Trajectories of health-related quality of life and symptom burden in patients with advanced cancer towards the end of life: Longitudinal results from the eQuiPe study.

BACKGROUND: Support for health-related quality of life (HRQOL) is an essential part of cancer care in the final stages of life, yet empirical guidance regarding HRQOL and symptom trajectories is lacking. AIM: To assess the change in HRQOL and symptom burden in the last year of life in patients with advanced cancer and its association with health care-related factors, cancer-specific treatment, and comorbidity. METHODS: A prospective, multicenter, observational study in patients with advanced cancer (eQuiPe). Three monthly questionnaires included European Organization for Research and Treatment of Cancer Quality of Life-C30 and reported continuity of care. Multivariable mixed-effects analysis was used to assess the association between HRQOL and health care-related factors. RESULTS: A total of 762 deceased patients were included with a mean age of 66 (SD, 10) years and 52% were male. The most common primary tumors were lung (29%), colorectal (20%), and breast cancer (13%). Mean overall HRQOL decreased in the last 9 months of life, with the greatest decrease in the last 3 months (ß -16.2). Fatigue, pain, appetite loss, dyspnea, constipation, and nausea worsened significantly in the last year of life. Multimorbidity (ß -7.5) and a better reported continuity of care (ß 0.7) were both significantly associated with the trajectory of HRQOL. CONCLUSION: Mean overall HRQOL begins to decline 9 months before death, highlighting the need for early identification and (re)assessment of different symptoms as aspects of HRQOL follow different trajectories. Multimorbidity and reported continuity of care may be associated with the trajectory of HRQOL.

A randomized controlled intervention trial to study the effect of a personalized lifestyle program on cancer-related fatigue among colorectal cancer survivors: protocol for the SoFiT study.

Observational studies suggest that a healthy diet in combination with ample physical activity is associated with a lower prevalence of cancer-related fatigue. The SoFiT trial (SoFiT: Study on Fatigue: a lifestyle intervention among colorectal cancer survivors) will assess the effect of a personalized lifestyle program on cancer-related fatigue in a randomised study.We designed a program that aims to increase adherence to lifestyle recommendations on diet and physical activity. The program was person-centred with regards to the lifestyle and personal characteristics of participants, to the determinants of behaviour of that participant, and to the preference, opportunities, and barriers of the participant.The effect of the program was tested in the SoFiT trial: a two-armed, parallel, randomized controlled trial among adult stage I-III colorectal cancer survivors, who experience cancer-related fatigue after treatment completion; intended sample size n=184. Participants randomized to the intervention group received the personalized lifestyle program. During six months, participants in the intervention group had individual sessions with a lifestyle coach of which four sessions were face-to-face and eight sessions were remote. After six months, participants randomized to the control group had access to two lifestyle coaching sessions and to the same materials that the intervention group also received.The primary endpoint of the trial is cancer-related fatigue. Secondary endpoints are: sleep quality and duration, health-related quality of life, physical performance, depression and anxiety, skeletal muscle echo intensity and cross-sectional area, and gut microbiota composition.This trial will show the effects of a personalized lifestyle program on cancer-related fatigue, and on an extensive set of secondary outcomes.

Outcomes of Combined Peritoneal and Local Treatment for Patients with Peritoneal and Limited Liver Metastases of Colorectal Origin: A Systematic Review and Meta-Analysis.

