Breaking bad news to cancer patients in times of COVID-19.

Breaking bad news is a mandatory provision in the professional life of nearly every physician. One of its most frequent occasions is the diagnosis of malignancy. Responding to the recipients' emotions is a critical issue in the delivery of unsettling information, and has an impact on the patient's trust in the treating physician, adjustment to illness and ultimately treatment. Since the World Health Organization (WHO) declared COVID-19 a pandemic on March 11, 2020, several measures of social distancing and isolation have been introduced to our clinical setting. In the wake of these restrictions, it is important to reexamine existing communication guidelines to determine their applicability to face-to-face counseling in the context of social distancing, as well as to new communication technologies, such as telemedicine. We address these issues and discuss strategies to convey bad news the most empathetic and comprehensible way possible.

Correction: Quality of life under extended continuous versus intermittent adjuvant letrozole in lymph node-positive, early breast cancer patients: the SOLE randomised phase 3 trial.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Treatment-induced symptoms, depression and age as predictors of sexual problems in premenopausal women with early breast cancer receiving adjuvant endocrine therapy.

PURPOSE: Sexual dysfunction is an important concern of premenopausal women with early breast cancer. We investigated predictors of sexual problems in two randomized controlled trials. METHODS: A subset of patients enrolled in TEXT and SOFT completed global and symptom-specific quality-of-life indicators, CES-Depression and MOS-Sexual Problems measures at baseline, six, 12 and 24 months. Mixed models tested the association of changes in treatment-induced symptoms (baseline to 6 months), depression at 6 months, and age at randomization with changes in sexual problems over 2 years. RESULTS: Sexual problems increased by 6 months and persisted at this level. Overall, patients with more severe worsening of vaginal dryness, sleep disturbances and bone or joint pain at 6 months reported a greater increase in sexual problems at all time-points. Depression scores were significantly associated with sexual problems in the short-term. All other symptoms had a smaller impact on sexual problems. Age was not associated with sexual problems at any time-point. CONCLUSION: Among several key symptoms, vaginal dryness, sleep disturbance, and bone and joint pain significantly predicted sexual problems during the first 2 years. Early identification of these symptoms may contribute to timely and tailored interventions.

Experiences of return to work after treatment for extremital soft tissue or bone sarcoma: Between distraction and leaving the disease behind.

OBJECTIVE: We aimed to explore the return to work (RTW) experience of individuals in remission from extremital sarcoma. METHODS: Using a qualitative survey design, we asked sarcoma survivors about their RTW experiences after treatment. Seven men and eight women (n = 15), 43 years old in average, participated. The majority had soft tissue sarcoma (n = 14) and no amputations (n = 14). We analysed data thematically through an inductive approach. RESULTS: Participants' motivation to RTW and their experiences of this transition could be understood under the main theme of "searching for distraction and wanting to leave the disease behind," followed by "problems of the new normal." RTW was the next step after treatment; however, being back at the same workplace/institution was challenging due to the interference of the effects of the disease and treatments and peer perceptions. In other subthemes, we identified that RTW was facilitated by different "signs of readiness," as well as by "motivating factors and the meaning of having an occupation." CONCLUSIONS: Readiness to RTW while primarily an autonomous decision can also be guided by third parties, including treating physicians. RTW can be challenging, since changes in performance as well as comments from peers become a constant reminder of the status prior to the illness. Given that RTW helps distract from the disease, these reminders can be confronting and highlight the role of health professionals and employers in preparing survivors and peers to facilitate the RTW.

Quality of life under extended continuous versus intermittent adjuvant letrozole in lymph node-positive, early breast cancer patients: the SOLE randomised phase 3 trial.

