Abiraterone acetate and prednisolone with or without enzalutamide for high-risk non-metastatic prostate cancer: a meta-analysis of primary results from two randomised controlled phase 3 trials of the STAMPEDE platform protocol (2022)

Type of publication:
Systematic Review

Author(s):
Attard, Gerhardt; Murphy, Laura; Clarke, Noel W; Cross, William; Jones, Robert J; Parker, Christopher C; Gillessen, Silke; Cook, Adrian; Brawley, Chris; Amos, Claire L; Atako, Nafisah; Pugh, Cheryl; Buckner, Michelle; Chowdhury, Simon; Malik, Zafar; Russell, J Martin; Gilson, Clare; Rush, Hannah; Bowen, Jo; Lydon, Anna; Pedley, Ian; O'Sullivan, Joe M; Birtle, Alison; Gale, Joanna; *Srihari, Narayanan; Thomas, Carys; Tanguay, Jacob; Wagstaff, John; Das, Prantik; Gray, Emma; Alzoueb, Mymoona; Parikh, Omi; Robinson, Angus; Syndikus, Isabel; Wylie, James; Zarkar, Anjali; Thalmann, George; de Bono, Johann S; Dearnaley, David P; Mason, Malcolm D; Gilbert, Duncan; Langley, Ruth E; Millman, Robin; Matheson, David; Sydes, Matthew R; Brown, Louise C; Parmar, Mahesh K B; James, Nicholas D; Systemic Therapy in Advancing or Metastatic Prostate cancer: Evaluation of Drug Efficacy (STAMPEDE) investigators

Citation:
Lancet; Dec 2021 [epub ahead of print]

