Nodal positivity in patients with clinically and radiologically node-negative breast cancer treated with neoadjuvant chemotherapy: multicentre collaborative study.

BACKGROUND: The necessity of performing a sentinel lymph node biopsy in patients with clinically and radiologically node-negative breast cancer after neoadjuvant chemotherapy has been questioned. The aim of this study was to determine the rate of nodal positivity in these patients and to identify clinicopathological features associated with lymph node metastasis after neoadjuvant chemotherapy (ypN+). METHODS: A retrospective multicentre study was performed. Patients with cT1-3 cN0 breast cancer who underwent sentinel lymph node biopsy after neoadjuvant chemotherapy between 2016 and 2021 were included. Negative nodal status was defined as the absence of palpable lymph nodes, and the absence of suspicious nodes on axillary ultrasonography, or the absence of tumour cells on axillary nodal fine needle aspiration or core biopsy. RESULTS: A total of 371 patients were analysed. Overall, 47 patients (12.7%) had a positive sentinel lymph node biopsy. Nodal positivity was identified in 22 patients (29.0%) with hormone receptor+/human epidermal growth factor receptor 2- tumours, 12 patients (13.8%) with hormone receptor+/human epidermal growth factor receptor 2+ tumours, 3 patients (5.6%) with hormone receptor-/human epidermal growth factor receptor 2+ tumours, and 10 patients (6.5%) with triple-negative breast cancer. Multivariable logistic regression analysis showed that multicentric disease was associated with a higher likelihood of ypN+ (OR 2.66, 95% c.i. 1.18 to 6.01; P = 0.018), whilst a radiological complete response in the breast was associated with a reduced likelihood of ypN+ (OR 0.10, 95% c.i. 0.02 to 0.42; P = 0.002), regardless of molecular subtype. Only 3% of patients who had a radiological complete response in the breast were ypN+. The majority of patients (85%) with a positive sentinel node proceeded to axillary lymph node dissection and 93% had N1 disease. CONCLUSION: The rate of sentinel lymph node positivity in patients who achieve a radiological complete response in the breast is exceptionally low for all molecular subtypes.

High-dose chemotherapy for relapsed germ cell tumours: outcomes in low-volume specialized centres.

OBJECTIVE: To report treatment patterns and survival outcomes of patients with relapsed and refractory metastatic germ cell tumours (GCTs) treated with high-dose chemotherapy (HDCT) and autologous stem-cell transplantation in low-volume specialized centres within the widely dispersed populations of Australia and New Zealand between 1999 and 2019. PATIENTS AND METHODS: We conducted a retrospective analysis of 111 patients across 13 institutions. Patients were identified from the Australasian Bone Marrow Transplant Recipient Registry. We reviewed treatment regimens, survival outcomes, deliverability and toxicities. Primary endpoints included overall (OS) and progression-free survival (PFS). Cox proportional hazards models were used to test the association of survival outcomes with patient and treatment factors. RESULTS: The median (range) age was 30 (14-68) years and GCT histology was non-seminomatous in 84% of patients. International Prognostic Factors Study Group (IPFSG) prognostic risk category was very low/low, intermediate, high and very high in 18%, 36%, 25% and 21% of patients, respectively. Salvage conventional-dose chemotherapy (CDCT) was administered prior to HDCT in 59% of patients. Regimens included paclitaxel, ifosfamide, carboplatin and etoposide (50%), carboplatin and etoposide (CE; 28%), carboplatin, etoposide and ifosfamide (CEI; 6%), carboplatin, etoposide and cyclophosphamide (CEC; 5%), CEC-paclitaxel (6%) and other (5%). With a median follow-up of 4.4 years, the 1-, 2- and 5-year PFS rates were 62%, 57% and 52%, respectively, and OS rates were 73%, 65% and 61%, respectively. There were five treatment-related deaths. Progression on treatment occurred in 17%. In a univariable analysis, worse International Germ Cell Cancer Collaborative Group (IGCCCG) and IPFSG prognostic groups were associated with inferior survival outcomes. An association of inferior survival was not found with the number of high-dose cycles received nor when HDCT was delivered after salvage CDCT. CONCLUSION: This large dual-national registry-based study reinforces the efficacy and deliverability of HDCT for relapsed and refractory metastatic GCT in low-volume specialized centres in Australia and New Zealand, with survival outcomes comparable to those found in international practice.