BACKGROUND: In the phase III SOLE trial, the extended use of intermittent versus continuous letrozole for 5 years did not improve disease-free survival in postmenopausal women with hormone receptor-positive breast cancer. Intermittent therapy with 3-month breaks may be beneficial for patients' quality of life (QoL). METHODS: In the SOLE QoL sub-study, 956 patients completed the Breast Cancer Prevention Trial (BCPT) symptom and further QoL scales up to 24 months after randomisation. Differences in change of QoL from baseline between the two administration schedules were tested at 12 and 24 months using repeated measures mixed-models. The primary outcome was change in hot flushes at 12 months. RESULTS: There was no difference in hot flushes at 12 months between the two schedules, but patients receiving intermittent letrozole reported significantly more improvement at 24 months. They also indicated less worsening in vaginal problems, musculoskeletal pain, sleep disturbance, physical well-being and mood at 12 months. Overall, 25-30% of patients reported a clinically relevant worsening in key symptoms and global QoL. CONCLUSION: Less symptom worsening was observed during the first year of extended treatment with the intermittent administration. For women experiencing an increased symptom burden of extended adjuvant endocrine therapy, an intermittent administration is a safe alternative. CLINICAL TRIAL INFORMATION: Clinical trial information: NCT00651456.

Quality of Life After Total Mesorectal Excision and Rectal Replacement: Comparing Side-to-End, Colon J-Pouch and Straight Colorectal Reconstruction in a Randomized, Phase III Trial (SAKK 40/04).

BACKGROUND: Functional outcomes of different reconstruction techniques have an impact on patients' quality of life (QoL), but information on long-term QoL is lacking. We compared QoL among three reconstruction techniques after total mesorectal excision (TME). METHODS: Quality of life was assessed within a randomized, multicenter trial comparing rectal surgery using side-to-end anastomosis (SEA), colon J-pouch (CJP), and straight colorectal anastomosis (SCA) by the Functional Assessment of Cancer Therapy-Colorectal scale (FACT-C) before randomization and every 6 months up to 2 years post-TME. The primary QoL endpoint was the change in the Trial Outcome Index (TOI), including the FACT-C subscales of physical and functional well-being and colorectal cancer symptoms (CSS), from baseline to month 12. Pair-wise comparisons of changes from baseline (presurgery) to each timepoint between the three arms were analyzed by Mann-Whitney tests. RESULTS: For the QoL analysis, 257 of 336 randomized patients were in the per protocol evaluation (SEA = 95; CJP = 63; SCA = 99). Significant differences between the reconstruction techniques were found for selected QoL scales up to 12 months, all in favor of CJP. Patients with SEA or SCA reported a clinically relevant deterioration for TOI and CSS at 6 months, those with SCA for CSS also at 12 months after TME. Patients with CJP remained stable. CONCLUSIONS: Although the three reconstruction techniques differ in their effects on QoL at months 6 and 12, these differences did not persist over the whole observation period of 24 months. Patients with a colon J-pouch may benefit with respect to QoL in the short-term.

Extended adjuvant intermittent letrozole versus continuous letrozole in postmenopausal women with breast cancer (SOLE): a multicentre, open-label, randomised, phase 3 trial.

