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Background: The suspension of breast cancer screening during the COVID‐19 pandemic altered patient diagnosis and management. This study investigates the impact of the COVID‐19 lockdowns, screening delays and reduced healthcare attendance on changes in tumour and treatment characteristics, particularly for biologically more aggressive breast cancers. Methods: This retrospective single‐hospital analysis utilized data from a prospective cancer database between July 2019 and June 2022. Patient, tumour and treatment factors were compared across pre‐pandemic, pandemic and post‐pandemic groups. Results: Symptomatic breast cancer increased from 42.3% in the pre‐, 53.1% in the pandemic and 57% in the post‐ respectively (P ≤ 0.05). Compared to the pre‐pandemic group (4.6%), an increase in stages 3 or 4 breast cancers in the pandemic (8.5%) and post‐pandemic (7.1%) was found. Increased node‐positivity in Ki67 > 20%, grade 3 or ER‐ tumours post‐pandemic (+5.4%, +14.8%, +33.4%, respectively) was identified. More neoadjuvant chemotherapy was found in both the pandemic (+4.3%) and post‐pandemic (+11.3%, P = 0.0261) groups. An increase in hypofractionated radiotherapy in the post‐pandemic group (+9.4%) was also identified. Conclusion: Our study identified a decrease in early‐stage cancers and an increase in node positivity, particularly for biologically more aggressive tumours. An increase in the number of patients receiving neoadjuvant chemotherapy or hypofractionated radiotherapy during the pandemic and post‐pandemic periods was also identified. [ABSTRACT FROM AUTHOR]

Studies of patients with castrate‐resistant prostate cancer at high risk of developing overt metastases but with no current evidence of evaluable disease on computed tomography or bone scan non‐metastatic castrate‐resistant prostrate cancer have demonstrated increased metastasis‐free survival and overall survival following treatment with the next‐generation oral anti‐androgen apalutamide (in addition to therapies that aim to lower testosterone to castrate levels) or luteinizing hormone‐releasing hormone antagonist or surgical castration. Patients receiving apalutamide can be managed by medical oncologists, radiation oncologists, or urologists, preferably as part of a multidisciplinary team. However, the importance of additional safety monitoring for significant adverse effects and drug interactions should not be underestimated. The toxicities of apalutamide are manageable with experience and should be managed proactively to minimize their impact on patients. Monitoring of patients for apalutamide‐specific toxicities, including skin rash, hypothyroidism, and QT prolongation should be carried out regularly, particularly in the first few months following initiation. Monitoring should continue alongside monitoring for toxicities of androgen deprivation, including cardiovascular risk, hot flashes, weight gain, bone health, muscle wasting, and diabetic risk. This review is a practical guide to the use of apalutamide describing the management of patients including dosing and administration, toxicities, potential drug interactions, and safety monitoring requirements. [ABSTRACT FROM AUTHOR]

Aim: There has been significant progress made in developing novel targeted therapies in the neoadjuvant setting for non‐metastatic HER2‐positive breast cancer, which may be used in combination with conventional chemotherapy to optimise pathological responses at surgery. However, these therapies, particularly the chemotherapeutic components, may portend significant and long‐lasting toxicity. Hence, de‐escalation of treatment intensity has been an area of interest and was evaluated in the phase II NeoSphere study. Herein, we report the real‐world pathological and survival outcomes from neoadjuvant taxane and dual HER2 blockade recorded at our centre. Methods: This was a retrospective cohort study of patients receiving neoadjuvant pertuzumab, trastuzumab and taxane chemotherapy for non‐metastatic HER2‐positive breast cancer at a single centre in Sydney, Australia. We collected data pertaining to baseline demographic characteristics, pathological response rates, post‐surgical prescribing patterns and also undertook survival analyses for invasive disease‐free survival (iDFS) as well as exploratory analyses for correlations between pre‐specified clinicopathologic factors and pathological response at surgery. Results: Our population was largely similar at baseline to the NeoSphere study. 71 patients were included in the final analysis. 61% achieved a pathological complete response (pCR). Three patients received conventional chemotherapy in the adjuvant setting. 92% of included patients were alive and disease‐free at 3 years of follow‐up. Only 3 events of recurrence or death were recorded at a median follow‐up of 32 months. No significant difference in iDFS was noted between patients achieving pCR and those with residual disease at surgery. Conclusion: This study demonstrates that de‐escalated adjuvant treatment for HER2‐positive early breast cancer achieved favourable pathological and long‐term outcomes comparable to large trials, some utilising more intensive chemotherapeutic components. [ABSTRACT FROM AUTHOR]

