The psycho-social impact of contralateral risk reducing mastectomy (CRRM) on women: a rapid review

Objectives: For women who have been diagnosed with unilateral breast cancer there is an increasing trend for them to request removal of the contralateral healthy breast, so called contralateral risk reducing mastectomy (CRRM). The current literature is only just beginning to identify patient-reported reasons for undergoing CRRM and associated patient reported outcomes. It is also unclear whether women at moderate/high risk of developing a subsequent primary contralateral breast cancer report similar outcomes to those considered to be at low/average risk. This lack of knowledge provides the rationale for this review. Methods: A rapid review methodology was undertaken to identify and explore the published research literature focused on the longer term (>5 years) psychosocial impacts on women who undergo CRRM. Results: 15 studies were identified. No UK studies were identified. High satisfaction and psychosocial wellbeing was consistently reported across all studies. Reducing the risk of a subsequent CBC and therefore reducing cancer related anxiety, and satisfaction with cosmesis, were key themes running across all studies explaining satisfaction. Dissatisfaction was associated with adverse effects such as poor cosmesis, body image changes, femininity, sexual relationships, re-operations for acute and longer term complications and reconstructive problems Conclusions: Satisfaction and psychological wellbeing following CRRM was consistently high across all studies. However, the findings suggest women need to be more fully informed of the risks and benefits of CRRM and/or immediate/delayed reconstruction in order to support informed decision making

Sister chromatid exchange and genomic instability in soft tissue sarcomas: potential implications for response to DNA-damaging treatments

Sarcomas are rare heterogenous malignancies of mesenchymal origin characterised by complex karyotypes but no specific abnormalities. Recurrence is common and metastatic disease carries poor survival despite standard DNA-damaging radiotherapy or chemotherapy. DNA double strand breaks (DSB) are either repaired by mechanisms such as homologous recombination (HR); or result in cell death by apoptosis. Endogenous γH2AX and SCE formation are early and late events, respectively and their levels are considered surrogate measures of genomic instability. Combined γH2AX and SCE analysis were used to evaluate endogenous DNA DSB levels (and their subsequent repair) in 9 primary sarcoma cell lines and compared with well-established commercial lines. All the sarcoma cell lines had elevated γH2AX and SCE levels, but there was no correlation between the DNA DSB frequency and subsequent SCE. Typically radio-resistant osteosarcoma cells had relatively low γH2AX frequency, but high SCE counts suggestive of efficient DNA repair. Conversely, liposarcoma cells derived from a radio-sensitive tumour had high H2AX but relatively lower SCE levels that may imply inefficient DNA DSB repair. To our knowledge, this is the first report that correlates H2AX and SCE levels in primary sarcoma cell lines and may provide insight into potential response to DNA damaging-treatments

Quality of life versus length of life considerations in cancer patients: a systematic literature review

BACKGROUND:Patients with cancer face difficult decisions regarding treatment and the possibility of trading quality of life (QoL) for length of life (LoL). Little information is available regarding patients' preferences and attitudes towards their cancer treatment and the personal costs they are prepared to exchange to extend their life. The aim of this review is to determine the complex trade-offs and underpinning factors that make patients with cancer choose quality over quantity of life. METHODS:A systematic review of the literature was conducted using MeSH terms: cancer, longevity or length of life, quality of life, decision-making, trade off and health utility. Articles retrieved were published between 1942 to October 2018. RESULTS:Out of 4393 articles, 30 were included in this review. Older age, which may be linked to declining physical status, was associated with a preference for QoL over LoL. Younger patients were more likely to undergo aggressive treatment to increase survival years. Preference for QoL and LoL was not influenced by gender, education, religion, having children, marital status or type of cancer. Patients with better health valued LoL and inversely those with poorer physical status preferred QoL. CONCLUSION:Baseline QoL and future expectations of life seem to be key determinants of preference for QoL versus LoL in cancer patients. In-depth studies are required to understand these trade-offs and the compromises patients are willing to make regarding QoL or LoL, especially in older patients with naturally limited life expectancy