BACKGROUND: In animal models of breast cancer, resistance to continuous use of letrozole can be reversed by withdrawal and reintroduction of letrozole. We therefore hypothesised that extended intermittent use of adjuvant letrozole would improve breast cancer outcome compared with continuous use of letrozole in postmenopausal women. METHODS: We did the multicentre, open-label, randomised, parallel, phase 3 SOLE trial in 240 centres (academic, primary, secondary, and tertiary care centres) in 22 countries. We enrolled postmenopausal women of any age with hormone receptor-positive, lymph node-positive, and operable breast cancer for which they had undergone local treatment (surgery with or without radiotherapy) and had completed 4-6 years of adjuvant endocrine therapy. They had to be clinically free of breast cancer at enrolment and without evidence of recurrent disease at any time before randomisation. We randomly assigned women (1:1) to treatment groups of either continuous use of letrozole (2·5 mg/day orally for 5 years) or intermittent use of letrozole (2·5 mg/day orally for 9 months followed by a 3-month break in years 1-4 and then 2·5 mg/day during all 12 months of year 5). Randomisation was done by principal investigators or designee at respective centres through the internet-based system of the International Breast Cancer Study Group, was stratified by type of previous endocrine therapy (aromatase inhibitors only vs selective oestrogen receptor modulators only vs both therapies), and used permuted block sizes of four and institutional balancing. No one was masked to treatment assignment. The primary endpoint was disease-free survival, analysed by the intention-to-treat principle using a stratified log-rank test. All patients in the intention-to-treat population who initiated protocol treatment during their period of trial participation were included in the safety analyses. This study is registered with ClinicalTrials.gov, number NCT00553410, and EudraCT, number 2007-001370-88; and long-term follow-up of patients is ongoing. FINDINGS: Between Dec 5, 2007, and Oct 8, 2012, 4884 women were enrolled and randomised after exclusion of patients at a non-adherent centre, found to have inadequate documentation of informed consent, immediately withdrew consent, or randomly assigned to intervention groups in error. 4851 women comprised the intention-to-treat population that compared extended intermittent letrozole use (n=2425) with continuous letrozole use (n=2426). After a median follow-up of 60 months (IQR 53-72), disease-free survival was 85·8% (95% CI 84·2-87·2) in the intermittent letrozole group compared with 87·5% (86·0-88·8) in the continuous letrozole group (hazard ratio 1·08, 95% CI 0·93-1·26; p=0·31). Adverse events were reported as expected and were similar between the two groups. The most common grade 3-5 adverse events were hypertension (584 [24%] of 2417 in the intermittent letrozole group vs 517 [21%] of 2411 in the continuous letrozole group) and arthralgia (136 [6%] vs 151 [6%]). 54 patients (24 [1%] in the intermittent letrozole group and 30 [1%] in the continuous letrozole group) had grade 3-5 CNS cerebrovascular ischaemia, 16 (nine [<1%] vs seven [<1%]) had grade 3-5 CNS haemorrhage, and 40 (19 [1%] vs 21 [1%]) had grade 3-5 cardiac ischaemia. In total, 23 (<1%) of 4851 patients died while on trial treatment (13 [<1%] of 2417 patients in the intermittent letrozole group vs ten [<1%] of 2411 in the continuous letrozole group). INTERPRETATION: In postmenopausal women with hormone receptor-positive breast cancer, extended use of intermittent letrozole did not improve disease-free survival compared with continuous use of letrozole. An alternative schedule of extended adjuvant endocrine therapy with letrozole, including intermittent administration, might be feasible and the results of the SOLE trial support the safety of temporary treatment breaks in selected patients who might require them. FUNDING: Novartis and the International Breast Cancer Study Group.

TNF blockers inhibit spinal radiographic progression in ankylosing spondylitis by reducing disease activity: results from the Swiss Clinical Quality Management cohort.

OBJECTIVES: To analyse the impact of tumour necrosis factor inhibitors (TNFis) on spinal radiographic progression in ankylosing spondylitis (AS). METHODS: Patients with AS in the Swiss Clinical Quality Management cohort with up to 10 years of follow-up and radiographic assessments every 2 years were included. Radiographs were scored by two readers according to the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) with known chronology. The relationship between TNFi use before a 2-year radiographic interval and progression within the interval was investigated using binomial generalised estimating equation models with adjustment for potential confounding and multiple imputation of missing values. Ankylosing Spondylitis Disease Activity Score (ASDAS) was regarded as mediating the effect of TNFi on progression and added to the model in a sensitivity analysis. RESULTS: A total of 432 patients with AS contributed to data for 616 radiographic intervals. Radiographic progression was defined as an increase in ≥2 mSASSS units in 2 years. Mean (SD) mSASSS increase was 0.9 (2.6) units in 2 years. Prior use of TNFi reduced the odds of progression by 50% (OR 0.50, 95% CI 0.28 to 0.88) in the multivariable analysis. While no direct effect of TNFi on progression was present in an analysis including time-varying ASDAS (OR 0.61, 95% CI 0.34 to 1.08), the indirect effect, via a reduction in ASDAS, was statistically significant (OR 0.75, 95% CI 0.59 to 0.97). CONCLUSION: TNFis are associated with a reduction of spinal radiographic progression in patients with AS. This effect seems mediated through the inhibiting effect of TNFi on disease activity.