BACKGROUND: Almost half of all colorectal cancer (CRC) patients will experience metastases at some point, and in the majority of cases, multiple organs will be involved. If the peritoneum is involved in addition to the liver, the current guideline-driven treatment options are limited. The reported overall survival ranges from 6 to 13 months for the current standard of care (systemic treatment). This study aimed to evaluate morbidity and clinical long-term outcomes from a combined local treatment of hepatic metastases with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) used to treat peritoneal metastases. METHODS: A systematic search was performed in PubMed, Embase.com, Web of Science, and Cochrane. Studies evaluating the clinicopathologic data of patients who had both peritoneal and hepatic metastases treated with CRS-HIPEC were included provided sufficient data on the primary outcomes (overall and disease-free survival) were presented. The quality of included studies was assessed using the Methodological Index for Non-Randomized Studies (MINORS). RESULTS: Patients treated for peritoneal and liver metastases (PMLM group) had a pooled mean survival of 26.4 months (95% confidence interval [CI] 22.4-30.4 months), with a 3-year survival rate of 34% (95% CI 26.7-42.0%) and a 5-year survival rate of 25% (95% CI 17.3-33.8%). Surgical complications occurred more frequently for these patients than for those with peritoneal metastasis only (40% vs 22%; p = 0.0014), but the mortality and reoperation rates did not differ significantly. CONCLUSION: This systematic review showed that CRS and HIPEC combined with local treatment of limited liver metastasis for selected patients is feasible, although with increased morbidity and an association with a long-term survival rate of 25%, which is unlikely to be achievable with systemic treatment only.

Molecular subtype-specific efficacy of anti-EGFR therapy in colorectal cancer is dependent on the chemotherapy backbone.

BACKGROUND: Patient selection for addition of anti-EGFR therapy to chemotherapy for patients with RAS and BRAF wildtype metastatic colorectal cancer can still be optimised. Here we investigate the effect of anti-EGFR therapy on survival in different consensus molecular subtypes (CMSs) and stratified by primary tumour location. METHODS: Retrospective analyses, using the immunohistochemistry-based CMS classifier, were performed in the COIN (first-line oxaliplatin backbone with or without cetuximab) and PICCOLO trial (second-line irinotecan with or without panitumumab). Tumour tissue was available for 323 patients (20%) and 349 (41%), respectively. RESULTS: When using an irinotecan backbone, anti-EGFR therapy is effective in both CMS2/3 and CMS4 in left-sided primary tumours (progression-free survival (PFS): HR 0.44, 95% CI 0.26-0.75, P = 0.003 and HR 0.12, 95% CI 0.04-0.36, P < 0.001, respectively) and in CMS4 right-sided tumours (PFS HR 0.17, 95% CI 0.04-0.71, P = 0.02). Efficacy using an oxaliplatin backbone was restricted to left-sided CMS2/3 tumours (HR 0.57, 95% CI 0.36-0.96, P = 0.034). CONCLUSIONS: The subtype-specific efficacy of anti-EGFR therapy is dependent on the chemotherapy backbone. This may provide the possibility of subtype-specific treatment strategies for a more optimal use of anti-EGFR therapy.

Bereaved relatives' quality of life before and during the COVID-19 pandemic: Results of the prospective, multicenter, observational eQuiPe study.

BACKGROUND: The death of a loved one is considered as one of the most stressful life events. During the COVID-19 pandemic, grief processes are potentially affected by measures such as social distancing and self-quarantine. AIM: The aim of this study was to give insight in the impact of the COVID-19 pandemic on quality of life, social support, and self-care of bereaved relatives of people with advanced cancer in order to evaluate whether care for bereaved relatives during the COVID-19 pandemic should be improved. DESIGN: A cross-sectional analysis using data from bereaved relatives of a prospective, longitudinal, multicenter, observational study on quality of care and quality of life of people with advanced cancer and their (bereaved) relatives (eQuiPe). SETTING/PARTICIPANTS: Quality of life, social support, and self-care of bereaved relatives who completed a questionnaire within 3-6 months after their relative died during COVID-19 (April-November 2020) were compared with bereaved relatives who completed this questionnaire pre-COVID-19 (April-November 2019). RESULTS: Ninety-one bereaved relatives were included in the analysis, 44 bereaved relatives completed the questionnaire pre-COVID-19 and 47 during COVID-19. The median age of the participants was 65 (IQR = 14) years and 58% were female. There were no significant differences between the pre-COVID-19 and during COVID-19 bereaved relatives in quality of life (68 vs 69), social support (17 vs 18), and self-care (20 vs 19). CONCLUSIONS: On the short-term, the COVID-19 pandemic did not have significant impact on bereaved relatives' wellbeing. However, long-term impact of the pandemic on their wellbeing should be assessed.

