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There is a lack of information on mental health outcomes for the increasing older population. Therefore, the aim of the current study is to assess depressive symptoms, loneliness, and apathy in older patients with breast cancer within the first 5 years after diagnosis. Women aged ≥70 years with early-stage breast cancer were included. Multivariate linear mixed models were used to assess longitudinal changes in symptoms of depression (according to the 15-item Geriatric Depression Scale), loneliness (according to the De Jong Gierveld Loneliness Scale) and apathy (according to the Starkstein Apathy Scale) over time at 3, 9, 15, 27 and 60 months follow-up. In total, 299 patients were included (mean [standard deviation (SD)] age: 75.8 [5.2] years). At 3 months follow-up, shortly after the acute treatment, 10% of patients had significant depressive symptoms, while loneliness and apathy were present in 31% and 41% of all patients, respectively. Depression, loneliness and apathy scores showed no clinically relevant changes over time in the whole cohort. Patients who received adjuvant systemic therapies (i.e. endocrine therapy and/or chemotherapy and/or targeted therapy (trastuzumab)) had similar mental health outcomes as those who did not. However, frail patients had more symptoms (p < 0.001) and were more prone to develop depressive symptoms over time than non-frail patients (p = 0.002). Depression, loneliness and apathy were frequently observed in older women with breast cancer and did not change over time. Patients who received adjuvant systemic therapies had similar mental health outcomes as those who did not. However, frail patients were at higher risk to experience these symptoms. • Depression, loneliness and apathy are common in older women with breast cancer. • Adjuvant systemic therapies were not associated with worse mental health outcomes. • Frailty exacerbates depressive symptoms, loneliness and apathy. [ABSTRACT FROM AUTHOR]

Lung cancer is the leading cause of cancer-related deaths in Europe. Europe's Beating Cancer Plan calls for a comprehensive approach to the disease in general but not specifically to lung cancer. Such a comprehensive approach, integrating efforts to strengthen anti-tobacco policies, early detection and underlying models of care, is sorely needed for lung cancer – particularly considering disruptions to care during the COVID-19 pandemic. In a recently published think piece, a multidisciplinary group of experts proposed four key policy priority areas. First, to reduce stigma and improve awareness of potential symptoms, there is a need to foster a better understanding of lung cancer – among the public and healthcare professionals. Second, opportunities for early detection should be enhanced, and the implementation of targeted screening through low-dose computed tomography should be encouraged as a complement to smoking cessation services. This complementarity should be recognised and built into joint policy proposals, with development and better integration of screening and smoking cessation programmes on the ground. Third, the socioeconomic inequalities underpinning disparities in outcomes in people with lung cancer must be addressed, with targeted approaches to overcome barriers to access Finally, the overall quality of lung cancer care must be improved, making multidisciplinary care available to all and ensuring survivorship is given due attention. [Display omitted] • Stigma remains a key issue for people with lung cancer, and needs urgent attention. • Targeted screening through low-dose computed tomography must be implemented. • Socioeconomic inequalities underpinning disparities in outcomes need to be tackled. • Multidisciplinary care should be available to all. [ABSTRACT FROM AUTHOR]

We aimed to develop a European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QoL) module tailored for patients with advanced (resectable or unresectable stage III/IV) melanoma receiving immune checkpoint inhibitors or targeted therapy. Following the EORTC QoL Group module development guidelines, we conducted phases 1 and 2 of the development process. In phase 1, we generated a list of health-related (HR)QoL issues through a systematic literature review and semi-structured interviews with healthcare professionals (HCPs) and patients with advanced melanoma. In phase 2, these issues were converted into questionnaire items to create the preliminary module. Phase 1: we retrieved 8006 articles for the literature review, of which 35 were deemed relevant, resulting in 84 HRQoL issues being extracted to create the initial issue list. Semi-structured interviews with 18 HCPs and 28 patients with advanced melanoma resulted in 28 issues being added to the initial issue list. Following EORTC module development criteria, 26 issues were removed, and two issues were added after review by patient advocates. Phase 2: To ensure uniformity and avoid duplication, 16 issues were consolidated into eight items. Additionally, an independent expert contributed one new item, resulting in a preliminary module comprising 80 HRQoL items. We identified a range of HRQoL issues (dry skin, xerostomia, and arthralgia) relevant to patients with stage III/IV melanoma. Future module development phases will refine the questionnaire. Once completed, this module will enable standardized assessment of HRQoL in patients with (locally) advanced melanoma. • We aimed to create a HRQoL module tailored for patients with advanced melanoma. • We identified the most important symptomatic HRQoL issues associated with ICI and TT. • Our study highlights the benefit of using a disease-specific instrument to measure HRQoL. [ABSTRACT FROM AUTHOR]

Different drug modification rules or growth factor support guidance may affect the results in oncology randomised controlled trials. We aimed to estimate the prevalence of unequal rules for dose modification rules or the use of myeloid growth factors in head-to-head registration Food and Drug Administration trials. This cross-sectional analysis included all head-to-head registration randomised controlled trials leading to a US Food and Drug Administration approval between 2009 and 2021. Trials examined anti-cancer drugs in the advanced or metastatic setting where a comparison could be made between arms regarding either dose modification rules or myeloid growth factors recommendations. Sixty-two registration trials met inclusion criteria. Information abstracted for each trial included tumour type, setting, phase, and type of sponsor. We assessed, according to pre-specified rules, imbalance in drug modification rules, myeloid growth factors recommendations or both. We find 40 of 62 (65%) selected trials have unequal rules for dose medication, granulocyte colony-stimulating factor (G-CSF) use or both. Six trials (10%) had rules favouring the control arm, while 55% of selected trials (34/62) favoured the experimental arm. Among these, 50% (17/34) had unequal drug modification rules, 41% (14/34) had unequal G-CSF rules and 9% contained both (3/34). We find that 55% of trials testing anti-cancer drugs against each other used protocol rules that favoured the experimental arm. This leaves open the question of whether new molecules are truly superior to older molecules or if instead different outcomes are due to more aggressive dosing or growth factor support. Trials should utilise equal rules for dose medication and G-CSF support. • Drug modification rules or growth factor use may affect results in oncology trials. • 65% of selected head-to-head registration trials (n = 62) had unequal protocol rules. • Most of them (55% of selected trials) favoured the experimental arm. • Randomised trials should utilise equal rules for dose medication and G-CSF support. [ABSTRACT FROM AUTHOR]

This study aims to assess the quality of life and quality of care as experienced by patients with advanced cancer and their relatives while taking their interdependency into account. A prospective multicentre observational study (eQuiPe study) was conducted. Quality of life scores (EORTC QLQ-C30) was compared to a matched normative population and logistic regression analyses were conducted to assess the relation between high emotional functioning (EF, measured with the EORTC QLQ-C30) and experienced quality of care (IN-PATSAT32, CQ-index PC). In total, 1103 (65%) patients and 831 (71%) relatives completed the baseline questionnaire, including 699 unique patient-relative couples. Patients experienced lower EF than the normative population (78 versus 87, p <.001). Compared to patients, relatives reported clinically relevantly lower EF (69 versus 78, p <.001). Being more satisfied with care in general (p <.05) and clarity about the key health-care provider (p <.05) was positively associated with high EF in patients. For relatives, experienced continuity of care (p <.01) and information for the patient (p <.05) were positively associated with high EF. The EF of patients (p <.001) and relatives (p <.001) were positively associated with each other and continuity of care as perceived by relatives was positively associated with high EF in patients (p <.01). Patients with advanced cancer reported low levels of EF but their relatives reported even lower levels of EF. Experienced integrated organisation and satisfaction with care were positively related to EF. The interdependent relation between patients' and relatives' EF and their care experiences suggests that a family-centred approach can optimise palliative cancer care. The eQuiPe study is registered as NTR6584 in the Netherlands Trial Register. • The quality of life of patients with advanced cancer was lower than the normative population. • The relatives' emotional functioning (EF) was lower than patients. • EF was associated with quality of care as experienced by patients and relatives. • EF and care experiences of patients and relatives were interdependent. [ABSTRACT FROM AUTHOR]