When do patient reported quality of life indicators become prognostic in breast cancer?

BACKGROUND: Various patient reported quality-of-life indicators are independently prognostic for survival in metastatic breast cancer and other cancers. The same measures recorded at first diagnosis of early breast cancer carry no corresponding prognostic information. The present study aims to assess at what time in the disease evolution the prognostic association appears. METHODS: Among 8024 patients enrolled in one of seven randomized controlled trials in early-stage breast cancer 3247 had a breast cancer relapse after a median follow-up of 12.1 years. Of these 677 had completed QL indicator assessments within defined windows 1, 2 or 3 months prior to relapse. We performed Cox regression analyses using these assessments and using identical instruments after relapse. All analyses were stratified by trial and adjusted for baseline clinicopathologic factors. RESULTS: QL indicators in the months before relapse were not significantly prognostic for subsequent survival with the possibly chance exception of mood at the second month before relapse. After relapse, physical well-being was statistically significantly associated with survival (P < 0.001). This prognostic significance increased in later post-relapse assessments. Similar findings were observed using patient-reported indicators for nausea and vomiting, appetite, coping effort, and health perception. CONCLUSIONS: Before cancer relapse, QL indicators were not generally prognostic for subsequent survival. After relapse, QL indicators substantially predicted OS, with a stronger association later in the course of relapsed disease. Simple patient perception of disease burden seems unlikely to explain this sudden change: rather the patient's awareness of disease relapse must contribute.

Effects of patient-centered communication on anxiety, negative affect, and trust in the physician in delivering a cancer diagnosis: A randomized, experimental study.

BACKGROUND: When bad news about a cancer diagnosis is being delivered, patient-centered communication (PCC) has been considered important for patients' adjustment and well-being. However, few studies have explored how interpersonal skills might help cancer patients cope with anxiety and distress during bad-news encounters. METHODS: A prospective, experimental design was used to investigate the impact of the physician communication style during a bad-news encounter. Ninety-eight cancer patients and 92 unaffected subjects of both sexes were randomly assigned to view a video of a clinician delivering a first cancer diagnosis with either an enhanced patient-centered communication (E-PCC) style or a low patient-centered communication (L-PCC) style. Participants rated state anxiety and negative affect before and immediately after the video exposure, whereas trust in the physician was rated after the video exposure only. Main and interaction effects were analyzed with generalized linear models. RESULTS: Viewing the disclosure of a cancer diagnosis resulted in a substantial increase in state anxiety and negative affect among all participants. This emotional response was moderated by the physician's communication style: Participants viewing an oncologist displaying an E-PCC style were significantly less anxious than those watching an oncologist displaying an L-PCC style. They also reported significantly higher trust in the physician. CONCLUSIONS: Under a threatening, anxiety-provoking disclosure of bad news, a short sequence of empathic PCC influences subjects' psychological state, insofar that they report feeling less anxious and more trustful of the oncologist. Video exposure appears to be a valuable method for investigating the impact of a physician's communication style during critical encounters. Cancer 2017;123:3167-75. © 2017 American Cancer Society.

Adjuvant exemestane with ovarian suppression in premenopausal breast cancer.