Abstract:
BACKGROUND Men with high-risk non-metastatic prostate cancer are treated with androgen-deprivation therapy (ADT) for 3 years, often combined with radiotherapy. We analysed new data from two randomised controlled phase 3 trials done in a multiarm, multistage platform protocol to assess the efficacy of adding abiraterone and prednisolone alone or with enzalutamide to ADT in this patient population. METHODS These open-label, phase 3 trials were done at 113 sites in the UK and Switzerland. Eligible patients (no age restrictions) had high-risk (defined as node positive or, if node negative, having at least two of the following: tumour stage T3 or T4, Gleason sum score of 8-10, and prostate-specific antigen [PSA] concentration ≥40 ng/mL) or relapsing with high-risk features (≤12 months of total ADT with an interval of ≥12 months without treatment and PSA concentration ≥4 ng/mL with a doubling time of <6 months, or a PSA concentration ≥20 ng/mL, or nodal relapse) non-metastatic prostate cancer, and a WHO performance status of 0-2. Local radiotherapy (as per local guidelines, 74 Gy in 37 fractions to the prostate and seminal vesicles or the equivalent using hypofractionated schedules) was mandated for node negative and encouraged for node positive disease. In both trials, patients were randomly assigned (1:1), by use of a computerised algorithm, to ADT alone (control group), which could include surgery and luteinising-hormone-releasing hormone agonists and antagonists, or with oral abiraterone acetate (1000 mg daily) and oral prednisolone (5 mg daily; combination-therapy group). In the second trial with no overlapping controls, the combination-therapy group also received enzalutamide (160 mg daily orally). ADT was given for 3 years and combination therapy for 2 years, except if local radiotherapy was omitted when treatment could be delivered until progression. In this primary analysis, we used meta-analysis methods to pool events from both trials. The primary endpoint of this meta-analysis was metastasis-free survival. Secondary endpoints were overall survival, prostate cancer-specific survival, biochemical failure-free survival, progression-free survival, and toxicity and adverse events. For 90% power and a one-sided type 1 error rate set to 1·25% to detect a target hazard ratio for improvement in metastasis-free survival of 0·75, approximately 315 metastasis-free survival events in the control groups was required. Efficacy was assessed in the intention-to-treat population and safety according to the treatment started within randomised allocation. STAMPEDE is registered with ClinicalTrials.gov, NCT00268476, and with the ISRCTN registry, ISRCTN78818544. FINDINGS Between Nov 15, 2011, and March 31, 2016, 1974 patients were randomly assigned to treatment. The first trial allocated 455 to the control group and 459 to combination therapy, and the second trial, which included enzalutamide, allocated 533 to the control group and 527 to combination therapy. Median age across all groups was 68 years (IQR 63-73) and median PSA 34 ng/ml (14·7-47); 774 (39%) of 1974 patients were node positive, and 1684 (85%) were planned to receive radiotherapy. With median follow-up of 72 months (60-84), there were 180 metastasis-free survival events in the combination-therapy groups and 306 in the control groups. Metastasis-free survival was significantly longer in the combination-therapy groups (median not reached, IQR not evaluable [NE]-NE) than in the control groups (not reached, 97-NE; hazard ratio [HR] 0·53, 95% CI 0·44-0·64, p<0·0001). 6-year metastasis-free survival was 82% (95% CI 79-85) in the combination-therapy group and 69% (66-72) in the control group. There was no evidence of a difference in metatasis-free survival when enzalutamide and abiraterone acetate were administered concurrently compared with abiraterone acetate alone (interaction HR 1·02, 0·70-1·50, p=0·91) and no evidence of between-trial heterogeneity (I2 p=0·90). Overall survival (median not reached [IQR NE-NE] in the combination-therapy groups vs not reached [103-NE] in the control groups; HR 0·60, 95% CI 0·48-0·73, p<0·0001), prostate cancer-specific survival (not reached [NE-NE] vs not reached [NE-NE]; 0·49, 0·37-0·65, p<0·0001), biochemical failure-free-survival (not reached [NE-NE] vs 86 months [83-NE]; 0·39, 0·33-0·47, p<0·0001), and progression-free-survival (not reached [NE-NE] vs not reached [103-NE]; 0·44, 0·36-0·54, p<0·0001) were also significantly longer in the combination-therapy groups than in the control groups. Adverse events grade 3 or higher during the first 24 months were, respectively, reported in 169 (37%) of 451 patients and 130 (29%) of 455 patients in the combination-therapy and control groups of the abiraterone trial, respectively, and 298 (58%) of 513 patients and 172 (32%) of 533 patients of the combination-therapy and control groups of the abiraterone and enzalutamide trial, respectively. The two most common events more frequent in the combination-therapy groups were hypertension (abiraterone trial: 23 (5%) in the combination-therapy group and six (1%) in control group; abiraterone and enzalutamide trial: 73 (14%) and eight (2%), respectively) and alanine transaminitis (abiraterone trial: 25 (6%) in the combination-therapy group and one (<1%) in control group; abiraterone and enzalutamide trial: 69 (13%) and four (1%), respectively). Seven grade 5 adverse events were reported: none in the control groups, three in the abiraterone acetate and prednisolone group (one event each of rectal adenocarcinoma, pulmonary haemorrhage, and a respiratory disorder), and four in the abiraterone acetate and prednisolone with enzalutamide group (two events each of septic shock and sudden death). INTERPRETATION Among men with high-risk non-metastatic prostate cancer, combination therapy is associated with significantly higher rates of metastasis-free survival compared with ADT alone. Abiraterone acetate with prednisolone should be considered a new standard treatment for this population. FUNDING Cancer Research UK, UK Medical Research Council, Swiss Group for Clinical Cancer Research, Janssen, and Astellas.

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Direct to surgery treatment of suspected lung cancer – results from a UK lung cancer multidisciplinary team (MDT) (2021)

Type of publication:
Conference abstract

Author(s):
*Manoj Marathe, *Tinaye Mandishona, *Harmesh Moudgil, *Nawaid Ahmad, *Emma Crawford, *Annabel Makan, *Koottalai Srinivasan

Citation:
European Respiratory Journal 2021 58 Suppl 65, OA2640

Abstract:
Introduction: The selective resection of suspicious nodules and masses without pre-operative tissue diagnosis is an established treatment that can shorten time to curative lung cancer treatment. We evaluated the outcomes of this practice in our local MDT.
Methods: We performed a retrospective review of 84 patients with curatively resectable single lung lesions who underwent surgical resection from January 2017 to December 2018 without histological diagnosis.
Results: Malignancy was confirmed in 68/84 (81%) patients. 57/68 patients were diagnosed with a primary lung malignancy and 11/68 with metastatic disease. Figures 1 and 2 show significant and non significant differentiators determined by the chi squared test.
Conclusion: These results support the use of spiculated and / or irregular lesion appearance along with SUV uptake >=2.5 as significant pre-histology differentiators of malignant and benign lesions. Neither past history of cancer nor size of lesion in isolation were predictive of malignancy. Our study gives further evidence that a direct-to-surgery approach is a suitable treatment option for appropriate suspicious nodules.

