Rates of paclitaxel hypersensitivity reactions using a modified Markman's infusion protocol as primary prophylaxis.

PURPOSE: Markman's desensitisation protocol allows successful retreatment of patients who have had significant paclitaxel hypersensitivity reactions. We aimed to reduce the risk and severity of paclitaxel hypersensitivity reactions by introducing this protocol as primary prophylaxis. METHODS: We evaluated all patients with a gynaecological malignancy receiving paclitaxel before (December 2018 to September 2019) and after (October 2019 to July 2020) the implementation of a modified Markman's desensitisation protocol. The pre-implementation group received paclitaxel over a gradually up-titrated rate from 60 to 180 ml/h. The post-implementation group received paclitaxel via 3 fixed-dose infusion bags in the first 2 cycles. Rates and severity of paclitaxel hypersensitivity reactions were compared. RESULTS: A total of 426 paclitaxel infusions were administered to 78 patients. The median age was 64 years (range 34-81), and the most common diagnosis was ovarian, fallopian tube and primary peritoneal cancer (67%, n = 52/78). Paclitaxel hypersensitivity reaction rates were similar in the pre-implementation (8%, n = 16/195) and post-implementation groups (9%, n = 20/231; p = 0.87). Most paclitaxel hypersensitivity reactions occurred within 30 min (pre- vs. post-implementation, 88% [n = 14/16] vs. 75% [n = 15/20]; p = 0.45) and were grade 2 in severity (pre- vs. post-implementation, 81% [n = 13/16] vs. 75% [n = 15/20]; p = 0.37). There was one grade 3 paclitaxel hypersensitivity reaction in the pre-implementation group. All patients were successfully rechallenged in the post-implementation group compared to 81% (n = 13/16) in the pre-implementation group (p = 0.43). CONCLUSION: The modified Markman's desensitisation protocol as primary prophylaxis did not reduce the rate or severity of paclitaxel hypersensitivity reactions, although all patients could be successfully rechallenged.

Exploring assessment of balance using virtual reality in patients at risk of chemotherapy-induced peripheral neuropathy.

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is a common dose-limiting toxicity for people treated for cancer. Impaired balance and falls are functional consequences of CIPN. Virtual reality (VR) technology may be able to assess balance and identify patients at risk of falls. AIMS: To assess the impact of potentially neurotoxic chemotherapy on balance using VR, and explore associations between VR balance assessment, falls and CIPN. METHODS: This prospective, repeated measures longitudinal study was conducted at two Australian cancer centres. Eligible participants were commencing adjuvant chemotherapy containing a taxane for breast cancer, or oxaliplatin for colorectal cancer (CRC), per institutional guidelines. Balance assessments using VR were conducted at baseline, end of chemotherapy and 3 and 6 months after completion of chemotherapy. Participants also completed a comprehensive CIPN assessment comprising clinical and patient-reported outcomes, and recorded falls or near falls. RESULTS: Out of 34 participants consented, 24 (71%) had breast cancer and 10 (29%) had CRC. Compared to baseline, balance threshold was reduced in 10/28 (36%) evaluable participants assessed at the end of chemotherapy, and persistent in 7/22 (32%) at 6 months. CIPN was identified in 86% at end of chemotherapy and persisted to 6 months after chemotherapy completion in 73%. Falls or near falls were reported by 12/34 (35%) participants, and were associated with impaired VR balance threshold (P = 0.002). CONCLUSIONS: While VR balance assessment was no better at identifying CIPN than existing measures, it is a potential surrogate method to assess patients at risk of falls from CIPN.

Prevalence and severity of scanxiety in people with advanced cancers: a multicentre survey.

