 months. Diagnosis and risk stratification were performed following the guidelines of the BFM 2002 protocol. All patients received treatment and monitoring according to this pediatric-inspired protocol. The median age of the patients was 17 years (range: 15-28 years). Eleven patients presented with mediastinal lymph node enlargement, 10% exhibited CNS involvement, and none had testicular involvement. Eleven patients had marrow blasts greater than 25%, indicative of acute lymphoblastic leukemia. All 21 patients were treated according to the intensive modified BFM 2002 protocol and achieved morphological remission after a median follow-up of 24 months (range: 18-36 months). Seventeen patients achieved minimal residual disease (MRD) negativity post-induction. MRD at day 33 showed a significant association with the probability of disease relapse ( p = 0.0015). There were five deaths (24%), one due to toxicity and four due to relapse. The study recorded an 18-month overall survival of 76%. These results were achieved despite financial constraints. Data were entered into a spreadsheet, and statistical analysis was performed using IBM SPSS version 23. Continuous data are presented as ranges and medians, while categorical variables are shown as percentages and numbers. A chi-squared test for association, with a significance level set at p < 0.05, was conducted as indicated. AYA T-ALL/LBL requires intensive treatment regimens. With biological characterization of LBL/ALL and close therapy monitoring, encouraging outcomes can be achieved even in resource-limited settings.

Metastatic Renal Cell Carcinoma: An Enigmatic Nasal Mass.

Metastatic Renal Cell Carcinoma rarely presents in head and neck and is even rarer in the sinonasal region. However, a sinonasal metastatic mass is usually of RCC origin. These metastases may present prior to the renal symptoms or may appear after primary treatment. Report a 60-year lady with epistaxis due to metastatic RCC. Calculate total published cases of sino-nasal metastasis of RCC. Classify according to sequence of primary and metastatic presentation. A computer aided search of PubMed and Google scholar databases was done using pertinent combinations of the keywords "renal cell carcinoma", "nose and paranasal sinus", "metastasis", "delayed metastasis" and "unusual presentation", revealing 1350 articles. 38 relevant articles were included in the review. Our case presented with epistaxis 3 years after primary RCC. She had a vascular left sided nasal mass which was excised enblock. Immunohistochemistry confirmed metastatic RCC. She is on oral chemotherapy and asymptomatic 1 year post excision. Literature search revealed 116 such cases. 19 patients presented within 10 years of RCC while 7 more were delayed metastasis. 17 cases presented primarily with nasal symptoms with subsequent incidental renal mass. Chronology of presentation was unavailable in the rest 73 cases. We recommend to consider the diagnosis of sinonasal metastatic RCC in a patient presenting with epistaxis or nasal mass, particularly with a past history of RCC. Also, any person with known diagnosis of RCC should undergo regular ENT examination for early diagnosis of sinonasal metastasis.

Green-synthesized, pH-stable and biocompatible carbon nanosensor for Fe3+: An experimental and computational study.

Brightly fluorescent Carbon Dots (CDs) were synthesized by green hydrothermal method using commonly available biomass (Aloe vera) as carbon precursor. Their physiochemical and optical characterization was done by standard microscopic and spectroscopic techniques. Photophysical features of their aqueous dispersion were investigated in detail. The influence of wide pH range (2-12), high ionic load (2M) and temperature on their photoluminescence behavior was investigated. Their in-vitro cytotoxicity examination was conducted on Human Cervical Cancer Cells (HeLa) using MTT assay. Testing of their ion-recognition property for common metal ions was done in aqueous medium. These CDs exhibited preferential interaction with Fe3+ over other tested metal ions, without any functionalization. Interaction between CDs and Fe3+ was analyzed in the light of Density Functional Theory (DFT). The work demonstrates that these CDs are acting as nanoprobe for Fe3+ and sensing it at ultra-trace level (5 nM).

Recent Advances in the Discovery of Antiviral Metabolites from Fungi.

