Evaluation of skull bone viability and effect of early surgical intervention in electrical contact burns using 18F-Sodium Fluoride PET-CT imaging.

OBJECTIVE: Electrical contact burns of the scalp cause serious morbidity and mortality. Early necrotic bone debridement and flap cover are crucial for successful wound closure. 18F Sodium Fluoride (NaF), with high bone-to-soft tissue activity ratio, is useful for bone viability assessment. This study evaluated the role of 18F NaF PET-computed tomography (CT) in objectively defining the extent and depth of nonviable calvarial bone, to guide adequate bone debridement. METHOD: Of 20 patients referred to our institute with electrical contact burns of the scalp during a 2-year period, 15 were enrolled in the study. Two weeks after the initial management, tracer uptake pattern was noted on 18F NaF PET-CT of the head and exposed bone measured. Surgical bone debridement was based on scan findings, followed by wound closure. All patients underwent clinical evaluation and follow-up scan 3 months after surgery. RESULTS: Eight patients showed a central photopenic area in the exposed bone (maximum standardized uptake value [SUVmax] of 0.76 ± 0.14 with mean maximum dimensions 4.10 ± 1.76/2.67 ± 1.54 cm). High tracer uptake (SUVmax, 9.66 ± 6.03) was seen peripheral to the exposed bone (mean maximum dimensions, 8.14 ± 3.03/4.75 ± 1.61 cm). Postoperatively, there was no significant change in tracer uptake in the central debrided region or peri-debridement bone area under the flap. Clinically all patients showed a well-healed flap. CONCLUSION: 18F NaF PET-CT appears useful for objective evaluation of skull bone viability and planning necrotic bone debridement in patients with electrical contact burns. However, additional studies with longer patient follow-up are required to validate these results.

Incidentally Detected Gallbladder Carcinoma: Can F-18 FDG PET/CT Aid in Staging and Prognostication?

Purpose: Incidental gallbladder carcinoma (IGBC) is diagnosed in post-cholecystectomy specimens for benign indications, where the role of 2-fluro-2-deoxyglucose positron emission tomography/computed tomography(FDG-PET/CT) is not clearly defined. The present study aimed to assess the benefits of staging and prognosticating with FDG-PET/CT in IGBC. Materials and Methods: A retrospective observational study from a tertiary-care center from January 2010 to July 2020 was performed. The demographic, clinical, histopathological, and treatment-related histories were collected. FDG-PET/CT-image findings were compared with survival outcomes through telephonic follow-up. The chi-square test was used for comparing frequencies. The univariate and multivariate survival estimates were analyzed using the Kaplan-Meier analysis and the Cox-proportional hazard model, respectively. Log-rank test was used to compare the Kaplan-Meier curves. Results: The study included 280 postcholecystectomy participants (mean age: 52 ± 11 years; women: 227) of whom 52.1% had open surgery(146/280). Residual disease in the gallbladder fossa (54.8% vs. 36.6%, p = 0.002) and liver infiltration (32.9% vs. 22.4%, p = 0.05) were seen more frequently in open surgery compared to laparoscopic surgery, while anterior abdominal wall deposits were more common in laparoscopy(35.1% vs. 24%,p = 0.041). FDG-PET/CT changed the management in 10% (n = 28) of patients compared to contrast-enhanced CT. The median survival was 14 months (95%CI-10.3-17.7). A higher stage of the disease on the FDG-PET/CT (loco-regional disease-HR 4.86, p = 0.006; metastatic disease-HR 7.53, p < 0.001) and the presence of liver infiltration (HR-1.92, p = 0.003) were independent predictors of poor survival outcomes. Conclusion: FDG-PET/CT detects residual and metastatic disease in patients with IGBC, enabling the institution of appropriate management and acting as a tool for prognostication of survival.

FDG PET/CT in the Diagnosis and After Sunitinib Follow-up of Synchronous Base of Tongue and Thyroid Metastases From Renal Cell Carcinoma.

ABSTRACT: Renal cell carcinoma (RCC) is a leading cause of mortality among genitourinary malignancies with limited therapeutic options. The hematogenous route, lymphatic spread, and direct invasion have been documented in RCC. Usually, metastases are regional lymph nodes, lungs, bone, liver, adrenal glands, contralateral kidney, and brain. Metastases to the rare sites such as skin, breast, head and neck were documented in the literature. In the present case, we describe the synchronous metastases to the base of the tongue and thyroid gland in RCC and the response to sunitinib therapy on 18F-FDG PET/CT.

