Perceived Barriers Toward Patient-Reported Outcome Implementation in Cancer Care: An International Scoping Survey.

PURPOSE: Implementation of patient-reported outcomes (PROs) collection is an important priority in cancer care. We examined perceived barriers toward implementing PRO collection between centers with and without PRO infrastructure and administrators and nonadministrators. PATIENTS AND METHODS: We performed a multinational survey of oncology practitioners on their perceived barriers to PRO implementations. Multivariable regression models evaluated for differences in perceived barriers to PRO implementation between groups, adjusted for demographic and institutional variables. RESULTS: Among 358 oncology practitioners representing six geographic regions, 31% worked at centers that did not have PRO infrastructure and 26% self-reported as administrators. Administrators were more likely to perceive concerns with liability issues (aOR, 2.00 [95% CI, 1.12 to 3.57]; P = .02) while having nonsignificant trend toward less likely perceiving concerns with disruption of workflow (aOR, 0.58 [95% CI, 0.32 to 1.03]; P = .06) and nonadherence of PRO reporting (aOR, 0.53 [95% CI, 0.26 to 1.08]; P = .08) as barriers. Respondents from centers without PRO infrastructure were more likely to perceive that not having access to a local PRO expert (aOR, 6.59 [95% CI, 3.81 to 11.42]; P < .001), being unsure how to apply PROs in clinical decisions (aOR, 4.20 [95% CI, 2.32 to 7.63]; P < .001), and being unsure about selecting PRO measures (aOR, 3.36 [95% CI, 2.00 to 5.66]; P < .001) as barriers. Heat map analyses identified the largest differences between participants from centers with and without PRO infrastructure in agreed-upon barriers were (1) not having a local PRO expert, (2) being unsure about selecting PRO measures, and (3) not recognizing the role of PROs at the institutional level. CONCLUSION: Perceived barriers toward PRO implementation differ between administrators and nonadministrators and practitioners at centers with and without PRO infrastructure. PRO implementation teams should consider as part of a comprehensive strategy including frontline clinicians and administrators and members with PRO experience within teams.

Patient-reported symptom monitoring: using (big) data to improve supportive care at the macro-, meso-, and micro-levels.

PURPOSE: This paper aims to provide a comprehensive understanding of the need for continued development of symptom monitoring (SM) implementation, utilization, and data usage at the macro-, meso-, and micro-levels. METHODS: Discussions from a patient-reported SM workshop at the MASCC/ISSO 2022 annual meeting were analyzed using a macro-meso-micro analytical framework of cancer care delivery. The workshop categories "initiation and implementation, barriers to adoption and utilization, and data usage" were integrated for each level. RESULTS: At the macro-level, policy development could encourage data sharing and international collaboration, including the exchange of SM methods, supportive care models, and self-management modules. At the meso-level, institutions should adjust clinical workflow and service delivery and promote a thorough technical and clinical integration of SM. At the micro-level, SM should be individualized, with timely feedback for patients, and should foster trust and understanding of AI decision support tools amongst clinicians to improve supportive care. CONCLUSIONS: The workshop reached a consensus among international experts on providing guidance on SM implementation, utilization, and (big) data usage pathways in cancer survivors across the cancer continuum and on macro-meso-micro levels.

Quality of life after patient-initiated vs physician-initiated response to symptom monitoring: the SYMPRO-Lung trial.