Circulating tumour cell enumeration does not correlate with Miller-Payne grade in a cohort of breast cancer patients undergoing neoadjuvant chemotherapy.

PURPOSE: The association between pathological complete response (pCR) in patients receiving neoadjuvant chemotherapy (NAC) for breast cancer and Circulating Tumour Cells (CTCs) is not clear. The aim of this study was to assess whether CTC enumeration could be used to predict pathological response to NAC in breast cancer as measured by the Miller-Payne grading system. METHODS: Twenty-six patients were recruited, and blood samples were taken pre- and post-NAC. CTCs were isolated using the ScreenCell device and stained using a modified Giemsa stain. CTCs were enumerated by 2 pathologists and classified as single CTCs, doublets, clusters/microemboli and correlated with the pathological response as measured by the Miller-Payne grading system. χ2 or ANOVA was performed in SPSS 24.0 statistics software for associations. RESULTS: 89% of patients had invasive ductal carcinoma (IDC) and 11% invasive lobular carcinoma (ILC). At baseline 85% of patients had CTCs present, median 7 (0-161) CTCs per 3 ml of whole blood. Post-chemotherapy, 58% had an increase in CTCs. This did not correlate with the Miller-Payne grade of response. No significant association was identified between the number of CTCs and clinical characteristics; however, we did observe a correlation between pre-treatment CTC counts and body mass index, p < 0.05. CONCLUSIONS: Patients with a complete response to NAC still had CTCs present, suggesting enumeration is not sufficient to aid surgery stratification. Additional characterisation and larger studies are needed to further characterise CTCs isolated pre- and post-chemotherapy. Long-term follow-up of these patients will determine the significance of CTCs in NAC breast cancer patients.

Self-concept and health anxiety relate to psychological outcomes for BRCA1/2 carriers.

OBJECTIVE: Leventhal's common sense model of self-regulation highlights how specific beliefs about illness influence psychological outcomes. Little is known on how such beliefs relate to BRCA1/2 adjustment. Furthermore, beliefs about one's self-concept may be relevant to genetic conditions and may relate to psychological wellbeing. METHODS: One-hundred and eighteen female BRCA1/2 carriers from an Irish University Hospital completed questionnaires for this cross-sectional study. Outcomes measured were state anxiety and physical and mental health-related quality of life (HRQOL). Explanatory variables included sociodemographics, health anxiety, illness perceptions, coping and self-concept. Hierarchical multiple regression analyses were conducted. RESULTS: Then, 44% of participants had clinically significant state anxiety and 12% had clinically significant health anxiety. Vulnerability, stigma, mastery and health anxiety explained 42% of the variance in state anxiety. Previous mental health difficulty, vulnerability, stigma, mastery and health anxiety explained 40% of the variance in mental HRQOL. Dysfunctional coping strategies were strongly related to the physical functioning aspect of quality of life. CONCLUSION: BRCA-specific beliefs related to self and health anxiety are important factors to consider in the adjustment to BRCA1/2 confirmation.

Impact of progesterone receptor status on response to neoadjuvant chemotherapy in estrogen receptor-positive breast cancer patients.

