Oncology

A Plasma Proteomics-Based Model for Clinical Benefit Prediction in Small Cell Lung Cancer Patients Receiving Immunotherapy (2024)

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Type of publication:

Conference abstract

Author(s):

Gandara D.R.; Carbone D.P.; Dicker A.P.; Christopoulos P.; Puzanov I.; Jain P.; Farrugia D.; Brown S.; Moskovitz M.; Bar J.; Hassani A.; *Chatterjee A.; Abu-Amna M.; Polychronis A.; Brewster A.; Lou Y.; VanderWalde N.A.; Gottfried M.; Lahav C.; Lowenthal G.; Sela I.; Harel M.; Elon Y.; Schneider M.A.

Citation:

Journal of Thoracic Oncology. Conference: The 2024 World Conference on Lung Cancer. San Diego United States. 19(10 Supplement) (pp S354-S355), 2024. Date of Publication: October 2024.

Abstract:

Introduction: Small cell lung cancer (SCLC) is an aggressive disease with limited treatment options. Immune checkpoint inhibitor (ICI) therapy with concurrent chemotherapy is the preferred first-line treatment for patients with extensive-stage SCLC. However, the addition of ICIs to chemotherapy only modestly improves clinical outcomes while posing a risk of ICI-related toxicities. Thus, identifying patients likely to benefit from ICIs is critical for optimizing treatment decisions. Here, we describe a test derived from a novel computational model that analyzes pretreatment plasma proteomic profiles to predict clinical outcomes in patients with SCLC receiving ICI-based therapies. Method(s): An observational study collected pretreatment plasma samples from 79 patients with extensive-stage SCLC treated with ICI-based therapy (NCT04056247). Proteomic profiling of plasma samples was performed using aptamer-based technology, measuring approximately 7000 proteins per sample. A machine learning model was developed to predict the clinical benefit (CB) from ICI-based therapy, where CB was defined as 6-month progression-free survival. Given the limited cohort size, CB prediction was achieved by integrating two computational models. Model 1, based on 146 plasma proteomic biomarkers, was developed from the SCLC dataset using cross-validation. Model 2, based on a 4-protein signature, was developed from a previously reported NSCLC dataset (Christopoulos et al. JCO prec. onc. 2024). The hybrid model stratified patients into two groups (i.e., 'positive' or 'negative') based on a pre-defined CB probability threshold. Bioinformatic analysis of the SCLC-specific proteomic biomarkers was performed to gain insight into the potential mechanisms driving ICI therapeutic benefit and resistance in SCLC. Result(s): The model displayed a robust predictive capability, as demonstrated by the area under the curve (AUC) of the receiver operating characteristic (ROC) plot of 0.63 (p-value = 0.02) and a high correlation between the predicted CB (i.e., model output) and the observed CB rate (R2 = 0.93). Furthermore, overall survival (OS) was significantly longer in patients stratified to the positive group compared to those in the negative group. Median OS was 14 months versus 8.8 months in positive versus negative patient groups (Hazard ratio = 0.47, 95% Confidence interval: 0.25-0.90, p-value = 0.02). Bioinformatic analysis of model proteins revealed significant enrichment of lung tumor-associated proteins, poor prognostic factors in lung cancer, extracellular matrix-related proteins, intermediate filaments, and replicative immortality (Fisher exact test; FDR<0.1). Multiple model proteins are also known to be involved in fibroblast growth factor signaling and glutathione metabolism. Given their association with different treatment resistance mechanisms, such proteins represent potential targets for intervention. Conclusion(s): We describe preliminary results from a novel pretreatment plasma proteomics-based predictive model that can potentially inform treatment decisions for patients with SCLC. Bioinformatic analysis demonstrates that the model is based on a composite of biologically and clinically relevant biomarkers. The potential clinical utility of this model is being investigated in a large prospective clinical trial.