Role of eHealth application Oncokompas in supporting self-management of symptoms and health-related quality of life in cancer survivors: a randomised, controlled trial.

BACKGROUND: Knowledge about the efficacy of behavioural intervention technologies that can be used by cancer survivors independently from a health-care provider is scarce. We aimed to assess the efficacy, reach, and usage of Oncokompas, a web-based eHealth application that supports survivors in self-management by monitoring health-related quality of life (HRQOL) and cancer-generic and tumour-specific symptoms and obtaining tailored feedback with a personalised overview of supportive care options. METHODS: In this non-blinded, randomised, controlled trial, we recruited patients treated at 14 hospitals in the Netherlands for head and neck cancer, colorectal cancer, breast cancer, Hodgkin lymphoma, or non-Hodgkin lymphoma. Adult survivors (aged ≥18 years) were recruited through the Netherlands Cancer Registry (NCR) and invited by their treating physician through the Patient Reported Outcomes Following Initial Treatment and Long term Evaluation of Survivorship (PROFILES) registry. Participants were randomly assigned (1:1) by an independent researcher to the intervention group (access to Oncokompas) or control group (access to Oncokompas after 6 months), by use of block randomisation (block length of 68), stratified by tumour type. The primary outcome was patient activation (knowledge, skills, and confidence for self-management), assessed at baseline, post-intervention, and 3-month and 6-month follow-up. Linear mixed models (intention-to-treat) were used to assess group differences over time from baseline to 6-month follow-up. The trial is registered in the Netherlands Trial Register, NTR5774 and is completed. FINDINGS: Between Oct 12, 2016, and May 24, 2018, 625 (21%) of 2953 survivors assessed for eligibility were recruited and randomly assigned to the intervention (320) or control group (305). Median follow-up was 6 months (IQR 6-6). Patient activation was not significantly different between intervention and control group over time (difference at 6-month follow-up 1·7 [95% CI -0·8-4·1], p=0·41). INTERPRETATION: Oncokompas did not improve the amount of knowledge, skills, and confidence for self-management in cancer survivors. This study contributes to the evidence for the development of tailored strategies for development and implementation of behavioural intervention technologies among cancer survivors. FUNDING: Dutch Cancer Society (KWF Kankerbestrijding).

Effect of a Skills Training for Oncologists and a Patient Communication Aid on Shared Decision Making About Palliative Systemic Treatment: A Randomized Clinical Trial.

BACKGROUND: Palliative systematic treatment offers uncertain and often limited benefits, and the burden can be high. Hence, treatment decisions require shared decision making (SDM). This trial examined the independent and combined effect of an oncologist training and a patient communication aid on SDM. METHODS: In this multicenter randomized controlled trial with four parallel arms (2016-2018), oncologists (n = 31) were randomized to receive SDM communication skills training or not. The training consisted of a reader, two group sessions, a booster session, and a consultation room tool (10 hours). Patients (n = 194) with advanced cancer were randomized to receive a patient communication aid or not. The aid consisted of education on SDM, a question prompt list, and a value clarification exercise. The primary outcome was observed SDM as rated by blinded observers from audio-recorded consultations. Secondary outcomes included patient-reported SDM, patient and oncologist satisfaction, patients' decisional conflict, patient quality of life 3 months after consultation, consultation duration, and the decision made. RESULTS: The oncologist training had a large positive effect on observed SDM (Cohen's d = 1.12) and on patient-reported SDM (d = 0.73). The patient communication aid did not improve SDM. The combination of interventions did not add to the effect of training oncologists only. The interventions affected neither patient nor oncologist satisfaction with the consultation nor patients' decisional conflict, quality of life, consultation duration, or the decision made. CONCLUSION: Training medical oncologists in SDM about palliative systemic treatment improves both observed and patient-reported SDM. A patient communication aid does not. The incorporation of skills training in (continuing) educational programs for medical oncologists is likely to stimulate the widely advocated uptake of shared decision making in clinical practice. TRIAL REGISTRATION: Netherlands Trial Registry NTR 5489. IMPLICATIONS FOR PRACTICE: Treatment for advanced cancer offers uncertain and often small benefits, and the burden can be high. Hence, treatment decisions require shared decision making (SDM). SDM is increasingly advocated for ethical reasons and for its beneficial effect on patient outcomes. Few initiatives to stimulate SDM are evaluated in robust designs. This randomized controlled trial shows that training medical oncologists improves both observed and patient-reported SDM in clinical encounters (n = 194). A preconsultation communication aid for patients did not add to the effect of training oncologists. SDM training effectively changes oncologists' practice and should be implemented in (continuing) educational programs.

