Hormone Receptor Expression and Activity for Different Tumour Locations in Patients with Advanced and Recurrent Endometrial Carcinoma.

BACKGROUND: Response to hormonal therapy in advanced and recurrent endometrial cancer (EC) can be predicted by oestrogen and progesterone receptor immunohistochemical (ER/PR-IHC) expression, with response rates of 60% in PR-IHC > 50% cases. ER/PR-IHC can vary by tumour location and is frequently lost with tumour progression. Therefore, we explored the relationship between ER/PR-IHC expression and tumour location in EC. METHODS: Pre-treatment tumour biopsies from 6 different sites of 80 cases treated with hormonal therapy were analysed for ER/PR-IHC expression and classified into categories 0-10%, 10-50%, and >50%. The ER pathway activity score (ERPAS) was determined based on mRNA levels of ER-related target genes, reflecting the actual activity of the ER receptor. RESULTS: There was a trend towards lower PR-IHC (33% had PR > 50%) and ERPAS (27% had ERPAS > 15) in lymphogenic metastases compared to other locations (p = 0.074). Hematogenous and intra-abdominal metastases appeared to have high ER/PR-IHC and ERPAS (85% and 89% ER-IHC > 50%; 64% and 78% PR-IHC > 50%; 60% and 71% ERPAS > 15, not significant). Tumour grade and previous radiotherapy did not affect ER/PR-IHC or ERPAS. CONCLUSIONS: A trend towards lower PR-IHC and ERPAS was observed in lymphogenic sites. Verification in larger cohorts is needed to confirm these findings, which may have implications for the use of hormonal therapy in the future.

Health-related conditions among long-term cancer survivors diagnosed in adolescence and young adulthood (AYA): results of the SURVAYA study.

BACKGROUND: With 5-year survival rates > 85%, gaining insight into the long-term and late health-related conditions of cancer survivors diagnosed in adolescence and young adulthood is of utmost importance to improve their quantity and quality of survival. This study examined the prevalence of and factors associated with, patient-reported health-related conditions and their latency times among long-term adolescent and young adult (AYA) cancer survivors. METHODS: AYA cancer survivors (5-20 years after diagnosis) were identified by the population-based Netherlands Cancer Registry (NCR), and invited to participate in the SURVAYA questionnaire study. Participants reported the prevalence and date of diagnosis of health-related conditions. Clinical data were retrieved from the NCR. RESULTS: Three thousand seven hundred seventy-six AYA cancer survivors (response rate 33.4%) were included for analyses. More than half of the AYAs (58.5%) experienced health-related conditions after their cancer diagnosis, of whom 51.4% were diagnosed with two or more conditions. Participants reported conditions related to vision (15.0%), digestive system (15.0%), endocrine system (14.1%), cardiovascular system (11.7%), respiratory system (11.3%), urinary tract system (10.9%), depression (8.6%), hearing (7.4%), arthrosis (6.9%), secondary malignancy (6.4%), speech-, taste and smell (4.5%), and rheumatoid arthritis (2.1%). Time since diagnosis, tumor type, age at diagnosis, and educational level were most frequently associated with a health-related condition. CONCLUSIONS: A significant proportion of long-term AYA cancer survivors report having one or more health-related conditions. IMPLICATIONS FOR CANCER SURVIVORS: Future research should focus on better understanding the underlying mechanisms of, and risk factors for, these health-related conditions to support the development and implementation of risk-stratified survivorship care for AYA cancer survivors to further improve their outcomes. CLINICAL TRIALS REGISTRATION: NCT05379387.

Pre-treatment fertility preservation and post-treatment reproduction in long-term survivors of adolescent and young adult (AYA) cancer.