Cancer of unknown primary (CUP) is a heterogeneous entity with limited overall survival (OS) in most patients. Prognostic biomarkers are needed, particularly for treatment stratification. We investigated the impact of programmed death-ligand 1 (PD-L1) expression as prognostic marker in immunotherapy-naïve CUP patients. Clinical data from patients with confirmed CUP diagnosis according to ESMO guidelines, treated at the West German Cancer Center, Essen from 2015 to 2021, were analyzed. Patients treated with checkpoint inhibitors were excluded. PD-L1 expression was assessed in tumor tissues following established guidelines. Of a cohort of 132 patients, 62 patients, including 30 patients with prognostically unfavorable CUP, met inclusion criteria and were evaluable for PD-L1 expression. Comparing PD-L1 Tumor Proportional Score (TPS) and Combined Positive Score (CPS) revealed almost complete concordance (96.2 %). Patients with PD-L1-positive CUP (TPS ≥1 %; n = 36; 58 %) had superior overall survival (median not reached) as compared to patients with PD-L1-negative CUP (median 14 months, 95 %CI 10.0–18.0; HR 0.3, p < 0.001). The benefit of PD-L1 positivity (n = 12; 40 %) was maintained in the unfavorable CUP subgroup (median 20 months, 95 %CI 3.0–37.0 versus 10 months, 95 %CI 3.1–16.9; HR 0.4, p = 0.032). In PD-L1-positive CUP there was a positive correlation between the level of PD-L1 expression and survival (TPS ≥50 %: median survival not reached, HR 0.1; TPS 1 to 49 %: OS: 77 months, HR 0.4). PD-L1 expression associates with favorable survival in checkpoint inhibitor-naïve CUP patients. This implies a role of cancer immunity in CUP biology and may nominate PD-L1 for patient stratification in further studies and clinical care. [Display omitted] • Favorable OS in checkpoint inhibitor-naïve CUP patients with PD-L1 expression. • In patients with CUP the level of PD-L1 expression correlates with survival. • PD-L1 expression could be used as a biomarker for prognosis in CUP patients. [ABSTRACT FROM AUTHOR]

Although the incidence of BTC is raising, national healthcare strategies to improve care lack. We aimed to explore patient clinical care pathways and strategies to improve biliary tract cancer (BTC) care. We analysed the French National Healthcare database of all BTC inpatients between January 1, 2017 and December 31, 2021. Multinomial logistic regression adjusted odds ratios (aOR) were used to identify healthcare organisation factors that influenced access to curative care both overall and in a longitudinal sensibility analysis using optimal matching and hierarchical ascending classification to detect a subgroup of curative-care patients with a high survival over a two-year period. A total of 19,825 new BTC patients and three clinical care pathways (CCP) were identified: 'Palliative care' (PC-CCP), 'Non-curative Care' (NCC-CCP) and 'Curative Care' (CC-CCP) involving 7669 (38.7%), 7721 (38.9%) and 4435 (22.4%) patients respectively. Out of 1200 centers involved in BTC treatment, 84%, 11% and 5% were of low- (<15 patients/year), medium- (15–30 patients/year) and high-volume (>30 patients/year) respectively. Among patient, tumor and hospital factors, BTC management in academic (aOR: 2.32; 95%CI: 1.98–2.71), private (2.51; 2.22–2.83), semi-private (2.25; 1.91–2.65) and in high- (2.09; 1.81–2.42) or medium-volume (1.49; 1.33–1.68) centers increased probability to CC-CCP. These results were maintained in a longitudinal cluster of 2363 (53%) CC-CCP patients presenting a higher two-year survival compared with the rest [96.4% (95.1; 97.6) vs. 38.8% (36.3; 41.4), log-rank p < 0.001]. Among factors subject to healthcare policy improvement, the volume and type of centers managing BTC strongly influenced access to curative care. • Biliary tract cancer management presents a high hospital dispersal in France. • Curative care only concerned 22.4% of patients with biliary tract cancer in France. • Among patients undergoing curative care only half presented a high 2-year survival. • Management in academic or high-volume centres maximizes the probability of 'cure'. [ABSTRACT FROM AUTHOR]

The aim of this nationwide cohort study was to examine the course of symptoms and trajectories of health-related quality of life (HR-QoL) and psychological distress during follow-up and to identify vulnerable patients. Patients with pathological stage I–III colorectal cancer (CRC) between 2013 and 2018 were included. Baseline characteristics were collected from the Netherlands Cancer Registry, and patients completed the European Organisation for Research and Treatment of Cancer QLQ-C30/CR29, Hospital Anxiety and Depression Scale and low anterior resection syndrome (LARS) questionnaires at the baseline and subsequently at 3, 6, 12, 18 and 24 months. Latent class growth and multinomial logistic regression analyses were performed to outline 24-month trajectories in HR-QoL and distress and to identify predictive factors. : A total of 1535 patients with colon cancer or rectal cancer were included. Trajectory analysis of HR-QoL identified three patient classes: high HR-QoL (62.7%), improving HR-QoL (29.0%) and low HR-QoL (8.3%). The following patient groups were identified with having low distress (64.0%), moderate distress (26.9%) and high distress (9.1%). Around 13% of the total cohort had either persistent low HR-QoL or high psychological distress throughout follow-up. Patients belonging to this vulnerable group were significantly more likely to be female, to be younger aged, to have lower education, to have disease stage II–III or to have major LARS. Although most patients treated for stage I–III CRC fared well, a small but significant proportion of around 13% did not recover during follow-up and reported low HR-QoL and/or high psychological distress levels throughout. This study's findings should be taken into account when organising and selecting patients for tailored follow-up. • The number of patients with colorectal cancer (CRC) requiring follow-up increased. • Quality of life (QoL) and distress among recently diagnosed patients with CRC are unclear. • Most patients with stage I–III CRC did well and reported high QoL and low distress. • Trajectory analysis revealed vulnerable patient groups and identified predictive factors. • Patient-reported outcome measures should be used when personalising CRC follow-up. [ABSTRACT FROM AUTHOR]

Patients with cancer are presumed a frail group at high risk of contracting coronavirus disease (COVID-19), and vaccination represents a cornerstone in addressing the COVID-19 pandemic. However, data on COVID-19 vaccination in cancer patients are fragmentary and poor. An observational study was conducted to evaluate the seropositivity rate and safety of a two-dose regimen of the BNT162b2 or messenger RNA-1273 vaccine in adult patients with solid cancer undergoing active anticancer treatment or whose treatment had been terminated within 6 months of the start of the study. The control group was composed of healthy volunteers. Serum samples were evaluated for SARS-COV-2 antibodies before vaccinations and 2–6 weeks after the administration of the second vaccine dose. Primary end-point: seropositivity rate. Secondary end-points: safety, factors influencing seroconversion, IgG titers of patients versus healthy volunteers, COVID-19 infection. Between 20th March 2021 and 12th June 2021, 293 consecutive patients with cancer-solid tumours underwent a program of COVID-19 vaccinations; of these, 2 patients refused vaccination, 13 patients did not receive the second dose of the vaccine because of cancer progression, and 21 patients had COVID-19 antibodies at baseline and were excluded. The 257 evaluable patients had a median age of 65 years (range 28–86), 66.15% with metastatic disease. Primary end-point: seropositivity rate in patients was 75.88% versus 100% in the control group. Secondary end-points: no Grade 3–4 side-effects, no COVID-19 infections were reported. Patients median IgG titer was significantly lower than in the control group; male sex and active anticancer therapy influenced negative seroconversion. BNT162b2 or messenger RNA-1273 vaccines were immunogenic in cancer patients, showing good safety profile. • Patients with cancer are at great risk of serious complications and death from coronavirus disease (COVID-19). • 257 patients with cancer vaccinated against COVID-19, 75.88% showed seroconversion. • 219 of the 257 patients (85.21%) were on active anticancer treatment. • No Grade 3–4 side-effects were reported. • Male sex and active anticancer treatment negatively influence serologic response. [ABSTRACT FROM AUTHOR]

Previous reports highlight the greater number of side effects that women experience during cancer treatment, but little is known about sex differences in symptoms and functioning in long-term survivors. We investigated sex differences in the prevalence of physical (EORTC QLQ-C30) and emotional symptoms (Hospital Anxiety and Depression Scale) and loss of functioning (EORTC QLQ-C30) in 5339 cancer survivors (55% males). General linear models were computed to assess the differences in symptoms and functioning between female and male cancer survivors and between survivors and an age-matched reference population. The direct comparison between female and male cancer survivors identified more symptoms, such as nausea and vomiting (M = 5.0 versus. 3.2), insomnia (M = 26.1 versus. 15.9), anxiety (M = 5.2 versus. 4.2), and lower physical (M = 77.5 versus. 82.5) and emotional functioning (M = 83.4 versus. 86.3), in female survivors. However, comparison with an age-matched reference population demonstrated that several symptoms, such as fatigue, dyspnea, anxiety and depression, appeared to be more frequent in male patients. The investigation of functioning domains — compared with a reference population — highlighted further sex-specific differences. Female survivors experienced a moderate net loss in physical and cognitive functioning (−6.1 [95% CI = −8.1; −4,1] and −5.2 respectively [95% CI = −7; −3.5]), whereas male survivors displayed a significant net loss in role and social functioning compared to the reference population (−9.9 [95% CI = −11.2; −8.6] and −7.7 [95% CI = −9.6; −7.6] respectively). To adequately capture sex differences in symptoms and functioning in long-term cancer survivors, a comparison with a reference population should always be considered. In our study population, this adjustment highlighted a significant and unexpected long-term impact on male patients. Role and social functioning were especially impacted in male patients, emphasizing the need to further investigate these gendered domains. • Long-term cancer survivors report sex-specific symptoms and functional impairments. • Comparison with age-and sex-matched reference group showed more impairment in males. • Loss of role and social functioning in males could represent a loss of gender role. [ABSTRACT FROM AUTHOR]

