Adjuvant Dose Dense Chemotherapy in Patients With Obesity: Short-Term Toxicities and Breast Cancer Outcome.

BACKGROUND: Dose dense adjuvant chemotherapy is associated with improved outcomes in breast cancer compared to standard dosing. Despite current guidelines recommending that chemotherapy is dosed according to actual body weight, reviews have shown patients with obesity often receive a capped chemotherapy dose. The latter is commonly undertaken as clinicians have concerns that adverse events are more frequent if full doses are administered. This study assessed surgical, radiotherapy and chemotherapy related adverse events between patients with and without obesity receiving dose dense adjuvant chemotherapy for breast cancer. MATERIALS AND METHODS: A retrospective review of prospective collected data for patients receiving adjuvant chemotherapy from 30 April 2018 from a single institution was analyzed. Data collected included demographic data, height, weight, pathological information, comorbidities, surgical, radiotherapy chemotherapy treatment, and toxicity. Primary outcomes were surgical complications at 30 days, radiotherapy skin toxicity at 30 days and chemotherapy side-effects. Secondary outcomes were rates of recurrence and time to recurrence. RESULTS: A total of 280 patients were included in the analysis: 55 obese and 225 nonobese. Obese status was associated with higher rates of grade >2 skin toxicity and this difference was significant after adjusting for age, comorbidity and radiotherapy field (P = .017). Obese status was not associated with higher rates of surgical or chemotherapy related adverse events. All patients regardless of obese status received adequate dose intensity with similar rates of recurrence and time to recurrence. CONCLUSION: Patients with obesity who receive dose dense adjuvant chemotherapy do not experience higher rates of surgical or chemotherapy related adverse events although they do experience higher rates of grade >2 radiotherapy related skin toxicity. This supports the use of dose dense chemotherapy being based on actual body weight in patients with obesity.

Evaluation of PD-L1 expression on circulating tumour cells in small-cell lung cancer.

Background: Antibodies against the programmed death-1 (PD-1) receptor and its ligand (PD-L1) have been recently approved for small-cell lung cancer (SCLC) treatment. Circulating tumour cells (CTCs) have emerged as an appealing liquid biopsy candidate that could enhance treatment decision-making in systemic therapy for SCLC patients. Several current technologies enrich CTCs using specific surface epitopes, size, rigidity, or dielectric properties. However, they are hampered by the heterogeneity of the enriched cells from blood samples. Methods: We evaluated two CTC enrichment systems: EpCAM conjugated to magnetic beads and a microfluidic device (Parsortix, Angle plc). PD-L1 expression was evaluated on the isolated CTCs. Twenty-three blood samples were collected from 21 patients with SCLC. PD-L1 expression was determined on CTCs through immunofluorescent staining. Results: CTCs were found in 14/23 (60.9%) of the samples, with 11/23 (47.8%) through EpCAM-coated magnetic beads (range, 4-1,611 CTCs/8 mL; median =5) and 11/20 (55.0%) using the Parsortix system (range, 1-165 CTCs/8 mL; median =4). Notably, a total of 17 EpCAM-negative CTCs were isolated using the Parsortix system. PD-L1 expression was detected on 268 of the 3,501 (7.7%) CTCs isolated with EpCAM-coated beads and in 33/366 (9.0%) of the CTCs isolated with the Parsortix system. No vimentin expression was observed in any of the detected CTCs. Conclusions: Overall, we identified a population of EpCAM-negative SCLC CTCs and showed that PD-L1 expression can be assessed on CTCs from SCLC patients. Comparison to tumour and treatment outcomes is needed to validate the potential of CTCs as an alternative sample for the assessment of PD-L1 expression in SCLC.

BreastSurgANZ members recommendations for adjuvant systemic treatment and patient compliance in Australian breast cancer patients.