Purpose: Endoscopic ultrasound‐guided gastro‐enterostomy (EUS‐GE) is a relatively novel technique that has been shown to require less re‐intervention than standard endoscopic enteral stenting for gastric outlet obstruction and is less invasive, quicker, and more cost‐effective than surgery. This study evaluated the outcomes and safety of EUS‐GE in patients treated for gastric outlet obstruction across two Australian centers. Methods: Retrospective data on demographics, presenting symptoms, disease, endoscopic and clinical outcomes, and safety were collected on all patients who underwent EUS‐GE from 2021 to 2022. Descriptive statistics were used to evaluate outcomes and safety and survival were calculated using Kaplan‐Meier analysis. Results: Eleven patients underwent EUS‐GE during the defined period, 10 of whom had a malignant etiology (median age 73 years, interquartile range [IQR] 13; 63.6% male). Technical success was 90.9%. Of those patients, clinical success (the ability to tolerate at least a full liquid diet during follow‐up) was 100%. The median length of hospital stay post‐procedure was 6 days (IQR 14 days). No severe adverse events occurred, and one patient (10%) required a repeat endoscopy. Median survival post‐EUS‐GE was 298 days (95% confidence interval 0–730.1 days) Conclusion: EUS‐GE is an effective, safe, and durable therapy for patients with gastric outlet obstruction. This study presents Australian data on outcomes and safety that is comparable to international literature. EUS‐GE should be considered for patients where local expertise allows. [ABSTRACT FROM AUTHOR]

Aim: There are many barriers to physical activity among cancer survivors. Survivors treated with neurotoxic chemotherapy may develop chemotherapy‐induced peripheral neuropathy (CIPN) and experience additional barriers related to sensorimotor and mobility deficits. This study examined physical activity behaviors, including physical activity predictors, among cancer survivors treated with neurotoxic chemotherapies. Methods: A cross‐sectional study of 252 participants, 3–24 months after neurotoxic chemotherapy, was undertaken. Physical activity was self‐reported (IPAQ). CIPN was self‐reported (FACT/GOG‐Ntx‐13), clinically graded (NCI‐CTCAE), and objectively measured using neurological grading scales and neurophysiological techniques (tibial and sural nerve conduction studies). Balance (Swaymeter) and fine motor skills (grooved pegboard) were assessed. Regression models were used to identify clinical, demographic and CIPN predictors of walking and moderate–vigorous physical activity. Results: Forty‐four percent of participants did not meet recommended physical activity guidelines (≥150 min/week). Sixty‐six percent presented with CIPN. Nineteen percent of participants with CIPN reported that symptoms interfered with their ability to be physically active. A lower proportion of survivors aged ≥60, with grade ≥1 CIPN or BMI ≥30, reported meeting physical activity guidelines (all p <.05). Regression models identified older age, higher BMI, and patient‐reported CIPN associated with lower walking, while higher BMI and females were associated with lower moderate–vigorous physical activity. Neurologically assessed CIPN did not associate with walking or moderate–vigorous physical activity. Conclusion: Cancer survivors exposed to neurotoxic chemotherapy have low physical activity levels. Further work should examine the factors causing physical activity limitations in this cohort and designing interventions to improve physical function and quality of life in survivors. [ABSTRACT FROM AUTHOR]

