Publications by authors named "Sameer Bakhshi"

396 Publications

Patterns and Trends of Childhood Cancer Incidence (0-14 Years) in Delhi, India: 1990-2014.

Indian Pediatr 2021 May;58(5):430-435

Department of Radiotherapy, Dr BRAIRCH, AIIMS, New Delhi, India.

Objectives: To investigate the patterns and temporal trends of childhood cancer incidence (0-14 years) in Delhi from 1990 to 2014.

Methods: The new childhood cancer cases diagnosed between 1990 and 2014 were extracted from the Delhi population-based cancer registry (PBCR). Joinpoint regression analysis was performed to assess the temporal behaviour of new childhood cancer. The magnitude of temporal trend was assessed by estimated annual percentage changes (EAPCs).

Results: The Delhi PBCR registered 12,637 cases (8484 boys and 4153 girls) during 1990-2014. The overall childhood cancer was twice in boys than girls (5.62% vs. 2.78%). The age-standardised incidence rates (ASIRs) of childhood cancer adjusted to the WHO World standard population distribution (year 2000) was 163 per one million in boys and 92 per one million in girls; median age at diagnosis being 6 and 7 years, respectively. Five-top childhood cancer sites was leukaemia, lymphoma, central nervous system (CNS), bone and retinoblastoma. A decreasing linear trend in proportion of new childhood cancer cases to total all age-group cancer was observed in both sexes during this period. The percentage increase in childhood cancer is similar in both sexes from 1990-94 to 2010-14 (97% vs. 93%). Increasing trend in ASIRs of childhood cancer was observed.

Conclusions: The new childhood cancer cases observed increasing trend during 1990 to 2014. Boys had nearly double the number of childhood cancer cases than girls while population ratio of boys and girls during the same period was 1.14:1.
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May 2021

Systemic neoadjuvant chemotherapy in non-resectable invasive squamous cell carcinoma of ocular surface.

Eur J Ophthalmol 2021 Apr 30:11206721211014376. Epub 2021 Apr 30.

Department of Medical Oncology, All India Institute of Medical Sciences, New Delhi, India.

Background/objectives: The conventional modality for management of advanced invasive ocular surface squamous neoplasia (OSSN) (AJCC grade T4 and T3 with fornicial involvement) is surgical excision which is not only challenging in terms of ability to achieve tumor free margins and tissue reconstruction but also has high morbidity. We describe the use of systemic neoadjuvant chemotherapy (NAC) in cases of advanced invasive OSSN.

Subjects/methods: This is a retrospective case series. Five cases of histopathologically proven advanced OSSN that were challenging to manage with surgical excision or required exenteration were treated with NAC. Demographic details, previous treatment history, location and extent of tumor, imaging findings, number of cycles and duration of NAC, response to treatment, and final outcome on follow-up were noted.

Results: A remarkable response to NAC was seen in 4/5(80%) cases. Complete regression was seen in 2/5, partial regression in 2/5, and no response in 1/5 cases. In 75% (3/4) cases who showed response to NAC, minimal or no surgery was required. Exenteration was avoided in 2/3 cases with orbital extension.

Conclusion: NAC appears to be an exciting option for management of surgically challenging cases of invasive OSSN and may be helpful in avoiding orbital exenteration. However, more studies are required to explore this treatment option.
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http://dx.doi.org/10.1177/11206721211014376DOI Listing
April 2021

IKZF1 Deletion Subtyping and Outcome Analysis in BCR-ABL1-Negative Pediatric B-Cell Acute Lymphoblastic Leukemia: A Single-Institution Experience from North India.

Clin Lymphoma Myeloma Leuk 2021 Mar 29. Epub 2021 Mar 29.

Division of Epidemiology and Biostatistics, National Institute of Epidemiology, Chennai, India.

Background: IKZF1 deletions are associated with adverse outcomes in B-cell acute lymphoblastic leukemia (B-ALL). We assessed the prevalence and clinical impact of functional subtypes of IKZF1 deletions in pediatric BCR-ABL1-negative B-ALL.

Patients And Methods: This retrospective study of IKZF1 deletions was done in cases of pediatric BCR-ABL1-negative B-ALL. The genomic DNA of cases, over a 53-month period, was analyzed using multiplex ligation-dependent probe amplification and multiplex fluorescent polymerase chain reaction. The deletions were divided into functional subgroups: (1) loss-of-function/haploinsufficiency, (2) dominant-negative, and (3) a combination of both types of deletion. The post-induction remission status, event-free survival (EFS), and overall survival (OS) were noted.

Results: Out of 320 cases, 47 (14.7%) had IKZF1 deletions. Thirty-six of the 47 (77%) had loss-of-function deletions, 10 (21%) had dominant-negative deletions, and one (2%) had a combination of both types. The post-induction remission rates in cases with loss-of-function deletions (22/30, 73%; P = .060) and dominant-negative deletions (4/5, 80%; P = .517) were lower compared with those without deletions (215/248, 86.7%). These cases also had worse median EFS: 21.1 months (P = .006) for loss-of-function and 15.4 months (P = .156) for dominant-negative deletions, compared with 46.4 months in cases without IKZF1 deletions. They also had worse median OS: 23.4 months (P = .012) for loss-of-function deletions and 15.7 months (P = .233) for dominant-negative deletions, compared with median not reached in cases without IKZF1 deletions.

Conclusion: The IKZF1 deletions were seen in 14.7% of BCR-ABL1-negative pediatric B-ALL. Most of these deletions (77%) were loss-of-function type. The cases with loss-of-function deletions had lower remission rates and poor EFS and OS compared with cases without IKZF1 deletions. A similar trend of poor outcome was seen in the few cases with dominant-negative IKZF1 deletions.
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http://dx.doi.org/10.1016/j.clml.2021.03.007DOI Listing
March 2021

PGC1A driven enhanced mitochondrial DNA copy number predicts outcome in pediatric acute myeloid leukemia.