BACKGROUND: Adjuvant therapy with an aromatase inhibitor improves outcomes, as compared with tamoxifen, in postmenopausal women with hormone-receptor-positive breast cancer. METHODS: In two phase 3 trials, we randomly assigned premenopausal women with hormone-receptor-positive early breast cancer to the aromatase inhibitor exemestane plus ovarian suppression or tamoxifen plus ovarian suppression for a period of 5 years. Suppression of ovarian estrogen production was achieved with the use of the gonadotropin-releasing-hormone agonist triptorelin, oophorectomy, or ovarian irradiation. The primary analysis combined data from 4690 patients in the two trials. RESULTS: After a median follow-up of 68 months, disease-free survival at 5 years was 91.1% in the exemestane-ovarian suppression group and 87.3% in the tamoxifen-ovarian suppression group (hazard ratio for disease recurrence, second invasive cancer, or death, 0.72; 95% confidence interval [CI], 0.60 to 0.85; P<0.001). The rate of freedom from breast cancer at 5 years was 92.8% in the exemestane-ovarian suppression group, as compared with 88.8% in the tamoxifen-ovarian suppression group (hazard ratio for recurrence, 0.66; 95% CI, 0.55 to 0.80; P<0.001). With 194 deaths (4.1% of the patients), overall survival did not differ significantly between the two groups (hazard ratio for death in the exemestane-ovarian suppression group, 1.14; 95% CI, 0.86 to 1.51; P=0.37). Selected adverse events of grade 3 or 4 were reported for 30.6% of the patients in the exemestane-ovarian suppression group and 29.4% of those in the tamoxifen-ovarian suppression group, with profiles similar to those for postmenopausal women. CONCLUSIONS: In premenopausal women with hormone-receptor-positive early breast cancer, adjuvant treatment with exemestane plus ovarian suppression, as compared with tamoxifen plus ovarian suppression, significantly reduced recurrence. (Funded by Pfizer and others; TEXT and SOFT ClinicalTrials.gov numbers, NCT00066703 and NCT00066690, respectively.).

Orteronel Switch Maintenance Therapy in Metastatic Castration Resistant Prostate Cancer After First-Line Docetaxel: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial (SAKK 08/11).

BACKGROUND: We tested whether a switch maintenance treatment with orteronel, an oral inhibitor of androgen biosynthesis, prolongs disease control in men with metastatic castration-resistant prostate cancer (mCRPC) after documented disease stabilization with docetaxel. METHODS: Men with mCRPC and non-progressive disease after a cumulative dose of ≥300 mg/m2 docetaxel for first line treatment were randomized 1:1 to receive orteronel 300 mg twice daily or placebo. The primary endpoint was event-free survival (EFS) defined as the time from randomization to death or the combination of at least two of radiographic, clinical, or PSA progression. Ninety-six patients per arm were planned to demonstrate an improvement of median EFS from 4 months on placebo to 6.7 months on orteronel (hazard ratio (HR) 0.6; type I error 5% and power 90%). RESULTS: Forty-seven patients (23 orteronel, 24 placebo) were randomized before premature closure of the trial because of discontinuation of clinical development of orteronel. Median EFS was 8.5 months with orteronel and 2.9 months with placebo (P = 0.001; HR 0.32; 95%CI 0.15-0.65). Median radiographic progression-free survival (rPFS) was 8.5 and 2.8 months (P = 0.02; HR 0.42; 95%CI 0.20-0.91) in the orteronel and placebo arm, respectively. PSA decline ≥50% was seen in 57% on orteronel and 4% on placebo. Toxicity was mainly mild, one patient on orteronel developed transient grade 3 adrenal insufficiency and one grade 4 pneumonitis. CONCLUSIONS: Orteronel significantly prolongs EFS in men with mCRPC who achieve disease stabilization with docetaxel. The concept of switch maintenance therapy in mCRPC warrants further research. Prostate 76:1519-1527, 2016. © 2016 Wiley Periodicals, Inc.

Adjuvant ovarian function suppression and cognitive function in women with breast cancer.

BACKGROUND: To examine the effect on cognitive function of adjuvant ovarian function suppression (OFS) for breast cancer. METHODS: The Suppression of Ovarian Function (SOFT) trial randomised premenopausal women with hormone receptor-positive breast cancer to 5 years adjuvant endocrine therapy with tamoxifen+OFS, exemestane+OFS or tamoxifen alone. The Co-SOFT substudy assessed objective cognitive function and patient reported outcomes at randomisation (T0), and 1 year later (T1); the primary endpoint was change in global cognitive function, measured by the composite objective cognitive function score. Data were compared for the pooled tamoxifen+OFS and exemestane+OFS groups vs the tamoxifen alone group using the Wilcoxon rank-sum test. RESULTS: Of 86 participants, 74 underwent both T0 and T1 cognitive testing; 54 randomised to OFS+ either tamoxifen (28) or exemestane (26) and 20 randomised to tamoxifen alone. There was no significant difference in the changes in the composite cognitive function scores between the OFS+ tamoxifen or exemestane groups and the tamoxifen group (mean±s.d., -0.21±0.92 vs -0.04±0.49, respectively, P=0.71, effect size=-0.20), regardless of prior chemotherapy status, and adjusting for baseline characteristics. CONCLUSIONS: The Co-SOFT study, although limited by small samples size, provides no evidence that adding OFS to adjuvant oral endocrine therapy substantially affects global cognitive function.