The pertuzumab study in the neoadjuvant setting for HER2+ nonmetastatic breast cancer in Australia (PeRSIA—ML39622) is an analysis of safety and effectiveness data from the pertuzumab patient registry. Although the prognosis of patients with early stage HER2+ breast cancer has been greatly improved by advances in chemotherapy approximately 25% to 30% of patients develop recurrent disease. Our study aimed to examine the effectiveness of neoadjuvant pertuzumab on surgical outcomes, describe the medium‐term effectiveness outcomes of patients treated with pertuzumab, and describe the planned and actual anticancer treatment regimens that patients received. Deidentified data were collected from the patients' medical records and entered into REDCap, between March 2018 and July 2019 (n = 95). The adverse events (AEs) reported most frequently were diarrhea (20; 21.1%), rash (4; 4.2%), and LVSD (4; 4.2%; two patients during neoadjuvant treatment and two patients during adjuvant treatment). AEs, ≥Grade 3 were diarrhea (2; 2.1%) and LVSD (1; 1.1%). Following surgery, a breast pathological complete response (bpCR) was achieved in 65 patients (70.7%; 95% CI: 60.2%‐79.7%) and total pathological complete response (tpCR) in 59 patients (64.1%; 95% CI: 53.4%‐73.9%). All patients who did not achieve a tpCR obtained a partial response (33/92, 35.9%). Our study is the first to capture real‐world data on the use of pertuzumab in the neoadjuvant setting in Australia. The effectiveness and safety data are consistent with those reported in clinical trials of pertuzumab in patients with HER2+ breast cancer, with no new safety concerns. [ABSTRACT FROM AUTHOR]

Introduction. The Oncotype DX test is a genomic assay that generates a Recurrence Score (RS) predicting the 10-year risk of recurrence and response to adjuvant chemotherapy in ER+/HER2− breast cancer patients. The aims were to determine breast cancer distant recurrence and correlate with adjuvant chemoendocrine prescribing patterns based on the Oncotype DX recurrence score. Methods. We conducted a retrospective single-institution case series of 71 patients who had Oncotype DX assay testing after definitive surgery between 2012 and 2016. Both node-positive and node-negative patients were included. Patients were divided into Oncotype DX low risk (RS < 11) (n = 10, 14%), intermediate risk (RS 11–25) (n = 45, 63%), and high risk (RS > 25) (n = 16, 23%). Median follow-up was 6.1 years (range 4–8.9 years). Adjuvant treatment regimens and oncological outcomes were determined. Results. Mean age at diagnosis was 56 years (range, 33–77). Invasive ductal carcinoma (IDC) accounted for the majority (87%), with most tumors measuring between 10–20 mm (52%). 48% of the cohort were node positive. 15 of 16 high-risk patients (94%) received chemotherapy. 96% of intermediate-risk patients received endocrine therapy alone, one patient received chemoendocrine therapy (2%), and one declined systemic therapy (2%). In the low-risk group, 100% received endocrine therapy only. The high-risk group had the lowest mean ER% (P < 0.05), greatest mean mitotic rate (P < 0.05), and greatest proportion of Ki67% > 14. Five patients developed distant recurrence (7%): three from the intermediate-risk group (7%), one from the low-risk group (10%), and one from the high-risk group (6%). Conclusion. This is the first Australian study reporting the experience with medium-term recurrence outcomes of using the Oncotype DX assay in breast cancer. Chemotherapy was rarely given for patients with low-to-intermediate RS and always offered in high RS. This pattern of prescribing was associated with low rates of distant recurrence. National funding models should be considered. [ABSTRACT FROM AUTHOR]