BACKGROUND: Previous studies using patient-reported outcomes measures (PROMs) to monitor symptoms during and after (lung) cancer treatment used alerts that were sent to the health-care provider, although an approach in which patients receive alerts could be more clinically feasible. The primary aim of this study was to compare the effect of weekly PROM symptom monitoring via a reactive approach (patient receives alert) or active approach (health-care provider receives alert) with care as usual on health-related quality of life (HRQOL) at 15 weeks after start of treatment in lung cancer patients. METHODS: The SYMPRO-Lung trial is a multicenter randomized controlled trial using a stepped wedge design. Stage I-IV lung cancer patients in the reactive and active groups reported PROM symptoms weekly, which were linked to a common alerting algorithm. HRQOL was measured by the EORTC QLQ-C30 at baseline and after 15 weeks. Linear regression analyses and effect size estimates were used to assess mean QOL-C30 change scores between groups, accounting for confounding. RESULTS: A total of 515 patients were included (160 active group, 89 reactive group, 266 control group). No differences in HRQOL were observed between the reactive and active group (summary score: unstandardized beta [B] = 0.51, 95% confidence interval [CI] = -3.22 to 4.24, Cohen d effect size [ES] = 0.06; physical functioning: B = 0.25, 95% CI = -5.15 to 4.64, ES = 0.02). The combined intervention groups had statistically and clinically significantly better mean change scores on the summary score (B = 4.85, 95% CI = 1.96 to 7.73, ES = 0.57) and physical functioning (B = 7.00, 95% CI = 2.90 to 11.09, ES = 0.71) compared with the control group. CONCLUSIONS: Weekly PRO symptom monitoring statistically and clinically significantly improves HRQOL in lung cancer patients. The logistically less intensive, reactive approach may be a better fit for implementation.

Minimal added value of wetting hair before scalp cooling to prevent chemotherapy-induced alopecia in cancer patients - results from the Dutch Scalp Cooling Registry.

PURPOSE: Preventing chemotherapy-induced alopecia (CIA) is related to the degree of temperature reduction during scalp cooling. Wetting hair before scalp cooling reduces the scalp skin temperature. This observational study investigated the effects of wetting hair before scalp cooling on preventing CIA and on tolerance in cancer patients. METHODS: This Dutch multi-center cohort study comprised 1825 patients receiving ≥1 cycle of docetaxel (D), 5-fluorouracil-epirubicin-cyclophosphamide (FEC), 5-fluorouracil-epirubicin-cyclophosphamide-docetaxel (FECD), paclitaxel (P), or paclitaxel-carboplatin (PC). Patients underwent scalp cooling with wet or dry hair. Primary and secondary outcomes were the effects of wetting hair on head cover use and tolerance, respectively. RESULTS: None of the associations between wetting hair and head cover use in patients on D, FEC, P, or PC was significant; however, results all tended to be in favor of wetting hair. For FECD, univariate (p=0.005; OR=1.6; CI=1.1-2.1) and multivariable associations (p=0.007; OR=1.8; CI=1.2-2.6) were significant. Scalp cooling discontinuation due to intolerance differed significantly between groups that wetted hair or not (3% and 1% respectively; p=0.034). CONCLUSION: In a large patient group with mainly a European hair type and a high hair mass, no convincing evidence was found whether wetting hair prior to scalp cooling contributes to better prevention of CIA. Since it is argued that a higher reduction in scalp skin temperature by wetting hair contributes positively to scalp cooling efficacy, only a randomized controlled trial can provide an ultimate conclusion at the highest level of evidence. Until that time, healthcare professionals have to take into account that wetting hair may introduce lower compliance to the scalp cooling procedure.

A Narrative Review on the Collection and Use of Electronic Patient-Reported Outcomes in Cancer Survivorship Care with Emphasis on Symptom Monitoring.

Electronic patient-reported outcome (ePRO) applications promise great added value for improving symptom management and health-related quality of life. The aim of this narrative review is to describe the collection and use of ePROs for cancer survivorship care, with an emphasis on ePRO-symptom monitoring. It offers many different perspectives from research settings, while current implementation in routine care is ongoing. ePRO collection optimizes survivorship care by providing insight into the patients' well-being and prioritizing their unmet needs during the whole trajectory from diagnosis to end-of-life. ePRO-symptom monitoring can contribute to timely health risk detection and subsequently allow earlier intervention. Detection is optimized by automatically generated alerts that vary from simple to complex and multilayered. Using ePRO-symptoms during in-hospital consultation enhances the patients' conversation with the health care provider before making informed decisions about treatments, other interventions, or self-management. ePRO(-symptoms) entail specific implementation issues and complementary ethics considerations. The latter is due to privacy concerns, digital divide, and scarcity of adequately representative data for particular groups of patients.

Comparable effectiveness of 45- and 20-min post-infusion scalp cooling time in preventing paclitaxel-induced alopecia - a randomized controlled trial.