INTRODUCTION: Breast cancer patients respond differently to neoadjuvant chemotherapy(NAC) based on receptor subtype. The aim of this study was to assess the impact of progesterone receptor (PgR) status on response to neoadjuvant chemotherapy (NAC) in estrogen receptor (ER)+, human epidermal growth factor receptor (HER)- breast cancer patients. METHODS: ER+ and HER- patients receiving NAC over a 7-year period (2011-2017) were identified. The primary outcome was breast complete pathological response (pCR) rate. Secondary outcomes included axillary pCR, axillary/breast pCR and complete radiological response (cRR). RESULTS: A total of 203 patients were identified (149 in the ER+, PgR+, and HER- group and 54 in the ER+, PgR-, and HER- group). Compared with the PgR+ group, PgR- patients were significantly associated with breast pCR (31.5% vs 7.4%; χ² test; P < .01). In multivariable analysis, PgR- status (odds ratio [OR], 4.58; 95% confidence interval [CI]: 1.58,13.28; P = .005), radiological size >50 mm (OR, 5.38; 95% CI: 1.07,27.04; P = .04) and grade (OR, 3.52;95% CI: 1.21,10.23;P = .02) were significant predictors of breast pCR. Only PgR- status was a significant predictor of cRR (OR, 6.234; 95% CI: 2.531, 15.355; P < .001). In node positive patients, PgR negativity was associated with a trend towards breast/axillary nodal pCR (22% vs 12.7%; χ² test; P = .055). CONCLUSION: Over 30% of ER+, PgR-, and HER- patients will have a breast pCR after NAC. PgR- is the only significant predictor of breast pCR/cRR in this tumor subtype. ER+, PgR-, and HER- patients should be considered for NAC.

Assessment of a candidate marker constituent predictive of a dietary substance-drug interaction: case study with grapefruit juice and CYP3A4 drug substrates.

Dietary substances, including herbal products and citrus juices, can perpetrate interactions with conventional medications. Regulatory guidances for dietary substance-drug interaction assessment are lacking. This deficiency is due in part to challenges unique to dietary substances, a lack of requisite human-derived data, and limited jurisdiction. An in vitro-in vivo extrapolation (IVIVE) approach to help address some of these hurdles was evaluated using the exemplar dietary substance grapefruit juice (GFJ), the candidate marker constituent 6',7'-dihydroxybergamottin (DHB), and the purported victim drug loperamide. First, the GFJ-loperamide interaction was assessed in 16 healthy volunteers. Loperamide (16 mg) was administered with 240 ml of water or GFJ; plasma was collected from 0 to 72 hours. Relative to water, GFJ increased the geometric mean loperamide area under the plasma concentration-time curve (AUC) significantly (1.7-fold). Second, the mechanism-based inhibition kinetics for DHB were recovered using human intestinal microsomes and the index CYP3A4 reaction, loperamide N-desmethylation (KI [concentration needed to achieve one-half kinact], 5.0 ± 0.9 µM; kinact [maximum inactivation rate constant], 0.38 ± 0.02 minute(-1)). These parameters were incorporated into a mechanistic static model, which predicted a 1.6-fold increase in loperamide AUC. Third, the successful IVIVE prompted further application to 15 previously reported GFJ-drug interaction studies selected according to predefined criteria. Twelve of the interactions were predicted to within the 25% predefined criterion. Results suggest that DHB could be used to predict the CYP3A4-mediated effect of GFJ. This time- and cost-effective IVIVE approach could be applied to other dietary substance-drug interactions to help prioritize new and existing drugs for more advanced (dynamic) modeling and simulation and clinical assessment.

A systematic review of the role of chemotherapy in retroperitoneal sarcoma by the Australia and New Zealand sarcoma association clinical practice guidelines working party.

BACKGROUND: In primary localised resectable retroperitoneal sarcoma (RPS), loco-regional and distant relapse occur frequently despite optimal surgical management. The role of chemotherapy in improving outcomes is unclear. METHODS: A systematic review was conducted, using the population, intervention, comparison outcome (PICO) model, to evaluate whether neoadjuvant or adjuvant chemotherapy improve outcomes in adults with primary localised resectable RPS. Medline, Embase and Cochrane Central were queried for publications from 1946 to June 2022 that evaluated recurrence free survival, overall survival, and post operative complications. Each study was screened by two independent reviewers for suitability. A qualitative synthesis of the results was performed. RESULTS: Twenty three studies were identified; one meta-analysis of retrospective studies and 22 retrospective studies including three with propensity matched cohorts. Most studies did not analyse outcomes by histology, detail treatment regimens, provide baseline characteristics or selection criteria for those receiving chemotherapy. Evidence of selection bias was illustrated in several studies. Newcastle-Ottawa quality of retrospective cohort studies was good for 12 studies and poor for 10 studies. All studies were assessed as Level III-2 evidence by the Australian NHMRC hierarchy. Overall, the addition of neoadjuvant or adjuvant chemotherapy to surgery was not associated with improvement in local recurrence, metastasis free survival, disease free survival or overall survival in primary localised resectable RPS. There is some evidence of an association of chemotherapy with worse overall survival. One single centre study showed that neoadjuvant chemotherapy was not associated with increased post operative complications compared to surgery alone in primary localised resectable RPS. CONCLUSIONS: There is currently no evidence that demonstrates the addition of chemotherapy to surgery improves outcomes in adult patients with primary localised resectable RPS. Available evidence is limited by its retrospective nature and high likelihood of selection bias with chemotherapy generally administered to patients at higher risk of recurrence and many patients not receiving care in high volume sarcoma centres. Randomised trials are required to conclusively determine the role of chemotherapy in primary localised resectable RPS.