Hypoxia-associated gene signatures are not prognostic in high-risk localised prostate cancers undergoing androgen deprivation therapy with radiotherapy (2024)

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Type of publication:

Journal article

Author(s):

Reardon, Mark D; Bibby, Becky As; Thiruthaneeswaran, Niluja; Pereira, Ronnie R; Mistry, Hitesh; More, Elisabet; Tsang, Yatman; Vickers, Alexander; Reeves, Kimberley; Henry, Ann; *Denley, Helen; Wylie, James; Spratt, Daniel; Hakansson, Alex; Ryu, Monica; Smith, Tim Ad; Hoskin, Peter J; Bristow, Robert; Choudhury, Ananya; West, Catharine Ml.

Citation:

International Journal of Radiation Oncology, Biology, Physics. 2024 Oct 16.

Abstract:

PURPOSE: Men with high-risk prostate cancer (PCa) are treated with androgen deprivation therapy (ADT) and radiotherapy, but the disease reoccurs in 30% of patients. Biochemical recurrence of PCa after treatment is influenced by tumour hypoxia. Tumours with high levels of hypoxia are aggressive, resistant to treatment, and have increased metastatic capacity. Gene expression signatures derived from diagnostic biopsies can predict tumour hypoxia and radiosensitivity, but none are in routine clinical use, due to concerns about the applicability of these biomarkers to new patient cohorts. There has been no or limited testing in cohorts of high-risk PCa. METHODS AND MATERIALS: We generated transcriptomic data for cohorts of high-risk PCa patients. Patients were treated with ADT followed by external beam radiotherapy with or without a brachytherapy boost. Biomarkers curated from the literature were calculated from pre-treatment biopsy gene expression data. The primary endpoint for survival analyses was biochemical recurrence-free survival (bRFS) and the secondary endpoints were distant metastasis-free survival (DMFS) and overall survival. RESULTS: The performance of the selected biomarkers was poor, with none achieving prognostic significance for bRFS or DMFS in any cohort. The brachytherapy boost cohort received shorter durations of ADT than the conventionally fractionated or hypofractionated cohorts (Wilcoxon rank sum test, p=2.1×10-18 and 2.3×10-10 respectively) and had increased risk of distant metastasis (log-rank test, p=8×10-4). There were no consistent relationships between biomarker score and outcome for any of the endpoints. CONCLUSIONS: Hypoxia and radiosensitivity biomarkers were not prognostic in high-risk PCa patients treated with ADT plus radiotherapy. We speculate that the lack of prognostic capability could be caused by the variable hypoxia-modifying effects of the ADT that these high-risk patients received before and during definitive treatment with radiotherapy. A deeper understanding of biomarker construction, performance and inter-cohort transferability in relation to patient characteristics, sample handling and treatment modalities is required before hypoxia biomarkers can be recommended for routine clinical use in the pre-treatment setting.

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LBA70 Adding metformin to androgen deprivation therapy (ADT) for patients (pts) with metastatic hormone sensitive prostate cancer (mHSPC): Overall survival (OS) results from the multi-arm, multi-stage randomised platform trial STAMPEDE (2024)

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Type of publication:

Conference abstract

Author(s):

Gillessen S.; Murphy L.R.; James N.D.; Sachdeva A.; Attard G.; Jones R.J.; Adler A.; El-Taji O.; Varughese M.; Gale J.; Brown S.J.; Srihari N.N.; Millman R.; Matheson D.; Amos C.L.; Murphy C.; McAlpine C.; Parmar M.K.; Brown L.C.; Clarke N.

Citation:

Annals of Oncology. Conference: ESMO Congress 2024. Barcelona Spain. 35(Supplement 2) (pp S1258-S1259), 2024. Date of Publication: September 2024.

Abstract:

Background: Metformin is a widely used, well tolerated anti-diabetic agent. Several studies suggest metformin has anti-cancer activity in different malignancies, including prostate cancer. We hypothesised that metformin also reduces the development of ADT-induced metabolic adverse effects, possibly improving OS via these mechanisms. Method(s): Non-diabetic pts with mHSPC were randomly allocated 1:1 to standard of care (SOC) or SOC+metformin within STAMPEDE. SOC included ADT +/- radiotherapy +/- docetaxel +/- androgen receptor pathway inhibitor (ARPI). The primary outcome was OS. Target hazard ratio (HR) 0.8 (92% power, 2.5% 1-sided significance). 7 subgroup analyses were pre-specified but not pre-powered. Result(s): 1874 pts with mHSPC were randomised Sep2016-Mar2023. Arms were well balanced: median age 69 years, IQR 63-73; median PSA 84ng/ml, IQR 24-352; de novo 1758 (94%) vs relapsed 116 (6%). Planned SOC included 82% Docetaxel and 3% ARPI. After a median follow-up of 60 months, the HR for OS between arms was 0.91 (p=0.148; 95% CI 0.80-1.03). The median (95%CI) OS was 63 (58-69) and 69 (63-73) months in the SOC and SOC+metformin arms respectively. In patients with high versus low volume disease (CHAARTED def), HR was 0.79 (p=0.006; 0.66-0.93) and 1.0 (p=0.992; 0.79-1.26) respectively. The interaction p-value = 0.086. For progression-free survival: Overall HR was 0.92 (p=0.164; 0.81-1.04) with HRs of 0.76 (p=0.001; 0.64-0.89) and 1.10 (p=0.401; 0.88-1.37) in the high and low volume subgroups respectively, interaction p-value = 0.006. Metabolic parameters that improved significantly with metformin included reduced weight gain, fasting glucose, HbA1c and total and LDL cholesterol. Fewer patients developed a metabolic syndrome. Adverse events (AE) >=grade 3 were reported in 52% and 57% in the SOC and SOC+metformin arms, respectively; Gastrointestinal AEs increased with metformin. Conclusion(s): Metformin does not improve survival in unselected metastati

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Stratification to Neoadjuvant Radiotherapy in Rectal Cancer by Regimen and Transcriptional Signatures (2024)

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Type of publication:
Journal article

Author(s):
Mahmood U; Blake A; Rathee S; Samuel L; Murray G; Sebag-Montefiore D; *Gollins S; West NP; Begum R; Bach SP; Richman SD; Quirke P; Redmond KL; Salto-Tellez M; Koelzer VH; Leedham SJ; Tomlinson I; Dunne PD; Buffa FM; Maughan TS; Domingo E

Citation:
Cancer Research Communications. 4(7):1765-1776, 2024 Jul 01.

Abstract:
Response to neoadjuvant radiotherapy (RT) in rectal cancer has been associated with immune and stromal features that are captured by transcriptional signatures. However, how such associations perform across different chemoradiotherapy regimens and within individual consensus molecular subtypes (CMS) and how they affect survival remain unclear. In this study, gene expression and clinical data of pretreatment biopsies from nine cohorts of primary rectal tumors were combined (N = 826). Exploratory analyses were done with transcriptomic signatures for the endpoint of pathologic complete response (pCR), considering treatment regimen or CMS subtype. Relevant findings were tested for overall survival and recurrence-free survival. Immune and stromal signatures were strongly associated with pCR and lack of pCR, respectively, in RT and capecitabine (Cap)/5-fluorouracil (5FU)-treated patients (N = 387), in which the radiosensitivity signature (RSS) showed the strongest association. Upon addition of oxaliplatin (Ox; N = 123), stromal signatures switched direction and showed higher chances to achieve pCR than without Ox (p for interaction 0.02). Among Cap/5FU patients, most signatures performed similarly across CMS subtypes, except cytotoxic lymphocytes that were associated with pCR in CMS1 and CMS4 cases compared with other CMS subtypes (p for interaction 0.04). The only variables associated with survival were pCR and RSS. Although the frequency of pCR across different chemoradiation regimens is relatively similar, our data suggest that response rates may differ depending on the biological landscape of rectal cancer. Response to neoadjuvant RT in stroma-rich tumors may potentially be improved by the addition of Ox. RSS in preoperative biopsies provides predictive information for response specifically to neoadjuvant RT with 5FU. SIGNIFICANCE: Rectal cancers with stromal features may respond better to RT and 5FU/Cap with the addition of Ox. Within patients not treated with Ox, high levels of cytotoxic lymphocytes associate with response only in immune and stromal tumors. Our analyses provide biological insights about the outcome by different radiotherapy regimens in rectal cancer.