Training for Medical Oncologists on Shared Decision-Making About Palliative Chemotherapy: A Randomized Controlled Trial.

BACKGROUND: Systemic treatment for advanced cancer offers uncertain and sometimes limited benefit, while the burden can be high. This study examines the effect of shared decision-making (SDM) training for medical oncologists on observed SDM in standardized patient assessments. MATERIALS AND METHODS: A randomized controlled trial comparing training with standard practice was conducted. Medical oncologists and oncologists-in-training (n = 31) participated in a video-recorded, standardized patient assessment at baseline (T0) and after 4 months (T1, after training). The training was based on a four-stage SDM model and consisted of a reader, two group sessions (3.5 hours each), a booster session (1.5 hours), and a consultation card. The primary outcome was observed SDM as assessed with the Observing Patient Involvement scale (OPTION12) coded by observers blinded for arm. Secondary outcomes were observed SDM per stage, communication skills, and oncologists' satisfaction with communication. RESULTS: The training had a significant and large effect on observed SDM in the simulated consultations (Cohen's f = 0.62) and improved observed SDM behavior in all four SDM stages (f = 0.39-0.72). The training improved oncologists' information provision skills (f = 0.77), skills related to anticipating/responding to emotions (f = 0.42), and their satisfaction with the consultation (f = 0.53). CONCLUSION: Training medical oncologists in SDM about palliative systemic treatment improves their performance in simulated consultations. The next step is to examine the effect of such training on SDM in clinical practice and on patient outcomes. IMPLICATIONS FOR PRACTICE: Systemic treatment for advanced cancer offers uncertain and sometimes limited benefit, while the burden can be high. Hence, applying the premises of shared decision-making (SDM) is recommended. SDM is increasingly advocated based on the ethical imperative to provide patient-centered care and the increasing evidence for beneficial patient outcomes. Few studies examined the effectiveness of SDM training in robust designs. This randomized controlled trial demonstrated that SDM training (10 hours) improves oncologists' performance in consultations with standardized patients. The next step is to examine the effect of training on oncologists' performance and patient outcomes in clinical practice.

Body composition is associated with risk of toxicity-induced modifications of treatment in women with stage I-IIIB breast cancer receiving chemotherapy.

PURPOSE: Initial dose of chemotherapy is planned based on body surface area, which does not take body composition into account. We studied the association between fat mass (kg and relative to total body weight) as well as lean mass (kg and relative to total body weight) and toxicity-induced modifications of treatment in breast cancer patients receiving chemotherapy. METHODS: In an observational study among 172 breast cancer patients (stage I-IIIB) in the Netherlands, we assessed body composition using dual-energy X-ray scans. Information on toxicity-induced modifications of treatment, defined as dose reductions, cycle delays, regimen switches, or premature termination of chemotherapy, was abstracted from medical records. Adjusted hazard ratios and 95% confidence intervals (95% CI) were calculated to assess associations between body composition and the risk of toxicity-induced modifications of treatment. RESULTS: In total, 95 out of 172 (55%) patients experienced toxicity-induced modifications of treatment. Higher absolute and relative fat mass were associated with higher risk of these modifications (HR 1.14 per 5 kg; 95% CI 1.04-1.25 and HR 1.21 per 5%; 95% CI 1.05-1.38, respectively). A higher relative lean mass was associated with a lower risk of modifications (HR 0.83 per 5%; 95% CI 0.72-0.96). There was no association between absolute lean mass and risk of toxicity-induced modifications of treatment. CONCLUSIONS: A higher absolute and a higher relative fat mass was associated with an increased risk of toxicity-induced modifications of treatment. Absolute lean mass was not associated with risk of these treatment modifications, while higher relative lean mass associated with lower risk of modifications. These data suggest that total fat mass importantly determines the risk of toxicities during chemotherapy in breast cancer patients.