Information needs of women with BRCA mutations regarding cancer risk management and decision-making.

PURPOSE: Providing women who have tested positive for a pathogenic variant in BRCA1 or BRCA 2 relevant information can help them to make informed decisions about managing their cancer risk. However, there is a lack of targeted informational support for BRCA positive women specific to the Irish context. The objective of this study is to identify the information needs of women diagnosed with a pathogenic variant in BRCA1 or BRCA 2 regarding cancer risk management and decision-making. METHODS: This is a descriptive qualitative study. Participants were recruited using purposive sampling and included women with a pathogenic variant in BRCA1 or BRCA2 without a history of breast or ovarian cancer. Two focus groups were held with women (n = 16) to enable them to generate ideas and understanding of their shared information needs. In addition, ten individual interviews were conducted to capture the additional perspectives of health care and relevant policy stakeholders. Interviews were analysed using inductive coding (Braun and Clarke, 2006), with NVivo software (Qsr international, 1999). RESULTS: Three main themes were identified, Cancer Risk Management, Receiving Information, and Implications to Health and Wellbeing. BRCA-positive women expressed a need for information about managing their cancer risk. They were particularly concerned with managing the impact of cancer risk-reducing interventions on their psychological and physical health, wellbeing, and family life. Many women felt they had to advocate for themselves to get treatment and receive information. Participants expressed a need for a comprehensive informational resource where all relevant information related to BRCA risk management could be accessed at a single location. CONCLUSION: This study suggests that women diagnosed with a pathogenic variant in BRCA1 or BRCA2 in Ireland need more accessible information about managing their cancer risk, and the impact of a BRCA diagnosis on their family, health and wellbeing. These results will be used to identify relevant content for developing an informational decision aid for Irish women.

Extrapleural pneumonectomy for sarcoma: Outcomes of adult patients at a specialized center.

BACKGROUND: Extrapleural pneumonectomy (EPP) is a complex surgical procedure involving en-bloc resection of the parietal and visceral pleura, lung, pericardium, and ipsilateral diaphragm. Small case series of pleural-based sarcoma of predominantly pediatric patients suggest EPP may be a life-prolonging surgical option. We aimed to describe the characteristics and outcomes of adults who underwent EPP at a specialized sarcoma center. METHODS: Clinicopathologic variables, surgical details, and follow-up information were extracted for patients undergoing EPP for pleural-based sarcoma between August 2017 and December 2020. Primary outcomes were event-free survival (EFS) and overall survival (OS) from the date of EPP. Secondary outcomes were disease-free interval (DFI) prior to EPP, and early and late postoperative complications. RESULTS: Eight patients were identified, seven with soft tissue sarcoma and one with bone sarcoma. Patients had either localized disease with a primary thoracic sarcoma, sarcoma recurrent to the thorax, or de novo metastatic disease. All patients underwent resection of their pleural-based sarcoma by an experienced cardiothoracic surgeon, and some patients had pre or postoperative treatment. The perioperative morbidity was comparable with previously published reports of EPP performed in mesothelioma patients. At median follow-up of 22.5 months, median EFS was 6.0 months and OS was 20.7 months. Six patients (75%) had disease recurrence; five (62.5%) died of progressive disease. Two patients (25%) had not recurred: one died of a radiation-related esophageal rupture, and one was alive with no evidence of disease at 37.0 months. Characteristics of those with the longest EFS included low-grade histology and achieving a metabolic response to preoperative chemotherapy. CONCLUSIONS: In adults with pleural-based sarcoma, EPP is rarely curative but appears to be a feasible salvage procedure when performed at specialized centers. Patient selection is critical with strong consideration given to multimodal therapy to optimize patient outcomes. In the absence of a confirmed response to neoadjuvant treatment, long term survival is poor and EPP should not be recommended.