Convoluted Neural Network for Detection of Clinically Significant Prostate Cancer on 68 Ga PSMA PET/CT Delayed Imaging by Analyzing Radiomic Features.

Purpose: To assess the utility of convoluted neural network (CNN) in differentiating clinically significant and insignificant prostate cancer in patients with 68 Ga PSMA PET/CT-targeted prostate biopsy-proven prostate cancer. Methods: In this retrospective study, 142 patients with clinical suspicion of prostate cancer were evaluated who underwent 68 Ga-PSMA PET/CT imaging followed by 68 Ga-PSMA PET/CT-targeted prostate biopsy from the PSMA-avid prostate lesion. Twenty patients with no PSMA-avid lesions were excluded. Local Image Features Extraction (LifeX) software was used to extract radiomic features (RF) from delayed 68 Ga-PSMA PET/CT images of 122 patients. LifeX failed to extract radiomic features in 24 patients, and the remaining 98 were evaluated. RFs were fed to an in-built CNN of the software for computation and results were achieved. Patients with Gleason Score ≥ 7 on histopathology were labeled clinically significant prostate cancer (csPCa). The diagnostic values of radiomic features were evaluated. Results: The csPCa was revealed in 69/98 (70.4%) patients, and insignificant PCa was noticed in 29/98 (29.6%) patients. The software extracted 124 RF from the delayed 68 Ga-PSMA PET/CT images. The accuracy of the CNN was 80.7% to differentiate clinically significant and clinically insignificant prostate cancer, with an error percentage (E %) of 19.3%. The sensitivity, specificity, positive predictive, and negative predictive values were 90.3%, 57.7%, 83.6%, and 71.4%, respectively, to detect csPCa. Conclusion: CNN is a feasible pre-biopsy screening tool for identifying clinically significant prostate cancer and can be used as an adjunct in the initial diagnosis and early treatment planning. Supplementary Information: The online version contains supplementary material available at 10.1007/s13139-023-00832-3.

68Ga-FAPI PET/CT in an Interesting Case of Metastatic Pulmonary Meningioma.

ABSTRACT: Meningiomas are one of the major primary CNS tumors. Most meningiomas are benign, but rarely, these metastasize to distant organs, the lungs being the commonest site of metastasis. 18F-FDG PET/CT has been used to evaluate metastatic pulmonary meningioma. However, 68Ga-FAPI PET/CT has not yet been evaluated. The present case highlights the 68Ga-FAPI uptake in metastatic pulmonary meningioma in a postoperated case of left tentorial meningioma presenting with lung masses. Image-guided biopsy from the lung mass was consistent with metastatic meningioma.

Unusual Sites of Visceral Spread in Prostate Cancer: A Prostate-Specific Membrane Antigen-Based Theranostic Imaging Series.

ABSTRACT: Prostate cancer commonly metastasizes to lymphatic and skeletal systems with lesser frequency to visceral organs; however, uncommon visceral sites have also been found and reported as case reports. We present a series of uncommon metastatic visceral spread in prostate cancer on prostate-specific membrane antigen-based diagnostic and posttherapeutic imaging modalities.

Reverse engineering protection: A comprehensive survey of reverse vaccinology-based vaccines targeting viral pathogens.

Vaccines have significantly reduced the impact of numerous deadly viral infections. However, there is an increasing need to expedite vaccine development in light of the recurrent pandemics and epidemics. Also, identifying vaccines against certain viruses is challenging due to various factors, notably the inability to culture certain viruses in cell cultures and the wide-ranging diversity of MHC profiles in humans. Fortunately, reverse vaccinology (RV) efficiently overcomes these limitations and has simplified the identification of epitopes from antigenic proteins across the entire proteome, streamlining the vaccine development process. Furthermore, it enables the creation of multiepitope vaccines that can effectively account for the variations in MHC profiles within the human population. The RV approach offers numerous advantages in developing precise and effective vaccines against viral pathogens, including extensive proteome coverage, accurate epitope identification, cross-protection capabilities, and MHC compatibility. With the introduction of RV, there is a growing emphasis among researchers on creating multiepitope-based vaccines aiming to stimulate the host's immune responses against multiple serotypes, as opposed to single-component monovalent alternatives. Regardless of how promising the RV-based vaccine candidates may appear, they must undergo experimental validation to probe their protection efficacy for real-world applications. The time, effort, and resources allocated to the laborious epitope identification process can now be redirected toward validating vaccine candidates identified through the RV approach. However, to overcome failures in the RV-based approach, efforts must be made to incorporate immunological principles and consider targeting the epitope regions involved in disease pathogenesis, immune responses, and neutralizing antibody maturation. Integrating multi-omics and incorporating artificial intelligence and machine learning-based tools and techniques in RV would increase the chances of developing an effective vaccine. This review thoroughly explains the RV approach, ideal RV-based vaccine construct components, RV-based vaccines designed to combat viral pathogens, its challenges, and future perspectives.

