Registry-derived stage (RD-Stage) for capturing cancer stage at diagnosis for endometrial cancer.

BACKGROUND: Capture of cancer stage at diagnosis is important yet poorly reported by health services to population-based cancer registries. In this paper we describe current completeness of stage information for endometrial cancer available in Australian cancer registries; and develop and validate a set of rules to enable cancer registry medical coders to calculate stage using data available to them (registry-derived stage or 'RD-Stage'). METHODOLOGY: Rules for deriving RD-stage (Endometrial carcinoma) were developed using the American Joint Commission on Cancer (AJCC) TNM (tumour, nodes, metastasis) Staging System (8th Edition). An expert working group comprising cancer specialists responsible for delivering cancer care, epidemiologists and medical coders reviewed and endorsed the rules. Baseline completeness of data fields required to calculate RD-Stage, and calculation of the proportion of cases for whom an RD stage could be assigned, was assessed across each Australian jurisdiction. RD-Stage (Endometrial cancer) was calculated by Victorian Cancer Registry (VCR) medical coders and compared with clinical stage recorded by the patient's treating clinician and captured in the National Gynae-Oncology Registry (NGOR). RESULTS: The necessary data completeness level for calculating RD-Stage (Endometrial carcinoma) across various Australian jurisdictions varied from 0 to 89%. Three jurisdictions captured degree of spread of cancer, rendering RD-Stage unable to be calculated. RD-Stage (Endometrial carcinoma) could not be derived for 64/485 (13%) cases and was not captured for 44/485 (9%) cases in NGOR. At stage category level (I, II, III, IV), there was concordance between RD-Stage and NGOR captured stage in 393/410 (96%) of cases (95.8%, Kendall's coefficient = 0.95). CONCLUSION: A lack of consistency in data captured by, and data sources reporting to, population-based cancer registries meant that it was not possible to provide national endometrial carcinoma stage data at diagnosis. In a sample of Victorian cases, where surgical pathology was available, there was very good concordance between RD-Stage (Endometrial carcinoma) and clinician-recorded stage data available from NGOR. RD-Stage offers promise in capturing endometrial cancer stage at diagnosis for population epidemiological purposes when it is not provided by health services, but requires more extensive validation.

The impact of single agent PD-1 or PD-L1 inhibition on advanced endometrial cancers: meta-analysis.

BACKGROUND: Immune checkpoint inhibitor (ICI) therapy is an emerging option for advanced endometrial cancer (EC). Mismatch repair (MMR) status is widely regarded as a biomarker predictive of response to ICIs. The predictive value of MMR based on small, single-arm trials, however, is conflicting. In this meta-analysis, we aimed to assess the activity of single-agent ICI in advanced EC, and compared the magnitude of treatment benefit in MMR deficient (dMMR) and MMR proficient (pMMR) EC. METHODS: We carried out an electronic search to identify prospective trials of single-agent ICI in advanced EC. Data on objective response rate (ORR) and progression-free survival (PFS) were extracted and pooled. ORR was estimated using the inverse variance method and subgroup difference by MMR status was examined. PFS difference according to MMR status was summarized using the Kaplan-Meier approach. RESULTS: From eight trials with 492 women, the pooled ORR was 19% [95% confidence interval (CI) 16% to 22%]. ORR was significantly greater in dMMR (n = 281) than pMMR EC (n = 211) (dMMR: 46%, pMMR: 8%; risk ratio 5.74, 95% CI 3.58-9.21; interaction P < 0.001). Complete response was 11% and 0.05% and median PFS was 8.3 and 2.1 months in dMMR and pMMR EC, respectively (hazard ratio PFS 0.58, 95% CI 0.38-0.89; P = 0.01). The 12-month PFS rates were 42.0% and 20.7%, respectively. CONCLUSION: Single-agent ICI is associated with a 5.74 times greater objective response and 42% reduction in risk of disease progression or death in dMMR compared with pMMR EC. MMR status should be determined prospectively and be used as a stratification factor in future trials of advanced EC. Further translational analysis is urgently required to identify the cause of dMMR and allow subclassification of EC into different dMMR molecular subtypes.

Women's responses and understanding of polygenic breast cancer risk information.