Impaired response to treatment with tumour necrosis factor α inhibitors in smokers with axial spondyloarthritis.

OBJECTIVES: To investigate the impact of smoking on the response to treatment with a first tumour necrosis factor inhibitor (TNFi) in patients with axial spondyloarthritis (axSpA) in a real-life cohort. METHODS: Patients fulfilling the Assessment of SpondyloArthritis international Society (ASAS) classification criteria for axSpA in the Swiss Clinical Quality Management Cohort were included in this study. The potential association between smoking status and differential response to TNFi in terms of the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and the Ankylosing Spondylitis Disease Activity Score (ASDAS) was analysed using multiple adjusted longitudinal mixed effect models. Binary response rates at 1 year were assessed with multiple adjusted logistic analyses. RESULTS: A first TNFi was initiated in 698 patients with axSpA with available smoking status and a baseline or follow-up BASDAI assessment, of which 490 (70%) had complete covariate data. In comparison to non-smokers, current smokers demonstrated significantly smaller reductions in BASDAI and ASDAS scores upon treatment with TNFi (0.75 BASDAI units and 0.69 ASDAS units less, p=0.005 and 0.001, respectively) for patients with elevated baseline C-reactive protein (CRP) level. This effect was numerically smaller in patients with normal CRP. The odds for reaching a 50% improvement in BASDAI response or the ASAS criteria for 40% improvement after 1 year were significantly lower in current smokers than in non-smokers (0.54, 95% CI 0.31 to 0.95, p=0.03 and 0.43, 95% CI 0.24 to 0.76, p=0.004, respectively). CONCLUSIONS: Current smoking is associated with an impaired response to TNFi in axSpA.

SAKK 24/09: safety and tolerability of bevacizumab plus paclitaxel vs. bevacizumab plus metronomic cyclophosphamide and capecitabine as first-line therapy in patients with HER2-negative advanced stage breast cancer - a multicenter, randomized phase III trial.

BACKGROUND: Adding bevacizumab to chemotherapy improves response rates and progression-free survival (PFS) in metastatic breast cancer (mBC). We aimed to demonstrate decreased toxicity with metronomic chemotherapy/bevacizumab compared with paclitaxel/bevacizumab. METHODS: This multicenter, randomized phase III trial compared bevacizumab with either paclitaxel (arm A) or daily oral capecitabine-cyclophosphamide (arm B) as first-line treatment in patients with HER2-negative advanced breast cancer. The primary endpoint was the incidence of selected grade 3-5 adverse events (AE) including: febrile neutropenia, infection, sensory/motor neuropathy, and mucositis. Secondary endpoints included objective response rate, disease control rate, PFS, overall survival (OS), quality of life (QoL), and pharmacoeconomics. The study was registered prospectively with ClinicalTrials.gov, number NCT01131195 on May 25, 2010. RESULTS: Between September 2010 and December 2012, 147 patients were included at 22 centers. The incidence of primary endpoint-defining AEs was similar in arm A (25 % [18/71]; 95 % CI 15-35 %) and arm B (24 % [16/68]; 95 % CI 13-34 %; P = 0.96). Objective response rates were 58 % (42/73; 95 % CI 0.46-0.69) and 50 % (37/74; 95 % CI 0.39-0.61) in arms A and B, respectively (P = 0.45). Median PFS was 10.3 months (95 % CI 8.7-11.3) in arm A and 8.5 months (95 % CI 6.5-11.9) in arm B (P = 0.90). Other secondary efficacy endpoints were not significantly different between study arms. The only statistically significant differences in QoL were less hair loss and less numbness in arm B. Treatment costs between the two arms were equivalent. CONCLUSION: This trial failed to meet its primary endpoint of a reduced rate of prespecified grade 3-5 AEs with metronomic bevacizumab, cyclophosphamide and capecitabine.