PURPOSE: To describe recall of fertility-related consultations and cryopreservation and to examine reproductive goals and reproduction post-treatment in long-term survivors of adolescent and young adult (AYA) (age, 18-39 years) cancer. METHODS: This study included n = 1457 male and n = 2112 female long-term survivors (Mage = 43-45 years; 5-22 years from diagnosis) who provided self-report. Clinical data were supplied by the Netherlands Cancer Registry. RESULTS: Most male survivors (72.7%) recalled fertility-related consultations and 22.6% completed sperm cryopreservation. Younger age (OR = 2.8; 95%CI [2.2-3.6]), not having children (OR = 5.0; 95%CI [3.2-7.7]), testicular cancer or lymphoma/leukemia (OR = 2.8/2.5 relative to "others"), and more intense treatments (OR = 1.5; 95%CI [1.1-2.0]) were associated with higher cryopreservation rates. Time since diagnosis had no effect. Of men who cryopreserved, 12.1% utilized assisted reproductive technologies (ART). Most men (88.5%) felt their diagnosis did not affect their reproductive goals, but 7.6% wanted no (additional) children due to cancer. Half of female survivors (55.4%; n = 1171) recalled fertility-related consultations. Rates of cryopreservation were very low (3.6%), but increased after 2013 when oocyte cryopreservation became non-experimental. Of women who cryopreserved, 13.2% successfully utilized ART. Most women (74.8%) experienced no effects of cancer on reproductive goals, but 17.8% wanted no (additional) children due to cancer. CONCLUSIONS: Cryopreservation in men varied by patient/clinical factors and was very low in women, but data of more recently treated females are needed. Utilizing cryopreserved material through ART was rare, which questions its cost-effectiveness, but it may enhance survivors' well-being. IMPLICATIONS FOR CANCER SURVIVORS: The extent to which cryopreservation positively affects survivors' well-being remains to be tested. Moreover, effects of cancer on reproductive goals require further attention, especially in women who refrain from having children due to cancer.

PAZEC: a Dutch Gynaecological Oncology Group open-label, multicenter, phase II study of pazopanib in metastatic and locally advanced hormone-resistant endometrial cancer.

OBJECTIVE: There is a continued need for improvement of second-line systemic treatment for metastatic and/or recurrent endometrial cancer. METHODS: In this phase II, open-label study, eligible patients had histologically or cytologically confirmed endometrial cancer, documented progressive disease, and a WHO performance status of ≤2. All participants received treatment with pazopanib 800 mg once daily until progression, unacceptable toxicity, or patient refusal. The primary endpoint was progression-free survival at 3 months, with secondary outcomes of overall response rate, progression-free survival, overall survival, and toxicity. The study was powered to demonstrate 50% progression-free survival at 3 months with α=0.05 and ß=80%. RESULTS: Between January 2011 and February 2016, 60 eligible patients were included (intention-to-treat population). Median age was 68 (range, 53-85) years. Previous treatment included pelvic radiotherapy (58%), chemotherapy (90%), and hormonal therapy (43%). Three-month progression-free survival was 63.3% in the intention-to-treat population, with median progression-free survival and overall survival of 3.4 and 7.5 months, respectively. Overall response rate was 8.3%, and median follow-up 7.6 months. The most common grade 3 or higher adverse events were gastrointestinal toxicity in 21% of participants, including two patients with a gut perforation, one fatal gastrointestinal hemorrhage, one enterocutaneous fistula, and one fatal enterovaginal fistula. Extensive peritoneal disease existed in 80% of the patients with severe gastrointestinal toxicity. A definite correlation with previous radiotherapy could not be established. CONCLUSIONS: Pazopanib met its primary endpoint of 3 months' progression-free survival in advanced endometrial cancer (63.3%), but response rates were modest. There may be a correlation for rare but severe gastrointestinal toxicity with previous treatments and/or disease site that has yet to be elucidated.

Adherence to the World Cancer Research Fund/American Institute for Cancer Research recommendations for cancer prevention in adolescent and young adult (AYA) cancer survivors: results from the SURVAYA study.