Mitochondrion 2021 May 1;58:246-254. Epub 2021 Apr 1.

Department of Medical Oncology, Dr. B.R.A. Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India. Electronic address:

Mitochondrial DNA (mtDNA) copy number alterations occur in acute myeloid leukemia (AML). We evaluated regulation and biological significance of mtDNA copy number in pediatric AML patients (n = 123) by qRT-PCR, and in-vitro studies. MtDNA copy number was significantly higher (p < 0.001) and an independent predictor of aggressive disease (p = 0.006), lower event free survival (p = 0.033), and overall survival (p = 0.007). Expression of TFAM, POLG, POLRMT, MYC and ND3 were significantly upregulated. In cell lines, PGC1A inhibition decreased mtDNA copy number while MYC inhibition had no effect. PGC1A may contribute to enhanced mtDNA copy number, which predicts disease aggressiveness and inferior survival outcome.
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http://dx.doi.org/10.1016/j.mito.2021.03.013DOI Listing
May 2021

An updated account on molecular heterogeneity of acute leukemia.

Am J Blood Res 2021 15;11(1):22-43. Epub 2021 Feb 15.

Laboratory Oncology Unit, Dr.B.R.A. Institute Rotary Cancer Hospital, All India Institute of Medical Sciences New Delhi 110029, India.

The progress in the field of personalized therapy has been the backbone for the improved mortality and morbidity figure in cancer especially with reference to acute leukemia. The same has been supported by evolving research and development in the field of genomics. The newer discoveries of mutations and the account of already discovered mutations have been playing a pivotal role to refine management strategy. Here, in this review, we are giving an account of relevant mutations and their potential role in the pathogenesis of acute leukemia. The article discusses the old and newly discovered mutations in acute myeloid/lymphoblastic leukemia. The various pathways and cross-talks between the mutations have been briefly described to develop insight towards their contributory and consequent role in the neoplastic process. The article is to sensitize the students, clinicians, and researchers towards the recent updates and development in genomics of acute leukemia.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8010602PMC
February 2021

Neuroblastoma With Opsoclonus-Myoclonus-Ataxia Syndrome: Role of Chemotherapy in the Management: Experience From a Tertiary Care Center in a Resource-limited Setting.

J Pediatr Hematol Oncol 2021 Mar 23. Epub 2021 Mar 23.

Departments of Pediatric Surgery Pediatrics Radiodiagnosis Department of Medical Oncology, BRAIRCH, AIIMS, New Delhi, India.

Children with neuroblastoma (NB) and opsoclonus-myoclonus-ataxia syndrome (OMAS) have a favorable oncologic outcome and overall survival. In contrast, despite intensive multidrug immunomodulation, the neurologic outcome is complicated by the relapsing nature of the neurologic symptoms and long-term neurobehavioral sequelae. Being associated with low-risk NB, there exists an ambiguity in the current literature regarding the administration of chemotherapy in these children. We reviewed our archives for children with NB-OMAS over a 22-year (January 1996 to January 2018) period. Eighteen children (10 female) with a median age at diagnosis of 23 months had NB-OMAS and were included. They had stage 1 (9/18; 50%), 2 (1/18; 5.5%), 3 (7/18; 39%), and 4 (1/18; 5.5%) disease according to the International Neuroblastoma Staging System. Multimodality therapy included surgery (16/18; 89%), chemotherapy (11/18; 61%), and immunomodulatory therapy (10/18; 55%). Complete oncologic remission was achieved in all children. Relapse of OMAS and presence of neurologic sequelae were observed in 1 (5.5%) and 5 (28%) cases, respectively. Presence of neurologic sequelae was significantly associated with low-tumor stage (P=0.036) and treatment without chemotherapy (P=0.003). Chemotherapy administration was the only variable significantly predicting a favorable neurologic outcome (95% confidence interval: 0.26-1.40, P=0.01). To conclude, our study including a limited cohort of patients highlights a favorable neurologic outcome associated with chemotherapy administration in children with NB-OMAS. However, further studies with larger sample size need to be conducted before drawing any definite conclusions.
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http://dx.doi.org/10.1097/MPH.0000000000002131DOI Listing
March 2021

Successful Multimodality Management of Atypical Teratoid/Rhabdoid Tumour of the Lower Dorsal Spine with Spinal Drop Metastasis: Illustrated Review.

Pediatr Neurosurg 2021 24;56(2):184-196. Epub 2021 Mar 24.

Department of Medical Oncology, All India Institute of Medical Sciences, New Delhi, India.

Introduction: Spinal atypical teratoid/rhabdoid tumour (AT/RT) is exquisitely rare and constitutes 2% of all AT/RTs.

Case Presentation: A 6-year-old boy presented with low backache for the last 5 months. MRI of the spine showed a 1.5 × 1.5 × 4.7 cm intradural extramedullary mass extending from D10 to D12, causing compression of the conus medullaris. With a preoperative diagnosis of ependymoma, a gross total resection (GTR) of tumour was performed. Post-operative histopathology showed AT/RT. The tumour cells were immunopositive for cytokeratin, epithelial membrane antigen, smooth muscle actin, and p53 and immunonegative for MIC2, desmin, glial fibrillary acidic protein, and INI1. Post-operative neuraxis MRI revealed post-operative changes (D10-D12) with a 9 mm enhancing lesion at L5-S1 junction suggesting drop metastasis. There was no lesion in brain. Cerebrospinal fluid cytology did not show any malignant cell. The metastatic work-up was normal. He received 3 cycles of chemotherapy with ICE regimen (ifosfamide, carboplatin, and etoposide). Subsequently, he received craniospinal irradiation (CSI)-36 Gy/20 fractions/4 weeks followed by focal boost to primary tumour bed and spinal drop metastasis-14.4 Gy/8 fractions/1.5 weeks. Thereafter, he received 3 more cycles of ICE regimen. End-of-treatment MRI spine showed post-op changes (D10-D12) and 38.9% reduction of the L5-S1 lesion suggesting partial response. Six monthly spinal MRI showed serial reduction of the metastatic lesion leading to complete response (CR) 1 year after completion of treatment. On last follow-up (30 months from the initial diagnosis), he was neurologically intact and in CR.