Patient-reported outcomes with adjuvant exemestane versus tamoxifen in premenopausal women with early breast cancer undergoing ovarian suppression (TEXT and SOFT): a combined analysis of two phase 3 randomised trials.

BACKGROUND: The combined efficacy analysis of the TEXT and SOFT trials showed a significant disease-free survival benefit with exemestane plus ovarian function suppression (OFS) compared with tamoxifen plus OFS. We present patient-reported outcomes from these trials. METHODS: Between Nov 7, 2003, and April 7, 2011, 4717 premenopausal women with hormone-receptor positive breast cancer were enrolled in TEXT or SOFT to receive unmasked adjuvant treatment with 5 years of exemestane plus OFS or tamoxifen plus OFS. Gonadotropin-releasing hormone analogue triptorelin, bilateral oophorectomy, or bilateral ovarian irradiation were used to achieve OFS. Chemotherapy use was optional. Randomisation with permuted blocks was done with the International Breast Cancer Study Group's internet-based system and was stratified by chemotherapy use and status of lymph nodes. Patients completed a quality of life (QoL) form comprising several global and symptom indicators at baseline, every 6 months for 24 months, and then every year during years 3 to 6. Differences in the change of QoL from baseline between the two treatments were tested at 6 months, 24 months, and 60 months with mixed-models for repeated measures for each trial with and without chemotherapy and overall. The analysis was by intention to treat. At the time of analysis, the median follow-up was 5·7 years (IQR 3·7-6·9); treatment and follow-up of patients continue. The trials are registered with ClinicalTrials.gov, as NCT00066703 (TEXT) and NCT00066690 (SOFT). FINDINGS: Patients on tamoxifen plus OFS were more affected by hot flushes and sweats over 5 years than were those on exemestane plus OFS, although these symptoms improved. Patients on exemestane plus OFS reported more vaginal dryness, greater loss of sexual interest, and difficulties becoming aroused than did patients on tamoxifen plus OFS; these differences persisted over time. An increase in bone or joint pain was more pronounced, particularly in the short term, in patients on exemestane plus OFS than patients on tamoxifen plus OFS. Changes in global QoL indicators from baseline were small and similar between treatments over the 5 years. INTERPRETATION: Overall, from a QoL perspective, there is no strong indication to favour either exemestane plus OFS or tamoxifen plus OFS. The distinct effects of the two treatments on the burden of endocrine symptoms need to be addressed with patients individually. FUNDING: Pfizer, International Breast Cancer Study Group, and US National Cancer Institute.

Tumor necrosis factor α inhibition in radiographic and nonradiographic axial spondyloarthritis: results from a large observational cohort.

OBJECTIVE: To evaluate the baseline characteristics of patients with radiographic axial spondyloarthritis (SpA; ankylosing spondylitis [AS]) and patients with nonradiographic axial SpA, to investigate determinants of anti-tumor necrosis factor (anti-TNF) agent prescription on the background of a nonrestrictive reimbursement policy, and to assess the response to TNF inhibition. METHODS: We compared the characteristics of radiographic axial SpA and nonradiographic axial SpA in 1,070 patients from the Swiss Clinical Quality Management (SCQM) Cohort who fulfilled the Assessment of SpondyloArthritis international Society (ASAS) classification criteria for axial SpA. By taking advantage of the situation that patients who are eligible for anti-TNF treatment are preferentially enrolled in the SCQM Cohort for patients with AS/axial SpA, we explored parameters leading to the initiation of anti-TNF treatment in single and multiple regression models and assessed treatment responses. RESULTS: We confirmed a similar burden of disease (as determined by self-reported disease activity, impaired function, and quality of life) in patients with nonradiographic axial SpA (n = 232) and those with radiographic axial SpA (n = 838). Patients with radiographic axial SpA had higher median levels of acute-phase reactants and higher median AS Disease Activity Scores (ASDAS; 3.2 versus 3.0). Anti-TNF treatment was initiated in 363 patients with radiographic axial SpA and 102 patients with nonradiographic axial SpA, preferentially in those with sacroiliitis on magnetic resonance imaging, peripheral arthritis, a higher C-reactive protein (CRP) level, a higher ASDAS, and a higher Bath Ankylosing Spondylitis Disease Activity Index level. The ASAS criteria for 40% improvement responses at 1 year were higher in patients with radiographic axial SpA compared with those with nonradiographic axial SpA (48.1% versus 29.6%; odds ratio [OR] 2.2, 95% confidence interval [95% CI] 1.12-4.46, P = 0.02). The difference was smaller in the subgroups of patients with elevated baseline CRP levels (51.6% in patients with radiographic axial SpA versus 38.5% in those with nonradiographic axial SpA; OR 1.7, 95% CI 0.68-4.48, P = 0.29). CONCLUSION: The indications for treatment with anti-TNF agents were comparable for patients with radiographic axial SpA and those with nonradiographic axial SpA. With the exception of patients with elevated CRP levels at baseline, higher rates of response to TNF inhibition were achieved in the group of patients with radiographic axial SpA than in the group with nonradiographic axial SpA.