PURPOSE: Scalp cooling can prevent chemotherapy-induced alopecia (CIA). Previously, the post-infusion cooling time (PICT) could be successfully reduced in docetaxel-treated patients from 90 to 45 and 20 min. Therefore, it seems plausible that the PICT can be shortened for paclitaxel-treated patients as well. METHODS: Patients treated with weekly paclitaxel were included in this multi-centre trial and randomly assigned to a PICT of 45 or 20 min. The results were compared to a standard PICT of 90 min, derived from prospective collected data from the Dutch Scalp Cooling Registry. The primary endpoint was the percentage of patients who decide to not wear a wig or head covering. Secondary endpoints were the degree of CIA assessed with the Dean scale for assessment of hair loss; alopecia graded according to NCI CTC toxicity version 4.03 (CTCAE4.03); tolerance of scalp cooling and perceived distress of CIA. RESULTS: Ninety-one patients were enrolled in this study; 74 patients were evaluable for hair loss. Hair preservation was successful in 27 patients (75%) with a PICT of 45 min and in 31 patients (82%) with a PICT of 20 min. There was no difference in success rate with the standard PICT of 90 min (85%, p = 0.29). Similar success rates were seen when using the Dean scale and CTCAE assessment, with no differences between groups (p = 0.12 and p = 0.38). CONCLUSIONS: A 20 min PICT is as effective as 45 and 90 min to prevent weekly paclitaxel-induced alopecia and should be the new standard of care. TRIAL REGISTER: ClinicalTrials.gov Identifier: NCT03266185.

The use of patient-reported outcomes in routine cancer care: preliminary insights from a multinational scoping survey of oncology practitioners.

BACKGROUND: There exists scant evidence on the optimal approaches to integrating patient-reported outcomes (PROs) in clinical practice. This study gathered oncology practitioners' experiences with implementing PROs in cancer care. METHODS: Between December 2019 and June 2020, we surveyed practitioners who reported spending > 5% of their time providing clinical care to cancer patients. Respondents completed an online survey describing their experiences with and barriers to using PROs in clinical settings. RESULTS: In total, 362 practitioners (physicians 38.7%, nurses 46.7%, allied health professionals 14.6%) completed the survey, representing 41 countries (Asia-Pacific 42.5%, North America 30.1%, Europe 24.0%, others 3.3%). One quarter (25.4%) identified themselves as "high frequency users" who conducted PRO assessments on > 80% of their patients. Practitioners commonly used PROs to facilitate communication (60.2%) and monitor treatment responses (52.6%). The most commonly reported implementation barriers were a lack of technological support (70.4%) and absence of a robust workflow to integrate PROs in clinical care (61.5%). Compared to practitioners from high-income countries, more practitioners in low-middle income countries reported not having access to a local PRO expert (P < .0001) and difficulty in identifying the appropriate PRO domains (P = .006). Compared with nurses and allied health professionals, physicians were more likely to perceive disruptions in clinical care during PRO collection (P = .001) as an implementation barrier. CONCLUSIONS: Only a quarter of the surveyed practitioners reported capturing PROs in routine clinical practice. The implementation barriers to PRO use varied across respondents in different professions and levels of socioeconomic resources. Our findings can be applied to guide planning and implementation of PRO collection in cancer care.

Health-Related Quality of Life and Survival in Metastasized Non-Small Cell Lung Cancer Patients with and without a Targetable Driver Mutation.

BACKGROUND: The aim of this study is to compare long-term health-related quality of life (HRQOL) and survival in metastatic NSCLC patients with (M+) and without (M-) a targetable driver mutation. METHODS: An observational study was performed within the prospective SYMPRO-lung study (NL7897). HRQOL questionnaires were completed at baseline, 15 weeks, and 6 months. Generalized estimating equations (GEE) were used to assess clinically significant declines in HRQOL (>10 points) over time. Kaplan-Meier survival curves were plotted for both progression-free survival (PFS) and overall survival (OS). RESULTS: 81 metastatic NSCLC patients were included (M+ patients; 16 (20%)). M+ patients had a significantly better global HRQOL (mean difference 12.8, ES 0.61), physical functioning (mean difference 13.4, ES 0.63), and less appetite loss (mean difference 23.1, ES 0.73) at 15 weeks of follow-up compared to M- patients. Patients with a clinically relevant decline in HRQOL at 6 months of follow-up had a significantly shorter PFS (5 months vs. 12 months, p-value < 0.001) and OS (11 months vs. 16 months, p-value 0.002). CONCLUSIONS: M- NSCLC patients have less favorable HRQOL over time compared to M+ patients. Furthermore, clinically relevant HRQOL declines over time were significantly associated with worse survival. HRQOL can therefore play an important role in in shaping patients' expectations of their prognosis.