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The largest transcriptomic resource for radiotherapy-treated high-risk prostate cancer: paving the way for companion diagnostic biomarkers (2021)

Type of publication:Conference abstract

Author(s):Thiruthaneeswaran N.; Bibby B.; Pereira R.; More E.; Hoskin P.; Bristow R.; Choudhury A.; West C.; Wylie J.; *Denley H.; Henry A.

Citation:Journal of Medical Imaging and Radiation Oncology; Sep 2021; vol. 65 ; p. 252

Abstract:Purpose: The Cancer Genome Atlas (TCGA) is a valuable resource for developing and validating gene signatures for personalising treatments. TCGA samples came from patients who received heterogeneous treatments-dominated by surgery. Improving the biological precision of radiotherapy is hampered by the lack of well annotated cohorts that reflect patient populations relevant for radiation oncologists. We aimed to generate transcriptomic data from needle core biopsies for a large multicentre cohort of high-risk prostate cancer patients and use the data to validate published gene signatures. Methods and materials: A total of 478 NCCN classified high-risk patients treated from 2008-2016 were identified: 244 patients received intensity modulated radiotherapy (IMRT) to the prostate only (BEDalpha/beta 1.5-3Gy of 120-180 Gy) and 234 patients received IMRT to the prostate and a high dose rate (HDR) brachytherapy boost (BEDalpha/beta 1.5-3Gy 159-265 Gy). Androgen deprivation was given to all patients for 3-36 months. Biochemical failure was defined as prostate-specific antigen (PSA) rise of >=2 ng/ml above nadir post-radiotherapy. The primary clinical end-point was 7-year biochemical relapse-free survival (bRFS). Gene expression data were generated from diagnostic needle core biopsies using Affymetrix Clariom S arrays. Two (28-gene and 32 gene) published hypoxia gene signatures and a tumour radiosensitivity index (RSI) were tested for prognostic significance [1-3]. Result(s): The median follow-up for the entire cohort was 6.3 years. Both the 28 gene (p = 0.021) and 32-gene (p = 0.033) hypoxia signatures were prognostic for 7-year bRFS. Non-prostate hypoxia signatures were not prognostic. The bRFS for radioresistant (RSI-R) vs radiosensitive (RSI-S) was prognostic in the IMRT EBRT only cohort (p = 0.01) and not in the HDR boost cohort (p = 0.8). Conclusion(s): We generated the largest high-risk prostate radiotherapy cohort with full gene expression data and showed its value in validating published gene signatures. The RSI signature should be explored further to select patients with high-risk prostate cancer who should benefit from dose escalation with a HDR brachytherapy boost. This resource will be a valuable asset for future research generating and validating signatures for personalising radiotherapy in men with prostate cancer.

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Effect of COVID-19 pandemic lockdowns on planned cancer surgery for 15 tumour types in 61 countries: an international, prospective, cohort study (2021)

Type of publication:
Journal article

Author(s):
COVIDSurg Collaborative (includes *Blair J, *Lakhiani A, *Parry-Smith W, *Sahu B of Shrewsbury and Telford Hospital NHS Trust)

Citation:
The Lancet Oncology;  November 2021, Volume 22, Issue 22, Pages 1507-1517

