Oncology

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, *Nawaid Ahmad, *Lyudmyla Nod

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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Social Isolation and Lung Cancer: Does This Impact the Length of Time on The Lung Cancer Pathway Or Uptake Of MDT Recommended Treatments (2024)

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Type of publication:
Conference abstract

Author(s):
Anderson V.; Dalrymple P.; Crowley G.; Shephard P.; Holmes C.; *McAdams J.; Morley J.; Sarah E.; Ivey S.; Bentley K.; Bate G.B.; English P.; Russell G.; Bostock L.

Citation:
Lung Cancer. Conference: 22nd Annual British Thoracic Oncology Group Conference 2024. Belfast United Kingdom. 190(Supplement 1) (no pagination), 2024. Article Number: 107683. Date of Publication: April 2024.

Abstract:
Aims "Bridging The Gap" report by UKLCC (2022) suggested addressing health inequalities in lung cancer has a significant impact on patient outcomes. LCNUK investigated a possible correlation between social isolation (lack of social contacts and having few people to interact with regularly) and time on pathway. Methods A Literature review conducted, highlighted a lack of UK research in this area. LCNUK members were surveyed for feedback and data was collected on 90 patients across 9 regions in the UK. Results 56 completed surveys were received from LCNUK members. 50% of responders felt that social isolation impacted patient progress on the pathway & 41% believed it influenced uptake of treatment. [Formula presented] Conclusion 50% of lung cancer nurses felt social isolation would negatively impact upon the length of the pathway, this project found that to be unproven. Data suggested a possible link between social isolation and uptake of MDT recommended treatment. This is a small sample size and may not be representative of the national picture and therefore more research is needed. Disclosure: No significant relationships.

The magnetic effect: sustainability of patient centric outcomes, time and cost saving following 5 years of Magseed experience (2024)

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Type of publication:
Conference abstract

Author(s):
*Lake B.; *Wilson M.; *Deane L.; *Cielecki L.; *Thomas G.; *Usman T.

Citation:
European Journal of Surgical Oncology. Conference: ESSO 42 2023. Florence Italy. 50(2) (no pagination), 2024. Article Number: 107333. Date of Publication: February 2024.

Abstract:
Background: Magseed has transformed the conventional guided procedures for impalpable breast cancer. In an initial service evaluation, we described "the triple effect of Magseed": reducing re-excision rates, reducing costs, and providing high patient satisfaction, with our cost saving analysis described in NICE guidance MIB236. Our change of practice service evaluation demonstrated that Magseed localisation for breast cancer promotes a patient-centric approach by reducing need for further surgery and ensuring high patient satisfaction. Other advantages are improved patient flow, as placement can occur prior to surgery, and cost saving in theatre and radiology. The aim of this study was to see if this described triple effect is sustainable in terms of patient outcomes and cost saving after 500 Magseeds and following 5 years of experience. Material(s) and Method(s): A 5-year service evaluation was conducted at Shrewsbury and Telford Hospital of all patients who had image-guided wide local excision for impalpable breast cancer from July 2017 to June 2022. Outcomes recorded included re-excision rate, theatre cost-saving analysis, radiology time and patient satisfaction. Result(s): 907 cases were performed, 501 Magseed guided procedures, and 406 coventional guided procedures. Significantly lower re-excision rates were maintained post-Magseed compared to pre-Magseed of 12.9% v 22.4% (chi2=11.1377 P<0.000846). Cost was saved in terms of surgery and radiology time. 94,321 was saved per year, with 58.6% fewer further operations, with an overall saving of 471,605. Significantly less radiology time with Magseed insertion average of 36 minutes, compared to wire insertion of 52 min (t-value =-2.24215, p-value<0.01854.) High patient satisfaction was maintained with the Magseed service described as "completely comfortable" and "quick and straightforward". Conclusion(s): Magseed continues to be the technique of choice for the detection of impalpable breast cancer, and its benefits of reducing re-excision rates, cost saving in surgery and radiology and high patient satisfaction are sustainable: the magnetic effect.

The additive effect of Magtrace: improved theatre efficiency, operative capacity and patient experience (2024)

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Type of publication:
Conference abstract

Author(s):
Lake B.; Wilson M.; Appleton D.

Citation:
European Journal of Surgical Oncology. Conference: ESSO 42 2023. Florence Italy. 50(2) (no pagination), 2024. Article Number: 107518. Date of Publication: February 2024.