SYMptom monitoring with Patient-Reported Outcomes using a web application among patients with Lung cancer in the Netherlands (SYMPRO-Lung): study protocol for a stepped-wedge randomised controlled trial.

INTRODUCTION: Lung cancer and its treatment cause a wide range of symptoms impacting the patients' health-related quality of life (HRQoL). The use of patient-reported outcomes (PRO) to monitor symptoms during and after cancer treatment has been shown not only to improve symptom management but also to improve HRQoL and overall survival (OS). Collectively, these results favour implementation of PRO-symptom monitoring in daily clinical care. However, these promising outcomes have been obtained under trial conditions in which patients were selected based on stringent inclusion criteria, and in countries with a dissimilar healthcare system than in the Netherlands.The primary aim of the SYMptom monitoring with Patient-Reported Outcomes using a web application among patients with Lung cancer in the Netherlands (SYMPRO-Lung) study is to evaluate the effect of PRO-symptom monitoring during and after lung cancer treatment on HRQoL in daily clinical practice. Secondary objectives include assessing the effect of PRO-symptom monitoring on progression-free survival, OS, the incidence and grade of PRO symptoms, medication adherence, implementation fidelity and cost-effectiveness. METHODS AND ANALYSIS: The SYMPRO-Lung study is a prospective, multicentre trial with a stepped wedge cluster randomised design. Study participants (n=292 intervention, n=292 controls) include patients with lung cancer (stages I-IV) starting treatment with surgery, systemic treatment, targeted treatment and/or radiotherapy.Every participating centre will consecutively switch from the control period to the intervention period, in which patients report their symptoms weekly via an online tool. In the intervention group, we evaluate two alert approaches: the active and reactive approach. If the symptoms exceed a predefined threshold, an alert is sent to the healthcare provider (active approach) or to the patient (reactive approach). Both the control and intervention group complete HRQoL questionnaires at 4 time points: at baseline, 15 weeks, 6 months and 1-year post treatment). Differences in HRQoL between the groups will be compared using linear mixed modelling analyses, accounting for within-centre clustering, potential time effects and confounding. ETHICS AND DISSEMINATION: The study protocol was approved by the Institutional Review Board and the Medical Ethics Committee of the Amsterdam UMC (under number NL 68440.029.18) and the institutional review boards of the participating study sites. The dissemination of the results will be conducted through publication in peer-reviewed journals and through scientific conferences. TRIAL REGISTRATION NUMBER: Trial register identifier: Netherlands Trial register Trial NL7897. Date of registration: 24 July 2019. https://www.trialregister.nl/trial/7897.

Prolonging the duration of post-infusion scalp cooling in the prevention of anthracycline-induced alopecia: a randomised trial in patients with breast cancer treated with adjuvant chemotherapy.

PURPOSE: Scalp cooling as a method to reduce the incidence of chemotherapy-induced alopecia (CIA) is increasingly used in daily practice worldwide. However, in patients treated with 5-fluorouracil, epirubicin and cyclophosphamide (FEC), scalp cooling fails in 48-67% of patients. This study investigated the efficacy of extended duration of post-infusion scalp cooling in breast cancer patients treated with this regimen. METHODS: In this prospective multi-centre randomised study, 102 patients with early breast cancer treated with adjuvant FEC chemotherapy were randomly assigned in a 1:1 ratio to a post-infusion cooling time of 90 or 150 min. The primary endpoint was the need to wear a wig or other head covering to mask visible hair loss. RESULTS: Sixteen out of 48 patients (33%) treated with 90 min of post-infusion cooling did not need any head covering, compared with 21 out of 46 patients (45%) treated with 150 min of post-infusion cooling (p = 0.2). WHO grades 2-3 (moderate-complete) alopecia were reported more often in patients treated with 90-min post-infusion cooling time (n = 25/51 (49%) versus n = 17/51 (33%); p = 0,02). Scalp cooling was well-tolerated (mean Visual Analogue Score 7.4) and only three patients (3%) stopped due to intolerance during treatment. CONCLUSIONS: Extending the duration of 90-min post-infusion scalp cooling to 150 min in patients treated with adjuvant FEC chemotherapy was well-tolerated but did not significantly diminish the need for head covering. However, grades 2-3 alopecia was seen less often with prolonged post-infusion scalp cooling.