Many haematology/oncology departments still provide a germ-free diet for neutropenic patients (neutropenic diet, ND) to minimise pathogen exposure, even though evidence on benefits is missing. We analysed the effects of a standard diet (SD) in neutropenic high-risk patients with cancer while focussing on infection-related outcomes. Based on the Cologne Cohort of Neutropenic Patients, we conducted a propensity score–matched case-control study in haematological/oncological patients with a period of neutropenia longer than five days treated at our department between January 2004 and December 2012 (implementation of SD in January 2008). We assessed the association between an SD and selected infection-related end-points in an adjusted multivariable regression model and time-to-event analysis. In total, 2086 neutropenic episodes (1043 per diet group) were included into analysis. The median days of neutropenia were 9 (interquartile range 7–16). The adjusted multivariable model revealed no association between the SD and severity and persistence of fever, death within 28 days, antibiotic treatment and weight loss >3 kg and a non-significant adjusted association between SD and duration of antibiotic treatment and blood stream infections. There was a significant association between SD and incidence of diarrhoea (odds ratio [OR], 0.55; 95% confidence interval [CI], 0.45–0.68; P < 0.001), nausea (OR, 0.53; 95% CI, 0.43–0.66; P < 0.001) and weight loss >1 kg (OR, 0.93; 95% CI, 0.89–0.98; P = 0.002) with fewer events in SD than in the ND group. The hazard ratios of SD for the analysed end-points were non-significant. In our study, the implementation of an SD for high-risk neutropenic patients with cancer was safe regarding infection-related end-points. • The benefits of a germ-free diet for neutropenic patients with cancer are scarce. • Food restrictions may increase malnutrition and gastrointestinal side-effects. • Standard diets do not increase infectious complications in neutropenic patients. • Incidence of diarrhoea and nausea can be reduced by standard diets. • Implementation of standard diets for neutropenic patients with cancer is safe. [ABSTRACT FROM AUTHOR]

The REGOMA trial showed that regorafenib significantly improved overall survival in patients with recurrent glioblastoma compared with lomustine. Patients treated with regorafenib experienced a higher occurrence of grade 3–4 drug-related adverse events than those receiving the standard treatment. Because this safety profile was expected, it was considered of great importance to assess the patient point of view regarding the disease and treatment impact on different aspects of life and patient well-being. We here report the final results of the health-related quality of life (HRQoL) assessment, a secondary end-point of the study. This trial is registered with ClinicalTrials.gov , NCT02926222. Patient-reported outcomes were assessed, within a prospective, randomised, multicentre, open-label phase II trial, by the European Organisation for Research and Treatment of Cancer core questionnaire and brain module at baseline and every 8-weekly neuroradiological assessment till disease progression. Mixed-effect linear models were fitted for each of the HRQoL domain to examine the change over progression-free time within and between arms. Furthermore, differences were also classified as clinically meaningful changes. To correct for multiple comparisons and avoid type I errors, the level of significance was set at P = 0.01 (2-sided). Of 119 enrolled patients, 56/59 (95%) patients and 58/60 (97%) patients treated with regorafenib and lomustime completed questionnaires at baseline, respectively. No significant differences were observed in any generic or cancer-specific domain during treatment in both arms, or between the two arms, except for the appetite loss and diarrhoea scales which were significantly worse in patients treated with regorafenib. The rate of patients with a clinically meaningful worsening for appetite loss, diarrhoea and for any other domain was not statistically different between the two arms. Regorafenib did not negatively affect HRQoL in patients with recurrent glioblastoma. These data combined with the survival benefit shown in the REGOMA trial support the use of regorafenib as a treatment option for these patients. • Regorafenib improved survival of patients with recurrent glioblastoma. • Adverse events associated with regorafenib did not deteriorate health-related quality of life. • No significant differences were observed in any domain between arms. • Regorafenib could represent a treatment option in this setting of disease. [ABSTRACT FROM AUTHOR]

To determine the prevalence of sexual dysfunction and to identify the factors associated with sexual dysfunction in young adult childhood cancer survivors. All survivors of childhood cancer (aged 19–40 years) in Sweden were invited to this population-based study, and 2546 men and women (59%) participated. Sexual function was examined with the PROMIS Sexual Function and Satisfaction Measure. Logistic regression was used to assess the differences between survivors and a general population sample (n = 819) and to identify the factors associated with sexual dysfunction in survivors. Sexual dysfunction in at least one domain was reported by 57% of female and 35% of male survivors. Among females, dysfunction was most common for Sexual interest (36%), Orgasm – ability (32%) and Vulvar discomfort – labial (19%). Among males, dysfunction was most common for the domains satisfaction with sex life (20%), Sexual interest (14%) and Erectile function (9%). Compared with the general population, male survivors more frequently reported sexual dysfunction in ≥2 domains (OR = 1.67, 95% CI: 1.03–2.71), with an increased likelihood of dysfunction regarding Orgasm – ability (OR = 1.82; 95% CI: 1.01–3.28) and Erectile function (OR = 2.30; 95% CI: 1.18–4.49). Female survivors reported more dysfunction regarding Orgasm – pleasure (9% versus 5%, OR = 1.86; 95% CI: 1.11–3.13). A more intensive cancer treatment, emotional distress and body image disturbance were associated with sexual dysfunction in survivors. The findings underscore the need for routine assessment of sexual health in follow-up care of childhood cancer survivors and highlight that those treated with more intensive cancer treatment and who experience concurrent psychological concerns may benefit from targeted screening and interventions. • Substantial proportions of childhood cancer survivors report sexual dysfunction. • Male survivors report more sexual problems than men in the general population. • Intensive treatment and psychological concerns are associated with dysfunction. • Follow-up care recommended to include assessment of sexual health. [ABSTRACT FROM AUTHOR]

The European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Group developed a questionnaire to assess sexual health in patients with cancer and cancer survivors. This study evaluates the psychometric properties of the questionnaire. The 22-item EORTC sexual health questionnaire (EORTC QLQ-SH22) was administered with the EORTC QLQ-C30 to 444 patients with cancer. The hypothesised scale structure, reliability and validity were evaluated through standardised psychometric procedures. The cross-cultural field study showed that the majority of patients (94.7%) were able to complete the QLQ-SH22 in less than 20 min; 89% of the study participants did not need any help to fill in the questionnaire. Multi-item multi-trait scaling analysis confirmed the hypothesised scale structure with two multi-item scales (sexual satisfaction, sexual pain) and 11 single items (including five conditional items and four gender-specific items). The internal consistency yielded acceptable Cronbach's alpha coefficients (.90 for the sexual satisfaction scale,.80 for the sexual pain scale). The test-retest correlations (Pearson's r) ranged from.70 to.93 except for the scale communication with professionals (.67) and male body image (.69). The QLQ-SH22 discriminates well between subgroups of patients differing in terms of their performance and treatment status. The study supports the reliability, the content and construct validity of the QLQ-SH22. The newly developed questionnaire is clinically applicable to assess sexual health of patients with cancer at different treatment stages and during survivorship for clinical trials and for clinical practice. • The validation study confirmed the psychometric properties of the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire–Sexual Health (QLQ-SH22). • The instrument is clinically applicable and valid. • The QLQ-SH22 can be used in clinical practice as well as in survivorship research. • The tool is available in 10 languages and can be obtained via the EORTC website. [ABSTRACT FROM AUTHOR]