Decision aids for female BRCA mutation carriers: a scoping review.

OBJECTIVES: Women who inherit a pathogenic BRCA1 or BRCA2 mutation are at substantially higher risk of developing breast and ovarian cancer than average. Several cancer risk management strategies exist to address this increased risk. Decisions about which strategies to choose are complex, personal and multifactorial for these women. Decision aids (DAs) are tools that assist patients in making health-related decisions. The aim of this scoping review was to map evidence relating to the development and testing of patient DAs for cancer unaffected BRCA mutation carriers. DESIGN: Scoping review conducted according to the Joanna Briggs Institute's (JBI's) scoping review methodological framework. DATA SOURCES: MEDLINE, EMBASE, CINAHL, Web of Science. No restrictions applied for language or publication date. A manual search was also performed. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Studies on DAs for cancer risk management designed for or applicable to women with a pathogenic BRCA1 or BRCA2 mutation who are unaffected by breast or ovarian cancer. DATA EXTRACTION AND SYNTHESIS: Data were extracted using a form based on the JBI instrument for extracting details of studies' characteristics and results. Data extraction was performed independently by two reviewers. Extracted data were tabulated. RESULTS: 32 evidence sources relating to development or testing of 21 DAs were included. Four DAs were developed exclusively for cancer unaffected BRCA mutation carriers. Of these, two covered all guideline recommended risk management strategies for this population though only one of these was readily available publicly in its full version. All studies investigating DA effectiveness reported a positive effect of the DA under investigation on at least one of the outcomes evaluated, however only six DAs were tested in randomised controlled trials. CONCLUSION: This scoping review has mapped the landscape of the literature relating to developing and testing, DAs applicable to cancer unaffected BRCA mutation carriers.

What is the association of preoperative biopsy with recurrence and survival in retroperitoneal sarcoma? A systematic review by the Australia and New Zealand Sarcoma Association clinical practice guidelines working party.

Preoperative biopsy for retroperitoneal sarcoma (RPS) enables appropriate multidisciplinary treatment planning. A systematic review of literature from 1990 to June 2022 was conducted using the population, intervention, comparison and outcome model to evaluate the local recurrence and overall survival of preoperative biopsy compared to those that had not. Of 3192 studies screened, five retrospective cohort studies were identified. Three reported on biopsy needle tract seeding, with only one study reporting biopsy site recurrence of 2 %. Two found no significant difference in local recurrence and one found higher 5-year local recurrence rates in those who had not been biopsied. Three studies reported overall survival, including one with propensity matching, did not show a difference in overall survival. In conclusion, preoperative core needle biopsy of RPS is not associated with increased local recurrence or adverse survival outcomes.

High-dose chemotherapy for Ewing sarcoma and Rhabdomyosarcoma: A systematic review by the Australia and New Zealand sarcoma association clinical practice guidelines working party.

