Hormonal therapy for cancer

Hormone therapy is an effective and non-toxic therapy for oestrogen and progesterone receptor-positive breast cancer and prostate cancer. Serum levels of oestradiol and testosterone are controlled by the hypothalamic–pituitary–gonadal pathway. Oestradiol is produced in premenopausal women from the ovaries and in postmenopausal women by peripheral conversion of adrenal androgens by aromatase. In premenopausal women with breast cancer and men with prostate cancer, treatment is primarily achieved by castration. In postmenopausal women selective oestrogen receptor modulators (e.g. tamoxifen) or aromatase inhibitors are used. Hormone therapy can be used to reduce the size of the primary cancer prior to radical surgery or radiotherapy or to reduce the risk of recurrence. Hormone therapy is highly effective in patients with locally advanced or metastatic disease, with a high response rate. Most patients eventually relapse with ‘castrate-refractory’ disease, for which increasing numbers of active agents are entering clinical practice

Methods of assessing late radiotherapy effects on bowel function

Purpose of review Pelvic radiation disease in the form of chronic radiation-induced consequences of treatment is under recognized by healthcare professionals and under reported by patients. Gastrointestinal symptoms are not routinely assessed, and may not be causally associated with previous radiotherapy. These symptoms are therefore often under treated.Recent findings A literature search was conducted in Ovid Medline, which included Epub Ahead of Print, In-Process & Other Non-Indexed Citations and Ovid Embase for articles published between 2016 and April 2018. A total of 11 articles were selected for review. A wide range of patient reported outcome measure instruments are used in research and practice. Clinical symptom grading is restricted to a fewer number of tools but may not always capture issues, such as urgency, that are important to the patient. Clinician and patient concordance in the assessment of outcomes is limited. Initiatives to prompt communication of the relative risks of the late consequences of treatment and comparative effectiveness of treatments decisions are developing, as are new techniques to limit irradiation of healthy tissue.Summary Nonstandardized outcome measurement reduces the ability to aggregate toxicity and patient outcomes across clinical trials. The development of standardized screening and treatment algorithms for gastrointestinal symptoms can systematically locate and treat gastrointestinal late effects of treatment

Hormonal therapy for cancer

Hormone therapy is an effective and non-toxic therapy for oestrogen and progesterone receptor-positive breast cancer and for prostate cancer. Serum concentrations of oestradiol and testosterone are controlled by the hypothalamic-pituitary-gonadal pathway. Oestradiol is produced in premenopausal women from the ovaries, and in postmenopausal women by peripheral conversion of adrenal androgens by aromatase. In premenopausal women with breast cancer and men with prostate cancer, treatment is primarily achieved by castration. In postmenopausal women, selective oestrogen receptor modulators (e.g. tamoxifen) or aromatase inhibitors are used. Hormone therapy can be used to reduce the size of the primary cancer before radical surgery or radiotherapy, or to reduce the risk of recurrence. Hormone therapy is highly effective in patients with locally advanced or metastatic disease, with high response rates. Most patients eventually relapse with hormone-refractory disease and can be offered novel hormonal agents, chemotherapy or molecularly targeted agents

Use of mobile devices to help cancer patients meet their information needs in non-inpatient settings: systematic review

Background: The shift from inpatient to outpatient cancer care means that patients are now required to manage their condition at home, away from regular supervision by clinicians. Subsequently, research has consistently reported that many patients with cancer have unmet information needs during their illness. Mobile devices, such as mobile phones and tablet computers, provide an opportunity to deliver information to patients remotely. To date, no systematic reviews have evaluated how mobile devices have been used specifically to help patients meet to their information needs. Objective: A systematic review was conducted to identify studies that describe the use of mobile interventions to enable patients with cancer to meet their cancer-related information needs in non-inpatient settings, and to describe the effects and feasibility of these interventions. Methods: MEDLINE EMBASE and PsychINFO databases were searched up until January 2017. Search terms related to ‘mobile devices’, ‘information needs’ and ‘cancer’. There were no restrictions on study type in order to be as inclusive as possible. Study participants were patients with cancer undergoing treatment. Interventions had to be delivered by a mobile or handheld device, attempt to meet patients’ cancer-related information needs, and be for use in non-inpatient settings. Critical Appraisal Skills Programme (CASP) checklists were used to assess the methodological quality of included studies. A narrative synthesis was performed and findings were organised by common themes found across studies. Results: The initial search yielded 1020 results. Twenty-three articles describing 20 studies were included. Interventions aimed to improve the monitoring and management of treatment-related symptoms (n=17, 85%), directly increase patients’ knowledge related to their condition (n=2, 10%) and improve communication of symptoms to clinicians in consultations (n=1, 5%). Studies were of adult (n=17; age range 24-87 years) and adolescent (n=3; age range 8-18 years) patients. Sample sizes ranged from 4-125, with 13 studies consisting of 25 participants or less. Most studies were conducted in the UK (n=12, 52%) or US (n=7, 30%). Of the 23 articles included, twelve were of medium quality, nine were of poor quality and two were of good quality. Overall, interventions were reported to be acceptable and were perceived as useful and easy to use. Few technical problems were encountered. Adherence was generally consistent and high (periods ranged from 5 days to 6 months), however there was considerable variation in use of intervention components within and between studies. Reported benefits of the interventions included improved symptom management, patient empowerment and improved clinician-patient communication, although mixed findings were reported for patients’ health-related quality of life and anxiety. Conclusions: The current review highlighted that mobile interventions for patients with cancer are only meeting treatment or symptom-related information needs. There were no interventions designed to meet patients’ full range of cancer-related information needs, from information on psychological support to how to manage finances during cancer, and the long-term effects of treatment. More comprehensive interventions are required for patients to meet their information needs when managing their condition in non-inpatient settings. Controlled evaluations are needed to further determine the effectiveness of these types of intervention