Changes in Circulating Levels of 25-hydroxyvitamin D3 in Breast Cancer Patients Receiving Chemotherapy.

Cancer treatments, toxicities and their effects on lifestyle, may impact levels of vitamin D. The aim of this study was to determine serum 25-hydroxyvitamin D3 (25(OH)D3) levels before, directly after and 6 months after chemotherapy in breast cancer patients (n = 95), and a comparison group of women (n = 52) not diagnosed with cancer. Changes in 25(OH)D3 levels over time were compared using linear mixed models adjusted for age and season of blood sampling. Before start of chemotherapy, 25(OH)D3 levels were lower in patients (estimated marginal mean 55.8 nmol/L, 95% confidence interval (95%CI) 51.2-60.4) compared to the comparison group (67.2 nmol/L, 95%CI 61.1-73.3, P = 0.003). Directly after chemotherapy, 25(OH)D3 levels were slightly decreased (-5.1 nmol/L, 95%CI -10.7-0.5, P = 0.082), but ended up higher 6 months after chemotherapy (10.9 nmol/L, 95%CI 5.5-16.4, P < 0.001) compared to pre-chemotherapy values. In women without cancer, 25(OH)D3 levels remained stable throughout the study. Use of dietary supplements did not explain recovery of 25(OH)D3 levels after chemotherapy. We reported lower 25(OH)D3 levels in breast cancer patients, which decreased during chemotherapy, but recovered to levels observed in women without cancer within 6 months after chemotherapy. Suboptimal 25(OH)D3 levels in the majority of the participants highlight the relevance of monitoring in this vulnerable population.

Screening and Stepped Care Targeting Psychological Distress in Patients With Metastatic Colorectal Cancer: The TES Cluster Randomized Trial.

BACKGROUND: This study evaluated the effectiveness of a screening and stepped care program (the TES program) in reducing psychological distress compared with care as usual (CAU) in patients with metastatic colorectal cancer starting with first-line systemic palliative treatment. PATIENTS AND METHODS: In this cluster randomized trial, 16 hospitals were assigned to the TES program or CAU. Patients in the TES arm were screened for psychological distress with the Hospital Anxiety and Depression Scale and the Distress Thermometer/Problem List (at baseline and 10 and 18 weeks). Stepped care was offered to patients with distress or expressed needs, and it consisted of watchful waiting, guided self-help, face-to-face problem-solving therapy, or referral to specialized mental healthcare. The primary outcome was change in psychological distress over time, and secondary outcomes were quality of life, satisfaction with care, and recognition and referral of distressed patients by clinicians. Linear mixed models and effect sizes were used to evaluate differences. RESULTS: A total of 349 patients were randomized; 184 received the TES program and 165 received CAU. In the TES arm, 60.3% of the patients screened positive for psychological distress, 26.1% of which entered the stepped care program (14.7% used only watchful waiting and 11.4% used at least one of the other treatment steps). The observed low use of the TES program led us to pursue a futility analysis, which showed a small conditional power and therefore resulted in halted recruitment for this study. No difference was seen in change in psychological distress over time between the 2 groups (effect size, -0.16; 95% CI, -0.35 to 0.03; P>.05). The TES group reported higher satisfaction with the received treatment and better cognitive quality of life (all P<.05). CONCLUSIONS: As a result of the low use of stepped care, a combined screening and treatment program targeting psychological distress in patients with metastatic colorectal cancer did not improve psychological distress. Our results suggest that enhanced evaluation of psychosocial concerns may improve aspects of patient well-being.