Mandatory communication skills training for oncologists: enforcement does not substantially impact satisfaction.

PURPOSE: Even though there is evidence that both patients and oncology clinicians are affected by the quality of communication and that communication skills can be effectively trained, so-called Communication Skills Trainings (CSTs) remain heterogeneously implemented. METHODS: A systematic evaluation of the level of satisfaction of oncologists with the Swiss CST before (2000-2005) and after (2006-2012) it became mandatory. RESULTS: Levels of satisfaction with the CST were high, and satisfaction of physicians participating on a voluntary or mandatory basis did not significantly differ for the majority of the items. CONCLUSIONS: The evaluation of physicians' satisfaction over the years and after introduction of mandatory training supports recommendations for generalized implementation of CST and mandatory training for medical oncologists.

Erectile function preservation after salvage radiation therapy for biochemically recurrent prostate cancer after prostatectomy: Five-year results of the SAKK 09/10 randomized phase 3 trial.

Objectives: To evaluate effects of dose intensified salvage radiotherapy (sRT) on erectile function in biochemically recurrent prostate cancer (PC) after radical prostatectomy (RP). Materials and methods: Eligible patients had evidence of biochemical failure after RP and a PSA at randomization of ≤ 2 ng/ml. Erectile dysfunction (ED) was investigated as secondary endpoint within the multicentre randomized trial (February 2011 to April 2014) in patients receiving either 64 Gy or 70 Gy sRT. ED and quality of life (QoL) were assessed using CTCAE v4.0 and the EORTC QoL questionnaires C30 and PR25 at baseline and up to 5 years after sRT. Results: 344 patients were evaluable. After RP 197 (57.3 %) patients had G0-2 ED while G3 ED was recorded in 147 (42.7 %) patients. Subsequently, sexual activity and functioning was impaired. 5 years after sRT, 101 (29.4 %) patients noted G0-2 ED. During follow-up, 44.2 % of patients with baseline G3 ED showed any improvement and 61.4 % of patients with baseline G0-2 ED showed worsening. Shorter time interval between RP and start of sRT (p = 0.007) and older age at randomization (p = 0.005) were significant predictors to more baseline ED and low sexual activity in the long-term. Age (p = 0.010) and RT technique (p = 0.031) had a significant impact on occurrence of long-term ED grade 3 and worse sexual functioning. During follow-up, no differences were found in erectile function, sexual activity, and sexual functioning between the 64 Gy and 70 Gy arm. Conclusion: ED after RP is a known long-term side effect with significant impact on patients' QoL. ED was further affected by sRT, but dose intensification of sRT showed no significant impact on erectile function recovery or prevalence of de novo ED after sRT. Age, tumor stage, prostatectomy and RT-techniques, nerve-sparing and observation time were associated with long-term erectile function outcome.ClinicalTrials.gov. Identifier: NCT01272050.