Impact of 18F-Choline PET scan acquisition time on delineation of GTV in prostate cancer [Poster Abstract]

Background: Dose painting radiotherapy requires accurate outlining of primary tumour volumes in the prostate. T2-Weighted (T2W) Magnetic Resonance Imaging (MRI) is the best imaging method for defining the gross tumour volume (GTV). Choline positron emission tomography (PET) is currently a controversial tracer. The image acquisition differs significantly in published studies. Many used early static imaging. One study found that 18F-choline PET/CT with late image acquisition has superior accuracy to T2W MR and functional MR alone1. We investigate whether increasing 18F-Choline PET scan acquisition time from 60 (PET-60) to 90 (PET-90) minutes improves GTV TVD. Methods. Analysis was performed on 9 18F-Choline PET scans. Patients were injected with 370MBq of activity. Three clinicians (C1, C2 and C3) independently and without reference to each other contoured GTVs on each of the T2W-MRI, PET-60 and PET-90 scans at differing times. Scans were registered by a clinician using rigid co-registration. The treating clinicians MRI contour was used as a reference contour. The resulting PET and MRI GTVs were transferred to the PET-60 and PET-90 scans after image registration. The Dice Similarity Coefficient (DSC), Specificity (Sp) and Sensitivity (S) were calculated from contour mask voxel analysis. Results. Table 1 shows the mean and range DSC, S and Sp scores on MRI, PET-60 and PET-90 for C1, C2 and C3 in comparison to the treating clinicians contour on MRI (C1). A 2 sampled T-test (P < 0.01) showed, no significant difference in the Sp, S and DSC between GTVs on PET-60 and PET-90 scans. Further to this, as shown in Figure 1, variability in GTV delineation is significant between observers in a singular case as well as across imaging modalities. Conclusion. Compared to MRI delineated GTVs, 18F-Choline PET GTVs are significantly different. This study found however that increasing the PET scan acquisition time from 60 to 90 minutes did not improve the performance of GTV TVD in comparison to MRI delineated GTV

The influence of dose distribution on treatment outcome in the SCOPE 1 oesophageal cancer trial

Purpose The first aim of this study was to assess plan quality using a conformity index (CI) and analyse its influence on patient outcome. The second aim was to identify whether clinical and technological factors including planning treatment volume (PTV) volume and treatment delivery method could be related to the CI value. Methods and materials By extending the original concept of the mean distance to conformity (MDC) index, the OverMDC and UnderMDC of the 95 % isodose line (50Gy prescribed dose) to the PTV was calculated for 97 patients from the UK SCOPE 1 trial (ISCRT47718479). Data preparation was carried out in CERR, with Kaplan-Meier and multivariate analysis undertaken in EUCLID and further tests in Microsoft Excel and IBM’s SPSS. Results A statistically significant breakpoint in the overall survival data, independent of cetuximab, was found with OverMDC (4.4 mm, p < 0.05). This was not the case with UnderMDC. There was a statistically significant difference in PTV volume either side of the OverMDC breakpoint (Mann Whitney p < 0.001) and in OverMDC value dependent on the treatment delivery method (mean IMRT = 2.1 mm, mean 3D-CRT = 4.1 mm Mann Whitney p < 0.001). Re-planning the worst performing patients according to OverMDC from 3D-CRT to VMAT resulted in a mean reduction in OverMDC of 2.8 mm (1.6–4.0 mm). OverMDC was not significant in multivariate analysis that included age, sex, staging, tumour type, and position. Conclusion Although not significant when included in multivariate analysis, we have shown in univariate analysis that a patient’s OverMDC is correlated with overall survival. OverMDC is strongly related to IMRT and to a lesser extent with PTV volume. We recommend that VMAT planning should be used for oesophageal planning when available and that attention should be paid to the conformity of the 95 % to the PTV

Can urinary exosomes act as treatment response markers in prostate cancer?

Background Recently, nanometer sized vesicles (termed exosomes) have been described as a component of urine. Such vesicles may be a useful non-invasive source of markers in renal disease. Their utility as a source of markers in urological cancer remains unstudied. Our aim in this study was to investigate the feasibility and value of analysing urinary exosomes in prostate cancer patients undergoing standard therapy. Methods Ten patients (with locally advanced PCa) provided spot urine specimens at three time points during standard therapy. Patients received 3–6 months neoadjuvant androgen deprivation therapy prior to radical radiotherapy, comprising a single phase delivering 55 Gy in 20 fractions to the prostate and 44 Gy in 20 fractions to the pelvic nodes. Patients were continued on adjuvant ADT according to clinical need. Exosomes were purified, and the phenotype compared to exosomes isolated from the prostate cancer cell line LNcaP. A control group of 10 healthy donors was included. Serum PSA was used as a surrogate treatment response marker. Exosomes present in urine were quantified, and expression of prostate markers (PSA and PSMA) and tumour-associated marker 5T4 was examined. Results The quantity and quality of exosomes present in urine was highly variable, even though we handled all materials freshly and used methods optimized for obtaining highly pure exosomes. There was approx 2-fold decrease in urinary exosome content following 12 weeks ADT, but this was not sustained during radiotherapy. Nevertheless, PSA and PSMA were present in 20 of 24 PCa specimens, and not detected in healthy donor specimens. There was a clear treatment-related decrease in exosomal prostate markers in 1 (of 8) patient. Conclusion Evaluating urinary-exosomes remains difficult, given the variability of exosomes in urine specimens. Nevertheless, this approach holds promise as a non-invasive source of multiple markers of malignancy that could provide clinically useful information