PURPOSE: Scan-associated anxiety ('scanxiety') is a problem for people with advanced cancer. We aimed to determine the prevalence, severity and associations of scanxiety in this population. METHODS: People with advanced cancer and a computed tomography scan within the last 4 months completed a multicentre survey including self-rated presence (yes/no) and severity (distress thermometer, 0-10) of scanxiety, state anxiety (STAI-6), clinical anxiety and depression (HADS), and fear of progression (FOP-Q-SF). Associations with scanxiety were evaluated. RESULTS: There were 222 participants: mean age 64 years (range 26 to 91), female (61%), most common cancer types (breast 37%, lung 19%, colorectal 16%) and > 1 year since cancer diagnosis (82%). Sixty-two percent had a scan within the last month, and 70% reported waiting > 2 days for the result. Over half (55%) of participants experienced scanxiety. On multivariable analysis, scanxiety was more prevalent in participants who were younger (mean age 62 years with v 66 years without scanxiety, p = 0.02) and more remote (v major city, OR 2.6, p = 0.04). Among participants with scanxiety, the mean severity score was 6 (range 1-10) with peak severity occurring when waiting for scan results. On multivariable analysis, scanxiety was 1.2 points higher in participants who had been diagnosed within the past year (v > 1 year, p = 0.04) and was higher in participants who had higher STAI-6 scores (ß = 0.06, p = 0.004). CONCLUSION: Scanxiety is common and can be severe. Strategies to reduce scanxiety are needed.

Experiences with scans and scanxiety in people with advanced cancer: a qualitative study.

PURPOSE: Scan-associated anxiety ('scanxiety') in people with advanced cancer is a common clinical problem. This study aims to explore the experiences of scans and scanxiety in people with advanced cancer, including their strategies to reduce scanxiety. METHODS: Semi-structured qualitative interviews were conducted with people with advanced cancers who had a computed tomography scan for monitoring of their cancer. Data was analysed with an interpretivist approach using framework analysis. RESULTS: Interviews with 16 participants identified three key themes: the scan experience, the scanxiety experience and coping with scans. Scans were viewed as a routine and normal part of cancer care. Scanxiety was experienced differently by each person. Scanxiety often related to the scan result rather than the scan and led to psycho-cognitive manifestations. Adaptive coping strategies were often self-derived. CONCLUSION: People with advanced cancer experience scanxiety, but often accept scanxiety as a normal part of the cancer process. The findings fit within a transactional model of stress and coping, which influences the level of scanxiety for each individual. Quantitative research to determine the scope of scanxiety will be useful to develop formal approaches to reduce scanxiety.

Ovarian suppression for adjuvant treatment of hormone receptor-positive early breast cancer.