Patient-reported outcome assessment and objective evaluation of chemotherapy-induced alopecia.

PURPOSE: Alopecia is one of the most distressing side effects of chemotherapy. Evaluating and comparing the efficacy of potential therapies to prevent chemotherapy-induced alopecia (CIA) has been complicated by the lack of a standardized measurement for hair loss. In this study we investigated the correlation between patient-reported outcome assessments and quantitative measurement with the hair check to assess CIA in clinical practice. METHOD: Scalp cooling efficacy was evaluated by patients by World Health Organisation (WHO) of CIA, Visual Analogue Scale (VAS) and wig use. The Hair Check was used to determine the amount of hair (in mm2) per unit of scalp skin area (in cm2) (Hair Mass Index, HMI). CIA was also evaluated by doctors, nurses and hairdressers. RESULTS: Baseline HMI was not predictive for hair loss. HMI declined throughout all chemotherapy cycles, which was not reflected by patient-reported measures. HMI correlated with patient-reported hair quantity before the start of the therapy, but not with WHO and/or VAS during therapy. Patient's opinion correlated moderately with the opinion of doctors and nurses (ρ = 0.50-0.56 respectively), but strongly with hair dressers (ρ = 0.70). CONCLUSIONS: The Hair check is suitable to quantify the amount of hair loss and could complement research on refining outcome of scalp cooling, but the patient's opinion should be considered as the best method to assess hair loss in clinical practice. TRIAL REGISTRATION: Trialregister.nl NTR number 3082.

Results of 20- versus 45-min post-infusion scalp cooling time in the prevention of docetaxel-induced alopecia.

PURPOSE: For patients, chemotherapy-induced alopecia (CIA) is one of the most distressing side effects of treatment. Scalp cooling can prevent or minimise CIA; the results may depend on the duration of cooling. Since a previous study on post-infusion cooling time in patients treated with docetaxel chemotherapy found no difference between 90 and 45 min, we investigated whether hair-preserving results could be maintained with a shorter post-infusion cooling time. METHODS: In this prospective, multi-centre randomised study, 134 patients who started treatment with docetaxel 75-100 mg/m(2) in a 3-weekly schedule were randomly assigned in a 1:1 ratio to a post-infusion cooling time of 45 or 20 min. The primary end point was the need for a wig or other head covering as assessed by the patient. A visual analogue scale (VAS) with a range from 0 (not tolerable) to 10 (very tolerable) was used to measure tolerance. RESULTS: Scalp cooling results were similar for 45- and 20-min post-infusion cooling times. Thirty-three out of 45 patients (73 %) treated with 20 min of post-infusion cooling did not need a form of head covering, compared with 41 out of 52 patients (79 %) treated with 45 min of post-infusion cooling (p = 0.5). The procedure was well tolerated (mean visual analogue score 8.3). Six patients stopped due to intolerance during the first treatment cycle. CONCLUSIONS: A 20-min post-infusion cooling time is effective and tolerable for patients treated with scalp cooling to prevent docetaxel-induced alopecia. TRIAL REGISTRATION: Trialregister.nl Identifier, NTR 1856.

Core temperature affects scalp skin temperature during scalp cooling.