18 F-FDG PET/CT in Lupus Enteritis Presenting With Fever and Abdominal Pain.

ABSTRACT: Systemic lupus erythematosus is a systemic autoimmune disease associated with various manifestations. Here, we report a compelling case of a 42-year-old woman who presented with lupus enteritis as a sole manifestation of systemic lupus erythematosus and underwent 18 F-FDG PET/CT. The resected bowel segment revealed vasculitis, and subsequent workup revealed positive antinuclear and anti-double-stranded antibody levels, confirming lupus enteritis, thus highlighting the diagnostic role of 18 F-FDG PET/CT in reaching the final diagnosis.

Gum acacia based hydrogels and their composite for waste water treatment: A review.

The non-toxic nature of natural polysaccharides and their biodegradability makes them the first choice of researchers. Various natural polysaccharides are available nowadays, like cellulose, starch, chitosan, gum acacia, guar gum etc. Among these, gum acacia is a common natural polysaccharide presently used in research and technology. It is highly biodegradable, pH stable and shows appropriate water solubility. It is used in research to synthesize hydrogels and hydrogel nanocomposites for various applications because of its antimicrobial, anti-inflammatory and excellent absorption properties. The major fields of applications include the stabilization of metal nanoparticles in the form of nanocomposites, wound dressing materials, delivery systems of various drugs and pharmaceutical agents, bioengineering, tissue engineering, purification of water, synthesis of antibacterial and antifungal composites for agricultural improvements, and many others. Due to the increasing problem of water pollution, the major focus is on research helping to reduce this problem. Gum acacia-based hydrogel and hydrogel composites were synthesized and tested for pollutant removal efficiency from wastewater by different researchers. The research on gum acacia hydrogel and their hydrogel composite applications for water purification, as well as their synthesis processes and properties, are summarized in this review article.

Structural-functional analysis of drug target aspartate semialdehyde dehydrogenase.

Aspartate ß-semialdehyde dehydrogenase (ASADH) is a key enzyme in the biosynthesis of essential amino acids in microorganisms and some plants. Inhibition of ASADHs can be a potential drug target for developing novel antimicrobial and herbicidal compounds. This review covers up-to-date information about sequence diversity, ligand/inhibitor-bound 3D structures, potential inhibitors, and key pharmacophoric features of ASADH useful in designing novel and target-specific inhibitors of ASADH. Most reported ASADH inhibitors have two highly electronegative functional groups that interact with two key arginyl residues present in the active site of ASADHs. The structural information, active site binding modes, and key interactions between the enzyme and inhibitors serve as the basis for designing new and potent inhibitors against the ASADH family.

Tubarial salivary glands on PSMA ligands based PET imaging and post 177Lu PSMA therapy scan: reiterating its importance.

68Ga-PSMA PET/CT has been routinely utilized in patients with intermediate to high-risk category prostate carcinoma for staging, biochemical recurrence and before planning the PSMA radioligand therapy (RLT). 177Lu-PSMA RLT has also been approved by FDA as a novel treatment modality in metastatic carcinoma prostate patients who have failed to other lines of treatment. The non-target organs like salivary and lacrimal glands have shown to have high physiological PSMA uptake on PSMA PET/CT. Recently, strong uptake of PSMA ligand has also been noted in the dorsal wall of the nasopharynx in the region of torus tubarius on PSMA PET/CT, which has led to the identification of new pair of salivary gland structures called "tubarial salivary glands". The clinical significance of these distinct anatomical structures lies in the fact these structures might be involved in a variety of immune related, inflammatory disorders, malignancies and could be a probable organ at risk during radiotherapy in case of head and neck malignancies, causing adverse effects to the patient.

Periprosthetic metastases in carcinoma of unknown primary: A rare association.