Abstract:
Background: Surgery is the main modality of cure for solid cancers and was prioritised to continue during COVID-19 outbreaks. This study aimed to identify immediate areas for system strengthening by comparing the delivery of elective cancer surgery during the COVID-19 pandemic in periods of lockdown versus light restriction.
Methods; This international, prospective, cohort study enrolled 20 006 adult (≥18 years) patients from 466 hospitals in 61 countries with 15 cancer types, who had a decision for curative surgery during the COVID-19 pandemic and were followed up until the point of surgery or cessation of follow-up (Aug 31, 2020). Average national Oxford COVID-19 Stringency Index scores were calculated to define the government response to COVID-19 for each patient for the period they awaited surgery, and classified into light restrictions (index <20), moderate lockdowns (20–60), and full lockdowns (>60). The primary outcome was the non-operation rate (defined as the proportion of patients who did not undergo planned surgery). Cox proportional-hazards regression models were used to explore the associations between lockdowns and non-operation. Intervals from diagnosis to surgery were compared across COVID-19 government response index groups. This study was registered at ClinicalTrials.gov, NCT04384926.
Findings; Of eligible patients awaiting surgery, 2003 (10·0%) of 20 006 did not receive surgery after a median follow-up of 23 weeks (IQR 16–30), all of whom had a COVID-19-related reason given for non-operation. Light restrictions were associated with a 0·6% non-operation rate (26 of 4521), moderate lockdowns with a 5·5% rate (201 of 3646; adjusted hazard ratio [HR] 0·81, 95% CI 0·77–0·84; p<0·0001), and full lockdowns with a 15·0% rate (1775 of 11 827; HR 0·51, 0·50–0·53; p<0·0001). In sensitivity analyses, including adjustment for SARS-CoV-2 case notification rates, moderate lockdowns (HR 0·84, 95% CI 0·80–0·88; p<0·001), and full lockdowns (0·57, 0·54–0·60; p<0·001), remained independently associated with non-operation. Surgery beyond 12 weeks from diagnosis in patients without neoadjuvant therapy increased during lockdowns (374 [9·1%] of 4521 in light restrictions, 317 [10·4%] of 3646 in moderate lockdowns, 2001 [23·8%] of 11 827 in full lockdowns), although there were no differences in resectability rates observed with longer delays.
Interpretation: Cancer surgery systems worldwide were fragile to lockdowns, with one in seven patients who were in regions with full lockdowns not undergoing planned surgery and experiencing longer preoperative delays. Although short-term oncological outcomes were not compromised in those selected for surgery, delays and non-operations might lead to long-term reductions in survival. During current and future periods of societal restriction, the resilience of elective surgery systems requires strengthening, which might include protected elective surgical pathways and long-term investment in surge capacity for acute care during public health emergencies to protect elective staff and services.

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Primary acinic cell carcinoma in a young female patient: a case report (2021)

Type of publication:
Journal article

Author(s):
*Venkatasami, M ; *Harrison, K

Citation:
Oral Surgery, Oral Medicine, Oral Pathology & Oral Radiology; Jul 2021; vol. 132 (no. 1)

Abstract:
Background: Acinic cell carcinoma (ACC) is a rare, low-grade tumor, accounting for about 5% of all primary salivary gland malignancies. ACCs predominate in the parotid gland, are seen in the fifth and sixth decades of life, and have a female predilection. Well-differentiated and low-grade tumors are associated with a favorable prognosis.
Description: We report a case of a 16-year-old female patient presenting with a right parotid lump that had been slowly increasing over the past year. Clinical examination revealed a 1.5-cm right parotid nodule with no facial nerve involvement and presence of cervical lymphadenopathy. Her past medical history was unremarkable.
Findings: Radiological investigations revealed a well-circumscribed, lobulated lesion in the anterior right parotid gland with presence of reactive lymph nodes bilaterally. Fine-needle aspiration showed granular cells with a differential diagnosis of oncocytoma, Warthin's tumor, or acinic cell carcinoma. Histologic examination showed a multinodular appearance with some marked granular cytoplasm with oncolytic and lymphoid infiltrate. The results of immunohistochemistry were negative for S100 and positive with DOG-1. There were widespread periodic acid-Schiff diastase-resistant granules throughout the tumor cells, with a Ki67 proliferation index of approximately 5%.
Outcome: The tumor was completely excised, and the patient made a full recovery and was considered to have a good long-term prognosis.
Conclusions: This is an unusual case of ACC seen in this age group and gender, where less than 4% of cases of ACC have been reported in patients younger than 20. It is important to consider differential diagnoses of salivary gland pathology, such as ACC, in the young female patient.

Craniofacial osteosarcoma: a case report (2021)

Type of publication:
Journal article

Author(s):
*Venkatasami, M ; *Harrison, K

Citation:
Oral Surgery, Oral Medicine, Oral Pathology & Oral Radiology; Jul 2021; vol. 132 (no. 1)