PURPOSE: For adolescent and young adult (AYA) cancer survivors with a good prognosis, having a healthy lifestyle prevents morbidity and mortality after treatment. The aim of this study was to investigate the prevalence of (un)healthy lifestyle behaviors and related determinants in AYA cancer survivors. METHODS: A population-based, cross-sectional study was performed among long-term (5-20 years) AYA cancer survivors (18-39 years old at diagnosis) registered within the Netherlands Cancer Registry. Self-reported questionnaires data about health behaviors were used to calculate the 2018 World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) adherence score. Associations between the score and clinical/sociodemographic determinants of (un)healthy behaviors were investigated using logistic regression models. RESULTS: The mean WCRF/AICR score was low to moderate, 3.8 ± 1.2 (0.5-7.0) (n = 3668). Sixty-one percent adhered to "limit the consumption of sugar sweetened drinks," 28% to "be a healthy weight," 25% to "fruit and vegetable consumption," and 31% to "limit alcohol consumption." Moderate and high adherence were associated with being a woman (ORmoderate = 1.46, 95% CI = 1.14-1.85, and ORhigh = 1.87, 95% CI = 1.46-2.4) and highly educated (ORmoderate = 1.54, 95% CI = 1.30-1.83, and ORhigh = 1.87, 95% CI = 1.46-2.4). Low adherence was associated with smoking (ORmoderate = 0.68, 95% CI = 0.50-0.92, and ORhigh = 0.30, 95% CI = 0.21-0.44) and diagnosis of germ cell tumor (ORmoderate = 0.58, 95% CI = 0.39-0.86, and ORhigh = 0.45, 95% CI = 0.30-0.69). CONCLUSIONS: Adherence to the 2018 WCRF/AICR lifestyle recommendations was low to moderate, especially regarding body weight, fruit, vegetables, and alcohol consumption. Men, current smokers, lower-educated participants, and/or those diagnosed with germ cell tumors were less likely to have a healthy lifestyle. IMPLICATIONS FOR CANCER SURVIVORS: Health-promotion programs (e.g., age-specific tools) are needed, focusing on high-risk groups.

Phenotype-guided targeted therapy based on functional signal transduction pathway activity in recurrent ovarian cancer patients: The STAPOVER study protocol.

Objective: Ovarian cancer is the fifth cause of cancer-related death among women. The benefit of targeted therapy for ovarian cancer patients is limited even if treatment is stratified by molecular signature. There remains a high unmet need for alternative diagnostics that better predict targeted therapy, as current diagnostics are generally inaccurate predictors. Quantitative assessment of functional signal transduction pathway (STP) activity from mRNA measurements of target genes is an alternative approach. Therefore, we aim to identify aberrantly activated STPs in tumour tissue of patients with recurrent ovarian cancer and start phenotype-guided targeted therapy to improve survival without compromising quality of life. Study design: Patients with recurrent ovarian cancer and either 1) have platinum-resistant disease, 2) refrain from standard therapy or 3) are asymptomatic and not yet eligible for standard therapy will be included in this multi-centre prospective cohort study with multiple stepwise executed treatment arms. Targeted therapy will be available for patients with aberrantly high functional activity of the oestrogen receptor, androgen receptor, phosphoinositide 3-kinase or Hedgehog STP. The primary endpoint of this study is the progression-free survival (PFS) ratio (PFS2/PFS1 ratio) according to RECIST 1.1 determined by the PFS on matched targeted therapy (PFS2) compared to PFS on prior therapy (PFS1). Secondary endpoints include among others best overall response, overall survival, side effects, health-related quality of life and cost-effectiveness. Conclusion: The results of this study will show the clinical applicability of STP activity in selecting recurrent ovarian cancer patients for effective therapies.

Exploring the interconnectedness between health-related quality of life factors among long-term adolescent and young adult cancer survivors (AYAs): a network analysis.

PURPOSE: Adolescent and young adult cancer survivors (AYAs) are at increased risk of long-term and late effects, and experience unmet needs, impacting their health-related quality of life (HRQoL). In order to provide and optimize supportive care and targeted interventions for this unique population, it is important to study HRQoL factors' interconnectedness on a population level. Therefore, this network analysis was performed with the aim to explore the interconnectedness between HRQoL factors, in the analysis described as nodes, among long-term AYAs. METHODS: This population-based cohort study used cross-sectional survey data of long-term AYAs, who were identified by the Netherlands Cancer Registry (NCR). Participants completed a one-time survey (SURVAYA study), including the EORTC survivorship questionnaire (QLQ-SURV111) to assess their long-term HRQoL outcomes and sociodemographic characteristics. The NCR provided the clinical data. Descriptive statistics and a network analysis, including network clustering, were performed. RESULTS: In total, 3596 AYAs (on average 12.4 years post diagnosis) were included in our network analysis. The network was proven stable and reliable and, in total, four clusters were identified, including a worriment, daily functioning, psychological, and sexual cluster. Negative health outlook, part of the worriment cluster, was the node with the highest strength and its partial correlation with health distress was significantly different from all other partial correlations. CONCLUSION: This study shows the results of a stable and reliable network analysis based on HRQoL data of long-term AYAs, and identified nodes, correlations, and clusters that could be intervened on to improve the HRQoL outcomes of AYAs.