BACKGROUND: Approximately 80% of breast cancers amongst premenopausal women are hormone receptor-positive. Adjuvant endocrine therapy is an integral component of care for hormone receptor-positive breast cancer and in premenopausal women includes oestrogen receptor blockade with tamoxifen, temporary suppression of ovarian oestrogen synthesis by luteinising hormone releasing hormone (LHRH) agonists, and permanent interruption of ovarian oestrogen synthesis with oophorectomy or radiotherapy. Recent international consensus statements recommend single-agent tamoxifen or aromatase inhibitors with ovarian function suppression (OFS) as the current standard adjuvant endocrine therapy for premenopausal women (often preceded by chemotherapy). This review examined the role of adding OFS to another treatment (i.e. chemotherapy, endocrine therapy, or both) or comparing OFS to no further adjuvant treatment. OBJECTIVES: To assess effects of OFS for treatment of premenopausal women with hormone receptor-positive early breast cancer. SEARCH METHODS: For this review update, we searched the Specialised Register of the Cochrane Breast Cancer Group, MEDLINE, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL; 2019, Issue 8), the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP), and ClinicalTrials.gov on 26 September 2019. We screened the reference lists of related articles, contacted trial authors, and applied no language restrictions. SELECTION CRITERIA: We included all randomised trials assessing any method of OFS, that is, oophorectomy, radiation-induced ovarian ablation, or LHRH agonists, as adjuvant treatment for premenopausal women with early-stage breast cancer. We included studies that compared (1) OFS versus observation, (2) OFS + chemotherapy versus chemotherapy, (3) OFS + tamoxifen versus tamoxifen, and (4) OFS + chemotherapy + tamoxifen versus chemotherapy + tamoxifen. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed risk of bias and certainty of evidence using the GRADE approach. Hazard ratios (HRs) were derived for time-to-event outcomes, and meta-analysis was performed using a fixed-effect model. The primary outcome measures were overall survival (OS) and disease-free survival (DFS). Toxicity, contralateral breast cancer, and second malignancy were represented as risk ratios (RRs), and quality of life data were extracted when provided. MAIN RESULTS: This review update included 15 studies involving 11,538 premenopausal women with hormone receptor-positive early breast cancer; these studies were conducted from 1978 to 2014. Some of these treatments are not current standard of care, and early studies did not assess HER2 receptor status. Studies tested OFS versus observation (one study), OFS plus chemotherapy versus chemotherapy (six studies), OFS plus tamoxifen versus tamoxifen (six studies), and OFS plus chemotherapy and tamoxifen versus chemotherapy and tamoxifen (two studies). Of those studies that reported the chemotherapy regimen, an estimated 72% of women received an anthracycline. The results described below relate to the overall comparison of OFS versus no OFS. High-certainty evidence shows that adding OFS to treatment resulted in a reduction in mortality (hazard ratio (HR) 0.86, 95% confidence interval (CI) 0.78 to 0.94; 11 studies; 10,374 women; 1933 reported events). This treatment effect was seen when OFS was added to observation, to tamoxifen, or to chemotherapy and tamoxifen. The effect on mortality was not observed when OFS was added to chemotherapy without tamoxifen therapy (HR 0.95, 95% CI 0.82 to 1.09; 5 studies; 3087 women; median follow-up: range 7.7 to 12.1 years). The addition of OFS resulted in improved DFS (HR 0.83, 95% CI 0.77 to 0.90; 10 studies; 8899 women; 2757 reported events; high-certainty evidence). The DFS treatment effect persisted when OFS was added to observation, to tamoxifen, and to chemotherapy and tamoxifen. The effect on DFS was reduced when OFS was added to chemotherapy without tamoxifen therapy (HR 0.90, 95% CI 0.79 to 1.01; 5 studies; 2450 women). Heterogeneity was low to moderate across studies for DFS and OS (respectively). Evidence suggests that adding OFS slightly increases the incidence of hot flushes (grade 3/4 or any grade; risk ratio (RR) 1.60, 95% CI 1.41 to 1.82; 6 studies; 5581 women; low-certainty evidence, as this may have been under-reported in these studies). Two other studies that could not be included in the meta-analysis reported a higher number of hot flushes in the OFS group than in the no-OFS group. Seven studies involving 5354 women collected information related to mood; however this information was reported as grade 3 or 4 depression, anxiety, or neuropsychiatric symptoms, or symptoms were reported without the grade. Two studies reported an increase in depression, anxiety, and neuropsychiatric symptoms in the OFS group compared to the no-OFS group, and five studies indicated an increase in anxiety in both treatment groups (but no difference between groups) or no difference overall in symptoms over time or between treatment groups. A single study reported bone health as osteoporosis (defined as T score < -2.5); this limited evidence suggests that OFS increases the risk of osteoporosis compared to no-OFS at median follow-up of 5.6 years (RR 1.16, 95% CI 1.10 to 28.82; 2011 women; low-certainty evidence). Adding OFS to treatment likely reduces the risk of contralateral breast cancer (HR 0.75, 95% CI 0.57 to 0.97; 9 studies; 9138 women; moderate-certainty evidence). Quality of life was assessed in five studies; four studies used validated tools, and the fifth study provided no information on how data were collected. Two studies reported worse quality of life indicators (i.e. vaginal dryness, day and night sweats) for women receiving OFS compared to those in the no-OFS group. The other two studies indicated worsening of symptoms (e.g. vasomotor, gynaecological, vaginal dryness, decline in sexual interest, bone and joint pain, weight gain); however these side effects were reported in both OFS and no-OFS groups. The study that did not use a validated quality of life tool described no considerable differences between groups. AUTHORS' CONCLUSIONS: This review found evidence that supports adding OFS for premenopausal women with early, hormone receptor-positive breast cancers. The benefit of OFS persisted when compared to observation, and when added to endocrine therapy (tamoxifen) or chemotherapy and endocrine therapy (tamoxifen). The decision to use OFS may depend on the overall risk assessment based on tumour and patient characteristics, and may follow consideration of all side effects that occur with the addition of OFS.

Oral contraceptive use in women at increased risk of breast/ovarian cancer: knowledge and attitudes.