INTRODUCTION: Patients with high-risk or metastatic Ewing sarcoma (ES) and rhabdomyosarcoma (RMS) have a guarded prognosis. High-dose chemotherapy (HDT) with autologous stem cell transplant (ASCT) has been evaluated as a treatment option to improve outcomes. However, survival benefits remain unclear, and treatment is associated with severe toxicities. METHODS: A systematic review was conducted, using the population, intervention, comparison outcome (PICO) model, to evaluate whether utilization of HDT/ASCT impacts the outcome of patients with ES and RMS compared to standard chemotherapy alone, as part of first line treatment or in the relapse setting. Medline, Embase and Cochrane Central were queried for publications from 1990 to October 2022 that evaluated event-free survival (EFS), overall survival (OS), and toxicities. Each study was screened by two independent reviewers for suitability. A qualitative synthesis of the results was performed. RESULTS: Of 1,172 unique studies screened, 41 studies were eligible for inclusion with 29 studies considering ES, 10 studies considering RMS and 2 studies considering both. In ES patients with high-risk localised disease who received HDT/ASCT after VIDE chemotherapy, consolidation with melphalan-based HDT/ASCT as first line therapy conveyed an EFS and OS benefit over standard chemotherapy consolidation. Efficacy of HDT/ASCT using a VDC/IE backbone, which is now standard care, has not been established. Survival benefits are not confirmed for ES patients with metastatic disease at initial diagnosis. For relapsed/refractory ES, four retrospective studies report improvement in outcomes with HDT/ASCT with the greatest evidence in patients who demonstrate a treatment response before HDT, and in patients under the age of 14. In RMS, there is no proven survival benefit of HDT/ASCT in primary localised, metastatic or relapsed disease. CONCLUSION: Prospective randomised trials are required to determine the utility of HDT/ASCT in ES and RMS. Selected patients with relapsed ES could be considered for HDT/ASCT.

A prospective investigation of predictive and modifiable risk factors for breast cancer in unaffected BRCA1 and BRCA2 gene carriers.

BACKGROUND: Breast cancer is the most common female cancer worldwide. The lifetime risk of a woman being diagnosed with breast cancer is approximately 12.5%. For women who carry the deleterious mutation in either of the BRCA genes, BRCA1 or BRCA2, the risk of developing breast or ovarian cancer is significantly increased. In recent years there has been increased penetrance of BRCA1 and BRCA2 associated breast cancer, prompting investigation into the role of modifiable risk factors in this group. Previous investigations into this topic have relied on participants recalling lifetime weight changes and subjective methods of recording physical activity. The influence of obesity-related biomarkers, which may explain the link between obesity, physical activity and breast cancer risk, has not been investigated prospectively in this group. This paper describes the design of a prospective cohort study investigating the role of predictive and modifiable risk factors for breast cancer in unaffected BRCA1 and BRCA2 gene mutation carriers. METHODS/DESIGN: Participants will be recruited from breast cancer family risk clinics and genetics clinics. Lifestyle risk factors that will be investigated will include body composition, metabolic syndrome and its components, physical activity and dietary intake. PBMC telomere length will be measured as a potential predictor of breast cancer occurrence. Measurements will be completed on entry to the study and repeated at two years and five years. Participants will also be followed annually by questionnaire to track changes in risk factor status and to record cancer occurrence. Data will be analysed using multiple regression models. The study has an accrual target of 352 participants. DISCUSSION: The results from this study will provide valuable information regarding the role of modifiable lifestyle risk factors for breast cancer in women with a deleterious mutation in the BRCA gene. Additionally, the study will attempt to identify potential blood biomarkers which may be predictive of breast cancer occurrence.

The presentation of metabolic dysfunction and the relationship with energy output in breast cancer survivors: a cross-sectional study.

BACKGROUND: Breast cancer prognosis can be adversely influenced by obesity, physical inactivity and metabolic dysfunction. Interventions aimed at improving surrogate markers of breast cancer risk such as insulin resistance may result in improved breast cancer outcomes. The design of such interventions may be improved through increased understanding of metabolic presentation in this cohort. This cross-sectional study aimed to characterise the metabolic profile of breast cancer survivors relative to abdominal obesity and insulin resistance. A secondary aim was to compare measures of energy output across these groups. METHODS: Sixty-nine women (mean (SD) age 53.43 (9.39) years) who had completed adjuvant chemotherapy and radiotherapy for breast cancer were recruited. All measures were completed during one assessment conducted 3.1 (1.0) years post diagnosis. Body composition was measured by bioimpedance analysis and waist circumference (WC). Fasting (12 hour) blood samples were drawn to measure lipid profile, glucose, insulin, glycosylated haemoglobin A1c (HBA1c) and C-reactive protein (CRP). Insulin resistance was estimated by the homeostatic model assessment index (HOMA-IR)). Energy output was evaluated by resting metabolic rate (RMR) measured by indirect calorimetry and physical activity measured by accelerometry. Characteristics were compared across four groups (1. WC <80 cm, not insulin resistant; 2. WC 80-87.9 cm, not insulin resistant; 3. WC >88 cm, not insulin resistant; 4. WC >80 cm, insulin resistant) using ANOVA (p < 0.05). RESULTS: Group 4 was characterised by significant disturbances in measures of glucose metabolism (glucose, insulin, HOMA-IR and HBA1c) and raised CRP compared to other groups. Group 4 also displayed evidence of dyslipidemia and higher body composition values compared to Groups 1 and 2. Both absolute and adjusted RMR were significantly higher in the Group 4 versus all other groups. Physical activity levels were similar for all groups. CONCLUSIONS: The results from this study suggest that participants who were both centrally obese and insulin resistant showed evidence of dyslipidemia, low-grade inflammation and glucose dysregulation. Metabolic profiles of participants who were centrally obese only were not significantly different from lean participants. Consideration of baseline metabolic presentation may be useful when considering the therapeutic targets for future interventions in this cohort.