Abstract:
Background: Osteosarcoma is the most common primary bone tumor, with 10% of cases affecting the head and neck. Demographics of head and neck osteosarcoma are different from those elsewhere in the musculoskeletal system. Prognosis is strongly dependent on negative resection margins with the use of neoadjuvant chemoradiotherapy in select cases.
Description: We present a case of a 58-year-old male nonsmoker patient who presented with a lump in his left upper jaw. Clinical examination revealed an exophytic mass in the upper left tuberosity of the maxilla suspicious for squamous cell carcinoma with no associated lymphadenopathy.
Findings: Radiological investigations revealed a metabolically active left maxillary lesion with destruction of the maxillary sinus. Histologic examination of a superficial biopsy initially suggested a proliferative fibro-osseous lesion; however, a second deeper biopsy was diagnostic of osteosarcoma, and the patient was referred to a sarcoma center. Immunohistochemistry showed AE1/AE3 and CK(MNF.116) positivity in occasional cells with a Ki67 proliferation index of 60%. This was diagnostic of grade 2-3 osteosarcoma. Multidisciplinary management of the patient included neoadjuvant chemotherapy and total maxillectomy and dental prosthetic rehabilitation. The patient is still under follow-up.
Conclusions: This case of primary osteosarcoma of the maxilla is rare and scarcely reported in the literature. Clinical differential diagnoses include squamous cell carcinoma, and histologic differential diagnosis includes fibro-osseous proliferative lesions in undersampled cases. It is important to consider osteosarcoma in destructive lesions, as it requires prompt and early specialist intervention to maximize the chances of negative surgical margins, which is the mainstay of treatment for this disease for prognosis.

A rare case of isolated laryngeal metastasis 23 years after nephrectomy for clear cell renal carcinoma (2021)

Type of publication:
Journal article

Author(s):
*Eastwood, Michael J ; *Ahsan, Syed F; *Harris, Richard

Citation:
British Journal of Hospital Medicine; Aug 2021; vol. 82 (no. 8); p. 1-3

Abstract:
The article describes the case of isolated laryngeal metastasis 23 years after nephrectomy for clear cell renal
carcinoma in an 84-year-old man.

Results of DARS: a randomised phase III trial of dysphagia-optimised intensity modulated radiotherapy (DO-IMRT) versus standard IMRT (S-IMRT) in oropharyngeal (OPC) and hypopharyngeal (HPC) cancer (2021)

Type of publication:
Conference abstract

Author(s):
Nutting C.; Roe J.; Tyler J.; Bhide S.; Rooney K.; Foran B.; *Pettit L.; Beasley M.; Finneran L.; Sydenham M.; Emson M.; Hall E.; Petkar I.; Frogley R.

Citation:
Oral Oncology; Jul 2021; vol. 118 Supplement ; p. 10-11

Abstract:
Presented by: Chris Nutting (Chris.Nutting@rmh.nhs.uk) Introduction Most newly diagnosed OPC & HPC are treated with (chemo)RT with curative intent but at the consequence of adverse effects on quality of life. DARS (ISRCTN:25458988) tested if using DO-IMRT to reduce RT dose to the dysphagia/aspiration related structures (DARS) improved swallowing function compared to S-IMRT. Materials and Methods Patients with T1-4, N0-3, M0 OPC/HPC were randomised 1:1 to S-IMRT (65 Gray (Gy)/30 fractions (f) to primary & nodal tumour; 54 Gy/ 30f to remaining pharyngeal subsite & nodal areas at risk of microscopic disease) or DO-IMRT. The volume of the superior & middle pharyngeal constrictor muscle (PCM) (OPC) or inferior PCM (HPC) lying outside the high-dose target volume was set a mandatory mean dose constraint in DO-IMRT. Treatment allocation was by minimisation balanced by centre, use of induction/concomitant chemotherapy, tumour site & AJCC stage. Primary endpoint was mean MD Anderson Dysphagia Inventory (MDADI) composite score 12 months after RT with 102 patients needed to detect a 10 point improvement (assuming S-IMRT score of 72, standard deviation (SD) 13.8; 90% power, 2-sided 5% alpha). Patients were blind to treatment allocation. Secondary endpoints assessing swallowing function included University of Washington (UW)-Qol & Performance Status Scale Head & Neck (PSS-HN) scores. Results 112 patients (56 S-IMRT, 56 DO-IMRT) were randomised from 22 UK centres from 06/2016 to 04/2018. Mean age was 57 years; 80% were male; 97% had OPC; 90% had AJCC stage 3&4 disease; 86% had concomitant chemotherapy only, 4% induction & concomitant and 10% no chemotherapy. 111/112 had RT doses as prescribed (1 patient died before RT). Median of the mean inferior PCM dose was SIMRT 49.8 Gy (IQR 47.1-52.4) vs. DO-IMRT 28.4 Gy (21.3-37.4), p < 0.0001; superior & middle PCM dose was
S-IMRT 57.2 Gy (56.3-58.3) vs. DO-IMRT 49.7 Gy (49.4-49.9), p < 0.0001. At 12 months, DO-IMRT had significantly higher MDADI scores: S-IMRT mean: 70.5 (SD 17.3) vs. DO-IMRT 77.7 (16.1), p = 0.037. At 12 months the proportion of patients reporting UW-QoL as being able to swallow "as well as ever" was 40.4% for DO-IMRT & 15.2% for S-IMRT; scores of?>50 were reported for PSS-HN normalcy of diet by 70.6% DO-IMRT & 58.1% S-IMRT patients & for eating in public scores by 84.3% DO-IMRT & 74.4% S-IMRT. Conclusions DOIMRT reduced RT dose to the DARS and improved patient reported swallowing function compared with S-IMRT. This is the first randomised study to demonstrate functional benefit of swallow-sparing IMRT in OPC.