It is estimated that polygenic factors can explain up to 18% of familial breast cancer. Clinical implementation of polygenic testing has begun, with several commercial laboratories now testing. Despite commercial implementation, there is little research investigating how women respond and understand polygenic risk information. This study aimed to explore women's experience receiving their personalised polygenic risk score (PRS) and compare responses of women at different levels of polygenic risk. Eligible participants were affected and unaffected women from families clinically assessed to be at high risk for breast cancer who had received their personalised PRS as part of the Variants in Practice Psychosocial Study (ViPPs). In-depth semi-structured interviews were conducted with 21 women (mean age 53.4 years) up to four weeks after receiving their PRS. Interviews were transcribed verbatim and analysed using thematic analysis. Eleven women received a PRS that was in the top quartile of PRS distribution and 10 in the lowest quartile. Women's lived experience with breast cancer informed how they responded to their PRS, constructed and made sense of breast cancer risk following receipt of their PRS, and integrated this new information into their breast cancer risk management. Regardless of polygenic risk level, all participants demonstrated broad knowledge of concepts related to polygenic information and were able to accurately describe the implications of their PRS. Receiving PRS did not appear to negatively impact women's reported distress levels. Our findings suggest polygenic breast cancer information is well received and understood by women at high-risk for breast cancer.

The development and evaluation of a nationwide training program for oncology health professionals in the provision of genetic testing for ovarian cancer patients.

BACKGROUND: BRCA1/2 mutation status has increasing relevance for ovarian cancer treatments, making traditional coordination of genetic testing by genetic services unsustainable. Consequently alternative models of genetic testing have been developed to improve testing at the initial diagnosis for all eligible women. METHODS: A training module to enable mainstreamed genetic testing by oncology healthcare professionals was developed by genetic health professionals. Oncology healthcare professionals completed questionnaires before and 12 months post-training to assess perceived skills, competence and barriers to their coordinating genetic testing for women with high-grade non-mucinous epithelial ovarian cancer. Genetic health professionals were surveyed 12 months post-training to assess perceived barriers to implementation of mainstreaming. RESULTS: 185 oncology healthcare professionals were trained in 42 workshops at 35 Australasian hospitals. Of the 273 tests ordered by oncology healthcare professionals post-training, 241 (93.1%) met national testing guidelines. The number of tests ordered by genetic health professionals reduced significantly (z = 45.0, p = 0.008). Oncology healthcare professionals' perceived barriers to mainstreamed testing decreased from baseline to follow-up (t = 2.39, p = 0.023), particularly perceived skills, knowledge and attitudes. However, only 58% reported either 'always' or 'nearly always' having ordered BRCA testing for eligible patients at 12 months, suggesting oncology healthcare professionals' perceived barriers were not systematically addressed through training. CONCLUSIONS: Oncology healthcare professionals have demonstrated a willingness to be involved in the provision of genetic testing in a mainstreaming model. If oncology services are to hold responsibility for coordinating genetic testing, their readiness will require understanding of barriers not addressed by training alone to inform future intervention design.

The impact and indications for Oncotype DX on adjuvant treatment recommendations when third-party funding is unavailable.

OBJECTIVES: Industry-supported decision impact studies demonstrate that Oncotype Dx (ODX) changes treatment recommendations (TR) in 24-40% of hormone receptor+/HER2- patients. ODX is not reimbursed by third-party payers in Australia, potentially resulting in more selective use. We sought to evaluate the impact of self-funded ODX on TRs. METHODS: Data collected included demographics, tumor characteristics, indication for ODX and pre- and post-recurrence score (RS) TR. Primary endpoint was frequency of TR change and associations with TR change were sought. RESULTS: Eighteen physicians contributed 382 patients (median age 54). A total of 232 (61%) of tumors were T1 and were grade 1, 2 and 3 in 49 (13%), 252 (66%) and 79 (21%). A total of 257 (67%) were node negative. Assay indications were: confirm need for chemotherapy (CT) (36%), confirm omission of CT (40%) and genuine equipoise (24%). RS was low (≤17) in 55%, intermediate (18-31) in 36% and high (≥32) in 9%. Thirty-eight percent of patients had TR change post-ODX. Sixty-five percent of patients recommended CT pre-ODX changed to hormone therapy alone (HT)-more likely if lower grade and if ER and/or PR > 10%. Fourteen percent of patients with pre-ODX TR for HT added CT-more likely if ER and/or PR ≤10% and if Ki67 > 15% Overall, TR for CT decreased from 47% to 24%. CONCLUSION: Patient-funded ODX changed TRs in 38% of patients, de-escalating 65% from CT to HT and adding CT to 14% of those recommended HT. These changes were greater than an industry-funded study suggesting that physicians can identify situations where the assay may influence decisions.

Madarosis: a qualitative study to assess perceptions and experience of Australian patients with early breast cancer treated with taxane-based chemotherapy.