The First Metatarsophalangeal Joint: Updates on Revision Arthrodesis and Malunions.

First metatarsophalangeal joint (MPJ) arthrodesis procedures are a mainstay of forefoot surgery and are associated with high rates of patient satisfaction for addressing a multitude of first ray pathologic conditions. This procedure is often also used as a fallback option for the revision of poor outcomes after other surgical procedures involving the first ray. Despite its successes, there remain instances of complications that can develop after primary first MPJ arthrodesis. This article reviews first MPJ arthrodesis as a procedure for revisional surgery of the first ray, and potential surgical options after failed primary first MPJ arthrodesis.

Quantitative proteomic studies addressing unmet clinical needs in sarcoma.

Sarcoma is a rare and complex disease comprising over 80 malignant subtypes that is frequently characterized by poor prognosis. Challenges in clinical management include uncertainties in diagnosis and disease classification, limited prognostic and predictive biomarkers, incompletely understood disease heterogeneity among and within subtypes, lack of effective treatment options, and limited progress in identifying new drug targets and novel therapeutics. Proteomics refers to the study of the entire complement of proteins expressed in specific cells or tissues. Advances in proteomics have included the development of quantitative mass spectrometry (MS)-based technologies which enable analysis of large numbers of proteins with relatively high throughput, enabling proteomics to be studied on a scale that has not previously been possible. Cellular function is determined by the levels of various proteins and their interactions, so proteomics offers the possibility of new insights into cancer biology. Sarcoma proteomics therefore has the potential to address some of the key current challenges described above, but it is still in its infancy. This review covers key quantitative proteomic sarcoma studies with findings that pertain to clinical utility. Proteomic methodologies that have been applied to human sarcoma research are briefly described, including recent advances in MS-based proteomic technology. We highlight studies that illustrate how proteomics may aid diagnosis and improve disease classification by distinguishing sarcoma histologies and identify distinct profiles within histological subtypes which may aid understanding of disease heterogeneity. We also review studies where proteomics has been applied to identify prognostic, predictive and therapeutic biomarkers. These studies traverse a range of histological subtypes including chordoma, Ewing sarcoma, gastrointestinal stromal tumors, leiomyosarcoma, liposarcoma, malignant peripheral nerve sheath tumors, myxofibrosarcoma, rhabdomyosarcoma, synovial sarcoma, osteosarcoma, and undifferentiated pleomorphic sarcoma. Critical questions and unmet needs in sarcoma which can potentially be addressed with proteomics are outlined.

Idiopathic granulomatous mastitis: a 5-year retrospective review of cases in a tertiary centre in Dublin, Ireland.