As the world manages the impact of a global pandemic caused by COVID-19, the discovery of new antiviral agents has become way more relevant and urgent. Viruses are submicroscopic infectious agents that replicate inside the living cells of different organisms. These viruses use nucleic acids (both DNA and RNA) for further replication and maturity inside the cells. Some of the viruses responsible for various human and plant diseases belong to the classes of Picornaviridae, Retroviridae, Orthomyxoviridae, Flaviviridae, Pneumoviridae, Virgaviridae, and Hepadnaviridae, and their treatment options are limited or non-existent. The consistent reemergence and resistance development in the viral strains demand the discovery and development of new antiviral drugs possessing better efficacy. Bio-active compounds isolated from fungi can be the source of new compounds with enhanced potency and new mechanisms of action. Fungi are known to produce a diverse lot of secondary metabolites due to their existence in harsh and testing climates which are often inhabitable for many organisms. Because of these unique environments, fungi produce a variety of secondary metabolites of different chemical classes like alkaloids, quinones, furanone, pyrones, benzopyranoids, xanthones, terpenes, steroids, peptides, and many acyclic compounds. Fungal metabolites are known to display a wide range of bioactive attributes, i.e., anticancer, antibacterial, antifungal, and anti-Alzheimer's, along with antiviral properties. In this review article, we report over 300 antiviral compounds from fungal sources during the period of 2009 to 2019. The source of these compounds is marine and endophytic fungi and they are arranged based on their antiviral action against different viral families. These compounds offer promise for their use and development as future antiviral drugs.

The Impact of COVID-19 Pandemic on Cancer Care in a Tertiary Care Facility.

Background Coronavirus disease 2019 (COVID-19) pandemic had an overwhelming impact on health care worldwide. Cancer patients represent a subgroup that is vulnerable and is under high risk. It is, therefore, necessary to analyze factors that predict outcomes in these patients so that they can be triaged accordingly to mitigate the effects of COVID-19 on cancer management. To date, the impact of COVID-19 on cancer patients remain largely unknown. Methods Data of 291 cancer patients undergoing active treatment from March 23 to August 15, 2020 were retrospectively reviewed; the incidence, demographic and clinical characteristics, treatment, and outcomes of cancer patients infected by COVID-19 were included in the analysis. Discussion During the index period (March 23-August 15, 2020), 4,494 confirmed cases of COVID-19 were admitted at our institute. In the department of medical oncology out of 578 patients presented to outpatient department, 291 patients were admitted for active treatment. Considering the cancer patients, infection rate was 7.9% (23/291) and mortality 13% (3/23). Median age was 40 years and the majority of patients were male (60%). The most common cancer type was acute lymphoblastic leukemia presented at various stages of treatment. Twenty patients (86.9%) were discharged after full clinical recovery and negative real-time polymerase chain reaction on a nasopharyngeal swab. Anticancer treatment was modified according to the type of cancer under intensive surveillance. Conclusion Although mortality rate in COVID-19 cancer patients is elevated, our results support the feasibility and safety of continuing anticancer treatment during pandemic by endorsing consistent preventive measures, but however should be modified based on the type and prognosis of cancer.

Comprehensive characterization of 536 patient-derived xenograft models prioritizes candidatesfor targeted treatment.

Development of candidate cancer treatments is a resource-intensive process, with the research community continuing to investigate options beyond static genomic characterization. Toward this goal, we have established the genomic landscapes of 536 patient-derived xenograft (PDX) models across 25 cancer types, together with mutation, copy number, fusion, transcriptomic profiles, and NCI-MATCH arms. Compared with human tumors, PDXs typically have higher purity and fit to investigate dynamic driver events and molecular properties via multiple time points from same case PDXs. Here, we report on dynamic genomic landscapes and pharmacogenomic associations, including associations between activating oncogenic events and drugs, correlations between whole-genome duplications and subclone events, and the potential PDX models for NCI-MATCH trials. Lastly, we provide a web portal having comprehensive pan-cancer PDX genomic profiles and source code to facilitate identification of more druggable events and further insights into PDXs' recapitulation of human tumors.

Pathogenic Germline Variants in Cancer Susceptibility Genes in Children and Young Adults With Rhabdomyosarcoma.