Conclusion: Multimodality management comprising GTR of tumour, CSI followed by focal boost, and multiagent chemotherapy (ICE) can lead to successful outcome in patients with this rare and aggressive spinal tumour.
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http://dx.doi.org/10.1159/000513936DOI Listing
March 2021

Prognostic significance of CD45 antigen expression in pediatric acute lymphoblastic leukemia.

Blood Cells Mol Dis 2021 Mar 16;89:102562. Epub 2021 Mar 16.

Laboratory Oncology Unit, Dr. BRAIRCH, AIIMS, New Delhi, India. Electronic address:

Objectives: The treatment of pediatric acute lymphoblastic leukemias (ALL) has seen remarkable advances recently. However, relapse occurs in approximately 20% of cases which necessitates identifying additional high risk parameters for treatment intensification. The aim of this study is to assess the prognostic significance of CD45 antigen expression in pediatric ALL.

Methods: We studied 363 pediatric patients with B cell precursor-ALL (BCP-ALL) (n = 313) and T-ALL (n = 50). The ratio of median fluorescence intensity of CD45 expressed in leukemic blasts and normal lymphocytes was calculated. The 75th percentile was taken as cut-off to categorise patients into CD45 high and CD45 low groups.

Results: The 75th percentile was 0.141 in BCP-ALL and 0.548 in T-ALL. In BCP-ALL, there was a statistically significant association of age (≥10 years) (p = 0.027) and National Cancer Institute high risk group (p = 0.001) with high CD45 expression but not in T-ALL. Worse event-free survival (EFS) was seen with high CD45 expression in BCP-ALL (42.17% versus 60.83%, p = 0.0053). In T-ALL, there was no association between CD45 expression and EFS (CD45 high 40.40% versus low 67.35%, p = 0.414). The overall survival (OS) was 70% versus 60% (p = 0.38) in BCP-ALL and the OS was 82% versus 68% (p = 0.16) in T-ALL for CD45 low versus CD45 high groups, respectively.

Conclusion: We conclude that high CD45 surface expression is associated with worse EFS in pediatric BCP-ALL.
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http://dx.doi.org/10.1016/j.bcmd.2021.102562DOI Listing
March 2021

Management of advanced melanoma in the current era: A medical oncology perspective for the Indian scenario.

Natl Med J India 2020 Mar-Apr;33(2):89-98

Department of Medical Oncology, Dr B.R. Ambedkar Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, Ansari Nagar, New Delhi 110029, India.

Malignant melanoma is an aggressive malignancy with high recurrence rates after curative surgery and in advanced stages is characterized by resistance to conventional chemotherapy. With better understanding of the genomic landscape and mutational signature of these tumours over the past decade, there has been a paradigm shift in management of melanoma using immunotherapy (anti-PD-1 and anti-CTLA-4 antibodies) and targeted drugs against BRAF and MEK. These drugs have shown survival benefits in both adjuvant and metastatic setting with patients being eligible for immunotherapy irrespective of any biomarker. However, these drugs have varying toxicity profiles and there are no studies comparing these two classes of drugs in either the adjuvant or metastatic setting leaving the question of sequencing open to clinical judgement. Moreover, availability and cost are issues that need to be considered before use of these drugs in the Indian setting.
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http://dx.doi.org/10.4103/0970-258X.310984DOI Listing
March 2021

An Ethnographic Study of the Moral Experiences of Children with Cancer in New Delhi, India.

Glob Qual Nurs Res 2021 Jan-Dec;8:2333393621995814. Epub 2021 Feb 23.

McGill University, Montreal, QC, Canada.

There is a paucity of research examining children's experiences with cancer in India. Childhood ethics is an emerging field, focusing on the moral dimension of children's experiences, to promote children's participation in their health care. A focused ethnography, using a moral experience framework, was conducted to better understand children's participation in decisions, discussions, and actions in three oncology settings in New Delhi, India. We interviewed key informants, retrieved key documents, and conducted semi-structured interviews and participant observations with children. All 22 children demonstrated interest in varying aspects of their cancer care. Certain factors facilitated or impeded their participation. Some children became distressed when they lacked information about their treatment or were not given opportunities to enhance their understanding. The results advance our understanding of the moral experiences of children with cancer in India for healthcare professionals, policy makers, families, and interested others.
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http://dx.doi.org/10.1177/2333393621995814DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7905724PMC
February 2021

Prognostic Relevance of Expression of , , and Genes in Pediatric B-Lineage Acute Lymphoblastic Leukemia.

Front Oncol 2021 5;11:606370. Epub 2021 Mar 5.

Laboratory Oncology Unit, Dr. B.R. Ambedkar-Insitute Rotary Cancer Hospital (BRAIRCH), All India Institute of Medical Sciences (AIIMS), New Delhi, India.

Glucocorticoid (GC), such as prednisolone, is an essential component of multidrug chemotherapy regimen for pediatric acute lymphoblastic leukemia (ALL). Resistance to GC in leukemia cells is associated with disease progression and poor prognosis. Despite the extensive use of GC for many years, molecular mechanisms underlying its resistance in ALL have not been fully uncovered. Recent studies have shown a potential role of , , and genes in prednisolone response. In this study on 148 pediatric B-ALL patients, we studied these three genes to assess their association with prednisolone response measured by day 8 blast count after 7 days of induction therapy with prednisolone. Intriguingly, ALL samples exhibited higher expression of along with a low expression of and compared to disease free normal bone marrow collected from patients with solid tumors. Among the three analyzed genes, only was found to be overexpressed in prednisolone poor responders (p=0.015). Further, a comparison of gene expression between cytogenetic subtypes revealed higher expression of in BCR-ABL subtype. Expression of in multiple gene expression datasets was used for gene set enrichment analysis, which revealed TNF-α, IL-2-STAT5 signaling, inflammatory responses and hypoxia as the major positively associated pathways and E2F targets as negatively associated pathways. Interestingly, the clinical remission rate was higher in high patients (p=0.048). In univariate survival analysis, higher expression was associated with poor prognostic measures while higher expression of and was associated with better prognostic measures in our data. Further, multivariate analysis revealed an independent association of high and with a better prognosis. This study strengthens the available evidence that mRNA expression of , , and may serve as potential biomarkers for risk stratification of pediatric B-ALL patients.
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http://dx.doi.org/10.3389/fonc.2021.606370DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7973229PMC
March 2021

Utility of 18F-FDG-PET/CT in management and prognostication of treatment naïve late-stage soft tissue sarcomas.