ABSTRACT: Septic or aseptic loosening may cause bone loss around artificial prosthesis leading to prosthesis failure. This occurrence due to metastatic infiltration of bone or surrounding soft tissues is rare but has been occasionally reported. We report a case of an elderly lady presenting with swelling and pain at the site of previous hemiarthroplasty performed for traumatic injury. On evaluation, she was found to have a lytic femur lesion with a large soft-tissue component around the prosthetic joint. Biopsy suggested a metastatic carcinoma of renal origin, but screening of kidneys did not reveal any primary lesion. She had additional skeletal metastatic lesions but no other primary site was detected either. She was given palliative radiotherapy and systemic therapy (sunitinib) based on the histologic diagnosis of renal cell origin but did not tolerate it. Thereafter, she is continuing on zoledronate every 4 weeks and best supportive management since 4 months from diagnosis.

Efficacy of Yttrium-90 Transarterial Radioembolisation in Advanced Hepatocellular Carcinoma: An Experience With Hybrid Angio-Computed Tomography and Glass Microspheres.

Background: Hepatocellular carcinoma is one of the most common malignancies worldwide. Transarterial radioembolisation (TARE) involves selective intra-arterial administration of microspheres loaded with a radioactive compound like Yttrium-90 (Y-90). Conventionally, C-arm-based cone-beam computed tomography has been extensively used during TARE. However, angio-computed tomography (CT) is a relatively new modality which combines the advantages of both fluoroscopy and fCT. There is scarce literature detailing the use of angio-CT in Y90 TARE. Methods: This was a retrospective study of primary liver cancer cases in which the TARE procedure was done from November 2017 to December 2021. Glass-based Y-90 microspheres were used in all these cases. All the cases were performed in the hybrid angio-CT suite. A single photon emission computed tomography-computed comography (SPECT-CT) done postplanning session determined the lung shunt fraction and confirmed the accurate targeting of the lesion. Postdrug delivery, positron emission tomography-computed tomography (PET-CT) was obtained to confirm the distribution of the Y-90 particles. The technical success, median follow-up, objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) were recorded. Results: A total of 56 hepatocellular carcinoma patients underwent TARE during this period, out of which 36 patients (30 males and 6 females) underwent Y90 TARE. The aetiology of cirrhosis included non-alcoholic steatohepatitis (NASH) (11), hepatitis C (HCV) (11), hepatitis B (HBV) (9), metabolic dysfunction and alcohol-associated liver disease (MetALD) (2), alcoholic liver disease (ALD) (1), cryptogenic (1), and autoimmune hepatitis (AIH) (1). The technical success was 100 % and the median follow-up was 7 months (range: 1-32 months). The median OS was 15 months (range 10.73-19.27 months; 95 % CI) and the median local PFS was 4 months (range 3.03-4.97 months; 95 % CI). The ORR (best response, CR + PR) was 58 %. No major complications were seen in this study. Conclusion: TARE is a viable option for liver cancer in all stages, but more so in the advanced stages. The use of angio-CT in TARE aids in the precise delivery of the particles to the tumour and avoids non-target embolisation.

68Ga-DOTA.SA.FAPi as a Versatile Diagnostic Probe for Various Epithelial Malignancies: A Head-to-Head Comparison with 18F-FDG.