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Patients' Preferences for Cytoreductive Treatments in Newly Diagnosed Metastatic Prostate Cancer: The IP5-MATTER Study (2024)

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Type of publication:
Journal article

Author(s):
Connor M.J.; Genie M.; Dudderidge T.; Wu H.; Sukumar J.; Beresford M.; Bianchini D.; Goh C.; Horan G.; Innominato P.; Khoo V.; Klimowska-Nassar N.; Madaan S.; Mangar S.; McCracken S.; Ostler P.; Paisey S.; Robinson A.; Rai B.; Sarwar N.; *Srihari N.; Jayaprakash K.T.; Varughese M.; Winkler M.; Ahmed H.U.; Watson V.

Citation:
European Urology Oncology. (no pagination), 2024. Date of Publication: 2024.

Abstract:
Background and objective: Cytoreductive treatments for patients diagnosed with de novo synchronous metastatic hormone-sensitive prostate cancer (mHSPC) confer incremental survival benefits over systemic therapy, but these may lead to added toxicity and morbidity. Our objective was to determine patients' preferences for, and trade-offs between, additional cytoreductive prostate and metastasis-directed interventions. Method(s): A prospective multicentre discrete choice experiment trial was conducted at 30 hospitals in the UK between December 3, 2020 and January 25, 2023 (NCT04590976). The individuals were eligible for inclusion if they were diagnosed with de novo synchronous mHSPC within 4 mo of commencing androgen deprivation therapy and had performance status 0-2. A discrete choice experiment instrument was developed to elicit patients' preferences for cytoreductive prostate radiotherapy, prostatectomy, prostate ablation, and stereotactic ablative body radiotherapy to metastasis. Patients chose their preferred treatment based on seven attributes. An error-component conditional logit model was used to estimate the preferences for and trade-offs between treatment attributes. Key findings and limitations: A total of 352 patients were enrolled, of whom 303 completed the study. The median age was 70 yr (interquartile range [IQR] 64-76) and prostate-specific antigen was 94 ng/ml (IQR 28-370). Metastatic stages were M1a 10.9% (33/303), M1b 79.9% (242/303), and M1c 7.6% (23/303). Patients preferred treatments with longer survival and progression-free periods. Patients were less likely to favour cytoreductive prostatectomy with systemic therapy (Coef. -0.448; [95% confidence interval {CI} -0.60 to -0.29]; p < 0.001), unless combined with metastasis-directed therapy. Cytoreductive prostate radiotherapy or ablation with systemic therapy, number of hospital visits, use of a "day-case" procedure, or addition of stereotactic ablative body radiotherapy did not impact treatment choice. Patients were willing to accept an additional cytoreductive treatment with 10 percentage point increases in the risk of urinary incontinence and fatigue to gain 3.4 mo (95% CI 2.8-4.3) and 2.7 mo (95% CI 2.3-3.1) of overall survival, respectively. Conclusions and clinical implications: Patients are accepting of additional cytoreductive treatments for survival benefit in mHSPC, prioritising preservation of urinary function and avoidance of fatigue. Patient Summary: We performed a large study to ascertain how patients diagnosed with advanced (metastatic) prostate cancer at their first diagnosis made decisions regarding additional available treatments for their prostate and cancer deposits (metastases). Treatments would not provide cure but may reduce cancer burden (cytoreduction), prolong life, and extend time without cancer progression. We reported that most patients were willing to accept additional treatments for survival benefits, in particular treatments that preserved urinary function and reduced fatigue.

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Patients' Preferences for Cytoreductive Treatments in Newly Diagnosed Metastatic Prostate Cancer: The IP5-MATTER Study (2024)

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Type of publication:
Journal article

Author(s):
Connor, Martin J; Genie, Mesfin; Dudderidge, Tim; Wu, Hangjian; Sukumar, Johanna; Beresford, Mark; Bianchini, Diletta; Goh, Chee; Horan, Gail; Innominato, Pasquale; Khoo, Vincent; Klimowska-Nassar, Natalia; Madaan, Sanjeev; Mangar, Stephen; McCracken, Stuart; Ostler, Peter; Paisey, Sangeeta; Robinson, Angus; Rai, Bhavan; Sarwar, Naveed; *Srihari, Narayanan; Jayaprakash, Kamal Thippu; Varughese, Mohini; Winkler, Mathias; Ahmed, Hashim U; Watson, Verity.