Nucl Med Commun 2021 Mar 18. Epub 2021 Mar 18.

Department of Nuclear Medicine, All India Institute of Medical Sciences, New Delhi, India Department of Medical Oncology, Dr. B. R. Ambedkar Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India Department of Radio-diagnosis, Dr. B. R. Ambedkar Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India.

Objective: This study evaluated the utility of 18F-fluorodexoyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) in staging, grading, and prognostication of Stage III and IV soft tissue sarcomas (STSs).

Methods: Forty patients (Median age = 32.5 years; 25 men) with histologically proven STSs, prospectively underwent 18F-FDG-PET/CTs at baseline. Three-dimensional region of interests were drawn encompassing the lesions to calculate standardized uptake values (SUVs) and metabolic tumor volumes (MTVs). After segmentation, Haralick statistical texture analysis was performed. Follow-up was available for 35 patients. Survival at 6 months was 71.4% and at 1 year was 57.1%.

Results: American Joint Committee on Cancer Stage III was seen in 23 and Stage IV in 17 patients. None of the baseline quantitative and semi-quantitative parameters could predict response or progression. Only reduction in SUVmax in interim PET/CT correlated with baseline SUVmax (Spearman's Rho = 0.533; P = 0.019). Textural parameters namely 'contrast' in CT (P = 0.039) and 'difference entropy' in PET/CT (P = 0.051) could differentiate intermediate from high-grade lesions, with corresponding area under curves being 0.736 (0.533-0.889) and 0.700 (0.518-0.882). M1 disease [Hazard ratio (HR): 3.184 (1.179-8.595); P = 0.022], absence of surgical treatment [HR 0.305 (0.106-0.873), P = 0.027 with surgery], lower MTV/total tumor volume (TTV) [HR: 0.975 (0.953-0.997; P = 0.028] and progressive disease in interim PET/CT [3.483 (0.898-13.515); P = 0.056] were predictors of lower survival in univariate analysis. Only M1 disease was found to be reaching significance in multivariate analysis [HR = 2.683 (0.949-7.580); P = 0.063]. Baseline PET/CT changed management in 12.5% of patients [compared to local-imaging and high-resolution CT chest]; with detection of extra-pulmonary metastases. Though, interim and end of treatment PET/CTs detected more metastatic lesions, management was not impacted.

Conclusion: 18F-FDG-PET/CT allows for more accurate M-staging in late-stage STSs, which in turn influences the option of curative surgical resection and thus impacts patient prognosis. Lower baseline MTV/TTV and progression in interim PET/CT are also associated with lower survival. Textural analysis may have a role in noninvasive grading.
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http://dx.doi.org/10.1097/MNM.0000000000001401DOI Listing
March 2021

Oral metronomic chemotherapy is a cost effective alternative to pazopanib in advanced soft tissue sarcoma.

J Oncol Pharm Pract 2021 Mar 9:10781552211000113. Epub 2021 Mar 9.

Department of Medical Oncology, All India Medical Sciences, New Delhi, India.

Introduction: Soft tissue sarcoma(STS) is a rare and heterogeneous group of disorders with dismal outcomes in metastatic setting. Pazopanib and oral metronomic chemotherapy (OMT) have been evaluated as therapeutic options in this cohort.

Materials And Methods: We conducted a retrospective, single center study evaluating 45 patients with unresectable and/or metastatic STS, who received pazopanib or oral metronomic regimen as per instituitonal protocol between January 2013 and December 2019. An informal cost minimisation analysis was conducted for both OMT and pazopanib arms, considering equivalent outcomes for both (PFS and OS).

Results: Median PFS in OMT and Pazopanib groups was 4.13 months and 3.53 months,respectively (HR1.31, 95% CI:0.68-2.51, p = 0.41) Only one patient in the OMT group achieved an objective response (partial response) and no objective response was noted in the pazopanib group. The incidence of grade III/IVtoxicities was higher with pazopanib than with OMT (p = 0.08). There were no toxicity related deaths noted in either arm.

Conclusions: Our study demonstrates that OMT have a similar progression free survival (PFS) and overall survival (OS) in metastatic STS. This study raises the possibility that OMT might be an equally efficacious and less toxic alternative to pazopanib, without compromising survival outcome especially in LMIC.
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http://dx.doi.org/10.1177/10781552211000113DOI Listing
March 2021

Langherhans cell histiocytosis presenting as primary infertility in a young male.

Gulf J Oncolog 2021 Jan;1(35):86-91

Department of Endocrinology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi 110029, India.

Langerhans cell histiocytosis (LCH) is a rare clonal neoplastic disorder of Langerhans cells, with an incidence rate of 5 per million individuals. In adults LCH usually affects bone followed by lung, skin, pituitary gland, liver, spleen, and orbits. LCH presenting with endocrinopathy is rare and commonly involves posterior pituitary with central diabetes insipidus (DI). Here, we present a rare case of LCH involving posterior pituitary but presenting as infertility in a 25-year-old married man. Later the thyroid gland was also found to be involved in the form of multiple nodules. Fine needle aspiration cytology (FNAC) from right lobe of thyroid showed sheets of Langerhans cells along with entrapped residual thyroid follicular cells which were further confirmed by immunocytochemistry as well as cell block preparation followed by immunohistochemistry. A final diagnosis of LCH involving pituitary and thyroid was made and patient was then started on treatment according to LCH treatment protocol LCH III-6 consisting of prednisolone and vinblastine (6 weeks with daily 40 mg/m2 oral prednisolone, and 6 mg/m2 i.v. vinblastine every 7 days). Patient is responding well to the therapy and is on follow up.
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January 2021

Diagnostic Utility of IGF2BP1 and Its Targets as Potential Biomarkers in ETV6-RUNX1 Positive B-Cell Acute Lymphoblastic Leukemia.