AIMS: Idiopathic granulomatous mastitis (IGM) is a rare, benign, inflammatory breast disorder of unknown aetiology usually affecting women of reproductive age. It classically presents as a unilateral painful breast mass. It is frequently mistaken for carcinoma or other inflammatory breast diseases. Diagnostic investigations include clinical examination, appropriate imaging and tissue sampling. A link between IGM and infection with the Corynebacterium species in particular Corynebacterium kroppenstedtii has been described. METHODS: A retrospective single-centre cohort study was conducted over a 5-year period (2017-2022); all cases of IGM were identified. RESULTS: Forty-one patients were diagnosed with IGM. Breast lump was the most common presenting complaint (n=29). The average age was 45 years. Eighteen patients had samples sent for culture and sensitivity, 11 of which had positive microbiology results indicative of Corynebacterium spp infection.An 82% resolution rate (27 of 33) was recorded in those who received either a short-antibiotic course or none at all. Eight patients reported persistent disease at 3 months, five of which had evidence of Corynebacterium spp. DISCUSSION: This 5-year review highlights the impact of IGM in a tertiary centre in Dublin, Ireland. Although no treatment guidelines exist, options include antibiotics, immunomodulators and surgery. Due to risk of fistulae and unfavourable cosmetic outcomes, surgery should be reserved for refractory IGM. We suspect that there may be a subset of patients where prolonged antibiotic therapy should be considered. Defining this subgroup requires further study, but likely includes those with cystic neutrophilic granulomatous mastitis, relapsing disease and in whom Corynebacterium spp is recovered.

Mesenchymal chondrosarcoma: An Australian multi-centre cohort study.

BACKGROUND: Mesenchymal chondrosarcoma (MCS) is an ultra-rare sarcoma that follows a more aggressive course than conventional chondrosarcoma. This study evaluates prognostic factors, treatments (surgery, chemotherapy, and radiation), and outcomes in an Australian setting. METHODS: We collected demographics, clinicopathological variables, treatment characteristics, and survival status from patients with MCS registered on the national ACCORD sarcoma database. Outcomes include overall survival (OS) and progression-free survival (PFS). RESULTS: We identified 22 patients with MCS between 2001-2022. Median age was 28 (range 10-59) years, 19 (86%) had localised disease at diagnosis of whom 16 had surgery (84%), 11 received radiation (58%), and 10 chemotherapy (53%). Ten (52%) developed recurrence and/or metastases on follow-up and three patients with initial metastatic disease received surgery, radiation, and chemotherapy. At a median follow-up of 50.9  (range 0.4-210) months nine patients had died. The median OS was 104.1 months (95% CI 25.8-182.3). There was improved OS for patients with localised disease who had surgical resection of the primary (p = 0.003) and those with ECOG 0-1 compared to 2-3 (p = 0.023) on univariate analysis. CONCLUSIONS: This study demonstrates contemporary Australian treatment patterns of MCS. The role of chemotherapy for localised disease remains uncertain. Understanding treatment patterns and outcomes help support treatment decisions and design of trials for novel therapeutic strategies.

Surgery at specialised sarcoma centres improves patient outcomes - A systematic review by the Australia and New Zealand sarcoma association clinical practice guidelines working party.

BACKGROUND: Optimal management of sarcoma requires multidisciplinary team input throughout the process of diagnosis, treatment and follow up. This systematic review aimed to evaluate the impact of surgery performed at specialised sarcoma centres on outcomes. METHODS: A systematic review was conducted using the population, intervention, comparison and outcome (PICO) model. Medline, Embase, Cochrane Central databases were queried for publications that evaluated the local control, limb salvage rate, 30-day and 90-day surgical mortality, and overall survival in patients undergoing surgery in a specialist sarcoma centre compared with non-specialist centre. Each study was screened by two independent reviewers for suitability. A qualitative synthesis of the results was performed. RESULTS: Sixty-six studies were identified. The majority of studies were Level III-3 as assessed by the NHMRC Evidence Hierarchy, whilst just over half of the studies were of good quality. Definitive surgery performed at specialised sarcoma centres was associated with improved local control as defined by lower rate of local relapse, higher rate of negative surgical margins, improved local recurrence free survival and higher limb conservation rate. Available evidences show a favourable pattern of lower 30-day and 90-day mortality rates, and greater overall survival when surgery was performed in specialist sarcoma centres compared with non-specialised centres. CONCLUSIONS: Evidences support better oncological outcomes when surgery is performed at specialised sarcoma centre. Patients with suspected sarcoma should be referred early to a specialised sarcoma centre for multidisciplinary management, which includes planned biopsy and definitive surgery.