Olaparib plus Durvalumab, with or without Bevacizumab, as Treatment in PARP Inhibitor-Naïve Platinum-Sensitive Relapsed Ovarian Cancer: A Phase II Multi-Cohort Study.

PURPOSE: Early results from the phase II MEDIOLA study (NCT02734004) in germline BRCA1- and/or BRCA2-mutated (gBRCAm) platinum-sensitive relapsed ovarian cancer (PSROC) showed promising efficacy and safety with olaparib plus durvalumab. We report efficacy and safety of olaparib plus durvalumab in an expansion cohort of women with gBRCAm PSROC (gBRCAm expansion doublet cohort) and two cohorts with non-gBRCAm PSROC, one of which also received bevacizumab (non-gBRCAm doublet and triplet cohorts). PATIENTS AND METHODS: In this open-label, multicenter study, PARP inhibitor-naïve patients received olaparib plus durvalumab treatment until disease progression; the non-gBRCAm triplet cohort also received bevacizumab. Primary endpoints were objective response rate (ORR; gBRCAm expansion doublet cohort), disease control rate (DCR) at 24 weeks (non-gBRCAm cohorts), and safety (all cohorts). RESULTS: The full analysis and safety analysis sets comprised 51, 32, and 31 patients in the gBRCAm expansion doublet, non-gBRCAm doublet, and non-gBRCAm triplet cohorts, respectively. ORR was 92.2% [95% confidence interval (CI), 81.1-97.8] in the gBRCAm expansion doublet cohort (primary endpoint); DCR at 24 weeks was 28.1% (90% CI, 15.5-43.9) in the non-gBRCAm doublet cohort (primary endpoint) and 74.2% (90% CI, 58.2-86.5) in the non-gBRCAm triplet cohort (primary endpoint). Grade ≥ 3 adverse events were reported in 47.1%, 65.6%, and 61.3% of patients in the gBRCAm expansion doublet, non-gBRCAm doublet, and non-gBRCAm triplet cohorts, respectively, most commonly anemia. CONCLUSIONS: Olaparib plus durvalumab continued to show notable clinical activity in women with gBRCAm PSROC. Olaparib plus durvalumab with bevacizumab demonstrated encouraging clinical activity in women with non-gBRCAm PSROC. No new safety signals were identified.

Patient-Reported Outcomes of Accelerated Aging: A Novel Approach to Investigate Second Cancer Risk in Adolescent and Young Adult (18-39 Years) Cancer Survivors.

BACKGROUND: Adolescent and young adult cancer survivors (AYAs, aged 18-39 years at first diagnosis) have a higher second cancer risk. Accelerated aging is hypothesized as underlying mechanism and has been described clinically by 6 indicators; fatigue, low quality of sleep, low mood, lack of motivation, subjective memory complaints, and poor exercise tolerance. Using patient-reported outcomes, we aimed to identify clusters of accelerated aging among AYA cancer survivors and to investigate their association with second cancer development. PATIENTS AND METHODS: Patient, tumor, and treatment data were obtained from the Netherlands Cancer Registry. Patient-reported clinical indicators and second cancer data were obtained from the SURVivors (5-20 years) of cancer in AYAs (SURVAYA) questionnaire study between 1999 and 2015. Latent class and multivariable logistic regression analyses were performed. RESULTS: In total, n = 3734 AYA survivors with known second cancer status (n = 278 [7.4%] second cancers) were included. Four latent clusters were identified and named based on their clinical indicator features; (1) high accelerated aging (31.3%), (2) intermediate accelerated aging without poor exercise tolerance (15.1%), (3) intermediate accelerated aging without lack of motivation (27.4%), and (4) low accelerated aging (26.2%). AYAs in the high accelerated aging cluster were more likely to have second cancer (odds ratio: 1.6; 95% CI, 1.1-2.3) compared to the low accelerated aging cluster. CONCLUSION: AYAs with a higher burden of accelerated aging were more likely to develop a second cancer. Validation of the clinical indicators and how to best capture them is needed to improve (early) detection of AYAs at high risk of developing second cancer.

Health-related quality of life of Adolescent and Young Adult Cancer Survivors before and during the COVID-19 pandemic: longitudinal improvements on social functioning and fatigue.