Rhabdomyosarcoma (RMS) is the most common pediatric soft-tissue sarcoma and accounts for 3% of all pediatric cancer. In this study, we investigated germline sequence and structural variation in a broad set of genes in two large, independent RMS cohorts. MATERIALS AND METHODS: Genome sequencing of the discovery cohort (n = 273) and exome sequencing of the secondary cohort (n = 121) were conducted on germline DNA. Analyses were performed on 130 cancer susceptibility genes (CSG). Pathogenic or likely pathogenic (P/LP) variants were predicted using the American College of Medical Genetics and Genomics (ACMG) criteria. Structural variation and survival analyses were performed on the discovery cohort. RESULTS: We found that 6.6%-7.7% of patients with RMS harbored P/LP variants in dominant-acting CSG. An additional approximately 1% have structural variants (ATM, CDKN1C) in CSGs. CSG variants did not influence survival, although there was a significant correlation with an earlier age of tumor onset. There was a nonsignificant excess of P/LP variants in dominant inheritance genes in the patients with FOXO1 fusion-negative RMS patients versus the patients with FOXO1 fusion-positive RMS. We identified pathogenic germline variants in CSGs previously (TP53, NF1, DICER1, mismatch repair genes), rarely (BRCA2, CBL, CHEK2, SMARCA4), or never (FGFR4) reported in RMS. Numerous genes (TP53, BRCA2, mismatch repair) were on the ACMG Secondary Findings 2.0 list. CONCLUSION: In two cohorts of patients with RMS, we identified pathogenic germline variants for which gene-specific therapies and surveillance guidelines may be beneficial. In families with a proband with an RMS-risk P/LP variant, genetic counseling and cascade testing should be considered, especially for ACMG Secondary Findings genes and/or with gene-specific surveillance guidelines.

Genomic Classification and Clinical Outcome in Rhabdomyosarcoma: A Report From an International Consortium.

PURPOSE: Rhabdomyosarcoma is the most common soft tissue sarcoma of childhood. Despite aggressive therapy, the 5-year survival rate for patients with metastatic or recurrent disease remains poor, and beyond PAX-FOXO1 fusion status, no genomic markers are available for risk stratification. We present an international consortium study designed to determine the incidence of driver mutations and their association with clinical outcome. PATIENTS AND METHODS: Tumor samples collected from patients enrolled on Children's Oncology Group trials (1998-2017) and UK patients enrolled on malignant mesenchymal tumor and RMS2005 (1995-2016) trials were subjected to custom-capture sequencing. Mutations, indels, gene deletions, and amplifications were identified, and survival analysis was performed. RESULTS: DNA from 641 patients was suitable for analyses. A median of one mutation was found per tumor. In FOXO1 fusion-negative cases, mutation of any RAS pathway member was found in > 50% of cases, and 21% had no putative driver mutation identified. BCOR (15%), NF1 (15%), and TP53 (13%) mutations were found at a higher incidence than previously reported and TP53 mutations were associated with worse outcomes in both fusion-negative and FOXO1 fusion-positive cases. Interestingly, mutations in RAS isoforms predominated in infants < 1 year (64% of cases). Mutation of MYOD1 was associated with histologic patterns beyond those previously described, older age, head and neck primary site, and a dismal survival. Finally, we provide a searchable companion database (ClinOmics), containing all genomic variants, and clinical annotation including survival data. CONCLUSION: This is the largest genomic characterization of clinically annotated rhabdomyosarcoma tumors to date and provides prognostic genetic features that refine risk stratification and will be incorporated into prospective trials.

Conservation of copy number profiles during engraftment and passaging of patient-derived cancer xenografts.

Patient-derived xenografts (PDXs) are resected human tumors engrafted into mice for preclinical studies and therapeutic testing. It has been proposed that the mouse host affects tumor evolution during PDX engraftment and propagation, affecting the accuracy of PDX modeling of human cancer. Here, we exhaustively analyze copy number alterations (CNAs) in 1,451 PDX and matched patient tumor (PT) samples from 509 PDX models. CNA inferences based on DNA sequencing and microarray data displayed substantially higher resolution and dynamic range than gene expression-based inferences, and they also showed strong CNA conservation from PTs through late-passage PDXs. CNA recurrence analysis of 130 colorectal and breast PT/PDX-early/PDX-late trios confirmed high-resolution CNA retention. We observed no significant enrichment of cancer-related genes in PDX-specific CNAs across models. Moreover, CNA differences between patient and PDX tumors were comparable to variations in multiregion samples within patients. Our study demonstrates the lack of systematic copy number evolution driven by the PDX mouse host.

Establishing guidelines to harmonize tumor mutational burden (TMB): in silico assessment of variation in TMB quantification across diagnostic platforms: phase I of the Friends of Cancer Research TMB Harmonization Project.