BRAF and MEK inhibitors combination, including dabrafenib (D) and trametinib (T) have transformed the treatment of BRAF V600 -mutant advanced melanoma patients, including patients with brain metastasis (BM). In a large phase IIIb, single-arm, open-label, multicenter French study, we assessed safety, response to treatment, progression-free survival (PFS) and factors associated with progression, and stratified the population into risk groups. Patients with unresectable, advanced, BRAF V600 -mutant melanoma were included, including those with the presence of BM, Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≤2, elevated lactate dehydrogenase (LDH) or previous melanoma treatments. Responses were determined locally, without central review. PFS was estimated using the Kaplan–Meier analysis and modelled with multivariate Cox model. Risk subgroups were identified using a regression tree analysis. Between March 2015 and November 2016, 856 patients received at least one D + T dose. Overall, 92% had stage IV melanoma, 38% ECOG PS ≥1, 32% BM and 37.5% elevated LDH. Median PFS was 8.02 months (95% confidence interval [CI] 7.33–8.77). Significant factors associated with lower PFS were ECOG PS ≥1, elevated LDH, ≥3 metastatic sites and presence of BM. Patients with <3 metastatic sites, ECOG = 0 and no BM had the highest probability of PFS at 6 months (83%, 95% CI 76–87) and 12 months (56%, 95% CI 47–64), respectively. This is the largest prospective study in advanced BRAF V600 -mutant melanoma patients treated with D + T, conducted in conditions close to 'real-world practice'. We confirm previous findings that LDH, ECOG PS and ≥3 metastatic sites are associated with shorter PFS, but the real-world setting introduces BM as a major prognostic factor. • This is the largest close to real-word study on BRAF V600-mutant melanoma patients. • The study included the largest population of melanoma patients with brain metastases. • The results confirm the clinical activity of trametinib associated to dabrafenib. • LDH, ECOG, number of metastatic sites and presence of brain metastases associated with PFS. [ABSTRACT FROM AUTHOR]

Metastatic breast cancer refractory to anthracycline and taxanes often shows rapid progression. The development of effective and tolerable combination regimens for these patients is needed. This phase II trial investigated the efficacy of pemetrexed plus vinorelbine in patients with metastatic breast cancer. This randomized, open-label, phase II trial was conducted in 17 centers in Korea. Patients with advanced breast cancer who had previously been treated with anthracyclines and taxanes were randomly assigned in a 1:1 ratio to receive either vinorelbine or pemetrexed plus vinorelbine. Randomization was stratified by prior capecitabine treatment and hormone receptor status. The primary endpoint was investigator-assessed progression-free survival (PFS). Secondary endpoints included the objective response rate, overall survival, safety, and quality of life. Between March 2017 and August 2019, a total of 125 patients were enrolled. After a median follow-up duration of 14.1 months, 118 progression events and 88 death events had occurred. Sixty-two patients were assigned to the pemetrexed plus vinorelbine arm, and 63 were assigned to the vinorelbine arm. Pemetrexed plus vinorelbine significantly prolonged PFS compared to vinorelbine (5.7 vs. 1.5 months, p < 0.001). The combination arm had higher disease control rate (76.8% vs. 45.9%, p = 0.001) and a tendency toward longer overall survival (16.8 vs. 10.5 months, p = 0.102). Anemia was more frequent in the pemetrexed plus vinorelbine arm per cycle compared with vinorelbine (7.9% vs. 1.9%, p < 0.001), but there was no difference in the incidence of grade 3–4 neutropenia per cycle between the pemetrexed plus vinorelbine arm and the vinorelbine single arm (14.7% vs. 19.5%, p = 0.066). This phase II study showed that pemetrexed plus vinorelbine led to a longer PFS than vinorelbine. Adverse events of pemetrexed plus vinorelbine were generally manageable. • This phase II trial revealed the efficacy and safety of pemetrexed plus vinorelbine. • Pemetrexed plus vinorelbine prolonged progression free survival. • Pemetrexed plus vinorelbine was associated with higher disease control rate. • Pemetrexed plus vinorelbine had a tendency of longer overall survival. • Toxicity of pemetrexed plus vinorelbine was generally manageable. [ABSTRACT FROM AUTHOR]

Age-related breast cancer treatment variance is widespread with many older women having primary endocrine therapy (PET), which may contribute to inferior survival and local control. This propensity-matched study determined if a subgroup of older women may safely be offered PET. Multicentre, prospective, UK, observational cohort study with propensity-matched analysis to determine optimal allocation of surgery plus ET (S+ET) or PET in women aged ≥70 with breast cancer. Data on fitness, frailty, cancer stage, grade, biotype, treatment and quality of life were collected. Propensity-matching (based on age, health status and cancer stage) adjusted for allocation bias when comparing S+ET with PET. A total of 3416 women (median age 77, range 69–102) were recruited from 56 breast units—2854 (88%) had ER+ breast cancer: 2354 had S+ET and 500 PET. Median follow-up was 52 months. Patients treated with PET were older and frailer than patients treated with S+ET. Unmatched overall survival was inferior in the PET group (hazard ratio, (HR) 0.27, 95% confidence interval (CI) 0.23–0.33, P < 0.001). Unmatched breast cancer–specific survival (BCSS) was also inferior in patients treated with PET (HR: 0.41, CI: 0.29–0.58, P < 0.001 for BCSS). In the matched analysis, PET was still associated with an inferior overall survival (HR = 0.72, 95% CI: 0.53–0.98, P = 0.04) but not BCSS (HR = 0.74, 95% CI: 0.40–1.37, P = 0.34) although at 4–5 years subtle divergence of the curves commenced in favor of surgery. Global health status diverged at certain time points between groups but over 24 months was similar when adjusted for baseline variance. For the majority of older women with early ER+ breast cancer, surgery is oncologically superior to PET. In less fit, older women, with characteristics similar to the matched cohort of this study (median age 81 with higher comorbidity and functional impairment burdens, the BCSS survival differential disappears at least out to 4–5 year follow-up, suggesting that for those with less than 5-year predicted life-expectancy (>90 years or >85 with comorbidities or frailty) individualised decision making regarding PET versus S+ET may be appropriate and safe to offer. The Age Gap online decision tool may support this decision-making process (https://agegap.shef.ac.uk/). ISRCTN: 46099296. • Propensity matched study of women >70 with breast cancer comparing surgery or PET • Unmatched analysis found surgery improves overall & disease-specific survival. • Matched analysis (stage, age, health, frailty) found similar disease-specific survival • Surgery led to adverse events in 19% & negative impacts on QoL and physical function • Less fit women >85 may be offered PET to reduce morbidity, without survival detriment [ABSTRACT FROM AUTHOR]

Maintenance chemotherapy is a reasonable choice for patients with metastatic non–small cell lung carcinoma (NSCLC) not progressing after induction therapy with a platinum-based doublet. Nevertheless, there have been no studies dedicated to elderly patients. We conducted a randomised trial in patients aged 70–89 years, with advanced NSCLC (with neither EGFR mutation nor ALK rearrangement), who had not progressed after four cycles of monthly carboplatin and weekly paclitaxel in order to compare maintenance with either pemetrexed (500 mg/m2 d1, 22) in patients with non–squamous cell carcinoma or gemcitabine (1,150 mg/m2 d1, 8, 22) in squamous cell carcinoma to simple observation. The patients were required to have a performance status (PS) 0–2, mini-mental score >23, and creatinine clearance ≥45 mL/min. The primary end-point was overall survival (OS). 632 patients were enrolled from May 2013 to October 2016. Of the 328 (52.3%) patients randomised after induction therapy, 166 patients were assigned to the observation arm, versus 162 to the switch maintenance arm, 119 of whom received pemetrexed and 43 gemcitabine. The median OS from randomisation was 14.1 months (95% confidence interval [CI]: 12.0–17.0) in the observation arm and 14 months (95% CI: 10.9–16.9) in the maintenance arm (p = 0.72). The median progression-free survival (PFS) from randomisation was 2.7 months (95% CI: 2.6–3.1) in the observation arm versus 5.7 months (95% CI: 4.8–7.1) in the maintenance arm (p < 0.001). Switch maintenance therapy significantly prolonged PFS but not OS and, thus, should not be proposed to elderly patients with advanced NSCLC. • Chemotherapy remains a backbone in lung cancer treatment. • Maintenance chemotherapy has proven beneficial in non–small cell lung carcinoma with metastatic stage. • There is a selection bias for older patients included in non-dedicated studies. • This trial shows that elderly do not derive any survival benefit with maintenance. • It illustrates that dedicated studies for elderly patients are mandatory. [ABSTRACT FROM AUTHOR]

The European Organisation for Research and Treatment of Cancer (EORTC) core questionnaire, QLQ-C30, is a frequently used patient-reported outcome (PRO) instrument to assess health-related quality of life of patients with cancer. To enhance the understanding and interpretation of PRO data, it is important to obtain norm data from the general population. This article presents updated general population norm data for the EORTC QLQ-C30 for Germany. Data were obtained as part of a larger study collecting EORTC QLQ-C30 norm data across 15 countries via an online survey. After linear transformation of EORTC QLQ-C30 raw scores, data were weighted based on the United Nations' population distribution statistics. Data are presented by age and sex/age. A total of 1006 Germans responded to the survey. Across EORTC QLQ-C30 domains, different response patterns were observed, with men generally scoring better, that is, higher in most function scales and lower in most symptom scales/items than women. For age, mixed patterns were observed. While older respondents scored worse/lower in physical and role functioning, emotional functioning scores appeared to increase with increasing age. For the symptom scales/items, some symptoms were relatively stable across age groups, while others either increased or decreased with increasing age. This study presents updated EORTC QLQ-C30 general population norm data for Germany that can readily be used for comparative purposes with data obtained from patients with cancer. • General population norm data enhance the interpretation of patient-reported outcomes (PRO) data. • This article presents updated EORTC QLQ-C30 normative data for Germany. • Data were collected as part of a multi-national survey enabling intra- & intercountry comparisons. • These new norm data can be readily used for comparative purposes with PRO data from cancer patients. [ABSTRACT FROM AUTHOR]