BACKGROUND: Several of the health benefits and risks associated with the combined oral contraceptive pill (COCP) are particularly relevant to women at risk of hereditary breast and/or ovarian cancer. METHODS: Eighty-three past female patients of an Australian hereditary cancer clinic aged 18-50 years completed a self-report questionnaire to assess their contraceptive practices, knowledge and information needs (44% response rate). RESULTS: Ninety-two percent of participants had previously used the COCP, with a mean knowledge score of 3.63 out of 8. Nearly 40% reported that their family history of cancer was one reason they discontinued/avoided using the COCP. Women reported receiving insufficient COCP information and preferred a targeted information leaflet to answer their questions. CONCLUSIONS: Although recall bias may have affected some women, there is a clear need to improve the consistency of information delivered to women at risk of hereditary breast and/or ovarian cancer, to ensure informed contraceptive choices are made.

Scanxiety Conversations on Twitter: Observational Study.

BACKGROUND: Scan-associated anxiety (or "scanxiety") is commonly experienced by people having cancer-related scans. Social media platforms such as Twitter provide a novel source of data for observational research. OBJECTIVE: We aimed to identify posts on Twitter (or "tweets") related to scanxiety, describe the volume and content of these tweets, and describe the demographics of users posting about scanxiety. METHODS: We manually searched for "scanxiety" and associated keywords in cancer-related, publicly available, English-language tweets posted between January 2018 and December 2020. We defined "conversations" as a primary tweet (the first tweet about scanxiety) and subsequent tweets (interactions stemming from the primary tweet). User demographics and the volume of primary tweets were assessed. Conversations underwent inductive thematic and content analysis. RESULTS: A total of 2031 unique Twitter users initiated a conversation about scanxiety from cancer-related scans. Most were patients (n=1306, 64%), female (n=1343, 66%), from North America (n=1130, 56%), and had breast cancer (449/1306, 34%). There were 3623 Twitter conversations, with a mean of 101 per month (range 40-180). Five themes were identified. The first theme was experiences of scanxiety, identified in 60% (2184/3623) of primary tweets, which captured the personal account of scanxiety by patients or their support person. Scanxiety was often described with negative adjectives or similes, despite being experienced differently by users. Scanxiety had psychological, physical, and functional impacts. Contributing factors to scanxiety included the presence and duration of uncertainty, which was exacerbated during the COVID-19 pandemic. The second theme (643/3623, 18%) was the acknowledgment of scanxiety, where users summarized or labeled an experience as scanxiety without providing emotive clarification, and advocacy of scanxiety, where users raised awareness of scanxiety without describing personal experiences. The third theme was messages of support (427/3623, 12%), where users expressed well wishes and encouraged positivity for people experiencing scanxiety. The fourth theme was strategies to reduce scanxiety (319/3623, 9%), which included general and specific strategies for patients and strategies that required improvements in clinical practice by clinicians or health care systems. The final theme was research about scanxiety (50/3623, 1%), which included tweets about the epidemiology, impact, and contributing factors of scanxiety as well as novel strategies to reduce scanxiety. CONCLUSIONS: Scanxiety was often a negative experience described by patients having cancer-related scans. Social media platforms like Twitter enable individuals to share their experiences and offer support while providing researchers with unique data to improve their understanding of a problem. Acknowledging scanxiety as a term and increasing awareness of scanxiety is an important first step in reducing scanxiety. Research is needed to guide evidence-based approaches to reduce scanxiety, though some low-cost, low-resource practical strategies identified in this study could be rapidly introduced into clinical care.

Scanxiety: a scoping review about scan-associated anxiety.