BACKGROUND: Tumor mutational burden (TMB), defined as the number of somatic mutations per megabase of interrogated genomic sequence, demonstrates predictive biomarker potential for the identification of patients with cancer most likely to respond to immune checkpoint inhibitors. TMB is optimally calculated by whole exome sequencing (WES), but next-generation sequencing targeted panels provide TMB estimates in a time-effective and cost-effective manner. However, differences in panel size and gene coverage, in addition to the underlying bioinformatics pipelines, are known drivers of variability in TMB estimates across laboratories. By directly comparing panel-based TMB estimates from participating laboratories, this study aims to characterize the theoretical variability of panel-based TMB estimates, and provides guidelines on TMB reporting, analytic validation requirements and reference standard alignment in order to maintain consistency of TMB estimation across platforms. METHODS: Eleven laboratories used WES data from The Cancer Genome Atlas Multi-Center Mutation calling in Multiple Cancers (MC3) samples and calculated TMB from the subset of the exome restricted to the genes covered by their targeted panel using their own bioinformatics pipeline (panel TMB). A reference TMB value was calculated from the entire exome using a uniform bioinformatics pipeline all members agreed on (WES TMB). Linear regression analyses were performed to investigate the relationship between WES and panel TMB for all 32 cancer types combined and separately. Variability in panel TMB values at various WES TMB values was also quantified using 95% prediction limits. RESULTS: Study results demonstrated that variability within and between panel TMB values increases as the WES TMB values increase. For each panel, prediction limits based on linear regression analyses that modeled panel TMB as a function of WES TMB were calculated and found to approximately capture the intended 95% of observed panel TMB values. Certain cancer types, such as uterine, bladder and colon cancers exhibited greater variability in panel TMB values, compared with lung and head and neck cancers. CONCLUSIONS: Increasing uptake of TMB as a predictive biomarker in the clinic creates an urgent need to bring stakeholders together to agree on the harmonization of key aspects of panel-based TMB estimation, such as the standardization of TMB reporting, standardization of analytical validation studies and the alignment of panel-based TMB values with a reference standard. These harmonization efforts should improve consistency and reliability of panel TMB estimates and aid in clinical decision-making.

Pembrolizumab in Relapsed and Refractory Mycosis Fungoides and Sézary Syndrome: A Multicenter Phase II Study.

PURPOSE: To assess the efficacy of pembrolizumab in patients with advanced relapsed or refractory mycosis fungoides (MF) or Sézary syndrome (SS). PATIENTS AND METHODS: CITN-10 is a single-arm, multicenter phase II trial of 24 patients with advanced MF or SS. Patients were treated with pembrolizumab 2 mg/kg every 3 weeks for up to 24 months. The primary end point was overall response rate by consensus global response criteria. RESULTS: Patients had advanced-stage disease (23 of 24 with stage IIB to IV MF/SS) and were heavily pretreated with a median of four prior systemic therapies. The overall response rate was 38% with two complete responses and seven partial responses. Of the nine responding patients, six had 90% or more improvement in skin disease by modified Severity Weighted Assessment Tool, and eight had ongoing responses at last follow-up. The median duration of response was not reached, with a median response follow-up time of 58 weeks. Immune-related adverse events led to treatment discontinuation in four patients. A transient worsening of erythroderma and pruritus occurred in 53% of patients with SS. This cutaneous flare reaction did not result in treatment discontinuation for any patient. The flare reaction correlated with high PD-1 expression on Sézary cells but did not associate with subsequent clinical responses or lack of response. Treatment responses did not correlate with expression of PD-L1, total mutation burden, or an interferon-γ gene expression signature. CONCLUSION: Pembrolizumab demonstrated significant antitumor activity with durable responses and a favorable safety profile in patients with advanced MF/SS.

APOBEC Mutagenesis and Copy-Number Alterations Are Drivers of Proteogenomic Tumor Evolution and Heterogeneity in Metastatic Thoracic Tumors.