Abstract:
Background: Magtrace is a non-radioactive magnetic tracer designed specifically for Sentinel Lymph Node biopsy, with multiple benefits including a flexible injection window up to 30 days prior to surgery, no requirement for nuclear medicine and has been statistically proven non-inferior to Technetium and Blue Dye, the current gold standard. The "conventional" patient pathway at the Shrewsbury and Telford Hospital involved the patient travelling to the Nuclear Medicine Department at the Royal Shrewsbury Hospital the day before or morning of surgery for Technetium injection. Surgery takes place at Princess Royal Hospital, necessitating two journeys for the patient. NICE Guidance GID-MT568 recommends Magtrace as an option to locate sentinel lymph nodes for breast cancer in hospitals with limited or no access to radio-pharmacy and thus eliminates patient travel and nuclear medicine resources. Magtrace can be injected either in outpatients or on the day of surgery. Magtrace also has the potential to reduce cost as described by NICE MTG72, with an expectation that its usage would lead to an additional sentinel node biopsy per week due to improved theatre utilisation. The aim of this study was to evaluate the use of Magtrace and its impact on theatre efficiency and patient experience. Material(s) and Method(s): A 4-month trial of Magtrace for sentinel node biopsy was conducted at the Shrewsbury & Telford NHS Trust from November 2022 to March 2023. Outcomes recorded were theatre utilisation, numbers of sentinel node biopsies performed per week and patient satisfaction. Result(s): 62 patients had Magtrace as the technique for SLNB combined either wide local excision or mastectomy during the trial period. Theatre utilisation improved from 77% to 85%, due to reduction in theatre delays due to waiting for patients to have radioisotope and improved theatre flow. Significantly more sentinel node biopsies were performed per week, increasing from 6.48 per week (Pre Magtrace 2022) to 8.52 per week (Post Magtrace November 22 to March 23) (t-value = -3.03541 p-value <0.00208), with a resultant net increase of 2 patients per week. High patient satisfaction was found with 100% finding injection more convenient on day of surgery and 100% would recommend technique if needed to friend or relative. Conclusion(s): Magtrace for sentinel node biopsy gives an "additive effect" by improving theatre utilisation, increasing the number of sentinel node biopsies per week and improving patient experience.

A hypoxia biomarker does not predict benefit from giving chemotherapy with radiotherapy in the BC2001 randomised controlled trial (2024)

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Type of publication:
Randomised controlled trial

Author(s):
Smith, Tim A D; West, Catharine M L; Joseph, Nuradh; Lane, Brian; Irlam-Jones, Joely; More, Elisabet; Mistry, Hitesh; Reeves, Kimberley J; Song, Yee Pei; Reardon, Mark; Hoskin, Peter J; Hussain, Syed A; *Denley, Helen; Hall, Emma; Porta, Nuria; Huddart, Robert A; James, Nick D; Choudhury, Ananya.

Citation:
EBioMedicine. 101:105032, 2024 Feb 21.

Abstract:
BACKGROUND: BC2001 showed combining chemotherapy (5-FU + mitomycin-C) with radiotherapy improves loco-regional disease-free survival in patients with muscle-invasive bladder cancer (MIBC). We previously showed a 24-gene hypoxia-associated signature predicted benefit from hypoxia-modifying radiosensitisation in BCON and hypothesised that only patients with low hypoxia scores (HSs) would benefit from chemotherapy in BC2001. BC2001 allowed conventional (64Gy/32 fractions) or hypofractionated (55Gy/20 fractions) radiotherapy. An exploratory analysis tested an additional hypothesis that hypofractionation reduces reoxygenation and would be detrimental for patients with hypoxic tumours. METHODS: RNA was extracted from pre-treatment biopsies (298 BC2001 patients), transcriptomic data generated (Affymetrix Clariom-S arrays), HSs calculated (median expression of 24-signature genes) and patients stratified as hypoxia-high or -low (cut-off: cohort median). PRIMARY ENDPOINT: invasive loco-regional control (ILRC); secondary overall survival. FINDINGS: Hypoxia affected overall survival (HR = 1.30; 95% CI 0.99-1.70; p = 0.062): more uncertainty for ILRC (HR = 1.29; 95% CI 0.82-2.03; p = 0.264). Benefit from chemotherapy was similar for patients with high or low HSs, with no interaction between HS and treatment arm. High HS associated with poor ILRC following hypofractionated (n = 90, HR 1.69; 95% CI 0.99-2.89 p = 0.057) but not conventional (n = 207, HR 0.70; 95% CI 0.28-1.80, p = 0.461) radiotherapy. The finding was confirmed in an independent cohort (BCON) where hypoxia associated with a poor prognosis for patients receiving hypofractionated (n = 51; HR 14.2; 95% CI 1.7-119; p = 0.015) but not conventional (n = 24, HR 1.04; 95% CI 0.07-15.5, p = 0.978) radiotherapy. INTERPRETATION: Tumour hypoxia status does not affect benefit from BC2001 chemotherapy. Hypoxia appears to affect fractionation sensitivity. Use of HSs to personalise treatment needs testing in a biomarker-stratified trial.

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