The health-related quality of life (HRQoL) among long-term Adolescent and Young Adult Cancer Survivors (AYACS) and an age- and sex-matched normative population was examined. Although the HRQoL of AYACS was worse compared to the normative population before and during the COVID-19 pandemic, the scores of AYACS improved over time in contrast to the normative population. Presumably, AYACS are used to adjusting their lives to stressful life events. Furthermore, the lockdown may have been beneficial for AYACS who face difficulties fully participating in society due to the impact of cancer. AYACS who encounter HRQoL issues could benefit from support interventions to empower them and build resilience.

Learning from long-term adolescent and young adult (AYA) cancer survivors regarding their age-specific care needs to improve current AYA care programs.

BACKGROUND: Despite growing (inter)national awareness and appreciation, age-specific care is still not always self-evident and accepted as standard of care for adolescent and young adult (AYA) cancer patients. It is unknown whether long-term AYA cancer survivors have missed age-specific care, and if so, which survivors missed it and regarding which topics. METHODS: The Netherlands Cancer Registry (NCR) identified all long-term AYA cancer survivors (aged 18-39 years at initial cancer diagnosis, 5-20 years past diagnosis) in the Netherlands, who were invited to participate in a population-based, observational, cross-sectional questionnaire study (SURVAYA study), including questions on care needs. RESULTS: In total, 3.989 AYAs participated (35.3% response rate). One-third of them had a need for age-specific care (33.5%), 41.2% had no need and 25.3% did not know whether they had a need. Those who had a need for age-specific care were significantly more often female, higher educated, diagnosed at a younger age, and treated with chemotherapy, radiotherapy or hormone therapy. Most frequent topics were disease and treatment (29.7%), emotions (24.1%), friends (22.6%), family and children (15.6%), fertility and pregnancy (14.8%), work and reintegration (10.5%), care not tailored (13.8%), and overarching care and life (27.7%). Palliative care (0.0%), spirituality (0.2%), death (0.7%), complementary care (0.7%), and late effects (1.3%) were mentioned least. CONCLUSIONS: A substantial proportion of long-term AYA cancer survivors showed a need for age-specific care, varying by sociodemographic and clinical factors, on a wide variety of topics, which could be targeted to improve current AYA care services.

The effect of progestin therapy in advanced and recurrent endometrial cancer: A systematic review and meta-analysis.

BACKGROUND: Fifteen percent of patients with endometrial cancer (EC) have advanced stage disease or develop a recurrence. Progestins have been applied as systemic treatment for decades, but there is limited evidence on response prediction with biomarkers and toxicity. OBJECTIVES: To review the response and toxicity of progestin therapy and stratify response to progesterone receptor (PR) expression and tumour grade. SEARCH STRATEGY: We used the search terms 'Endometrial cancer', 'Progestins', 'Disease progression', 'Recurrence' and related terms in Pubmed, Embase and Cochrane databases. SELECTION CRITERIA: Studies on patients with advanced stage or recurrent EC treated with progestin monotherapy were included. Studies on adjuvant therapy, with fewer than ten cases and with sarcoma histology were excluded. DATA COLLECTION AND ANALYSIS: Evaluation for bias was performed with the Revised Cochrane RoB2 tool for randomised studies and the ROBINS-I tool for non-randomised studies. A random effects meta-analysis was performed with the overall response rate (ORR), clinical benefit rate and toxicity as primary outcome measures. MAIN RESULTS: Twenty-six studies (1639 patients) were included. The ORR of progestin therapy was 30% (95% CI 25-36), the clinical benefit rate was 52% (95% CI 42-61). In PR-positive EC, the ORR was 55%, compared with 12% in PR-negative disease (risk difference 43%, 95% CI 15-71). Severe toxicity occurred in 6.5%. CONCLUSIONS: Progestin therapy is a viable treatment option in patients with advanced stage and recurrent EC with low toxicity and high ORR in PR-positive disease. The role of PR expression in relation to progression-free survival and overall survival is unclear.

"Finding my way in a maze while the clock is ticking": The daily life challenges of adolescents and young adults with an uncertain or poor cancer prognosis.