Aims: Internationally, there has recently been growing interest in the use of neoadjuvant pertuzumab and trastuzumab in patients with non‐metastatic HER‐2 positive breast cancer following the NEOSPHERE trial in 2012. However, pertuzumab is currently not funded by the Pharmaceutical Benefits Scheme (PBS) in Australia for use in this setting. The authors sought to assess the clinical and pathological response rates at the time of surgery in patients who received neoadjuvant dual anti‐HER2 and taxane therapy in a multidisciplinary breast cancer unit. Methods: A retrospective case series of all patients treated with the neoadjuvant therapy, and who had definitive surgery was conducted. Demographic data, size, grade, tumor type, receptor status prior to neoadjuvant treatment, pathological complete response (pCR) rates, and adverse effects were analyzed. Results: Nineteen patients were included in the study. Sixty‐eight percent of all patients achieved pCR, of which 54% further demonstrated no residual ductal carcinoma in situ. Eight patients (42%) had N1 disease pretreatment, of these 88% demonstrated total pCR in the axilla and the breast. Most adverse effects to treatment were manageable grade 1–2 side effects. Conclusion: This is the first reported Australian experience using neoadjuvant dual anti‐HER2 and taxane therapy for HER‐2 positive nonmetastatic breast cancer. The authors have demonstrated favorable pCR rates for invasive disease compared to the NEOSPHERE trial (68% vs 46%), with reasonable patient tolerability. Larger collaborative data sets are required to fully evaluate correlation of pCR with survival outcomes, and cost‐effectiveness. National funding models need to be considered. [ABSTRACT FROM AUTHOR]

Background: In Australia, data generated from the carefully selected, treated and monitored patients enrolled in clinical trials largely inform routine care and funding approvals. Medicine Access Programmes (MAP) enable drug access and while potentially a rich source of data, historically have not collected data beyond a participant list. Aims: To explore the feasibility of using MAP to identify patient populations for inclusion in non‐interventional studies. Methods: Clinicians affiliated with the Walter and Eliza Hall Institute engaged with Roche to implement PeRSIA, a secondary data use non‐interventional study of patients receiving neoadjuvant pertuzumab for non‐metastatic HER2+ breast cancer. The study utilised a pre‐existing Roche‐sponsored MAP to identify clinicians as data contributors. Data security, ownership and reporting issues were addressed utilising the BioGrid platform and standards developed for existing Walter and Eliza Hall Institute registries. Disease experts developed project‐specific Case Report Forms documenting treatment, surgical and cancer‐specific outcomes, and adverse events. Results: To date, 12 of 16 (75%) clinicians approached to participate in PeRSIA are contributing de‐identified data. From February through September 2018, data on 41 patients from seven centres were collected. Median patient age is 56 years (range 36–81), 36 (88%) had Stage 2 to 3 disease and 27 (66%) were node positive. The median number of cycles of neoadjuvant pertuzumab planned was 4. Conclusions: This initial report is, to our knowledge, the first description of a secondary data use non‐interventional study collecting comprehensive data on patients enrolled, independently, in a MAP. This effort continues and opportunities with other industry partners are being pursued. [ABSTRACT FROM AUTHOR]

Aromatase inhibitors are the gold standard in the treatment of hormone receptor‐positive breast cancer, but lead to an arthralgia syndrome which is implicated in 13–22% of noncompliance. This is the first systematic review of the efficacy of existing management strategies for this side effect. Eligible studies were retrieved from computer searches of Medline, Cochrane and Embase and the significant intervention groups were identified. The risk of bias of selected studies was evaluated and the relevant data items were extracted, summarized and analyzed. A total of 21 studies were discussed in this review representing 12 different interventions. While several trials had positive findings, the major methodological limitations of the studies meant that no definitive evidence could be found supporting any of the interventions. Future trials are needed which address the methodological problems identified in this review. Exercise holds promise for future research based on its proven benefit in breast cancer. [ABSTRACT FROM AUTHOR]