Intratumor mutational heterogeneity has been documented in primary non-small-cell lung cancer. Here, we elucidate mechanisms of tumor evolution and heterogeneity in metastatic thoracic tumors (lung adenocarcinoma and thymic carcinoma) using whole-exome and transcriptome sequencing, SNP array for copy-number alterations (CNAs), and mass-spectrometry-based quantitative proteomics of metastases obtained by rapid autopsy. APOBEC mutagenesis, promoted by increased expression of APOBEC3 region transcripts and associated with a high-risk APOBEC3 germline variant, correlated with mutational tumor heterogeneity. TP53 mutation status was associated with APOBEC hypermutator status. Interferon pathways were enriched in tumors with high APOBEC mutagenesis and IFN-γ-induced expression of APOBEC3B in lung adenocarcinoma cells, suggesting that the immune microenvironment may promote mutational heterogeneity. CNAs occurring late in tumor evolution correlated with downstream transcriptomic and proteomic heterogeneity, although global proteomic heterogeneity was significantly greater than transcriptomic and CNA heterogeneity. These results illustrate key mechanisms underlying multi-dimensional heterogeneity in metastatic thoracic tumors.

Low mutation burden and frequent loss of CDKN2A/B and SMARCA2, but not PRC2, define premalignant neurofibromatosis type 1-associated atypical neurofibromas.

BACKGROUND: Neurofibromatosis type 1 (NF1) is a tumor-predisposition disorder caused by germline mutations in NF1. NF1 patients have an 8-16% lifetime risk of developing a malignant peripheral nerve sheath tumor (MPNST), a highly aggressive soft-tissue sarcoma, often arising from preexisting benign plexiform neurofibromas (PNs) and atypical neurofibromas (ANFs). ANFs are distinct from both PN and MPNST, representing an intermediate step in malignant transformation. METHODS: In the first comprehensive genomic analysis of ANF originating from multiple patients, we performed tumor/normal whole-exome sequencing (WES) of 16 ANFs. In addition, we conducted WES of 3 MPNSTs, copy-number meta-analysis of 26 ANFs and 28 MPNSTs, and whole transcriptome sequencing analysis of 5 ANFs and 5 MPNSTs. RESULTS: We identified a low number of mutations (median 1, range 0-5) in the exomes of ANFs (only NF1 somatic mutations were recurrent), and frequent deletions of CDKN2A/B (69%) and SMARCA2 (42%). We determined that polycomb repressor complex 2 (PRC2) genes EED and SUZ12 were frequently mutated, deleted, or downregulated in MPNSTs but not in ANFs. Our pilot gene expression study revealed upregulated NRAS, MDM2, CCND1/2/3, and CDK4/6 in ANFs and MPNSTs, and overexpression of EZH2 in MPNSTs only. CONCLUSIONS: The PN-ANF transition is primarily driven by the deletion of CDKN2A/B. Further progression from ANF to MPNST likely involves broad chromosomal rearrangements and frequent inactivation of the PRC2 genes, loss of the DNA repair genes, and copy-number increase of signal transduction and cell-cycle and pluripotency self-renewal genes.

Primary gastrointestinal diffuse large B-cell lymphoma: A prospective study from South India.

BACKGROUND: Gastrointestinal tract (GIT) is the most common extranodal site for non-Hodgkin's lymphoma (NHL) and constitutes about 10%-15% of all NHL. This was a prospective study to evaluate the epidemiological, clinicopathological characteristics, and treatment outcome of primary GIT diffuse large B-cell lymphoma (PGIL). MATERIALS AND METHODS: Newly diagnosed patients of PGIL with DLBCL histology were eligible. Lugano staging system was used. All patients were treated with prephase treatment (1 mg vincristine and 100 mg prednisolone) followed by CHOP-based chemotherapy (with or without rituximab) as definitive treatment. RESULTS: A total of 21 patients of PGIL were diagnosed. The median age was 46 years (range: 27-69 years) with male:female ratio of 2:1. Dull aching abdominal pain was the most common presenting complaint. Stomach was the most common site involved (52.4%, n = 11) followed by the colon (23.8%, n = 5). The estimated median survival in patients with Stage IV disease was significantly lower as compared to patients with localized disease (Stage I and II) (6.23 months vs. 23.4 months; P = 0.04). Patients, who did not achieve complete response (CR), had 15.5 times higher risk of death, as compared to those who achieved CR (P = 0.01). CONCLUSIONS: Stomach was the most common site for PGIL. Localized disease and CR after first-line chemotherapy were associated with better survival. A higher cost of rituximab was the prohibitive factor for cure in these patients.

Relationship of DNA methylation to mutational changes and transcriptional organization in fusion-positive and fusion-negative rhabdomyosarcoma.