Citation:
European Urology Oncology. 2024 Jul 06. [epub ahead of print]

Abstract:
BACKGROUND AND OBJECTIVE: Cytoreductive treatments for patients diagnosed with de novo synchronous metastatic hormone-sensitive prostate cancer (mHSPC) confer incremental survival benefits over systemic therapy, but these may lead to added toxicity and morbidity. Our objective was to determine patients' preferences for, and trade-offs between, additional cytoreductive prostate and metastasis-directed interventions. METHODS: A prospective multicentre discrete choice experiment trial was conducted at 30 hospitals in the UK between December 3, 2020 and January 25, 2023 (NCT04590976). The individuals were eligible for inclusion if they were diagnosed with de novo synchronous mHSPC within 4 mo of commencing androgen deprivation therapy and had performance status 0-2. A discrete choice experiment instrument was developed to elicit patients' preferences for cytoreductive prostate radiotherapy, prostatectomy, prostate ablation, and stereotactic ablative body radiotherapy to metastasis. Patients chose their preferred treatment based on seven attributes. An error-component conditional logit model was used to estimate the preferences for and trade-offs between treatment attributes. KEY FINDINGS AND LIMITATIONS: A total of 352 patients were enrolled, of whom 303 completed the study. The median age was 70 yr (interquartile range [IQR] 64-76) and prostate-specific antigen was 94 ng/ml (IQR 28-370). Metastatic stages were M1a 10.9% (33/303), M1b 79.9% (242/303), and M1c 7.6% (23/303). Patients preferred treatments with longer survival and progression-free periods. Patients were less likely to favour cytoreductive prostatectomy with systemic therapy (Coef. -0.448; [95% confidence interval {CI} -0.60 to -0.29]; p < 0.001), unless combined with metastasis-directed therapy. Cytoreductive prostate radiotherapy or ablation with systemic therapy, number of hospital visits, use of a "day-case" procedure, or addition of stereotactic ablative body radiotherapy did not impact treatment choice. Patients were willing to accept an additional cytoreductive treatment with 10 percentage point increases in the risk of urinary incontinence and fatigue to gain 3.4 mo (95% CI 2.8-4.3) and 2.7 mo (95% CI 2.3-3.1) of overall survival, respectively. CONCLUSIONS AND CLINICAL IMPLICATIONS: Patients are accepting of additional cytoreductive treatments for survival benefit in mHSPC, prioritising preservation of urinary function and avoidance of fatigue. PATIENT SUMMARY: We performed a large study to ascertain how patients diagnosed with advanced (metastatic) prostate cancer at their first diagnosis made decisions regarding additional available treatments for their prostate and cancer deposits (metastases). Treatments would not provide cure but may reduce cancer burden (cytoreduction), prolong life, and extend time without cancer progression. We reported that most patients were willing to accept additional treatments for survival benefits, in particular treatments that preserved urinary function and reduced fatigue.

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A Systemic Review of Primary Malignant Long Bone Tumors in Children and Adolescents (2024)

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Type of publication:
Systematic Review

Author(s):
Khan, M; *Patel, R; *Youssef, M; Banerjee, R; Pardiwala, A; Belen, C.

Citation:
Acta Chirurgiae Orthopaedicae et Traumatologiae Cechoslovaca. 91(2):77-87, 2024.