OBJECTIVES: To identify available literature on prevalence, severity and contributing factors of scan-associated anxiety ('scanxiety') and interventions to reduce it. DESIGN: Systematic scoping review. DATA SOURCES: Ovid MEDLINE, Ovid EMBASE, Ovid PsycINFO, Ovid Cochrane Central Register of Controlled Trials, Scopus, EBSCO CINAHL and PubMed up to July 2020. STUDY SELECTION: Eligible studies recruited people having cancer-related non-invasive scans (including screening) and contained a quantitative assessment of scanxiety. DATA EXTRACTION: Demographics and scanxiety outcomes were recorded, and data were summarised by descriptive statistics. RESULTS: Of 26 693 citations, 57 studies were included across a range of scan types (mammogram: 26/57, 46%; positron-emission tomography: 14/57, 25%; CT: 14/57, 25%) and designs (observation: 47/57, 82%; intervention: 10/57, 18%). Eighty-one measurement tools were used to quantify prevalence and/or severity of scanxiety, including purpose-designed Likert scales (17/81, 21%); the State Trait Anxiety Inventory (14/81, 17%) and the Hospital Anxiety and Depression Scale (9/81, 11%). Scanxiety prevalence ranged from 0% to 64% (above prespecified thresholds) or from 13% to 83% ('any' anxiety, if no threshold). Mean severity scores appeared low in almost all measures that quantitatively measured scanxiety (54/62, 87%), regardless of whether anxiety thresholds were prespecified. Moderate to severe scanxiety occurred in 4%-28% of people in studies using descriptive measures. Nine of 20 studies assessing scanxiety prescan and postscan reported significant postscan reduction in scanxiety. Lower education, smoking, higher levels of pain, higher perceived risk of cancer and diagnostic scans (vs screening scans) consistently correlated with higher scanxiety severity but not age, gender, ethnicity or marital status. Interventions included relaxation, distraction, education and psychological support. Six of 10 interventions showed a reduction in scanxiety. CONCLUSIONS: Prevalence and severity of scanxiety varied widely likely due to heterogeneous methods of measurement. A uniform approach to evaluating scanxiety will improve understanding of the phenomenon and help guide interventions.

Targeted Molecular Treatments in Non-Small Cell Lung Cancer: A Clinical Guide for Oncologists.

Targeted molecular treatments have changed the way non-small cell lung cancer (NSCLC) is managed. Epidermalgrowthfactorreceptor (EGFR),anaplasticlymphomakinase (ALK),v-rafmurine sarcoma viral oncogene homolog B1 (BRAF), and c-rosoncogene 1 (ROS1) mutations are now used to guide specific anti-cancer therapies to improve patient outcomes. New targeted molecular treatments are constantly being developed and evaluated as a means to improve efficacy, overcome resistance, or minimise toxicity. This review article summarises the current evidence for the efficacy, resistance mechanisms, and safety of targeted molecular treatments against specific mutations in NSCLC.

Longer duration of transient elastography predicts unreliable liver stiffness measurements.

BACKGROUND: Transient elastography (TE) is a noninvasive, validated method to assess liver fibrosis by obtaining liver stiffness measurements (LSM). However, TE can be limited by unreliable measurement (UM). The relationship between the time taken to perform TE (duration) and UM has not been studied. OBJECTIVES: To determine whether the duration of TE correlates with UM. MATERIALS AND METHODS: We prospectively studied the frequency and predictors of UM over a 5-year period. UM was defined as follows: less than 10 successful measurements, success rate less than 60%, or interquartile range more than 30% of the median LSM value (IQR/LSM>30%). RESULTS: Among the 2834 patients with LSM analysed, UM occurred in 19.0%. Duration [odds ratio (OR) 4.2, 95% confidence interval (CI) 2.8-6.4; P<0.0001] was the strongest predictor of UM, followed by BMI more than 28 kg/m (OR 2.1, 95% CI 1.5-3.0; P<0.0001), age more than 52 (OR 1.6, 95% CI 1.1-2.3; P=0.007) and non-HBV aetiology (OR 1.6, 95% CI 1.1-2.3; P=0.02). An optimal cut-off of 3 min 47 s was calculated for predicting UM (sensitivity 70%, specificity 65%, OR 4.2, 95% CI 2.7-6.6, P<0.0001). Examinations that took longer than 8 min 10 s had a 90% chance of UM. CONCLUSION: In experienced hands, duration is a strong predictor of UM in patients undergoing TE. Examinations longer than 4 min are more likely to be unreliable. Examinations longer than 8 min are unlikely to yield a valid result and should be considered a futility endpoint. Older age and increased BMI and nonhepatitis B aetiology are independent, albeit weaker, predictors of UM.