Front Oncol 2021 23;11:588101. Epub 2021 Feb 23.

Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India.

Around 85% of childhood Acute Lymphoblastic Leukemia (ALL) are of B-cell origin and characterized by the presence of different translocations including , , , and fusion proteins. The current clinical investigations used to identify translocation include FISH and fusion transcript specific PCR. In the current study we assessed the utility of , an oncofetal RNA binding protein, that is over expressed specifically in translocation positive B-ALL to be used as a diagnostic marker in the clinic. Further, public transcriptomic and Crosslinked Immunoprecipitation (CLIP) datasets were analyzed to identify the putative targets of IGF2BP1. We also studied the utility of using the mRNA expression of two such targets, and as potential diagnostic markers separately or in conjunction with . We observed that the expression of alone measured by RT-qPCR is highly sensitive and specific to be used as a potential biomarker for the presence of translocation in future.
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http://dx.doi.org/10.3389/fonc.2021.588101DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7940665PMC
February 2021

Prognostic impact of Notch1 receptor and clinicopathological High-Risk Predictors in lacrimal gland adenoid cystic carcinoma.

Acta Ophthalmol 2021 Mar 6. Epub 2021 Mar 6.

Department of Pathology, All India Institute of Medical Sciences, New Delhi, India.

Purpose: Adenoid Cystic Carcinoma (ACC) is an aggressive malignant lacrimal gland tumour associated with poor prognosis. Aberrant Notch signalling has been investigated in various tumours. However, very few studies on Notch signalling in lacrimal gland ACC are reported. The aim of the present study was to evaluate the status of Notch1 receptor and activated Notch1 (NICD1) in lacrimal gland ACC and to correlate it with high-risk clinicopathological features.

Methods: A total of 23 cases of histopathologically proven lacrimal gland ACC, who underwent surgical treatment, were included in this study. Expression of Notch1 receptor and NICD1 was evaluated by immunohistochemistry on formalin fixed paraffin embedded tissues. The results obtained were correlated with clinicopathological high-risk features and survival of the patients. Kaplan-Meier survival and multivariate analysis was performed to determine the prognostic significance.

Results: Overexpression of Notch1 receptor and NICD1 was observed in 65% and 39% of lacrimal gland ACC cases, respectively. On Kaplan-Meier survival analysis, patients with Notch1 receptor overexpression had reduced disease free survival. On univariate analysis, male gender, bone erosion, perineural invasion, solid histologic pattern, intracranial extension and advanced tumour stage were also indicators of poor prognosis. On multivariate analysis bone erosion was the most significant poor prognostic indicator.

Conclusion: Our study demonstrates that overexpression of Notch1 receptor plays a critical role in the biology and aggressive behaviour of lacrimal gland ACC. Bone erosion, solid histologic pattern, advanced T stage, perineural invasion and intracranial extension are other high-risk clinicopathological predictors of lacrimal gland ACC.
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http://dx.doi.org/10.1111/aos.14812DOI Listing
March 2021

Blood-filled masses on scalp in a middle-aged woman.

Indian J Dermatol Venereol Leprol 2021 Jan-Feb;87(1):82-85

Department of Dermatology and Venereology Dr. B. R. A. Institute Rotary Cancer Hospital, New Delhi, India.

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http://dx.doi.org/10.25259/IJDVL_400_19DOI Listing
June 2019

Health-related quality of life and utility outcomes with selinexor in relapsed/refractory diffuse large B-cell lymphoma.

Future Oncol 2021 Apr 2;17(11):1295-1310. Epub 2021 Feb 2.

Department of Haematology, Somogy County Kaposi Mór Hospital, Kaposvár, 7400, Hungary.

Evaluate health-related quality of life (HRQoL) and health utility impact of single-agent selinexor in heavily pretreated patients with relapsed/refractory diffuse large B-cell lymphoma. Functional Assessment of Cancer Therapy (FACT) - Lymphoma and EuroQoL five-dimensions five-levels data collected in the single-arm Phase IIb trial SADAL (NCT02227251) were analyzed with mixed-effects models. Treatment responders maintained higher FACT - Lymphoma (p ≤ 0.05), FACT - General (p < 0.05) and EuroQoL five-dimensions five-levels index scores (p < 0.001) beginning in cycle 3. The estimated difference in health state utilities for treatment response and progressive disease was both statistically significant and clinically meaningful (mean difference: 0.07; p = 0.001). In patients with relapsed/refractory diffuse large B-cell lymphoma, objective response to selinexor was associated with HRQoL maintenance, reduction in disease-related HRQoL decrements and higher health utilities.
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http://dx.doi.org/10.2217/fon-2020-0946DOI Listing
April 2021

Outcome of Children with Stage IV Wilms Tumor - Our Experience of 15 Years.

J Indian Assoc Pediatr Surg 2020 Nov-Dec;25(6):372-377. Epub 2020 Oct 27.

Department of Pediatric Surgery, All India Institute of Medical Sciences, New Delhi, India.

Context: Stage IV Wilms tumor is associated with poor prognosis, and recent changes in management have been suggested based on genetic markers and response to chemotherapy in this subgroup of patients.

Objective: The objective was to evaluate the outcomes of children with Stage IV Wilms tumor who were managed with the AIIMS-WT-99 protocol.