Effective implementation of an advanced clinical practitioner role in breast imaging (2021)

Type of publication:
Conference abstract

Author(s):
*Deane L.; *Williams S.; *Cielecki L.; *Burley S.

Citation:
Breast Cancer Research 2021, 23(Suppl 1):P57

Abstract:
Background: Due to the immense pressure to provide capacity for women with breast symptoms, to be seen  within two weeks, a new innovative role has been created to provide increased capacity. Introduction: The breast services see many women with conditions that are benign and easily identified upon ultrasound. The majority of these conditions occur in women under the age of 40years. The role of an advanced clinical practitioner was created to answer a service need. This role requires a highly specialised cohort of skills combining breast image interpretation, breast ultrasound and breast biopsying alongside a range of clinical competences enabling autonomous practice within clear governance.
Method(s): A new clinic was created for under 40 aged women only requiring only a breast clinical specialist and an advanced clinical practitioner, using ultrasound for assessment. Unexpected findings suspicious upon ultrasound-would be redirected to the next consultant led clinic for full imaging assessment and biopsy.
Result(s): Increased capacity was achieved, without increased costs. Anxiety levels were reduced due to these patients seen within these clinics and more specialist skills could be directed to more complex cases in the traditional cancer clinics.
Conclusion(s): The use of this specialist role has proven to be innovative and specialised in answering capacity issues within the workforce. The ACP role is utilised as a support to all clinics working alongside consultant radiographers as well as in an autonomous role, thereby freeing up the consultants for cases requiring specialist skills. The stability of the breast service has been ensured

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Male breast ultrasound: 2019 audit results (2021)

Type of publication:
Conference abstract

Author(s):
*Ozcan U.A.; *Williams S.; *Metelko M

Citation:
Breast Cancer Research 2021, 23(Suppl 1):O3.3

Abstract:
Background and Purpose: Male breast cancer is rare whereas gynaecomastia is very common. Only asymmetrical gynaecomastia require breast imaging and focal lumps are amenable to clinical core biopsy. So the use of ultrasound in the assessment of male breast should be limited. The aim of this study is to audit the referral indications and ultrasound outcomes in male breast US (MBUS) patients against local guidelines.
Method(s): In the last 5 years, 968 patients were referred for MBUS in our Trust. This audit includes the patients between 02/01/2019-04/12/2019. The duplicate patients and follow-ups were excluded from the study. In total, 197 patients were analysed (mean age: 58 (8-90) retrospectively. Referral diagnosis, age, US grading and clinical outcomes were noted.
Result(s): Of the 197 patients, 79% were gynecomastia (133), lipoma (21) or fat necrosis (2), and 15% (30) were normal. There was 1 chest wall lymphoma and 1 DCIS, and 9 (5%) patients had benign breast disease (fibroepithelial lesions, abscess, papilloma, sebaceous cysts, haematoma). In 122 patients (62%) clinical grade was not given, 66 had P2, 8 had P3, 1 had P5. 2 patients were scored as U4 and 4 patients as U3.
Conclusion(s): These results clearly show that 99% of the patients referred to MBUS were benign. And also 95% of the patients were clinically benign or not assessed. The excessive use of MBUS without a clinical indication leads to patient anxiety, increased waiting times and might delay the proper imaging to the patients who should have the priority in terms of clinical indication. Careful clinical assessment before ultrasound referral is mandatory for better care.

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