An increased risk of death by suicide in cancer patients has been documented since decades. We evaluated the risk of death by suicide in an Italian population-based cancer case series and added the results to a systematic review and meta-analysis of the literature. The Italian series, including 127,042 primary cancer patients diagnosed between 1996 and 2014, was obtained from the Romagna Cancer Registry (northern Italy). Standardised mortality ratios (SMRs) were calculated. Regarding the systematic review and meta-analysis, the PubMed database was searched for English language studies published up to 2017. Fifty-seven potentially eligible papers were reviewed in full, and 19 of them were selected for analysis. The SMR was the first outcome, replaced by rate ratio if the SMR was not available. In the Italian case series, an increased suicide risk was found for both sexes combined (SMR = 1.5; 95% confidence interval [CI]: 1.3–1.8), for males (SMR = 1.6; 95% CI: 1.4–1.9) but not females (SMR = 1.1; 95% CI: 0.7–1.7), for patients aged ≥55 years, with poor prognosis and advanced-stage disease and during the first year after diagnosis. The absolute excess risk of suicide was 0.9 per 10,000 patient-years. Multivariate analysis confirmed the role of univariate factors except for poor prognosis. Meta-analysis showed a strong heterogeneity between studies. The risk was significantly elevated for both sexes combined (pooled SMR = 1.7; 95% CI: 1.5–1.9), men (pooled SMR = 1.8; 95% CI: 1.6–2.0) and women (pooled SMR = 1.4; 95% CI: 1.3–1.6). There was no evidence for small-study effects. The Italian study confirmed the previous common finding that cancer patients are at increased risk for suicide. A clinical multidisciplinary approach to support them is needed. • A study on the risk of death by suicide among northern Italian cancer patients was included in a meta-analysis of the literature. • The meta-analysis confirmed a robust increase in the risk of death by suicide for cancer patients. • A multidisciplinary approach to detect symptoms of anxiety and depression is needed. [ABSTRACT FROM AUTHOR]

This study evaluated the effect of early integrated palliative care (PC) in oncology on quality of life (QOL) near the end of life and use of health care resources near the end of life. Patients with advanced cancer and a life expectancy of approximately 1 year were randomly assigned to either early and systematic integration of PC into oncological care (intervention) or standard oncological care alone (control). QOL was assessed with the EORTC QLQ-C30 global health status/QOL scale and McGill Quality of Life (MQOL) Single Item Scale and Summary Scale at baseline, 12 weeks and 6 weekly thereafter until death. Use of health care resources was collected from chart review in patient's electronic medical file for patients who died while participating in the study. Of the 186 randomised patients, 185 participants had a baseline measurement and were analysed. By November 2017, 128 patients had died while participating in the study. When applying the terminal decline model, patients in the intervention group scored significantly higher on global health status/QOL of the EORTC QLQ C30, at 6 months (difference: 5.9 [0.06; 11.1], p = 0.03), 3 (difference: 6.8 [1.0; 12.6], p = 0.02), and 1 month (difference: 7.6 [0.7; 14.5], p = 0.03) prior to the patient's death compared to the control group. Similar results were found for the Single Item Scale and Summary Score of the MQOL. We did not observe differences in use of health care resources between groups. Early integrated palliative care in oncology is a valuable approach since it also increases QOL near the end of life and not only soon after initiation of PC. • Palliative care consultations from diagnosis of advanced cancer improve quality of life. • The benefit in patient's quality of life increases towards the end of life. • Integration of palliative care in oncology results in patient-centred care. [ABSTRACT FROM AUTHOR]

In KEYNOTE-119 (ClinicalTrials.gov, NCT02555657), overall survival (primary end-point) was similar between pembrolizumab and chemotherapy in patients with previously treated metastatic triple-negative breast cancer (TNBC), although the pembrolizumab treatment effect increased with tumour PD-L1 expression. We report results of prespecified health-related quality of life (HRQoL) analyses from KEYNOTE-119. Eligible patients were randomised 1:1 to pembrolizumab 200 mg Q3W intravenously for up to 35 cycles or treatment of physician's choice per local/country guidelines. Prespecified exploratory end-points were the change from baseline in HRQoL (EORTC QLQ-C30, QLQ-BR23) and to characterise utilities (EQ-5D-3L). Time to deterioration (TTD) was the time from start of treatment to first onset of a ≥10-point worsening from baseline. HRQoL analyses included 187 patients with tumour PD-L1 combined positive score (CPS) ≥10. Changes from baseline at 6 weeks (primary analysis time point) were directionally better with pembrolizumab versus chemotherapy for QLQ-C30 GHS/QoL (between-group difference in least-squares mean scores of 4.21 [95% CI, −1.38 to 9.80]), QLQ-C30 functional scales (physical, role, cognitive, social), QLQ-C30 symptom scales/items (fatigue, nausea/vomiting, dyspnoea, appetite loss), and QLQ-BR23 symptom scales/items (systemic therapy side-effects, upset by hair loss). Median TTD was directionally longer for pembrolizumab versus chemotherapy for QLQ-C30 QHS/QoL (4.3 versus 1.7 months), QLQ-C30 nausea/vomiting (7.7 versus 4.8 months), and QLQ-BR23 systemic therapy side-effects (6.1 versus 3.4 months). Minimal treatment differences were observed for other HRQoL end-points. HRQoL results were consistent with clinical outcomes and appeared to be driven by results for patients with tumour PD-L1 CPS ≥10. • We report health-related quality of life (HRQoL) analyses from KEYNOTE-119. • First HRQoL data on anti-PD1 versus chemo in metastatic triple-negative breast cancer. • Most HRQoL results favored pembrolizumab in combined positive score-enriched patients. • HRQoL was consistent with previously reported safety findings in overall patients. • HRQoL was consistent with efficacy data in combined positve score-enriched patients. [ABSTRACT FROM AUTHOR]

Although the link between severe mental illness (SMI) and elevated cancer mortality is well established, few studies have examined lung cancer survival and SMI in detail. Our study compared cancer-specific mortality in patients with lung cancer with and without a history of SMI and analysed whether mortality differences could be explained by cancer stage at presentation, comorbidity or differences in cancer treatment. We identified patients with their first lung cancer diagnosis in 1990–2013 from the Finnish Cancer Registry, their preceding hospital admissions due to SMI from the Hospital Discharge Register and deaths from the Causes of Death statistics. Competing risk analyses were used to estimate hazard ratios (HRs) for the impact of SMI on mortality. Of the 37,852 lung cancer cases, 12% had a history of SMI. Cancer-specific mortality differences were found between patient groups in some cancer types after controlling for stage at representation and treatment. Men with a history of psychosis had excess mortality risk (HR = 1.24, 1.06–1.45) in squamous cell carcinoma. Similar excess risk was found among women with psychosis in small-cell carcinoma (HR = 1.76, 1.41–2.19) and in squamous cell carcinoma (HR = 1.67, 1.26–2.20) and among women with mood disorders in adenocarcinoma (HR = 1.37, 1.08–1.74). Patient group differences in HRs in five-year mortality did not markedly change from the 1990s. We found elevated cancer-specific mortality among persons with a history of SMI. Collaboration between patients, mental healthcare professionals and oncological teams is needed to reduce the mortality gap between patients with cancer with and without SMI. • We studied the effect of mental illness on cancer-specific mortality in lung cancer. • We found elevated cancer-specific mortality in patients with mental illness history. • The mortality gap persisted after controlling for cancer stage and treatment. • Patients' psychiatric team should be included in cancer care to enhance outcomes. • Smoking cessation interventions should be an integral component of lung cancer care. [ABSTRACT FROM AUTHOR]