Materials And Methods: All the children with Stage IV Wilms tumor who were managed by us from October 2000 to December 2012 were included in the study. All the patients who had received primary treatment elsewhere were excluded from the study. All patients were managed as per the AIIMS-WT-99 protocol. After appropriate investigations, tumors that were deemed resectable underwent an upfront surgery. Unresectable and inoperable tumors received chemotherapy after cytological confirmation of the diagnosis. Chemotherapy was administered as per the NWTS-5 study. Pulmonary and flank radiotherapy was advised to all patients. Patients with poor response to chemotherapy or with recurrence were managed with an alternative chemotherapy regimen. The outcomes that were assessed the 4-year overall survival (OS) and the 4-year event-free survival (EFS).

Statistical Analysis Used: Kaplan-Meier survival estimates.

Results: During the study period, 219 patients with Wilms tumor were treated. Of these, 36 (16.4%) had Stage IV disease, and they formed the study group. The 4-year OS was 48% with a mean survival time of 59 months limited to 115 months (95% confidence interval: 41.3-75.9 months). The 4-year EFS was 42.4%. Patients with liver metastases had a poor outcome, whereas patients with good response to chemotherapy had a good outcome.

Conclusion: Stage IV Wilms had a poor prognosis, and the survival rates in the index study are lower than those quoted in the literature. Although the exact reason for this poor result eludes us, these patients may benefit from the intensification of chemotherapy.
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http://dx.doi.org/10.4103/jiaps.JIAPS_168_19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7815034PMC
October 2020

Lymphoma subtypes in India: a tertiary care center review.

Clin Exp Med 2021 May 22;21(2):315-321. Epub 2021 Jan 22.

Department of Pathology, All India Institute of Medical Sciences, New Delhi, 110029, India.

Lymphomas are a group of neoplasm arising from immune cells with varied clinical presentation, molecular profile, morphology and immunophenotype. The epidemiology and response to treatment varies among patients from different geographical locations. We analyze the demographic characteristics of lymphomas in a tertiary care center of India over a period of five years. This was a retrospective study including cases from 2015 to 2019 which were classified according to WHO classification 2017. A total of 4115 lymphoma cases were diagnosed. Hodgkin lymphomas (HL) comprised 30.35% (n = 1249), and non-Hodgkin lymphoma (NHL) was 69.65% (n = 2866). Site of presentation was nodal in 64.76% cases, and 35.23% were extranodal. There was an overall male predominance. Among the NHLs, B-cell type comprised of 84.08% and 15.38% was T- and NK cell lymphomas. Mature B cell lymphomas comprised 82.41% with predominant being diffuse large B cell lymphoma type (42.53%) followed by follicular lymphoma (10.81%) and small lymphocytic lymphoma (6.10%). Among the T-cell type, PTCL NOS (2.65%) was the predominant subtype followed by ALK positive anaplastic large cell lymphoma (ALCL-ALK+) (2.44%), extranodal NK-T cell lymphoma (2.02%) and others. Classical type was predominant type (97.91%) among HL, and 2.08% were nodular lymphocyte predominant type. Among the classical HL, nodular sclerosis (28.1%) and mixed cellularity (32.18%) co-dominated. Our study indicates that the Indian population differs in the prevalence, presentation and the subtyping among various lymphomas. Higher prevalence of Hodgkin lymphoma, DLBCL, ALK + ALCL and immature cell neoplasm was noted.
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http://dx.doi.org/10.1007/s10238-021-00683-2DOI Listing
May 2021

Quality of life in paediatric solid tumours: a randomised study of metronomic chemotherapy versus placebo.

BMJ Support Palliat Care 2021 Jan 19. Epub 2021 Jan 19.

Department of Medical Oncology, All India Institute of Medical Sciences, New Delhi, Delhi, India

Objective: Health-related quality of life (HRQoL) is an important outcome for paediatric cancer studies. We compared the HRQoL between patients of progressive paediatric solid tumours randomised to metronomic chemotherapy versus placebo.

Methods: In this double-blinded, placebo-controlled randomised study of 108 children with progressive malignancies, HRQoL was evaluated using the PedsQOL Cancer module V.3 at baseline (A1), A2 (9 weeks or earlier if progressed) or A3 (18 weeks or earlier if progressed).

Results: There was no statistically significant difference in the change in quality of life produced by each arm from A1 to A2 in either mean total scores or individual domain scores, reported by children or their parents. On analysing the response according to the minimal clinically important difference, defined as an improvement by 4.5 points, we found no significant differences, be it among bone-sarcomas, other tumours, responders (those who received ≥9 weeks of treatment) or non-responders.

Conclusions: The present study concludes that there was no significant difference in HRQoL, between the patients in the two arms at second and later assessments. This is consistent with the other survival endpoints in the study.

Trial Registration Number: Clinical trial registration: clinicaltrials.gov Identifier: NCT01858571.
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http://dx.doi.org/10.1136/bmjspcare-2020-002731DOI Listing
January 2021

Retinoblastoma in Children Older than 6 Years of Age.

Ocul Oncol Pathol 2020 Dec 23;6(6):395-404. Epub 2020 Oct 23.

Dr. Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India.

Objective: The aim of this work was to study the clinical and histopathology features and treatment outcome in retinoblastoma cases presenting at an older age (>6 years).

Design: This was a retrospective study. We recruited 48 retinoblastoma patients who were treated at our institute over 7 consecutive years and were older than 6 years at presentation.

Methods: Medical records were reviewed for data, including age at diagnosis, gender, laterality, family history, lag time, first symptom, misdiagnosis, clinical findings, grade and stage of disease at diagnosis, treatment, outcome, and follow-up status. Histopathology slides were reviewed and assessed for the presence of histopathological high-risk features (HRF) for metastasis. The main outcome measures were the frequency of atypical clinical features like hyphema, pseudohypopyon, glaucoma, cataract, vitreous hemorrhage, and phthisis, and misdiagnosis, prior intervention, stage of disease at presentation, and treatment outcome.