Our previous study of DNA methylation in the pediatric soft tissue tumor rhabdomyosarcoma (RMS) demonstrated that fusion-positive (FP) and fusion-negative (FN) RMS tumors exhibit distinct DNA methylation patterns. To further examine the significance of DNA methylation differences in RMS, we investigated genome-wide DNA methylation profiles in discovery and validation cohorts. Unsupervised analysis of DNA methylation data identified novel distinct subsets associated with the specific fusion subtype in FP RMS and with RAS mutation status in FN RMS. Furthermore, the methylation pattern in normal muscle is most similar to the FN subset with wild-type RAS mutation status. Several biologically relevant genes were identified with methylation and expression differences between the two fusion subtypes of FP RMS or between the RAS wild-type and mutant subsets of FN RMS. Genomic localization studies showed that promoter and intergenic regions were hypomethylated and the 3' untranslated regions were hypermethylated in FP compared to FN tumors. There was also a significant difference in the distribution of PAX3-FOXO1 binding sites between genes with and without differential methylation. Moreover, genes with PAX3-FOXO1 binding sites and promoter hypomethylation exhibited the highest frequency of overexpression in FP tumors. Finally, a comparison of RMS model systems revealed that patient-derived xenografts most closely recapitulate the DNA methylation patterns found in human RMS tumors compared to cell lines and cell line-derived xenografts. In conclusion, these findings highlight the interaction of epigenetic changes with mutational alterations and transcriptional organization in RMS tumors, and contribute to improved molecular categorization of these tumors.

T-Cell Prolymphocytic Leukemia: An Experience from a Tertiary Cancer Centre in South India.

Background: T-cell prolymphocytic leukemia (T-PLL) is a rare lymphoid malignancy with dismal prognosis. Most patients have increased lymphocyte count (>1,00,000/dL) and widespread disease at presentation. Despite high response rate seen with alemtuzumab, the disease relapse is inevitable. Materials andMethods: This was a retrospective observational study done at a tertiary cancer center in South India. All patients diagnosed with T-PLL from August 2010 to July 2015 were studied for the clinical characteristics, pathological findings and treatment outcomes. Results: Seven patients were diagnosed as T-PLL over a period of 5 years. The median age at diagnosis was 51 years. In the present series, 6 patients (86%) had splenomegaly and 3 had hepatomegaly (43%). Generalized lymphadenopathy was seen in 4 (57%) patients at presentation. Skin lesions were seen in 5 (71%) patients, whereas pleural effusion was seen in only one patient (14%). All had elevated total leukocyte count, with more than 1, 00,000/dL in 4 patients. The median survival was 5 months with different chemotherapy (CT) regimens (5 patients treated with CT and 2 received best supportive care). Conclusion: T-PLL is a rare disease with no definite treatment guidelines. At present, the best outcomes are achieved if treatment with alemtuzumab is followed by stem cell transplant, but the disease invariably relapses. Countries where affordability remains a big challenge, the best approach needs to be defined beyond the monoclonal antibodies and transplant.

Clinical profile and treatment outcomes of metastatic neuroendocrine carcinoma: A single institution experience.

BACKGROUND: Neuroendocrine carcinoma (NEC) is a rare tumor arising from the diffuse neuroendocrine system. Most of these present in the advanced stage and palliative chemotherapy remains the only option. The prognosis remains poor with the standard chemotherapy regimen of platinum and etoposide (EP) providing modest survival benefit. METHODS: The study was done for 3 years at a tertiary cancer center in South India. Patients with a diagnosis of metastatic NEC were analyzed for clinical and pathological characteristics. The treatment outcomes and prognostic factors were evaluated using appropriate statistical test. RESULTS: A total of 114 patients of metastatic NEC satisfied the inclusion criteria and were analyzed. Gastrointestinal including hepatobiliary tract (33%) was the most common site of primary disease followed by lung (26%), genitourinary (15%), head and neck (14%), and unknown primary (9%). On analysis of pattern of metastasis, liver (65%) was the most common site followed by bone (54%) and lung (42%). The median overall survival was 11 months with a statistically significant difference between pulmonary and extrapulmonary disease (8 vs. 13 months; P = 0.003). Ki67% value was strongly associated with prognosis (hazard ratio 0.517, 95% confidence interval; 0.318-0.840, P = 0.008) whereas age, sex, and lactate dehydrogenase level did not show any relation with survival. CONCLUSION: The outcome of advanced NEC with standard chemotherapy remains poor. Larger studies with other therapeutic and novel agents are warranted to improve the treatment outcomes.