Platinum-resistant ovarian cancer (PROC) is associated with a variable prognosis and unpredictable survival times. We have developed and validated a prognostic nomogram with the objective of improving the prediction of overall survival (OS) in patients treated with chemotherapy. The nomogram was developed using data from a training cohort of patients from two trials, including the chemotherapy-only arm in AURELIA and all randomised patients in CARTAXHY. Multivariable proportional hazards models were generated based on pretreatment characteristics to develop a nomogram that classifies patients based on OS. We subsequently assessed the performance of the nomogram in terms of discrimination and calibration in independent validation patient cohorts: PENELOPE and the bevacizumab-chemotherapy arm of AURELIA. The nomogram included six significant OS predictors, in order of importance: performance status, ascites, size of the largest tumour, CA-125, platinum-free interval and primary platinum resistance (C-statistic 0.69). In the training cohort, the median OS in the good, intermediate and poor prognosis groups was 25.3, 15.2 and 7.4 months, respectively. In the PENELOPE validation cohort (C-statistic 0.59), the median OS in the good, intermediate and poor prognosis groups was 18.5, 10.3 and 5.8 months, respectively. In the AURELIA bevacizumab-chemotherapy validation cohort (C-statistic 0.67), the median OS in good, intermediate and poor prognosis groups was 26.7, 13.8 and 10.0 months, respectively. This nomogram with six pretreatment characteristics allows prediction of OS in PROC and could be used for stratification of patients in clinical trials as well as for counselling patients about prognosis. • Performance status, ascites, largest tumour size, CA-125, platinum-free interval and platinum resistance predict survival in ovarian cancer. • These factors formed a prognostic nomogram that has been developed and validated in patients who participated in clinical trials. • The prognostic nomogram could be used for stratification of patients in clinical trials and for counselling of patients about survival times. [ABSTRACT FROM AUTHOR]

Cancer patients frequently suffer from fatigue and depression. Dysregulation of the immune system, tumour recurrence and metastasis are more common in cancer patients with depression. 5-Hydroxytryptamine (5-HT), a neurotransmitter, contributes to immune evasion in lung adenocarcinoma patients by activating 5-HTRs, but the mechanism for this phenomenon is still unclear. In this study, we examined the function of 5-HT1a receptors (5-HT1aRs) in immune evasion in a mouse model and in samples from lung adenocarcinomas patients. Sixty-four human lung adenocarcinoma patients with depression and 64 lung adenocarcinoma patients without depression were recruited for this study. The expression of 5-HT receptors on lung adenocarcinoma cells from tumour tissues were detected by using immunohistochemistry (IHC) and fluorescence-activated cell sorting (FACS). The depression models were established in vitro and in vivo. The effects of immunosuppression were evaluated by testing the function of cytotoxic lymphocyte (CTLs) and Tregs, measuring tumour weight or volume, assessing the survival of mice and staining of tissues by IHC. Changes in the expression of immunoregulatory factor genes were assessed to elucidate the mechanism of immune evasion induced by the 5- hydroxytryptamine receptor (HTRs). Higher levels of 5-HT, increased expression of 5-HT1Rs and decreased overall survival were observed in lung adenocarcinomas patients with depression compared with those without depression. Moreover, 5-HT1aR, a critical factor for increasing the number of CD4+CD25+Foxp3+ Treg cells and decreasing the ratio of Th1/Th2 cells, which suggested immune system dysregulation. In addition, expression of 5-HT1aR on tumour cells was also negatively associated with CTL activity in both peripheral blood and tumour infiltrating lymphocytes. In a depressive state, 5-HT1aR activates p-signal transducer and activator of transcription 3 (STAT3) and autophagy, and programmed death ligand-1, a downstream gene of autophagy/p-STAT3 signalling, mediates an immunosuppressive environment. Moreover, in both the mouse model and lung adenocarcinoma patients, the activation of 5HT1aR and the elevated tumour autophagy/p-STAT3 axis were associated with reduced overall survival. The 5-HT1aR/autophagy/p-STAT3 axis influences both tumour cells and immune cells, resulting in immunosuppression in lung adenocarcinomas patients with depression. • 5-HT1aR (5-hydroxytryptamine1a receptor) in tumours cells was higher from lung adenocarcinomas patients in depression. • The higher expression of 5-HT1aR in tumour cells was associated with worse overall survival. • 5HT1aR could influence both tumour cells and T-cells to create an immunosuppressive environment though activation of autophagy/p-STAT3-programmed death ligand-1 signal under depression stress. [ABSTRACT FROM AUTHOR]

It is estimated only 8–11% of patients with glioblastoma (GBM) enrol in clinical trials, limiting treatment development. We analysed the clinical and demographic features of patients with GBM enroled in clinical trials at the University of Texas MD Anderson Cancer Center (MDACC). We reviewed the records of adult patients treated for primary GBM between 2007 and 2012 at the MDACC. A total of 755 patients were identified: 133 were deemed non-eligible, 111 were deemed trial eligible but received standard care and 511 participated in a clinical trial (311 for newly diagnosed glioblastoma [nGBM] and 200 for recurrent glioblastoma [rGBM]). Population characteristics were analysed using descriptive statistics, and survival end-points were evaluated with the Kaplan–Meier method. The median age of clinical trial participants and trial eligible patients was 53.2 years (standard deviation 12.1). Most patients (49.4%) were enroled in a clinical trial protocol for nGBM. The majority of nGBM trial participants were male patients (65.1%), white (86.3%), married (84.4%) and in state (59.9%). Employment status, education, symptoms, tumour location, performance status, extent of resection and treatment facility differed between nGBM trial participants and non-participants. Patients who were eligible but did not enrol tended to be older, have worse performance status and live farther away from the MDACC. Numerous disease and demographic barriers exist in trial enrolment in patients with GBM. This study highlights some of these obstacles, which require attention to improve patient enrolment to clinical trials. Patient and physician engagement in novel therapeutic strategies is essential to improving outcomes in this disease. • A small minority of patients with glioblastoma enrol in therapeutic clinical trials. • Demographic, disease and treatment-related variables influence trial enrolment. • Older age and poor functional status are associated with not enroling in trials. • Patients living farther from the treating centre were less likely to enrol. [ABSTRACT FROM AUTHOR]

Abstract Background Even if borderline ovarian tumours (BOTs) in young women treated with fertility-sparing treatment (FST) have an excellent outcome, the type of surgery might affect relapse and fertility. We investigated the effect of surgical approach (open surgery vs. laparoscopy) and type of surgery (salpingo-oophorectomy [SO] vs. cystectomy [Cy]) on oncologic and fertility outcomes in patients with BOT. Patients and methods Patients with BOT treated at San Gerardo Hospital, Monza, with FST in 1978–2013 period were included. Cox models, stratified by decade of surgery, were used to investigate the association between time to first recurrence or conception and clinical factors. Results Among 535 patients included, 271 underwent unilateral SO and 264 underwent Cy. Median follow-up was 13.5 years. Ten-year (10-yr) recurrence rate was 23% (95% confidence interval [CI]: 18–29%) for SO and 31% (95% CI: 24–38%) for Cy group (P = 0.10) in patients with unilateral tumour, whereas it was 62% (95% CI: 44–79%) and 72% (95% CI: 59–84%), respectively, (P = 0.35) in patients with bilateral tumour. Multivariable analysis showed no association between recurrence and surgical approach (P = 0.44), type of surgery (P = 0.06) and a negative association with advanced stage (hazard ratio [HR] = 3.18; 95% CI: 2.11–4.78; P < 0.001) and bilateral tumours (HR = 2.48; 95% CI: 1.78–3.47; P < 0.001). Among 252 patients (47.1%) with pregnancy desire, multivariable analysis showed no association between conception success and the type of surgery, surgical approach, histology and tumour laterality. Fertility after surgery was positively associated with prior pregnancy (HR = 1.68; 95% CI: 1.17–2.41; P = 0.005) and negatively associated with the number of surgical procedures (HR = 0.62; 95% CI: 0.53–0.73; P < 0.001). Conclusions The type of surgical procedures did not influence recurrence rate or fertility. However, additional surgical procedures decreased the fertility potential. These data can support clinicians in tailoring the best strategy for FST in young patients with BOT. Highlights • Fertility-sparing treatment for borderline ovarian tumour can be safely treated by laparoscopy compared with open surgery. • Cystectomy did not increase risk of relapse and infertility compared with oophorectomy. • The total number of gonadal surgeries was the most detrimental factor for fertility. • The less demolitive approach for ovarian tissue should be preferred for fertility-sparing treatment in young women. [ABSTRACT FROM AUTHOR]