RATIONALE AND OBJECTIVES: Fibroblast Activation Protein (FAP) expressing cancer-associated fibroblasts has been a major breakthrough causing a paradigm shift in targeted theranostics focusing on the tumor microenvironment. In this study, a squaric acid derivative DOTA.SA.FAPi (SA.FAPi) has been evaluated as a potential diagnostic probe in diverse epithelial cancers and compared to the standard-of-care 18F-FDG. METHODS: 25 patients enrolled in this prospective study underwent 18F-FDG and 68Ga-SA.FAPi PET scans on two different days. For biodistribution, standardized uptake values (SUV) were computed by delineating region-of-interest on various body organs. For comparative analysis in disease identification, lesion tracer uptake was quantified using SUVs corrected for lean body mass (SUL), SUVmax, tumor-to-background ratio (TBR) with liver and blood pool as the reference, total lesion glycolysis (TLG for 18F-FDG) and total lesion FAP expression (TLF for 68Ga-SA.FAPi). RESULTS: 25 patients (mean age: 58 ± 8 years) with four types of cancers including hepatocellular carcinoma (HCC, 56% of cohort), gall bladder carcinoma (GB Ca, 12%), adrenocortical carcinoma (ACC, 16%), and breast carcinoma (breast Ca, 16%) were prospectively evaluated. Physiological tracer uptake of 68Ga-SA.FAPi was noted in the salivary glands, thyroid, liver, pancreas, muscles and kidneys with variable uptake in the lacrimal glands, extra-ocular muscles, oral mucosa and uterus. Lesion-based comparative analysis between both the radiotracers demonstrated complete concordant findings in detection of all primary lesions and distant metastases in liver, bones, adrenals and peritoneum whereas discordant findings were noted in lung nodules (20%) and lymph nodes (13%). In overall analysis, 68Ga-SA.FAPi exhibited significantly higher SUVmax (10.3 vs 8.8, p-0.019), SULpeak (6.8 vs 4.9, p-0.000) and SULavg (5.4 vs 4.1, p-0.019) in comparison to 18F-FDG whereas TBR was comparable for both the tracers [TBRLiver: median 1.9 (IQR: 2.6-1.4) vs 1.8 (2.6-1.1), p-0.275; TBRBloodpool: 2.1 (3.7-1.4) vs 2.0 (2.7-1.4), p-0.207]. In subcategorical analysis, 68Ga-SA.FAPi demonstrated higher SUVmax, SULpeak and SULavg values for primary disease (SUVmax: 14.8 (18.7-9.7) vs (12.9-6.6), p-0.087; SULpeak: 8.2 (11.2-6.8) vs 6.3 (8.5-4.4), p-0.037; SULavg: 6.9 ± 2.5 vs 5.1 ± 2.2, p-0.023] and distant metastases (8.8 vs 7.2, p-0.038); 6.3 (8.8-4.4) vs 3.6 (4.4-2.0), p-0.000; 5.4 vs 3.5, p-0.000] whereas comparable values were noted for both the tracers in nodal metastases [9 (13.5-4.1) vs 8 (12.7-4.7), p-0.726; 4.5 (6.2-1.8) vs 4.3 (5.7-2.2), p-0.727; 4.1 ± 2.3 vs 3.7 ± 1.8, p-0.129]. In primary disease, highest 68Ga-SA.FAPi avidity was noted in ACC followed by GB Ca and HCC. In distant metastases, gall bladder, lung and skeletal lesions demonstrated higher 68Ga-SA.FAPi avidity. Moreover, 68Ga-SA.FAPi identified five additional lung lesions which were missed by 18F-FDG in one case of ACC. CONCLUSION: 68Ga-SA.FAPi emerged as an effective, versatile diagnostic probe for imaging various epithelial malignancies similar to 18F-FDG.

Potential role of 68Ga-PSMA PET/CT in metastatic renal cell cancer: A prospective study.

PURPOSE: Prostate-specific membrane antigen (PSMA), in addition to its utility in prostate cancer, is also an angiogenic imaging marker for hypervascular tumors like renal cell carcinoma (RCC). Our study aims to assess the potential role of 68Ga-PSMA-11 positron emission tomography (PET)/CT in metastatic RCC and compare it with contrast-enhanced computed tomography (CECT). METHODS: Biopsy-proven RCC patients with known or suspected distant metastases who underwent 68Ga-PSMA-11 PET/CT for staging/restaging were prospectively recruited. Those patients who had undergone 18F-FDG PET/CT within six weeks of 68Ga-PSMA PET/CT were also included retrospectively for comparative analysis. A patient-based and lesion-based analysis was done to compare the lesion detection rates of CECT, 68Ga-PSMA-11 PET and 18F-FDG PET. PET-based quantitative parameters were also compared between both the PET modalities. Impact of baseline parameters on survival was assessed using Cox regression analysis. A p-value of < 0.05 was considered significant. RESULTS: Thirty-seven patients with median age 60 years ± 13 years (range = 26-76 years) were included in the study. Twenty-seven patients had clear cell (cc) RCC, six had papillary RCC (pRCC), and one each had an eosinophilic variant of ccRCC, collecting duct RCC, translocation RCC and poorly differentiated RCC. 68Ga-PSMA-11 PET performed better in detecting marrow and equivocal bone lesions and worse in detecting liver lesions compared to CECT. 68Ga-PSMA-11 PET-based angiogenic tumor burden estimation using Total Lesion-PSMA (TL-PSMA) and PSMA-Total volume (PSMA-TV) had a prognostic impact on the survival of patients. 68Ga-PSMA-11 PET also detected more lesions and showed significantly higher SUVmax than 18F-FDG PET. CONCLUSION: 68Ga-PSMA-11 PET/CT performs better than CECT and 18F-FDG PET/CT in metastatic evaluation and has prognostic value in the management of clear cell RCC.