Efficacy and cost-utility of the eHealth application 'Oncokompas', supporting patients with incurable cancer in finding optimal palliative care, tailored to their quality of life and personal preferences: a study protocol of a randomized controlled trial.

BACKGROUND: Patients with incurable cancer have to deal with a wide range of symptoms due to their disease and treatment, influencing their quality of life. Nowadays, patients are expected to adopt an active role in managing their own health and healthcare. Oncokompas is an eHealth self-management application developed to support patients in finding optimal palliative care, tailored to their quality of life and personal preferences. A randomized controlled trial will be carried out to determine the efficacy and cost-utility of Oncokompas compared to care as usual. METHODS: 136 adult patients with incurable lung, breast, colorectal and head and neck cancer, lymphoma and glioma, will be included. Eligible patients have no curative treatment options and a prognosis of at least three months. Patients will be randomly assigned to the intervention group or the control group. The intervention group directly has access to Oncokompas alongside care as usual, while the waiting list control group receives care as usual and will have access to Oncokompas after three months. The primary outcome measure is patient activation, which can be described as a patient's knowledge, skills and confidence to manage his or her own health and healthcare. Secondary outcome measures comprise self-efficacy, health-related quality of life, and costs. Measures will be assessed at baseline, two weeks after randomization, and three months after the baseline measurement. DISCUSSION: This study will result in knowledge on the efficacy and cost-utility of Oncokompas among patients with incurable cancer. Also, more knowledge will be generated into the need for and costs of palliative care from a societal and healthcare perspective. TRIAL REGISTRATION: Netherlands Trial Register identifier: NTR 7494 . Registered on 24 September 2018.

The relationship between rash, tumour KRAS mutation status and clinical and quality of life outcomes in patients with advanced colorectal cancer treated with cetuximab in the NCIC CTG/AGITG CO.17.

BACKGROUND: The NCIC CTG/AGITG CO.17 trial demonstrated that cetuximab monotherapy improved overall and progression-free survival (OS and PFS) in patients previously treated for advanced colorectal cancer. A strong relationship was observed between benefit from cetuximab and development of rash. In this analysis, the association of rash and benefit from cetuximab is explored and presented by KRAS mutation status. MATERIAL AND METHODS: Rash was graded by NCI CTC 2.0 criteria. Landmark analysis was performed by excluding patients who died or dropped out within 28 days and then grouping by worst grade of rash experienced by day 28. Multivariate Cox models were conducted separately for patients with KRAS wild-type (WT) tumours and KRAS mutated (MUT) tumours. CO.17 primary outcome was OS. RESULTS: Development of grade 2 + rash on cetuximab was associated with a trend towards increased OS (HR 0.61 with 95% CI 0.36-1.02 and p = 0.06) and PFS (HR 0.68 with 95% CI 0.45-1.03 and p = 0.07) as compared to grade 0/1 rash in patients with WT tumours. In patients with WT tumours on cetuximab both grade 0/1 and grade 2 + rash were associated with increased PFS (HR 0.57 95% CI 0.38-0.86; p = 0.008; and HR 0.32 95% CI 0.21-0.49; p < 0.0001) respectively, in comparison with best supportive care (BSC). Only development of grade 2 + rash on cetuximab was associated with increased OS (HR 0.52 with 95% CI 0.34-0.80 and p = 0.003) in comparison with BSC. No significant difference was found in OS or PFS among patients on cetuximab with MUT tumours with either rash grade as compared to BSC. No consistent trend was observed for the association of severity of rash and quality of life (QoL). CONCLUSION: As all patients with WT tumours benefitted to some extent from cetuximab regardless of the grade of rash, grade of rash was not a useful predictive marker.

Transcriptomic subtyping of gastrointestinal malignancies.