Abstract Purpose Because the role of the primary tumour location in the adjuvant setting has not been clearly established in colon cancer, we analysed the clinical outcome according to the primary tumour location from three Italian trials assessing adjuvant therapy in colon cancer. Patients and methods Overall survival (OS) and disease-free survival (DFS) were assessed globally and in each trial, according to right-sided, transverse and left-sided primary colon cancer. Analysis was planned to provide overall and stage-specific results. Results Individual data of 5239 patients were included in this analysis. The right-sided tumours were 1540 (29%), tumours originating in the transverse were 815 (16%) and left-sided tumours were 2884 (55%). At the multivariate analysis, DFS findings from the comparison of the right-sided versus left-sided tumours (hazard ratio [HR] = 1.00; 95% confidence interval [CI] = 0.89–1.14) were not statistically associated with clinical outcomes in the overall population. On the contrary, OS findings, from the comparison of the right-sided versus left-sided tumours, were significantly associated with outcomes (HR = 1.20; 95% CI = 1.04–1.39). In stage II patients, there was no difference in terms of DFS and OS among the three different tumour locations, whereas in stage III patients, the left-sided tumours showed an improved prognosis in terms of OS (HR: 1.36 95% CI = 1.14–1.62, p < 0.001). Conclusion This is the largest analysis demonstrating a prognostic effect of the tumour location on patients with colon cancer receiving adjuvant chemotherapy. Nevertheless, the effect is limited to OS in stage III colon cancer. In stage II tumours, the primary location has a lesser impact. The transverse tumours should be prognostically considered in between the right-sided and left-sided tumours. Highlights • The primary tumour location has a prognostic effect even on patients with colon cancer receiving an adjuvant chemotherapy. • The effect is limited to overall survival in stage III colon cancer. • The transversum tumours should be prognostically considered between right-sided and left-sided tumours. [ABSTRACT FROM AUTHOR]

Abstract Background Sunitinib is administered on a rigid schedule that may not be optimal for all patients. We hypothesised that toxicity-driven dose and schedule changes would optimise drug exposure and outcome for each patient. Materials and methods In a phase 2 trial, 117 patients with metastatic clear cell renal cell cancer were started on sunitinib 50 mg/day with the aim to treat for 28 days. Treatment breaks were reduced to 7 days. Sunitinib dose and the number of days on therapy were individualised based on toxicity aiming for ≤ grade II toxicity with dose escalation in patients with minimal toxicity. The null hypothesis for the primary end-point was a progression-free survival (PFS) of 8.5 months based on a study with similar eligibility criteria. Results The null hypothesis was rejected (p < 0.001) with a median PFS of 12.5 months (95% confidence interval [CI]: 9.6–16.5). The median overall survival was 38.5 months (95% CI: 28.3-not reached). The objective response rate (46.1%) and stable disease rate (38.5%) translated into a clinical benefit for 84.6% of patients with no decline in quality of life scores during therapy. Fewer patients were dose reduced (26.5% vs. 50%) or discontinued due to toxicity (7.7 vs. 18–20%) compared to standard sunitinib dosing, and 20 (18.4%) patients were dose escalated to 62.5 mg (12) and 75 mg (8) with a wide individual variation in the optimal dose and treatment duration. Conclusions : Individualised sunitinib therapy is feasible, safe and an effective method to manage toxicity with one of the best efficacy seen for oral vascular endothelial growth factor inhibitors in metastatic renal cell carcinoma. Clinicaltrials.gov identifier NCT01499121. Highlights • Individualised sunitinib therapy is feasible, safe and an effective method to manage toxicity. • There was a wide interindividual variation in the optimal sunitinib dose and treatment duration. • About 18.5% of patients were dose escalated above the standard 50 mg dose. • Fewer patients were dose reduced or discontinued therapy due to toxicity vs. standard dosing. • With one of the best efficacy seen for oral vascular endothelial growth factor drugs with no decline in quality of life on therapy. [ABSTRACT FROM AUTHOR]

Abstract Objective The European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 health-related quality of life questionnaire is one of the most widely used cancer-specific health-related quality of life questionnaires worldwide. General population norm data can facilitate the interpretation of QLQ-C30 data obtained from cancer patients. This study aimed at systematically collecting norm data from the general population to develop European QLQ-C30 norm scores and to generate comparable norm data for individual countries in Europe and North America. Methods We collected QLQ-C30 data from the general population across 11 European Union (EU) countries, Russia, Turkey, Canada and United States (n ≥ 1000/country). Representative samples were stratified by sex and age groups (18–39, 40–49, 50–59, 60–69 and ≥ 70 years). After applying weights based on the United Nations population distribution statistics, we calculated QLQ-C30 domain scores to generate a 'European QLQ-C30 Norm' based on the EU countries. Further, we calculated QLQ-C30 norm scores for all 15 individual countries. Results A total of 15,386 respondents completed the online survey. For the EU sample, most QLQ-C30 domains showed differences by sex/age, with men scoring somewhat better health than women, while age effects varied across domains. Substantially larger differences were seen in inter-country comparisons, with Austrian and Dutch respondents reporting consistently better health compared with British and Polish respondents. Conclusions This study is the first to systematically collect EORTC QLQ-C30 general population norm data across Europe and North America applying a consistent data collection method across 15 countries. These new norm data facilitate valid intra-country as well as inter-country comparisons and QLQ-C30 score interpretation. Highlights • Updated general population norm data for EORTC QLQ-C 30 based on 15,386 persons across 13 European countries, Canada, and USA. • Study strength: all individual country QLQ-C30 norm data collected based on a common sampling strategy and survey design. • New normative data facilitate valid intracountry and especially intercountry comparisons and QLQ-C30 score interpretation. [ABSTRACT FROM AUTHOR]

Abstract Objective The computer-adaptive test (CAT) of the European Organisation for Research and Treatment of Cancer (EORTC), the EORTC CAT Core, assesses the same 15 domains as the EORTC QLQ-C30 health-related quality of life questionnaire but with increased precision, efficiency, measurement range and flexibility. CAT parameters for estimating scores have been established based on clinical data from cancer patients. This study aimed at establishing the European Norm for each CAT domain based on general population data. Methods We collected representative general population data across 11 European Union (EU) countries, Russia, Turkey, Canada and the United States (n ≥ 1000/country; stratified by sex and age). We selected item subsets from each CAT domain for data collection (totalling 86 items). Differential item functioning (DIF) analyses were conducted to investigate cross-cultural measurement invariance. For each domain, means and standard deviations from the EU countries (weighted by country population, sex and age) were used to establish a T-metric with a European general population mean = 50 (standard deviation = 10). Results A total of 15,386 respondents completed the online survey (n = 11,343 from EU countries). EORTC CAT Core norm scores for all 15 countries were calculated. DIF had negligible impact on scoring. Domain-specific T-scores differed significantly across countries with small to medium effect sizes. Conclusion This study establishes the official European Norm for the EORTC CAT Core. The European CAT Norm can be used globally and allows for meaningful interpretation of scores. Furthermore, CAT scores can be compared with sex- and age-adjusted norm scores at a national level within each of the 15 countries. Highlights • This study establishes the official European Norm for the computer-adaptive test EORTC CAT Core based on 15,386 persons. • The European CAT Norm can be used globally and allows for meaningful interpretation of scores derived from EORTC CAT Core. • EORTC CAT Core scores can also be compared with sex- and age-adjusted norm scores at national levels of 15 included countries. [ABSTRACT FROM AUTHOR]

Abstract Background Inadequate understanding of interpretation of quality of life (QoL) instruments leads to unsatisfactory data reporting and clinical decision-making, including in gastric cancer care. Materials and methods Pooled QoL data from two phase III studies of ramucirumab with or without paclitaxel in previously treated patients with gastric or gastroesophageal junction cancer were used to explore associations with clinical attributes, including tumour response, disease measurability and performance status (PS). The European Organisation for Research and Treatment of Cancer (EORTC) Quality-of-Life Questionnaire (QLQ)-C30 was used in both studies. Changes in QLQ-C30 scores from baseline to week 6 as a predictor of clinical outcomes and impacts of changes in clinical status on QoL were estimated by multivariate logistic regression and analyses of variance, respectively. Results Baseline QoL data were available for 989 patients. Fatigue, pain and appetite loss were prominent baseline symptoms. Disease progression resulted in worse QoL in all functional scales (p < 0.0001 to p = 0.0306), global QoL (p = 0.0011) and symptom scales (fatigue, p < 0.0001; nausea/vomiting, p = 0.0007; pain, p = 0.0052; appetite loss, p = 0.0061). Similar trends were seen with deterioration of PS on QoL. A 15- to 20-point change in global QoL and functional scale scores predicted change in tumour status as did change in fatigue, pain and appetite loss scores. Smaller QoL changes (5–15 points) predicted PS change. Results were similar in patients regardless of baseline disease measurability. Conclusions Our study underscores the importance of disease control for maintaining or improving QoL. These data could improve future trial design and routine clinical care for patients receiving therapy for previously treated gastric cancer. NCT00917384, NCT01170663. Highlights • Quality of life (QoL) data from two ramucirumab phase III gastric cancer trials were analysed. • Disease progression resulted in worse QoL in most European Organisation for Research and Treatment of Cancer (EORTC) Quality-of-Life Questionnaire (QLQ)-C30 scales. • Deterioration of performance status was similarly associated with worse QoL. • 15- to 20-point changes in QoL scales predicted change in tumour status. • 5- to 15-point changes in QoL scales predicted change in performance status. [ABSTRACT FROM AUTHOR]