The ESSO core curriculum committee update on surgical oncology

Cancer care; Curriculum; Surgical oncologyCuidado del cancer; Plan de estudios; Oncología quirúrgicaCura del càncer; Pla d'estudis; Oncologia quirúrgicaIntroduction Surgical oncology is a defined specialty within the European Board of Surgery within the European Union of Medical Specialists (UEMS). Variation in training and specialization still occurs across Europe. There is a need to align the core knowledge needed to fulfil the criteria across subspecialities in surgical oncology. Material and methods The core curriculum, established in 2013, was developed with contributions from expert advisors from within the European Society of Surgical Oncology (ESSO), European Society for Radiotherapy and Oncology (ESTRO) and European Society of Medical Oncology (ESMO) and related subspeciality experts. Results The current version reiterates and updates the core curriculum structure needed for current and future candidates who plans to train for and eventually sit the European fellowship exam for the European Board of Surgery in Surgical Oncology. The content included is not intended to be exhaustive but, rather to give the candidate an idea of expectations and areas for in depth study, in addition to the practical requirements. The five elements included are: Basic principles of oncology; Disease site specific oncology; Generic clinical skills; Training recommendations, and, lastly; Eligibility for the EBSQ exam in Surgical Oncology. Conclusions As evidence-based care for cancer patients evolves through research into basic science, translational research and clinical trials, the core curriculum will evolve, mature and adapt to deliver continual improvements in cancer outcomes for patients

Gene expression profiling and expanded immunohistochemistry tests to guide selection of chemotherapy regimens in breast cancer management: a systematic review

OBJECTIVES: The aim of this report was to assess the clinical effectiveness of two Gene expression profiling (GEP) and two expanded immunohistochemistry (IHC) tests compared with current prognostic tools in guiding the use of adjuvant chemotherapy in patients with early breast cancer. METHODS: A systematic review of the evidence on clinical effectiveness of OncotypeDX, IHC4, MammaPrint and Mammostrat, compared with current clinical practice using clinicopathological parameters, in women with early breast cancer was conducted. Ten databases were searched to include citations to May 2016. RESULTS: Searches identified 7064 citations, of which 41 citations satisfied the criteria for the review. A narrative synthesis was performed. Evidence for OncotypeDX demonstrated the impact of the test on decision-making and there was some support for OncotypeDX predicting chemotherapy benefit. There were relatively lower levels of evidence for the other three tests included in the analysis. MammaPrint, Mammostrat and IHC4 tests were limited to a small number of studies. Limitations in relation to study design were identified for all tests. CONCLUSIONS: The evidence base for OncotypeDX is considered to be the most robust. Methodological weaknesses relating to heterogeneity of patient cohorts and issues arising from the retrospective nature of the evidence were identified. Further evidence is required for all of the tests using prospective randomised controlled trial data

The decision-making process for senior cancer patients: treatment allocation of older women with operable breast cancer in the UK.

Objective: Up to 40% of women over 70 years with primary operable breast cancer in the UK are treated with primary endocrine therapy (PET) as an alternative to surgery. A variety of factors are important in determining treatment for older breast cancer patients. This study aimed to identify the patient and tumor factors associated with treatment allocation in this population. Methods: Prospectively collected data on treatment received (surgery vs. PET) were analysed with multivariable logistic regression using the variables age, modified Charlson Comorbidity Index (CCI), activities of daily living (ADL) score, Mini-Mental State Examination (MMSE) score, HER2 status, tumour size, grade and nodal status. Results: Data were available for 1,122 cancers in 1,098 patients recruited between February 2013 and June 2015 from 51 UK hospitals. About 78% of the population were treated surgically, with the remainder being treated with PET. Increasing patient age at diagnosis, increasing CCI score, large tumor size (5 cm or more) and dependence in one or more ADL categories were all strongly associated with non-surgical treatment (P<0.05). Conclusion: Increasing comorbidity, large tumor size and reduced functional ability are associated with reduced likelihood of surgical treatment of breast cancer in older patients. However, age itself remains a significant factor for non-surgical treatment; reinforcing the need for evidence-based guidelines

Senescence and cancer : a review of clinical implications of senescence and senotherapies

Cellular senescence is a key component of human aging that can be induced by a range of stimuli, including DNA damage, cellular stress, telomere shortening, and the activation of oncogenes. Senescence is generally regarded as a tumour suppressive process, both by preventing cancer cell proliferation and suppressing malignant progression from pre-malignant to malignant disease. It may also be a key effector mechanism of many types of anticancer therapies, such as chemotherapy, radiotherapy, and endocrine therapies, both directly and via bioactive molecules released by senescent cells that may stimulate an immune response. However, senescence may contribute to reduced patient resilience to cancer therapies and may provide a pathway for disease recurrence after cancer therapy. A new group of drugs, senotherapies, (drugs which interact with senescent cells to interfere with their pro-aging impacts by either selectively destroying senescent cells (senolytic drugs) or inhibiting their function (senostatic drugs)) are under active investigation to determine whether they can enhance the efficacy of cancer therapies and improve resilience to cancer treatments. Senolytic drugs include quercetin, navitoclax, and fisetin and preclinical and early phase clinical data are emerging of their potential role in cancer treatments, although none are yet in routine use clinically. This article provides a review of these issues