BACKGROUND: The efficacy of hair loss prevention by scalp cooling to prevent chemotherapy induced hair loss has been shown to be related to scalp skin temperature. Scalp skin temperature, however, is dependent not only on local cooling but also on the thermal status of the body. OBJECTIVES: This study was conducted to investigate the effect of body temperature on scalp skin temperature. METHODS: We conducted experiments in which 13 healthy subjects consumed ice slurry to lower body temperature for 15 minutes after the start of scalp cooling and then performed two 12-minute cycle exercise sessions to increase body core temperature. Esophageal temperature (Tes ), rectal temperature (Tre ), mean skin temperature (eight locations, Tskin ), and mean scalp temperature (five locations, Tscalp ) were recorded. RESULTS: During the initial 10 minutes of scalp cooling, Tscalp decreased by >15 °C, whereas Tes decreased by 0.2 °C. After ice slurry ingestion, Tes , Tre , and Tskin were 35.8, 36.5, and 31.3 °C, respectively, and increased after exercise to 36.3, 37.3, and 33.0 °C, respectively. Tscalp was significantly correlated to Tes (r = 0.39, P < 0.01): an increase of 1 °C in Tes corresponded to an increase of 1.6 °C in Tscalp . CONCLUSIONS: Slight cooling of patients with an elevated body temperature during scalp cooling contributes to the decrease in scalp temperature and may improve the prevention of hair loss. This may be useful if the desired decrease of scalp temperature cannot be obtained by scalp cooling systems.

Factors influencing the effectiveness of scalp cooling in the prevention of chemotherapy-induced alopecia.

The success of scalp cooling in preventing or reducing chemotherapy-induced alopecia (CIA) is highly variable between patients and chemotherapy regimens. The outcome of hair preservation is often unpredictable and depends on various factors. Methods. We performed a structured search of literature published from 1970 to February 2012 for articles that reported on factors influencing the effectiveness of scalp cooling to prevent CIA in patients with cancer. Results. The literature search identified 192 reports, of which 32 studies were considered relevant. Randomized studies on scalp cooling are scarce and there is little information on the determinants of the result. The effectiveness of scalp cooling for hair preservation depends on dose and type of chemotherapy, with less favorable results at higher doses. Temperature seems to be an important determinant. Various studies suggest that a subcutaneous scalp temperature less than 22 °C is required for hair preservation. Conclusions. The effectiveness of scalp cooling for hair preservation varies by chemotherapy type and dose, and probably by the degree and duration of cooling.

Evaluation of Cohen's cross-section trichometer for measuring hair quantity.

BACKGROUND: Until now, there has been no reliable, simple method available for measuring hair quantity that is suitable in clinical practice. Recently, the cross-section trichometer by Cohen has been introduced. This study was designed to test its clinical utility. METHODS: The hair mass index (HMI) is ratio of the cross-sectional area of an isolated bundle of hair and the premeasured area of skin from which it was taken using the trichometer device. The intra- and interobserver reproducibility of measurements at the same location and after relocation were evaluated. RESULTS: For intraobserver reproducibility, the HMI ranged from 3 to 120 (mean difference .2, 95% confidence interval [CI] = -4.7-5.1, correlation coefficient [r] = .99. For interobserver reproducibility, the HMI ranged from 18 to 119 (mean difference -.4, 95% CI = -8,0-7,2, r = .98). With relocation, the HMI ranged from 2 to 113 (mean difference -1.0, 95% CI = -10.1-8.1, r = .97). Measurements took 5-10 minutes per area. CONCLUSION: Measurements were simple to perform, and the data showed high reproducibility. The trichometer is a promising technology for hair quantity measurements and has multiple clinical and research applications.

[Scalp cooling for chemotherapy-induced alopecia]. / Hoofdhuidkoeling tegen alopecia door chemotherapie.

Alopecia is a very common side effect of cytostatic therapy and is considered one of the most emotionally distressing effects. To prevent alopecia scalp cooling is currently used in some indications in medical oncology in 59 hospitals in the Netherlands. The success of scalp cooling depends on various factors such as type of chemotherapy, dose, infusion time, number of treatment cycles and combinations of drugs. In general, scalp cooling is well tolerated. The reported side-effects are headache, coldness, dizziness and sometimes claustrophobia. An increase in the risk of scalp metastases has not been demonstrated. Proceeding from the South Netherlands Comprehensive Cancer Centre a national working group is put together in order to draw up a national guideline for chemotherapy-induced alopecia.

Unfavourable pattern of metastases in M0 breast cancer patients during 1978-2008: a population-based analysis of the Munich Cancer Registry.