Abstract: Aim: Decisions regarding adjuvant chemotherapy for early breast cancer are complex. Ki67 is increasingly used, in conjunction with conventional prognostic markers, to help decide the use of adjuvant chemotherapy for early breast cancer. Ki67 has been proposed as an economical alternative to Oncotype DX recurrence score (RS), which is a validated prognostic marker for disease recurrence and predictive marker for benefit from chemotherapy. This study aimed to determine in patients where conventional prognostic markers did not provide a clear recommendation for adjuvant chemotherapy, whether Ki67 could be a substitute for RS. Methods: We reviewed all cases of luminal‐type node‐negative early breast cancer (T1‐2, N0‐1mi, M0, estrogen receptor positive, HER2 negative) referred for Oncotype DX testing by the multidisciplinary team at an Australian tertiary private hospital from 14th December 2006 to 31st December 2013, when conventional prognostic markers did not provide a clear recommendation for adjuvant chemotherapy. RS was correlated with Ki67, along with other conventional prognostic markers including tumor size, grade, mitotic rate and lymphovascular invasion. Spearman's rank order correlation coefficient and Pearson product‐moment correlation coefficient (r) were used for ordinal and continuous variables, respectively. Results: A total of 58 patients were analyzed, median Ki67 was 15% (range 2–50%) and the median RS was 16 (range 3–65). There was no positive correlation between Ki67 and RS (r = 0.01, P = 0.93). No single conventional prognostic marker was shown to significantly correlate with RS, including tumor size (r = −0.02, P = 0.88), grade (r = 0.10, P = 0.44), mitotic rate (r = −0.07, P = 0.69) and lymphovascular invasion (r = −0.12, P = 0.39). Conclusion: Ki67 and conventional prognostic markers do not correlate with Oncotype DX RS. In the setting where conventional prognostic markers do not show a clear indication for or against adjuvant chemotherapy as determined by consensus in a multidisciplinary team, Ki67 is not a substitute for Oncotype DX testing. RS may provide additional information to aid decision making for adjuvant chemotherapy. [ABSTRACT FROM AUTHOR]

Oxaliplatin is a platinum-derivative chemotherapeutic agent used for colorectal cancer in the adjuvant and metastatic setting in combination with folinic acid and 5-fluorouracil. Oxaliplatin causes an acute cold-induced neurotoxicity and a chronic cumulative neuropathy, which can require dose modification and impact quality of life. To date, no prevention and treatment strategies have proved effective thus reinforcing the importance of identifying at-risk patients in order to maximize therapeutic benefit while minimizing neurotoxicity. Here we reviewed studies on risk and prognostic factors associated with the development and severity of oxaliplatin-induced peripheral neuropathy. A systematic search was conducted in MEDLINE and Embase, and studies investigating clinical and patient-related factors associated with oxaliplatin-induced peripheral neuropathy as their primary focus were identified, and quantitative data were extracted when available. We identified 15 studies, of which only three were prospective. Notable factors were acute neurotoxicity symptoms predicting chronic neuropathy, baseline laboratory findings, patient demographics such as age and gender, comorbidities, and environmental factors. No factor was consistently identified across multiple studies other than the association with oxaliplatin dose. Further investigation into these factors may yield insight into potential neuropathy prevention and treatment strategies. [ABSTRACT FROM AUTHOR]

Lipids are known to influence tumour growth, inflammation and chemoresistance. However, the association of circulating lipids with the clinical outcome of metastatic castration-resistant prostate cancer (CRPC) is unknown. We investigated associations between the plasma lipidome and clinical outcome in CRPC. Lipidomic profiling by liquid chromatography-tandem mass spectrometry was performed on plasma samples from a Phase 1 discovery cohort of 96 CRPC patients. Results were validated in an independent Phase 2 cohort of 63 CRPC patients. Unsupervised analysis of lipidomic profiles (323 lipid species) classified the Phase 1 cohort into two patient subgroups with significant survival differences (HR 2.31, 95% CI 1.44-3.68, p = 0.0005). The levels of 46 lipids were individually prognostic and were predominantly sphingolipids with higher levels associated with poor prognosis. A prognostic three-lipid signature was derived (ceramide d18:1/24:1, sphingomyelin d18:2/16:0, phosphatidylcholine 16:0/16:0) and was also associated with shorter survival in the Phase 2 cohort (HR 4.8, 95% CI 2.06-11.1, p = 0.0003). The signature was an independent prognostic factor when modelled with clinicopathological factors or metabolic characteristics. The association of plasma lipids with CRPC prognosis suggests a possible role of these lipids in disease progression. Further research is required to determine if therapeutic modulation of the levels of these lipids by targeting their metabolic pathways may improve patient outcome. [ABSTRACT FROM AUTHOR]