Gastrointestinal (GI) cancers are highly heterogeneous at multiple levels. Tumor heterogeneity can be captured by molecular profiling, such as genetic, epigenetic, proteomic, and transcriptomic classification. Transcriptomic subtyping has the advantage of combining genetic and epigenetic information, cancer cell-intrinsic properties, and the tumor microenvironment (TME). Unsupervised transcriptomic subtyping systems of different GI malignancies have gained interest because they reveal shared biological features across cancers and bear prognostic and predictive value. Importantly, transcriptomic subtypes accurately reflect complex phenotypic states varying not only per tumor region, but also throughout disease progression, with consequences for clinical management. Here, we discuss methodologies of transcriptomic subtyping, proposed taxonomies for GI malignancies, and the challenges posed to clinical implementation, highlighting opportunities for future transcriptomic profiling efforts to optimize clinical impact.

Incidence, clinical management and prognosis of patients with small intestinal adenocarcinomas from 1999 through 2019: A nationwide Dutch cohort study.

BACKGROUND: Small intestinal adenocarcinomas (SIAs) are rare. Hence, randomized controlled trials are lacking and understanding of the disease features is limited. This nationwide cohort investigates incidence, treatment and prognosis of SIA patients, to improve disease outcome. PATIENTS AND METHODS: Data of 2697 SIA patients diagnosed from January 1999 through December 2019 were retrieved from the Netherlands Cancer Registry and Pathology Archive. Incidence was calculated using the revised European Standardized Rate. The influence of patient and tumor characteristics on overall survival (OS) was studied using survival analyses. RESULTS: The age-standardized incidence rate almost doubled from 0.58 to 1.06 per 100,000 person-years, exclusively caused by an increase in duodenal adenocarcinomas. OS did not improve over time. Independent factors for a better OS were a younger age, jejunal tumors, Lynch syndrome and systemic therapy. Only 13.8% of resected patients was treated with adjuvant chemotherapy, which improved OS compared to surgery alone in stage III disease (HR 0.47 (0.35-0.61)), but not in the limited group of deficient mismatch repair (MMR) patients (n = 53, HR 0.93 (0.25-3.47)). In the first-line setting, CAPOX was associated with improved OS compared to FOLFOX (HR 0.51 (0.36-0.72)). For oligometastatic patients, a metastasectomy significantly improved OS (HR 0.54 (0.36-0.80)). CONCLUSIONS: The incidence of SIAs almost doubled in the past 20 years, with no improvement in OS. This retrospective non-randomized study suggests the use of adjuvant chemotherapy for stage III disease and first-line CAPOX for metastatic patients. For selected oligometastatic patients, a metastasectomy may be considered. MMR-status testing could aid in clinical decision-making.

Potential Adverse Outcomes of Shared Decision Making about Palliative Cancer Treatment: A Secondary Analysis of a Randomized Trial.

BACKGROUND: While shared decision making (SDM) is advocated for ethical reasons and beneficial outcomes, SDM might also negatively affect patients with incurable cancer. The current study explored whether SDM, and an oncologist training in SDM, are associated with adverse outcomes (i.e., patient anxiety, tension, helplessness/hopelessness, decisional uncertainty, and reduced fighting spirit). DESIGN: A secondary analysis of a randomized clinical trial investigating the effects of SDM interventions in the context of advanced cancer. The relations between observed SDM (OPTION12), specific SDM elements (4SDM), oncologist SDM training, and adverse outcomes were analyzed. We modeled adverse outcomes as a multivariate phenomenon, followed by univariate regressions if significant. RESULTS: In total, 194 patients consulted by 31 oncologists were included. In a multivariate analysis, observed SDM and adverse outcomes were significantly related. More specifically, more observed SDM in the consultation was related to patients reporting more tension (P = 0.002) and more decisional uncertainty (P = 0.004) at 1 wk after the consultation. The SDM element "informing about the options" was especially found to be related to adverse outcomes, specifically to more helplessness/hopelessness (P = 0.002) and more tension (P = 0.016) at 1 wk after the consultation. Whether the patient consulted an oncologist who had received SDM training or not was not significantly related to adverse outcomes. No relations with long-term adverse outcomes were found. CONCLUSIONS: It is important for oncologists to realize that for some patients, SDM may temporarily be associated with negative emotions. Further research is needed to untangle which, when, and how adverse outcomes might occur and whether and how burden may be minimized for patients. HIGHLIGHTS: Observed shared decision making was related to more tension and uncertainty postconsultation in advanced cancer patientsHowever, training oncologists in SDM did not affect adverse outcomes.Further research is needed to untangle which, when, and how adverse outcomes might occur and how burden may be minimized.