Introduction: Increasingly more adolescent and young adult (AYA, aged 18-39 years) patients with an uncertain and/or poor cancer prognosis (UPCP) are gaining life-years because of novel treatments or refinement of established therapies, and sometimes even face the prospect of long-term disease control. This study aims to examine the challenges of AYAs with a UPCP in daily life to inform the development of AYA care programs. Methods: Semi-structured in-depth interviews were conducted among AYAs with a UPCP. Since we expected differences in experiences between three AYA subgroups, we interviewed patients of these subgroups (1): traditional survivors (2), low-grade glioma survivors, and (3) new survivors. Interviews were analyzed using elements of grounded theory. AYA patients were actively involved as research partners. Results: In total 46 AYAs with UPCP participated and shared their challenges in daily life. They were on average 33.4 years old (age range 23-44) and most of them were women (63%). The most common tumor types were low-grade gliomas (16), sarcomas (7), breast cancers (6), and lung cancers (6). We identified five primary themes: (1) feeling inferior to previous self and others (e.g. feeling useless, who wants me in a relationship), (2) feeling of being alone (e.g. lonely thoughts, nobody really gets me), (3) ongoing confrontation (e.g. it is always there, own decline), (4) grief about life (e.g. grief about life I did not get, grief about old life), and (5) loss of control over the future (e.g. not able to make future plans, waiting for growth). Although all of the challenges were identified in the three AYA subgroups, the perceived intensity of the challenges differed slightly between the subgroups. Discussion: AYAs living with a UPCP experience challenges associated to their sense of altered identity, their position in the social network, and the future uncertainties. This study highlights the importance to recognize and acknowledge the unique challenges of this group. To provide age-specific care, it is important to embed acceptance and commitment therapy and AYA peer support within the healthcare system and other care programs to support AYAs to live well with their disease.

A Negative Body Image among Adolescent and Young Adult (AYA) Cancer Survivors: Results from the Population-Based SURVAYA Study.

Adolescent and young adult (AYA) cancer survivors (18-39 years at diagnosis) often experience negative body changes such as scars, amputation, and disfigurement. Understanding which factors influence body image among AYA survivors can improve age-specific care in the future. Therefore, we aim to examine the prevalence, and association of a negative body image with sociodemographic, clinical, and psychosocial factors, among AYA cancer survivors (5-20 years after diagnosis). A population-based cross-sectional cohort study was conducted among AYA survivors (5-20 years after diagnosis) registered within the Netherlands Cancer Registry (NCR) (SURVAYA-study). Body image was examined via the EORTC QLQ-C30 and QLQ-SURV100. Multivariable logistic regression models were used. Among 3735 AYA survivors who responded, 14.5% (range: 2.6-44.2%), experienced a negative body image. Specifically, AYAs who are female, have a higher Body Mass Index (BMI) or tumor stage, diagnosed with breast cancer, cancer of the female genitalia, or germ cell tumors, treated with chemotherapy, using more maladaptive coping strategies, feeling sexually unattractive, and having lower scores of health-related Quality of Life (HRQoL), were more likely to experience a negative body image. Raising awareness and integrating supportive care for those who experience a negative body image into standard AYA survivorship care is warranted. Future research could help to identify when and how this support for AYA survivors can be best utilized.

Recruiting Adolescent and Young Adult Cancer Survivors for Patient-Reported Outcome Research: Experiences and Sample Characteristics of the SURVAYA Study.

BACKGROUND: Participation of Adolescents and Young Adults with cancer (AYAs: 18-39 years at time of diagnosis) in patient-reported outcome studies is warranted given the limited knowledge of (long-term) physical and psychosocial health outcomes. We examined the representativeness of AYAs participating in the study, to observe the impact of various invitation methods on response rates and reasons for non-participation. METHODS: A population-based, cross-sectional cohort study was performed among long-term (5-20 years) AYA cancer survivors. All participants were invited using various methods to fill in a questionnaire on their health outcomes, including enclosing a paper version of the questionnaire, and sending a reminder. Those who did not respond received a postcard in which they were asked to provide a reason for non-participation. RESULTS: In total, 4.010 AYAs (response 36%) participated. Females, AYAs with a higher socio-economic status (SES), diagnosed more than 10 years ago, diagnosed with a central nervous system tumor, sarcoma, a lymphoid malignancy, stage III, or treated with systemic chemotherapy were more likely to participate. Including a paper questionnaire increased the response rate by 5% and sending a reminder by 13%. AYAs who did not participate were either not interested (47%) or did want to be reminded of their cancer (31%). CONCLUSIONS: Study participation was significantly lower among specific subgroups of AYA cancer survivors. Higher response rates were achieved when a paper questionnaire was included, and reminders were sent. To increase representativeness of future AYA study samples, recruitment strategies could focus on integrating patient-reported outcomes in clinical practice and involving AYA patients to promote participation in research.