Objectives To determine whether local treatment of primary prostate cancer gives palliative benefit to men who later develop castrate-resistant prostate cancer ( CRPC)., Local treatments of primary prostate cancer are defined as radical retropubic prostatectomy ( RRP) or external beam radiation therapy ( EBRT)., Patients and Methods Patient records were reviewed in five different hospitals in Sydney, Australia, and 263 men with CRPC were identified., Eligible patients comprised men who had progressive disease during androgen deprivation therapy with castrate levels of testosterone., Clinical and pathological data were reviewed and evaluated using the chi-squared test and relative risk analysis to determine the relationship between previous local prostate treatment and complications secondary to local disease., The end-point was complications and morbidity attributed to cancer progression locally (i.e. from the prostate)., Results Primary treatment of the prostate by either RRP or EBRT significantly reduces the incidence of local complications compared to no primary treatment (32.6% vs 54.6%; P = 0.001)., RRP showed a significantly lower level of local complications compared to EBRT (20.0% vs 46.7%; P = 0.007)., The most common local complications were bladder outlet obstruction (35.0%) and ureteric obstruction (15.2%)., Conclusions The present retrospective analysis supports the hypothesis that primary local prostatic treatment gives palliative benefit to men who later develop CRPC., RRP was associated with the lowest local complication rate experienced at the stage of metastatic disease. [ABSTRACT FROM AUTHOR]

Advanced esophagogastric carcinoma has a poor prognosis. Palliative chemotherapy provides a survival advantage and improved quality of life. Epirubicin, cisplatin and continuous infusional 5-fluorouracil (5-FU) (ECF) is a well-established chemotherapy regimen but a continuous chemotherapy infusion is not always feasible or acceptable. We conducted a phase I and II trial of a modified version of ECF, utilizing 5-FU as a 24-h infusion on day 1 and day 8 of a 21-day cycle, administered with sodium folinate as a modulator of 5-FU (ECSF). In the phase I study the dose of 5-FU was increased in successive cohorts from 1250 mg/m, 1500 mg/m, and 1750 mg/m to 2000 mg/m per 24 h. Dose limiting toxicity of febrile neutropenia was encountered at 2000 mg/m. The recommended dose for 5-FU was 1750 mg/m. Overall 29 patients were treated with ECSF of whom 27 were evaluable for toxicity. The response rate was 45% on an intention-to-treat analysis with a complete response rate of 3%. The median response rate was 4.1 months and the median survival was 10.7 months. A total of 23 patients (72%) obtained clinical benefit with improvement in dysphagia or weight gain. central venous catheter (CVC) complications were observed in 12 (41%) patients. ECSF was associated with a response rate and survival similar to that reported with standard ECF. ECSF may provide an alternative regimen to standard ECF when a continuous ambulatory infusion pump is not feasible or not preferred by the patient. CVC complications are a limitation. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented regarding a case of a 91-year old woman with symptomatic bone-dominant metastatic breast cancer who developed symptomatic hypocalcaemia after treated with denosumab.

The article presents a case study of a 68-year-old man with metastatic basal cell carcinoma (BCC) with symptoms and signs consistent with a drug reaction of eosinophilia and systemic symptoms (DRESS). It mentions that the patient had developed disease of the left parotid, left upper neck and lung. It also mentions the use of C-reactive protein (CRP) 61 and gammaglutamyl transferase 210 for non-specific biochemical abnormalities.