Abstract Background Bone metastases (BMs) are associated with significant morbidity and shorter survival in renal cell carcinoma (RCC). Our purpose was to identify prognostic factors for overall survival (OS) in RCC patients with BMs. Methods Data from patients with BMs from RCC treated at Gustave Roussy between April 1992 and March 2016 were retrospectively collected. Age, sex, Eastern Cooperative Oncology Group-Performance Status, Memorial Sloan-Kettering Cancer Center (MSKCC) risk groups, histology, number and site of bone lesions, concomitant metastases (presence and sites), therapy for BMs (radical resection or palliative surgery, radiotherapy and other local and systemic treatments) and time from diagnosis to BMs were analysed. Synchronous solitary bone metastasis (SSBM) was defined as a single BM without concomitant visceral lesions at the initial diagnosis of RCC. OS was calculated from the date of BMs diagnosis to death or last follow-up using Kaplan–Maier method and modelled with Cox regression analysis. Results From 1750 patients with diagnosis of RCC followed at Gustave Roussy Cancer Campus, 300 patients with BMs were identified. Median time from diagnosis to BMs was 32.4 months (range 0–324 months). In 64 patients (21%), bone was the only metastatic site, and 22 patients (7%) had an SSBM and 236 patients (79%) had concomitant metastases in other sites. Median OS was 23.2 months (95% confidence interval 19.9–26.2). SSBM patients had better OS than those with concomitant metastases (40 vs 20 months; P < 0.001). At multivariate analysis, concomitant metastases remained predictor of poor prognosis, while MSKCC risk group, radical resection and SSBM were predictors of better OS. Conclusions This study suggests that MSKCC score, numbers of BMs and radical resection are important prognostic factors for RCC patients with BMs. Additionally, in the presence of solitary BM without concomitant metastases at the initial diagnosis of RCC, bone surgery should be considered to achieve local tumour control and likely increase OS. Highlights • Renal cell carcinoma (RCC) accounts for 3% of all cancers and commonly occurs in Western countries. • Most common metastases in RCC occurs to lung, followed by bone involvement in 20–35%, lymph nodes and liver. • Bone metastases are very destructive in RCC patients, leading to mainly osteolytic lesions that compromise bone integrity. • Skeletal involvement is associated with skeletal-related events, which may require surgical intervention and other therapy. • The presence of bone metastases in RCC has negative impact on progression free survival and overall survival of patients. [ABSTRACT FROM AUTHOR]

Abstract Background The NAPOLI-1 study (NCT01494506) reported that liposomal irinotecan plus 5-fluorouracil and leucovorin (nal-IRI+5-FU/LV) improved overall survival vs 5-FU/LV with manageable toxicity in patients with metastatic pancreatic adenocarcinoma previously treated with gemcitabine-based therapy. Yet, clinicians need treatment strategies that also maintain the patient's health-related quality of life (HRQOL). Here, we report the HRQOL data. Methods Patients completed the European Organisation for Research and Treatment of Cancer QOL core questionnaire C30 (EORTC QLQ-C30) at baseline, every 6 weeks, and at 30 days after discontinuation of study treatment. Patient-reported outcomes (PROs) were scored according to EORTC guidelines. nal-IRI+5-FU/LV HRQOL was compared with 5-FU/LV. The PRO population comprised intent-to-treat patients who completed baseline and at least one subsequent assessment on the EORTC QLQ-C30. Data were also analysed for missingness. Results Of 236 patients in the intent-to-treat population, 128 (54.2%) comprised the PRO population (71 in the nal-IRI+5-FU/LV arm; 57 the in 5-FU/LV arm). Of the remaining 108 patients (45.8%) not included in the PRO population, most progressed rapidly, making participation difficult. Median change from baseline was ≤10 points at weeks 6 and 12 in global health status or functional and symptom scale scores, except for fatigue, which deteriorated by 11.1 points with nal-IRI+5-FU/LV but did not change vs 5-FU/LV. The proportion of patients whose HRQOL improved or deteriorated was not significantly different between the arms. Conclusion In the NAPOLI-1 study, HRQOL was maintained with nal-IRI+5-FU/LV in patients with metastatic pancreatic adenocarcinoma previously treated with a gemcitabine-based regimen, while survival was significantly extended. Highlights • Pancreatic cancer and chemotherapy can have a detrimental impact on health-related quality of life (HRQOL). • HRQOL was assessed in metastatic pancreatic ductal adenocarcinoma that had progressed on prior gemcitabine-based therapy. • In the NAPOLI-1 study, patients received liposomal irinotecan plus 5-flurouracil/leucovorin (nal-IRI+5-FU/LV) or 5-FU/LV. • HRQOL was maintained over time for nal-IRI+5-FU/LV vs 5-FU/LV alone. • Maintained patient HRQOL and survival benefit were seen with nal-IRI+5-FU/LV vs 5‑FU/LV alone in this global phase 3 study. [ABSTRACT FROM AUTHOR]

Abstract Background Receiving a diagnosis of cancer may be associated with increased risk of mental disorders. Yet, in this context, no factor predicts the onset of a mental disorder besides the diagnosis of cancer itself. If patients with a history of mental disorder are at particular risk is unknown. Methods Data were derived from a large national sample of the US population. Face-to-face surveys were conducted on 36309 adults during 2012–2013 period. Data were used to examine the associations among the past-year prevalence of mental disorders (according to the Diagnostic and Statistical Manual of Mental Disorders-5), the treatment-seeking rates and a recent cancer diagnosis. Data were analysed according to the antecedents of mental disorder in participants and according the presence of a recent cancer diagnosis. Results Participants recently diagnosed with cancer (n = 1300) were significantly at higher risk to present suicide attempt (adjusted odds ratio [AOR] = 3.52; 95% confidence interval [CI] = 1.23–10.04), post-traumatic stress disorder (AOR = 2.25; 95% CI = 1.71–2.96), bipolar disorder (AOR = 2.22; 95% CI = 1.46–3.38) and drug use disorder (AOR = 1.64; 95% CI = 1.13–3.39). The prevalence of most of the mental disorders considered was significantly higher for participants with a history of mental disorder compared with participants without such a history. Conversely, a recent diagnosis of cancer was not associated with significant differences in the incidence of mental disorders in participants with no history of mental disorder. Conclusions Patients with a history of mental disorder receiving a cancer diagnosis are at high risk of relapse and should be closely monitored. Highlights • This study is based on a population-based representative sample and uses interview-based diagnoses. • Persons with a recent diagnosis of cancer were at higher risk than other persons to present various mental disorders. • The prevalence of the mental disorders considered was higher for participants with a history of mental disorder. • No difference was observed in participants with no history of mental disorder after cancer diagnosis. [ABSTRACT FROM AUTHOR]

Abstract Background Anti-HER2 therapy has not demonstrated a survival advantage in the second-line setting of patients with HER2-positive gastric cancer. We conducted this study to assess changes in HER2 status and to identify possible biomarkers for acquired resistance after the use of trastuzumab as the first-line therapy. Patients and methods Patients with advanced or recurrent HER2-positive gastric adenocarcinoma who were diagnosed with progressive disease after the first-line trastuzumab-based therapy and developed pathologically confirmed adenocarcinoma within 3 months after completion of trastuzumab-based therapy were enrolled in this study. We collected re-biopsied samples from the HER2-positive patients who had developed resistance to trastuzumab and re-evaluated their HER2 status. Amplification of EGFR and c-met , as well as PIK3CA mutation, were comparatively analysed when samples were available. Results Among 33 eligible patients, loss of HER2 was identified in 20 patients (60.6%) with refractory disease. Immunohistochemistry showed that the rate of HER2 overexpression was greatly reduced after therapy (pre-HER2 3+: 24 [72.7%] vs. post-HER2 3+: 13 [39.4%]). We found that the use of fixatives other than 10% neutral buffered formalin significantly reduced the HER2-positive rate. EGFR amplification, c-met amplification and PIK3CA mutation before and after trastuzumab-based therapy were observed in 10.3% and 3.8%, 17.9% and 4.2% and 4.0% and 4.2% of cases, respectively. Conclusion Re-evaluation of HER2 status is needed to determine the appropriate use of anti-HER2–targeted therapy after disease progression. Our results also highlight the importance of formalin fixation conditions for HER2 testing. Highlights • The HER2 status was re-evaluated using re-biopsied samples from the patients with HER2-positive gastric cancer. • Among 33 eligible patients, the loss of HER2 was identified in 20 patients (60.6%) with refractory disease. • The use of fixatives, other than 10% neutral buffered formalin, reduced the HER2-positive rate. [ABSTRACT FROM AUTHOR]