Abstract:
PURPOSE OF THE STUDY: Managing bone tumours is complex, relying on limited evidence, expert opinions, and retrospective reviews. Multidisciplinary approaches and early diagnosis are crucial for better outcomes, especially in young patients with growing skeletons. The aim of this systemic review and meta-analysis is to give a comprehensive review of common malignant tumors affecting long bones in children and adolescents. MATERIAL AND METHODS: A PubMed/Medline search for "primary malignant long bone tumours in children" initially retrieved 1120 papers, which were subsequently narrowed down to 110 articles based on inclusion and exclusion criteria. These articles were reviewed, focusing on clinical presentation, diagnostic workup, treatment options, surgical planning, and variations in presentation, including rare tumours. The two most commonly reported tumours were osteosarcoma and Ewing sarcoma, leading to the division of studies into five groups. The inclusion criteria encompassed malignancies in patients aged 2-25 years, work-up, imaging, surgical treatment, rare tumour case reports, and surgical management principles, resulting in a heterogeneous group of articles. To enhance categorisation, it was clarified that studies with 10 or more cases were considered retrospective reviews. RESULTS: Reviewing of results thus demonstrate that the two likely tumours in children under consideration were osteosarcoma and Ewing sarcoma. Their presentation findings and clinical features were discussed in detail in the review. It is worth noting here that in case of differential diagnosis this should be the first on the list. DISCUSSION AND CONCLUSIONS: Although focus of literature is more on the two most common tumours. However, rare tumours should be considered as they can mimic these common tumors.

Persistent sweet taste dysgeusia diagnosed with probable SIADH: Unmasking underlying lung cancer in a high-risk individual: A case report (2024)

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Type of publication:
Journal article

Author(s):
*Praveenkumar Katarki, *Lyudmyla Nod, *Nawaid Ahmad

Citation:
Clinical Medicine 2024. Volume 24, Supplement, April 2024

Abstract:
Introduction: The timely identification of lung cancer is critical but difficult due to its broad and often nonspecific symptoms. This case report highlights the importance of taking into consideration unusual manifestations, especially in persons at high risk, and emphasises the necessity of a thorough diagnostic approach. Case presentation: A 66-year-old female referred from the general practitioner (GP)to the same day emergency care (SDEC) with persistent sweet taste dysgeusia, headache and hyponatraemia (118). Notably, her chest X-ray was unremarkable (image 1) despite a 30-pack-year smoking history. Initial suspicion was on drug-induced syndrome of inappropriate antidiuretic hormone secretion (SIADH) potentially due to her long-term use of gabapentin (for 25 years), as reported in a retrospective study conducted in Sweden.1 However, an inadequate response to treatment prompted further investigation, CT thorax (image 2) revealing primary lung malignancy with liver metastases. A histological evidence is awaited, the radiological diagnosis of the lung cancer was considered after discussion at Lung cancer at the multidisciplinary team. Discussion: This case further strengthens the growing body of evidence suggesting sweet taste dysgeusia as a rare paraneoplastic symptom of small cell lung cancer (SCLC), as documented in previous studies.2–5 The potential mechanisms underlying this phenomenon remain unclear, but possibilities include ectopic antidiuretic hormone (ADH) production4, tumour-derived substances affecting taste pathways5 or metabolic disturbances associated with the malignancy itself.4,5 This case underscores the critical need for heightened suspicion for malignancy, especially in high-risk individuals like smokers, even when presenting with seemingly common diagnoses like SIADH. Additionally, it highlights the limitations of solely relying on initial symptoms and investigations. Notably, the patient had an unremarkable chest X-ray (image 1) despite a significant 40-pack-year smoking history, emphasising the importance of employing a comprehensive diagnostic approach. This approach should encompass a detailed medical history and risk factor evaluation, thorough physical examination for potential malignancy signs, targeted laboratory investigations including electrolytes, renal function, and tumour markers, and appropriate imaging studies based on clinical suspicion and initial findings (chest X-ray, CT scan). While this case showcases the potential of sweet taste dysgeusia as a paraneoplastic sign, several limitations must be acknowledged. First, this symptom remains rare and its specificity for SCLC is uncertain; Second, potential selection bias towards atypical presentations could overestimate its prevalence.7 Finally, confounding factors like hyponatraemia itself can affect taste perception.4. Conclusion: This case contributes to the growing evidence suggesting sweet taste dysgeusia could be an atypical early warning sign of lung cancer, particularly in high-risk individuals. While limitations exist and further research is warranted, this association necessitates further investigation due to its potential implications for earlier detection and improved patient outcomes. Recognising limitations, advocating for further research, and emphasising potential clinical impact contribute to ongoing efforts in improving lung cancer diagnosis and management.