Unusual Perineal Metastasis in a Case of Prostate Cancer on 68 Ga-PSMA-11 PET/CT.

ABSTRACT: Prostate cancer is the fifth leading cause of death in the male population worldwide. 68 Ga-PSMA PET/CT has proved to be an excellent modality with greater accuracy for nodal and bone/visceral metastases staging than bone scintigraphy and CT scan, with high sensitivity and specificity. Common sites of metastasis include bone (84%), lymph nodes (10.6%), liver (10.2%), lung, and pleura (9.1%); however, metastasis to the skin is quite rare (≤0.36%). The present case demonstrates PSMA-avid perineal metastasis in a patient of prostate cancer postchemoradiotherapy on 68 Ga-PSMA PET/CT scan.

68 Ga-PSMA-11 Uptake in a Large Fibroadenoma in a Male Axillary Accessory Breast.

ABSTRACT: Prostate-specific membrane antigen PET imaging has revolutionized the role of prostate cancer diagnosis and management, with very high sensitivity and specificity. To prevent misdiagnosis and for accurate therapy planning, prostate-specific membrane antigen (PSMA) uptake in nonprostatic diseases needs to be recognized correctly. Besides the physiological PSMA expression, 68 Ga-PSMA-11 uptake has been mentioned in multiple oncological and nononcological lesions. The present case report exhibits 68 Ga-PSMA-11 uptake in fibroadenoma in a male accessory breast in the right axillary region.

18 F-FDG PET/CT in Renal Allograft Tuberculosis Mimicking as Posttransplant Malignancy.

ABSTRACT: The most common complications after the renal transplant are infections and malignancies, including posttransplant lymphoproliferative disorders. Tubercular infection in renal allograft recipients is a relatively rare entity. However, nonspecific constitutional symptoms often delay diagnosis, leading to significant morbidity and mortality. We present the 18 F-FDG PET/CT findings in a patient with renal allograft tuberculosis who had clinical and imaging suspicion of posttransplant lymphoproliferative disorder or renal cell carcinoma. Histopathology from the renal lesion revealed tuberculosis.

Incidental Detection of 68 Ga-DOTA-RGD-2 Uptake in Uterine Fibroid.

ABSTRACT: Uterine fibroids are benign tumors originating from the smooth muscle cells of the myometrium seen in approximately 20%-50% of women of reproductive age. The Arg-Gly-Asp (RGD) binds to αvß3 integrin expressed on the surface of angiogenic blood vessels or tumor cells. 18 F-FDG PET/CT has been used to evaluate uterine fibroids, with moderate 18 F-FDG uptake. However, angiogenesis imaging in uterine fibroids has not been evaluated. The present case presents a rare finding of RGD uptake in the uterine fibroid on 68 Ga-DOTA-RGD-2 PET/CT in a patient who underwent angiogenesis imaging for left ankle joint pain and swelling.

Recurrent mutations in Refractory/Relapsed Diffuse Large B cell Lymphoma by targeted gene sequencing.

Introduction-Whole genome sequencing of diffuse large B-cell lymphoma [DLBCL] has identified recurrent mutations involved in pathogenesis and potentially affecting response to therapy. In this pilot study, a targeted gene panel was created to identify mutations associated with relapse/refractoriness. Material and methods- A 14-gene targeted panel was designed to sequence thirteen patients who were in remission and nine eight cases that had relapsed/refractory to treatment. A paired diagnostic biopsy and a relapse biopsy were sequenced to find genes repeatedly altered in relapse. Results- A total of 751 nonsynonymous and truncating mutations were identified. Truncated mutations in NOTCH1, TNFAIP3, and CD58 were associated with poor treatment outcomes. In cases that did not respond to treatment, a high number of mutations were found in the EZH2 gene, followed by the DNA-binding domain of TP53 and MYD88. Termination mutations in the intracellular domain of NOTCH were found in 75% of non-responsive cases. Co-occurrence of loss of function mutations of TNFAIP3 and missense mutations in MYD88 was associated with a non-responsive cohort. Discussion-The study highlights mutations associated with chemotherapeutic response in DLBCL with implications for initial diagnostic biopsy response prediction.