BACKGROUND: We aimed to identify compliance with systemic treatment recommendations in early breast cancer (EBC) patients managed by Australian BreastSurgANZ members. METHODS: A retrospective analysis of patients diagnosed with EBC included in BreastSurgANZ prospective database from January 2002 to December 2016 was conducted. Data was available on patients with BC treated by over 350 surgeons across the six states and two territories of Australia. RESULTS: Over the 15 year period, 102 660 EBC episodes were recorded in 99 800 patients. As a group, the five key performance indicators (KPIs) set by the BreastSurgANZ relating to systemic treatment were achieved. Overall, patients were compliant with systemic treatment recommendations with 89.1% of patients receiving treatment in accordance with recommendations from their treating surgeon. The highest rate of non-compliance with systemic treatment was for endocrine therapy (11.9%). Of the 2368 patients who did not proceed with the recommended endocrine treatment, 1284 (54%) patients did so because of patient refusal. Failure to receive chemotherapy was associated with older age (aOR 1.02; p < 0.001), patients living in regional areas (aOR 1.23; p = 0.001) and those with node negative disease (aOR 0.97; p = 0.003). CONCLUSIONS: The majority of Australian patients with EBC are being recommended for adjuvant systemic therapy in accordance with BreastSurgANZ KPI's. Treatment compliance was very high. This finding emphasises the importance of prospective data collection and auditing of established KPIs by surgeons, in areas other than direct surgical outcomes. Further research into the reasons why patients refuse treatment is needed.

Male Breast Cancer in Australia.

AIMS: Male breast cancer is rare and treatment recommendations are based on female breast cancer guidelines. We analyzed an Australian dataset of patients with early breast cancer (including ductal carcinoma in situ, DCIS) for demographic, pathological and treatment information. The primary objective was to compare treatment delivery for males versus females. METHODS: Australian data from the BreastSurgANZ Quality Audit (BQA) from 1 October 2006 and 30 September 2016 were analyzed. Demographic and pathological information was obtained and compared between males and females. Treatment recommendations were compared to BreastSurgANZ Key Performance Indicators (KPIs) and National Comprehensive Cancer Network (NCCN) guidelines to assess for adherence to national and international guidelines, respectively. RESULTS: A total of 99,768 breast cancer episodes were analyzed, comprising 585 males (544 invasive; 41 DCIS) and 99 183 (99.4%) females (85 596 invasive; 13 525 DCIS; 62 unknown). Compared with females, males were older at diagnosis, more likely to be hormone receptor-positive and lymph node-positive disease, and more likely to have mastectomy. The proportion of males undergoing breast conserving surgery receiving radiotherapy was the only BreastSurgANZ KPI that was not met. Males were less likely to receive adjuvant chemotherapy than females using NCCN guidelines. CONCLUSION: Australian males with breast cancer account for 0.6% of breast cancer incidence and have similar clinico-pathological features as reported internationally. Overall, there is good compliance with the surgical KPIs, and adherence to NCCN guidelines for adjuvant systemic treatment is similar to previous international studies.

Clinical Oncology Society of Australia: Position statement on cancer-related malnutrition and sarcopenia.

This position statement describes the recommendations of the Clinical Oncology Society of Australia (COSA) regarding management of cancer-related malnutrition and sarcopenia. A multidisciplinary working group completed a review of the literature, focused on evidence-based guidelines, systematic reviews and meta-analyses, to develop recommendations for the position statement. National consultation of the position statement content was undertaken through COSA members. All people with cancer should be screened for malnutrition and sarcopenia in all health settings at diagnosis and as the clinical situation changes throughout treatment and recovery. People identified as "at risk" of malnutrition or with a high-risk cancer diagnosis or treatment plan should have a comprehensive nutrition assessment; people identified as "at risk" of sarcopenia should have a comprehensive evaluation of muscle status using a combination of assessments for muscle mass, muscle strength and function. All people with cancer-related malnutrition and sarcopenia should have access to the core components of treatment, including medical nutrition therapy, targeted exercise prescription and physical and psychological symptom management. Treatment for cancer-related malnutrition and sarcopenia should be individualised, in collaboration with the multidisciplinary team (MDT), and tailored to meet needs at each stage of cancer treatment. Health services should ensure a broad range of health care professionals across the MDT have the skills and confidence to recognise malnutrition and sarcopenia to facilitate timely referrals and treatment. The position statement is expected to provide guidance at a national level to improve the multidisciplinary management of cancer-related malnutrition and sarcopenia.