PURPOSE: Eyebrow and eyelash loss (madarosis) is a common and distressing side effect of chemotherapy for which no protective strategies have yet been developed. The purpose of this study was to develop an overview of perceptions and experiences of women undergoing taxane-based treatment for early breast cancer. METHODS: A total of 25 women with a diagnosis of invasive early breast cancer participated in a focus group (n = 5), ages ranging from 35 to 64 (median 50), all had completed therapy with a taxane-based chemotherapy treatment. This focus group used targeted questions to explore participants' perceptions and experience of madarosis during and following chemotherapy and identified issues associated with impact of madarosis on quality of life (QoL). Thematic analysis was conducted to identify important issues experienced by participants. RESULTS: Seven themes emerged from the data: (1) timing of regrowth and permanent changes, (2) meaning/importance of eyebrow/eyelashes, (3) preparedness/information given, (4) impact of the hair loss of self, (5) impact of hair loss on others, (6) physiological side effects of loss of eyebrows/eyelashes, and (7) management of loss of eyebrows/eyelashes. In addition, participants noted physical symptoms of eye irritation during their treatment that they attributed to madarosis. CONCLUSION: This study highlights the significant impact of madarosis on patients, providing the first published analysis of patient's attitude and perception of eyelash and eyebrow loss during chemotherapy. Further research in this area is required and will be benefitted from the development of a dedicated instrument/questionnaire that can capture and measure the impact of madarosis on QoL and allow development of clinical trial strategies.

When knowledge of a heritable gene mutation comes out of the blue: treatment-focused genetic testing in women newly diagnosed with breast cancer.

Selection of women for treatment-focused genetic testing (TFGT) following a new diagnosis of breast cancer is changing. Increasingly a patient's age and tumour characteristics rather than only their family history are driving access to TFGT, but little is known about the impact of receiving carrier-positive results in individuals with no family history of cancer. This study assesses the role of knowledge of a family history of cancer on psychosocial adjustment to TFGT in both women with and without mutation carrier-positive results. In-depth semistructured interviews were conducted with 20 women who had undergone TFGT, and who had been purposively sampled to represent women both family history and carrier status, and subjected to a rigorous qualitative analysis. It was found that mutation carriers without a family history reported difficulties in making surgical decisions quickly, while in carriers with a family history, a decision regarding surgery, electing for bilateral mastectomy (BM), had often already been made before receipt of their result. Long-term adjustment to a mutation-positive result was hindered by a sense of isolation not only by those without a family history but also those with a family history who lacked an affected relative with whom they could identify. Women with a family history who had no mutation identified and who had not elected BM reported a lack of closure following TFGT. These findings indicate support deficits hindering adjustment to positive TFGT results for women with and without a family history, particularly in regard to immediate decision-making about risk-reducing surgery.

Rapid screening for depression--validation of the Brief Case-Find for Depression (BCD) in medical oncology and palliative care patients.

Depression in oncology patients is under-recognised and associated with poor outcomes. Screening can increase case recognition. The Brief Case-Find for Depression (BCD) is a four-question, interviewer-administered instrument that has been previously validated in a general medical setting. The primary aim of this study was to validate the BCD in a medical oncology/palliative care setting, primarily by comparing its association with physical illness measures and with the Primary Care Evaluation of Mental Disorders (PRIME-MD), the Beck Depression Inventory (BDI) and the Hospital Anxiety and Depression Scale (HADS). Eligible adult oncology patients gave informed consent and completed the above measures and a pain scale. Agreement between the BCD and other instruments was assessed. Construct validity was determined by comparing depressed/nondepressed patients with respect to performance status, symptoms, pain score and functional impairment. A total of 100 patients had a median age of 58 (range 21-90) and ECOG performance status (PS) 2 (0-4). In all, 60% had metastatic disease. The therapeutic goal was curative/adjuvant in 39% and palliative in 61%. Prevalence of depression according to the various measures was: BCD 34%, PRIME-MD 12%, BDI 19% and HADS 14%. In total, 45% of patients responded positively to a single-item screening question. The BCD showed fair agreement with the PRIME-MD (kappa=0.21), moderate agreement with the BDI (kappa=0.43) and fair agreement with the HADS (kappa=0.27). Against the PRIME-MD diagnosis of depression, the BCD had greater sensitivity, but lesser specificity and overall agreement, compared with the BDI and depression scale of the HADS. Patients with probable depression (according to BCD) had inferior PS (P=0.0064), increased pain (P=0.045) and greater impairment of functioning (PRIME-MD: P=0.0003). There was no association with gender, age, disease status or therapeutic goal. Depression is common in oncology patients. The BCD is a quick, easy-to-administer screen for depression, which has reasonable psychometric properties in this population.