Development and external validation of a prediction model for tube feeding dependency for at least four weeks during chemoradiotherapy for head and neck cancer.

BACKGROUND & AIMS: Patients who receive chemoradiotherapy or bioradiotherapy (CRT/BRT) for locally advanced head and neck squamous cell carcinoma (LAHNSCC) often experience high toxicity rates interfering with oral intake, causing tube feeding (TF) dependency. International guidelines recommend gastrostomy insertion when the expected use of TF exceeds 4 weeks. We aimed to develop and externally validate a prediction model to identify patients who need TF ≥ 4 weeks and would benefit from prophylactic gastrostomy insertion. METHODS: A retrospective multicenter cohort study was performed in four tertiary head and neck cancer centers in the Netherlands. The prediction model was developed using data from University Medical Center Utrecht and the Netherlands Cancer Institute and externally validated using data from Maastricht University Medical Center and Radboud University Medical Center. The primary endpoint was TF dependency ≥4 weeks initiated during CRT/BRT or within 30 days after CRT/BRT completion. Potential predictors were extracted from electronic health records and radiotherapy dose-volume parameters were calculated. RESULTS: The developmental and validation cohort included 409 and 334 patients respectively. Multivariable analysis showed predictive value for pretreatment weight change, texture modified diet at baseline, ECOG performance status, tumor site, N classification, mean radiation dose to the contralateral parotid gland and oral cavity. The area under the receiver operating characteristics curve for this model was 0.73 and after external validation 0.62. Positive and negative predictive value for a risk of 90% or higher for TF dependency ≥4 weeks were 81.8% and 42.3% respectively. CONCLUSIONS: We developed and externally validated a prediction model to estimate TF-dependency ≥4 weeks in LAHNSCC patients treated with CRT/BRT. This model can be used to guide personalized decision-making on prophylactic gastrostomy insertion in clinical practice.

Impact of hormonal biomarkers on response to hormonal therapy in advanced and recurrent endometrial cancer.

BACKGROUND: Approximately 20% of women with endometrial cancer have advanced-stage disease or suffer from a recurrence. For these women, prognosis is poor, and palliative treatment options include hormonal therapy and chemotherapy. Lack of predictive biomarkers and suboptimal use of existing markers for response to hormonal therapy have resulted in overall limited efficacy. OBJECTIVE: This study aimed to improve the efficacy of hormonal therapy by relating immunohistochemical expression of estrogen and progesterone receptors and estrogen receptor pathway activity scores to response to hormonal therapy. STUDY DESIGN: Patients with advanced or recurrent endometrial cancer and available biopsies taken before the start of hormonal therapy were identified in 16 centers within the European Network for Individualized Treatment in Endometrial Cancer and the Dutch Gynecologic Oncology Group. Tumor tissue was analyzed for estrogen and progesterone receptor expressions and estrogen receptor pathway activity using a quantitative polymerase chain reaction-based messenger RNA model to measure the activity of estrogen receptor-related target genes in tumor RNA. The primary endpoint was response rate defined as complete and partial response using the Response Evaluation Criteria in Solid Tumors. The secondary endpoints were clinical benefit rate and progression-free survival. RESULTS: Pretreatment biopsies with sufficient endometrial cancer tissue and complete response evaluation were available in 81 of 105 eligible cases. Here, 22 of 81 patients (27.2%) with a response had estrogen and progesterone receptor expressions of >50%, resulting in a response rate of 32.3% (95% confidence interval, 20.9-43.7) for an estrogen receptor expression of >50% and 50.0% (95% confidence interval, 35.2-64.8) for a progesterone receptor expression of >50%. Clinical benefit rate was 56.9% for an estrogen receptor expression of >50% (95% confidence interval, 44.9-68.9) and 75.0% (95% confidence interval, 62.2-87.8) for a progesterone receptor expression of >50%. The application of the estrogen receptor pathway test to cases with a progesterone receptor expression of >50% resulted in a response rate of 57.6% (95% confidence interval, 42.1-73.1). After 2 years of follow-up, 34.3% of cases (95% confidence interval, 20-48) with a progesterone receptor expression of >50% and 35.8% of cases (95% confidence interval, 20-52) with an estrogen receptor pathway activity score of >15 had not progressed. CONCLUSION: The prediction of response to hormonal treatment in endometrial cancer improves substantially with a 50% cutoff level for progesterone receptor immunohistochemical expression and by applying a sequential test algorithm using progesterone receptor immunohistochemical expression and estrogen receptor pathway activity scores. However, results need to be validated in the prospective Prediction of Response to Hormonal Therapy in Advanced and Recurrent Endometrial Cancer (PROMOTE) study.