Efficient development and usability testing of decision support interventions for older women with breast cancer

Around a third of breast cancers diagnosed each year in the UK are in women aged 70 years and older. However, there are currently no decision support interventions for older women who have a choice between primary endocrine therapy and surgery followed by adjuvant endocrine therapy (surgery+endocrine therapy), or who can choose whether or not to have chemotherapy following surgery. There is also little evidence-based guidance specifically on the management of these older patients. A large UK cohort study is currently underway to address this lack of evidence and to develop two decision support interventions (DESIs) to facilitate shared decision-making with older women about breast cancer treatments. Here we present the development and initial testing of these two DESIs. An initial prototype DESI was developed for the choice of primary endocrine therapy or surgery+endocrine therapy. Semi-structured interviews with healthy volunteers and patients explored DESI acceptability, usability and utility. A framework approach was used for analysis. A second DESI for the choice of having chemotherapy or not was subsequently developed based on more focused development and testing. Participants (n=22, aged 75-94 years, 64% healthy volunteers, 36% patients) found the primary endocrine therapy/surgery+endocrine therapy DESI acceptable, and contributed to improved wording and illustrations to address misunderstandings. The chemotherapy DESI (tested with 14 participants, aged 70-87 years, 57% healthy volunteers, 43% patients) was mostly understandable, however suggestions for re-wording sections were made. Most participants considered the DESIs helpful, but highlighted the importance of complementary discussions with clinicians. It was possible to use a template DESI to efficiently create a second prototype for a different treatment option (chemotherapy). Both DESIs were acceptable and considered helpful to support/augment consultations. Development of acceptable additional DESIs for similar target populations using simplified methods may be an efficient way to develop future DESIs. Further research is needed to test the effectiveness of the DESIs

Near-infrared fluorescent imaging for parathyroid identification and/or preservation in surgery for primary hyperparathyroidism

IntroductionNear infrared autofluorescence (NIRAF) is a novel intraoperative technology that has shown promising results in the localisation of parathyroid glands (PGs) over the last decade. This study aimed to assess the potential utility of NIRAF in first time surgery for primary hyperparathyroidism (PHPT).MethodsAn observational study over a period of 3 years in patients who underwent surgery for PHPT was designed. Data on the use of NIRAF and fluorescent patterns in different organs (thyroid and parathyroid) and parathyroid pathology (single versus multi-gland disease) were explored. In addition, cure rates and operating times were compared between the NIRAF and no-NIRAF groups to determine the potential value of NIRAF in this cohort.ResultsIn 230 patients undergoing first time surgery for PHPT, NIRAF was used in 50 patients. Of these 50 patients, NIRAF was considered to aid parathyroid identification in 9 patients (18%). The overall cure rate at 6 months of follow-up was 96.5% (98% in NIRAF and 96.1% without NIRAF; p=1.0). The median (interquartile range) operating time was longer in the NIRAF arm at 102 minutes (74-120 minutes) compared to the no-NIRAF arm at 75 minutes (75-109 minutes); however, this difference was not statistically significant (p=0.542). Although the median parathyroid to thyroid (P/T) auto-fluorescence (AF) ratio was similar between single gland and multi gland disease (2.5 vs to 2.76; p=1.0), the P/T AF ratio correlated negatively with increasing gland weight (p=0.038).ConclusionThe use of NIRAF resulted in some potential “surgeon-perceived” benefit but did not lead to improvements in cure rates. The negative correlation between fluorescent intensity and gland weight suggests loss of fluorescence with pathology, which needs further investigation. Further studies on larger cohorts of patients, in depth analysis of fluorescence patterns between normal, adenomatous, and hyperplastic glands and evaluation of user experience are needed. Primary hyperparathyroidism, hyperparathyroidism, autofluorescence, near-infrared fluorescence, parathyroid glands, endocrine, surgery