Results: In total, 48/610 (7.8%) patients were older than 6 years, with a median age of 7 years (range 6-31). Retinoblastoma was bilateral in 7 cases. The most common initial symptom was white reflex followed by a decrease in vision. The median lag time was 9 months. Fourteen cases (29.2%) were misdiagnosed, with endophthalmitis the most common misdiagnosis. Twenty-six (54%) patients had intraocular disease, 12 (25%) had locally advanced disease, and 10 (21%) had metastatic disease at presentation. Overall, 67% (14/21) of the eyes that were enucleated upfront for presumed intraocular disease had histopathological HRF. At last follow-up, 31/36 (86%) who were treated were alive and healthy, while 5 (14%) patients had disease progression.

Conclusions: This is the largest study of older age retinoblastoma and shows that it forms a significant percentage of retinoblastoma in developing countries, is misdiagnosed in one-third of cases, and may present at an advanced stage in 46% of cases.
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http://dx.doi.org/10.1159/000509040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7772882PMC
December 2020

Treating children with cancer in India - Navigating unique challenges.

Authors:
Sameer Bakhshi

EBioMedicine 2021 Jan 6;63:103199. Epub 2021 Jan 6.

Department of Medical Oncology, Dr. B.R.A. Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India. Electronic address:

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http://dx.doi.org/10.1016/j.ebiom.2020.103199DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7804840PMC
January 2021

Platelet Normalized Serum Vascular Endothelial Growth Factor Levels in Progressive Pediatric Solid Malignancies: Authors' Reply.

Indian Pediatr 2020 12;57(12):1188-1189

Department of Medical Oncology, All India Institute of Medical Sciences, New Delhi, India.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7781814PMC
December 2020

Radiation-Associated Glioblastoma after Prophylactic Cranial Irradiation in a Patient of ALL: Review of Literature and Report of a Rare Case.

Pediatr Neurosurg 2020 3;55(6):409-417. Epub 2020 Dec 3.

Medical Oncology, All India Institute of Medical Sciences, New Delhi, India.

Introduction: The cumulative incidence of radiation-induced second malignancy is 1-2% per decade after radiotherapy (RT). Radiation-induced malignant glioma (RIMG) is a rare complication of cranial RT.

Case Presentation: We herein describe a case of left frontal glioblastoma arising 5 years after prophylactic cranial irradiation (12.6 Gy/7 fractions/1.5 weeks) as a part of INCTR-02-04 protocol in a 3-year-old boy with B-cell ALL. He underwent gross total excision (GTE) of the tumour followed by post-operative intensity modulated RT (59.4 Gy/33 fractions/6.5 weeks) and concurrent and adjuvant (3 cycles) temozolomide. Thereafter, he had rapid disease progression, which entailed re-excision of the recurrent tumour. Subsequently, there was widespread subependymal and leptomeningeal spread of tumour, leading to death 10.5 months after the initial diagnosis.

Conclusion: RIMG is an aggressive malignancy with a dismal prognosis, and in spite of multimodality management, it exhibits relentless progression, occasionally characterized by subependymal and leptomeningeal dissemination, leading to eventual death within a year of diagnosis.
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http://dx.doi.org/10.1159/000511996DOI Listing
December 2020

expression, but not absence of bi-allelic deletion of TCR gamma chains (ABD), is a predictor of patient outcome in Indian T-acute lymphoblastic leukemia.

Am J Blood Res 2020 15;10(5):294-304. Epub 2020 Oct 15.

Laboratory Oncology Unit, Dr. BRAIRCH, AIIMS New Delhi, India.

Emerging evidence suggests existence of three prognostically relevant molecular entities among immature T-ALL-early thymic precursor ALL (ETP-ALL), T-ALL with the absence of biallelic deletion of TCRγ chains (ABD) and (Myocyte Enhancer Factor 2C) high T-ALL. However, the usefulness of ETP-ALL immunophenotype and assessment of ABD for this purpose has been questioned and, has not been studied in much detail. In this prospective analysis of 143 T-ALL patients, we evaluated the mutual association of these three entities and also determined how immunophenotypically-defined poor prognosis immature T-ALL relates to these entities. We found that all three of them, especially ABD, nearly completely characterized the immature group. High expression reflected ETP-ALL somewhat poorly and a few ABD and -high patients had non-immature immunophenotype-findings, that though in accord with published literature, call for exploration per T-cell receptor (TCR) classification scheme. ETP-ALL and high but not ABD had a higher frequency of minimal residual disease positivity and poor event-free survival. high, not ETP-ALL immunophenotype or ABD, had poorer overall survival. The value of ETP-ALL immunophenotype and status, as indicators of poor treatment response, needs further evaluation for possible incorporation in standard T-ALL management practice.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7675123PMC
October 2020

Peripheral blood involvement in angioimmunoblastic T-cell lymphoma: a case report and review of the literature.

Am J Blood Res 2020 15;10(5):257-265. Epub 2020 Oct 15.

Laboratory Oncology Unit, Dr. B.R.A.I.R.C.H, All India Institute of Medical Sciences New Delhi, India.

Angioimmunoblastic T-cell lymphoma (AITL) is an aggressive variant of peripheral T-cell lymphoma, occurring in elderly patients without any gender predisposition. It accounts for 1-2% of all non-Hodgkin lymphoma. Although characterized by some peculiar histological features, diagnosis of AITL can sometimes be challenging and a definite diagnosis requires a complete immunophenotypic and molecular workup. Peripheral Blood (PB) involvement in AITL has not been studied in detail and there is a paucity of published data about leukemic presentation of AITL. We present a case of a 38-year-old female diagnosed as AITL with PB involvement. Flow cytometric (FCM) examination of PB showed 40% abnormal lymphoid cells which were CD45+, CD4+, CD2+, cCD3+, CD5+, CD10+, CD16+ and TCRγδ restricted. PB involvement by AITL appears to be more common and under-reported. Nevertheless, detection of these tumoral T lymphocytes needs to be assessed in large case studies for assessing the true incidence of PB involvement. FCM analysis is an effective and reliable approach in the identification of leukemic phase of AITL and can lead to timely and effective intervention.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7675121PMC
October 2020

Hotspots mutational analysis of Wilms tumor 1 gene in acute myeloid leukaemia; prevalence and clinical correlation in North Indian population.