Chemotherapy dosing and toxicity in a patient with muscular dystrophy.

BACKGROUND: Chemotherapy dosing has traditionally been based on a body surface area (BSA) calculation despite BSA dosing being problematic in a number of conditions, such as renal failure, liver failure, obesity, and sarcopenia. This case highlights another condition in which BSA dosing is problematic. CASE: A 57-year-old man with limb-girdle muscular dystrophy presents with stage IIA inoperable squamous cell carcinoma of the lung. He is treated with chemotherapy and radiotherapy with curative intent but develops significant chemotherapy related toxicity affecting chemotherapy scheduling and dosing. Later, his cancer progresses, and he is commenced on palliative chemotherapy resulting in further significant chemotherapy toxicity. CONCLUSION: Sarcopenia is known to increase risk of chemotherapy toxicity. This case postulates that changes in muscle mass seen in muscular dystrophy increases risk of chemotherapy toxicity, similar to sarcopenia.

Isolation and detection of circulating tumour cells from metastatic melanoma patients using a slanted spiral microfluidic device.

Circulating Tumour Cells (CTCs) are promising cancer biomarkers. Several methods have been developed to isolate CTCs from blood samples. However, the isolation of melanoma CTCs is very challenging as a result of their extraordinary heterogeneity, which has hindered their biological and clinical study. Thus, methods that isolate CTCs based on their physical properties, rather than surface marker expression, such as microfluidic devices, are greatly needed in melanoma. Here, we assessed the ability of the slanted spiral microfluidic device to isolate melanoma CTCs via label-free enrichment. We demonstrated that this device yields recovery rates of spiked melanoma cells of over 80% and 55%, after one or two rounds of enrichment, respectively. Concurrently, a two to three log reduction of white blood cells was achieved with one or two rounds of enrichment, respectively. We characterised the isolated CTCs using multimarker flow cytometry, immunocytochemistry and gene expression. The results demonstrated that CTCs from metastatic melanoma patients were highly heterogeneous and commonly expressed stem-like markers such as PAX3 and ABCB5. The implementation of the slanted microfluidic device for melanoma CTC isolation enables further understanding of the biology of melanoma metastasis for biomarker development and to inform future treatment approaches.

Circulating tumor DNA to monitor treatment response and detect acquired resistance in patients with metastatic melanoma.

Repeat tumor biopsies to study genomic changes during therapy are difficult, invasive and data are confounded by tumoral heterogeneity. The analysis of circulating tumor DNA (ctDNA) can provide a non-invasive approach to assess prognosis and the genetic evolution of tumors in response to therapy. Mutation-specific droplet digital PCR was used to measure plasma concentrations of oncogenic BRAF and NRAS variants in 48 patients with advanced metastatic melanoma prior to treatment with targeted therapies (vemurafenib, dabrafenib or dabrafenib/trametinib combination) or immunotherapies (ipilimumab, nivolumab or pembrolizumab). Baseline ctDNA levels were evaluated relative to treatment response and progression-free survival (PFS). Tumor-associated ctDNA was detected in the plasma of 35/48 (73%) patients prior to treatment and lower ctDNA levels at this time point were significantly associated with response to treatment and prolonged PFS, irrespective of therapy type. Levels of ctDNA decreased significantly in patients treated with MAPK inhibitors (p < 0.001) in accordance with response to therapy, but this was not apparent in patients receiving immunotherapies. We show that circulating NRAS mutations, known to confer resistance to BRAF inhibitors, were detected in 3 of 7 (43%) patients progressing on kinase inhibitor therapy. Significantly, ctDNA rebound and circulating mutant NRAS preceded radiological detection of progressive disease. Our data demonstrate that ctDNA is a useful biomarker of response to kinase inhibitor therapy and can be used to monitor tumor evolution and detect the early appearance of resistance effectors.