Little is known about time trends in metastases in the patients treated in routine health care facilities without metastases at diagnosis (M0) and about survival after these metastases. Data on 33,771 M0 patients with primary breast cancer diagnosed between 1978 and 2003 were obtained from the Munich Cancer Registry. Survival analyses were restricted to the patients with metastases within 5 years of the initial diagnosis. The incident number of the patients approximately doubled each period and 5-year overall survival increased from 77% in the first to 82% percent in the last period. 5490 (16%) M0 patients developed metastases within 5 years after the initial diagnosis. The hazard of developing metastases was lowest in the most recent period compared to the first period (HR = 0.50, P < 0.001). The hazard of dying after metastases was equal for patients diagnosed between 1978-1984 and 1995-2003 (HR 1.08, P = 0.3). The percentage of the patients that developed bone metastases decreased each time period, but the percentage primary liver and CNS metastases increased. Exclusion of site of metastases in the multivariate analysis led to a 20% (P = 0.02) higher hazard of dying following metastases in the last versus the first period. In the period 1978-2008, unfavourable changes in the pattern of metastases were exhibited and no improvement was observed in survival of the patients after occurrence of metastases. An explanation might be the increased use of adjuvant systemic treatment, which has less effect on the highly lethal liver and CNS metastases than on bone metastases. The increased use also appeared to contribute to the overall prevention of metastases in breast cancer and therefore to improve overall survival.

[Allow scalp cooling during adjuvant chemotherapy in patients with breast cancer; scalp metastases rarely occur]. / Hoofdhuidkoeling toelaten bij adjuvante chemotherapie van borstkankerpatiënten; incidentie hoofdhuidmetastasen zeer gering.

OBJECTIVE: To investigate the incidence of scalp metastases in high-risk breast cancer patients in order to assess whether caution is warranted with scalp cooling during adjuvant therapy. DESIGN: Observational study. METHODS: The incidence of scalp metastases and the disease course were studied in 885 very well evaluated high-risk breast cancer patients. These patients, who had at least four positive axillary lymph nodes, were treated in a randomised study with either classical chemotherapy, or the same chemotherapy followed by high-dose chemotherapy and autologous stem cell transplantation (the so-called N4+ study). RESULTS: After a median follow up of 110 months, 403 of the 885 patients (46%) had relapsed or developed metastases. 25 patients (3%) had developed skin metastasis; 4 of these patients (0.5%) had developed hairy scalp metastasis. The scalp metastases always occurred at the same time as or later than metastases elsewhere. CONCLUSION: Scalp metastases occur with a very low frequency and not as the first sign of metastatic disease. It is therefore unlikely that scalp cooling (to prevent baldness) decreases the local working of chemotherapy to such an extent that the risk of scalp metastases increases.

Impact of alopecia and scalp cooling on the well-being of breast cancer patients.

OBJECTIVE: Chemotherapy-induced alopecia, a common and distressing side effect of chemotherapy, may be prevented by scalp cooling, which reduces toxicity of cytostatics in hair root cells. This is the first study designed to assess the effect of scalp cooling on well-being. METHODS: A prospective multi-centre study was performed in 13 hospitals. Breast cancer patients treated with (N=98) and without (N=168) scalp cooling completed questionnaires (EORTC QLQ-C30 and EORTC-QLQ-BR23, BIS, MBA, HADS) before chemotherapy, and three weeks and six months after the last chemotherapy cycle. RESULTS: Scalp cooling was effective in 52% of the cases. Alopecia was considered among the most distressing problems at all three moments of measurement. A trend towards higher well-being was found in successfully scalp-cooled patients, as indicated by a general better health-related quality of life and better body image, whereas unsuccessfully scalp-cooled patients reported lowest well-being. CONCLUSIONS: Scalp cooling contributes not only to the well-being of successfully scalp-cooled patients but also seems to cause additional distress when patients lose their hair despite scalp cooling. This might be related to disappointment due to alopecia despite scalp cooling or possibly to a general higher biological availability of cytostatics. We recommend additional support for patients when scalp cooling is not successful and to spend more effort to maximise the effectiveness of scalp cooling.