Trends over time in the incidence and use of hormonal therapy in endometrial cancer: a population-based study in the Netherlands.

INTRODUCTION: According to current guidelines, hormonal therapy may be applied in endometrioid type endometrial cancer as an alternative to surgery for fertility preservation and in medically unfit patients. Since it is unknown how often hormonal therapy is applied, the objective of this study was to investigate trends over time in hormonal therapy use in the background of the overall incidence of endometrial cancer. METHODS: All patients with endometrial cancer (n=48 222) registered in the Netherlands Cancer Registry in the period 1989-2018 were included. European age-standardized incidence rates with corresponding estimated annual percentage change were calculated to describe trends in the incidence of endometrial cancer. The use of hormonal therapy was analyzed in the three periods 1989-1998, 1999-2008, and 2009-2018 for the following sub-groups: primary and adjuvant therapy, International Federation of Gynecology and Oncology (FIGO) stage I-II and III-IV, and by age group. RESULTS: The European age-standardized incidence rate of endometrioid endometrial cancer peaked in 2004 with a significant increase from 1989 to 2004 (annual percentage change 0.55; 95% CI 0.10 to 0.99, p=0.020) and a subsequent decrease from 2005 to 2018 (annual percentage change -1.79; 95% CI -2.28 to -1.31, p<0.001). The incidence rate of non-endometrioid type endometrial cancer increased significantly in the study period. Hormonal therapy was used in 1482 (3.5%) patients with endometrioid endometrial cancer. Among patients with FIGO stage I aged ≤40 years, hormonal therapy increased from 0% in 1989-1998 to 27% in 2009-2018. Primary hormonal treatment increased from 175 patients (5.5%) to 329 patients (7.8%) in those aged ≥75 years. Adjuvant hormonal treatment was mostly used in advanced stage endometrial cancer. CONCLUSIONS: The use of primary hormonal therapy in endometrioid type endometrial cancer increased over time in patients aged ≤40 years and among elderly patients. The observed trends in the current use of hormonal therapy support the need to study the effect of hormonal treatment in elderly patients and as adjuvant treatment in advanced stage endometrial cancer.

The Successful Return-To-Work Questionnaire for Cancer Survivors (I-RTW_CS): Development, Validity and Reproducibility.

BACKGROUND: Cancer survivors' perspectives on a successful return to work (RTW) may not be captured in the common measure of RTW, namely time until RTW. OBJECTIVE: The purpose of this study was therefore to develop an RTW outcome measure that reflects employed cancer survivors' perspectives, with items that could be influenced by an employer, i.e. the Successful Return-To-Work questionnaire for Cancer Survivors (I-RTW_CS), and to assess its construct validity and reproducibility. METHODS: First, three focus groups with cancer survivors (n = 14) were organized to generate issues that may constitute successful RTW. Second, a two-round Delphi study among 108 cancer survivors was conducted to select the most important issues. Construct validity of the I-RTW_CS was assessed using correlations with a single-item measure of successful RTW and the Quality of Working Life Questionnaire for Cancer Survivors (QWLQ-CS; n = 57). Reproducibility (test-retest reliability) was assessed using the intraclass correlation coefficient (ICC; n = 50). RESULTS: Forty-eight issues were generated, of which seven were included: 'enjoyment in work'; 'work without affecting health'; 'confidence of employer without assumptions about work ability'; 'open communication with employer'; 'feeling welcome at work'; 'good work-life balance'; and 'joint satisfaction with the situation (employer and cancer survivor)'. Correlations with single-item successful RTW and QWLQ-CS were 0.58 and 0.85, respectively. The reproducibility showed an ICC of 0.72. CONCLUSIONS: The I-RTW_CS provides an RTW outcome measure that includes cancer survivors' perspectives and weights its items on an individual basis, allowing a more meaningful evaluation of cancer survivors' RTW. This study provides preliminary evidence for its construct validity and reproducibility.