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Reflector-guided localisation of non-palpable breast lesions: A prospective evaluation of the SAVI SCOUT system on 137 patients (2024)

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Type of publication:
Conference abstract

Author(s):
Taj S.; Han S.; *Lefroy R.; Hajiesmaeili H.; Alamgir C.F.; Rahman E.; Khosla M.; Bowen N.; Troman P.; Vidya R.; Verma R.; Mylvaganam S.; Clarke D.; Ingle H.; Sircar T.

Citation:
European Journal of Surgical Oncology. Conference: The Association of Breast Surgery Conference 2024. Bournemouth International Centre, Bournemouth United Kingdom. 50(Supplement 1) (no pagination), 2024. Article Number: 108190. Date of Publication: May 2024.

Abstract:
Introduction: Traditionally, wire-guided localisation has been the gold-standard for localising non-palpable breast lesions. However, this method has some limitations, including patient discomfort, wire migration and scheduling radiology appointments on the day of surgery, causing delay in start of theatre list. Various wire-less alternatives have been developed. Therefore, the aim of this study was to evaluate the safety and effectiveness of the SAVI SCOUT localisation technique. Method(s): This was a prospective study of 137 consecutive patients with SAVI SCOUT reflector, deployed between December 2020 and November 2023. We studied the rate of successful localisation and retrieval of SCOUT, imaging modality used for localisation, re-excision rate, pathology, median weight of specimen and SCOUT-related complications. Result(s): A total of 137 SAVI SCOUT reflectors were deployed in 137 consecutive patients undergoing breast conserving surgery for non-palpable lesions which included malignancy 97% (n=133), high risk lesions 2.18% (n=3) and benign lesion in 0.72% (n=1). The rate of radiological localisation and retrieval of the reflector at surgery was 97.8% (n=134) and 100% (n=137) respectively. The most common modality for localisation was ultrasound 97% (n=133). The median specimen weight was 21.5gm. The mean duration between deployment day and surgery was 2 days (range 0-30). The re-excision rate was 8% (n=11). There was no specific technique-related surgical complication. Conclusion(s): Our study demonstrates that the SAVI SCOUT localisation system is a safe, effective, and reliable localization modality for non-palpable breast lesions with low re-excision rate.

Frequency of CLAR and JAK2 mutations in Sudanese chronic myeloid leukemia patients with Philadelphia-positive disease (2024)

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Type of publication:
Journal article

Author(s):
Yasin E.B.; *Yasin A.

Citation:
Asian Journal of Pharmaceutical and Clinical Research. 16(8) (pp 133-137), 2023. Date of Publication: August 2023.

Abstract:
Objective: It is well-established that myeloproliferative diseases coexist with CLAR and JAK2. In Ph+ chronic myeloid leukemia (CML), only a few case reports indicate the existence of CLAR, JAK2V617F, and JAK2 exon 12 mutations. Method(s): This study examined CALR and JAK2 mutation profiles in Sudanese Chronic Myeloid Leukemia patients with Philadelphia-positive patients. Blood samples were collected from 100 patients with Ph+ CML chromosomes. Results for the JAK2V617F mutation were confirmed using the TaqMan Mutation Detection Assay, and the four common mutations on exon 12 and CLAR mutations were confirmed using allele-specific PCR (AS-PCR) and Sanger sequencing. Result(s): CML patients with CALR frameshift mutations were detected in two patients (2%), patients with JAK2 exon 12 mutations were found in two patients (2%), and patients with JAK2V617F mutations made up 4 (4%) of the total CML patients. No significant relationships existed between mutations and age, WBC, RBC, Hb, HCT, or platelet parameters. Patients with CLAR, JAK2 exon 12, and JAK2V617F mutations have normal leukocyte counts and lower values compared to triple-negative Ph+ CML, but these differences are not statistically significant (p values for each 0.084, 0.173, and 0.072). Conclusion(s): It is conceivable for Ph+ CML and all mutations to coexist.

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