Am J Blood Res 2020 15;10(5):179-189. Epub 2020 Oct 15.

Laboratory Oncology Unit, Dr. B. R. A. Institute Rotary Cancer Hospital, All India Institute of Medical Sciences New Delhi-110029, India.

Background: The pathogenic role of gene (WT1) is well known in renal cancer. However, recently, its over expression is been documented in cases of acute myeloid leukaemia (AML), acute lymphoblastic leukaemia (ALL) and myelodysplastic syndrome (MDS). WT1 mutations is found in about 6%-15% of cases of AML affecting mainly hotspot exon 7 and 9, and less frequently in other exon such as 1, 2, 3, and 8. Different studies have shown equivocal findings with few of them depicting poorer prognosis, while others suggesting lack of any significant clinical impact.

Objective: This study was planned to evaluate prevalence of gene mutation on exon 7 & 9 in cases of AML and its correlation with their clinical features and disease course.

Methodology: A total of newly diagnosed and treatment naive 100 cases of AML, having blast count of ≥20% in peripheral blood or bone marrow were enrolled. Genomic DNA of all participants was extracted from blood/bone marrow sample using Qiagen DNA extraction kit. Haematological workup for counts and flow cytometry based immunophenotypes was done. Mutation on exon 7 & 9 were detected with the help of Sanger sequencing.

Results: WT1 mutations were detected in both types of cases having normal vs. abnormal cytogenetics. The overall prevalence of WT1 mutation of 2% was found. We have reported one novel mutation on exon 9 of WT1 gene. Twelve cases (12%) among all analyzed AMLs were found to have synonymous single nucleotide polymorphism (SNPs) on exon 7 which has been previously reported in SNP database (rs16754).

Conclusion: In our study, presence of synonymous SNP was not associated with any change at protein level. We also evaluated mutational status with deaths during induction remission and concluded that presence of WT1 gene mutation was associated with death during induction therapy.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7675118PMC
October 2020

Allogeneic hematopoietic stem cell transplant in pediatric acute myeloid leukemia: Lessons learnt from a tertiary care center in India.

Pediatr Transplant 2021 May 3;25(3):e13918. Epub 2020 Nov 3.

Department of Medical Oncology, Dr. BRAIRCH, AIIMS, New Delhi, India.

There is paucity of data on outcomes of MSD-HSCT in children with relapsed or high-risk AML from developing countries, which have unique challenges including adverse host factors and resource constraints. We retrospectively reviewed records of children (age ≤ 18 years) who underwent MSD-HSCT for AML at our center from 2009 to 2019 to evaluate clinical outcome and its predictors using Cox proportional hazards model. There were 46 children (36 boys and 10 girls) with mean age 10.7 ± 4.8 years. Indication for HSCT was relapsed AML in CR2 (n = 37), primary refractory (n = 3), or relapsed refractory disease (n = 3); high-risk (n = 1) or secondary (n = 2) AML in CR1. Five-year EFS and OS were 33.3 ± 7.2% and 36.3 ± 7.6%, respectively. On multivariate analysis, CR1 duration less than 12 months, presence of active disease at transplant, and use of bone marrow stem cell graft were associated with poorer EFS and OS. There was one (2.2%) TRM, while disease relapse occurred in 20/40 patients who underwent HSCT in remission. Though the 5-year EFS and OS were inferior to results reported from high-income countries, relapse (and not TRM) was the major cause of treatment failure. A well-sustained CR1, achievement of disease remission, and use of peripheral blood allograft seem imperative to a successful transplant. Targeted therapy along with HSCT may be the option for those with early relapse.
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http://dx.doi.org/10.1111/petr.13918DOI Listing
May 2021

Prognostic significance of PD-1/PD-L1 expression in uveal melanoma: correlation with tumor-infiltrating lymphocytes and clinicopathological parameters.

Cancer Immunol Immunother 2021 May 2;70(5):1291-1303. Epub 2020 Nov 2.

Department of Ocular Pathology, Dr. R P. Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India.

Background: To understand how to improve the effect of immune checkpoint inhibitors in uveal melanoma (UM), we need a better understanding of the expression of PD-1 and PD-L1, their relation with the presence of tumor-infiltrating lymphocytes (TILs), and their prognostic relevance in UM patients.

Materials And Methods: Expression of PD-1 and PD-L1 was assessed in 71 UM tissue samples by immunohistochemistry and quantitative real-time PCR (qRT-PCR), and further validated by western blotting. The effect of interferon gamma (IFN-γ) on PD-1/PD-L1 expression was determined on four UM cell lines.

Results: Immunoreactivity of PD-1 was found in 30/71 cases and of PD-L1 in 44/71 UM samples. Tumor-infiltrating lymphocytes were found in 46% of UM tissues. PD-1 was expressed on TILs while tumor cells expressed PD-L1. UM with and without TILs showed expression of PD-1 in 69% and 18% cases, respectively (p = 0.001). Similarly, PD-L1 was found in 75% of UM with TILs and in 50% of cases without TILs, respectively (p = 0.03). DFS rate were lower in patients with TILs with expression of PD-1 and PD-L1, but the rate of DFS was higher with expression of PD-L1 in patients without TILs. After treatment of UM cell lines with IFN-γ, PD-1 expression was induced in all UM cell lines whereas PD-L1 expression was found at a lower level in untreated cells, while expression also increased following treatment with IFN-γ.

Conclusion: Our study suggests that increased infiltration with TILs promotes the aggressive behavior and suppresses the immune response of UM cells, thereby inhibiting immunotherapy.
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http://dx.doi.org/10.1007/s00262-020-02773-8DOI Listing
May 2021