A consensus molecular subtypes classification strategy for clinical colorectal cancer tissues.

Consensus Molecular Subtype (CMS) classification of colorectal cancer (CRC) tissues is complicated by RNA degradation upon formalin-fixed paraffin-embedded (FFPE) preservation. Here, we present an FFPE-curated CMS classifier. The CMSFFPE classifier was developed using genes with a high transcript integrity in FFPE-derived RNA. We evaluated the classification accuracy in two FFPE-RNA datasets with matched fresh-frozen (FF) RNA data, and an FF-derived RNA set. An FFPE-RNA application cohort of metastatic CRC patients was established, partly treated with anti-EGFR therapy. Key characteristics per CMS were assessed. Cross-referenced with matched benchmark FF CMS calls, the CMSFFPE classifier strongly improved classification accuracy in two FFPE datasets compared with the original CMSClassifier (63.6% versus 40.9% and 83.3% versus 66.7%, respectively). We recovered CMS-specific recurrence-free survival patterns (CMS4 versus CMS2: hazard ratio 1.75, 95% CI 1.24-2.46). Key molecular and clinical associations of the CMSs were confirmed. In particular, we demonstrated the predictive value of CMS2 and CMS3 for anti-EGFR therapy response (CMS2&3: odds ratio 5.48, 95% CI 1.10-27.27). The CMSFFPE classifier is an optimized FFPE-curated research tool for CMS classification of clinical CRC samples.

Hormonal treatment in recurrent and metastatic gynaecological cancers: a review of the current literature.

For many years hormonal treatment has played a role in the treatment of a selected group of patients with a variety of recurrent or metastatic gynaecological cancers, including ovarian and endometrial carcinomas, endometrial stromal sarcomas and granulosa cell tumours. Hormonal agents that are typically used include luteinizing-hormone-releasing hormone analogues, progestogens, selective oestrogen-receptor-modulating drugs such as tamoxifen, and more recently aromatase inhibitors. The rates of response to these drugs differ considerably depending on the tumour type, disease grade and stage as well as the type of drug used. Patients with granulosa cell tumours and endometrial stromal sarcomas have the highest response rates; owing to the rarity of these tumour types, the documented response rates are based on case reports and small series. Response rates in patients with recurrent and metastatic endometrial and ovarian carcinoma have been lower. It has been suggested that patients with well-differentiated and hormone-receptor-positive carcinomas are more likely to benefit from hormonal treatment. However, the data to support this are limited, and at times conflicting, with very few prospective studies to date. This review updates the evidence for the use of hormonal treatment in patients with potentially hormone responsive recurrent and metastatic gynaecological cancers.

Long-term Survival Update and Extended RAS Mutational Analysis of the CAIRO2 Trial: Addition of Cetuximab to CAPOX/Bevacizumab in Metastatic Colorectal Cancer.

BACKGROUND: Here we present updated survival of the CAIRO2 trial and assessed whether the addition of anti-EGFR to anti-VEGF therapy could still be an effective treatment option for patients with extended RAS/BRAF wildtype and left-sided metastatic colorectal cancer (mCRC). MATERIALS AND METHODS: Retrospective updated survival and extended RAS and BRAF V600E mutational analysis were performed in the CAIRO2 trial, a multicenter, randomized phase III trial on the effect of adding cetuximab to a combination of capecitabine, oxaliplatin (CAPOX), and bevacizumab in mCRC. RESULTS: Updated survival analysis confirmed that the addition of cetuximab did not provide a benefit on either progression free (PFS) or overall survival (OS) in the intention-to-treat population. With the extended mutational analyses 31 KRAS, 31 NRAS and 12 BRAF V600E additional mutations were found. No benefit of the addition of cetuximab was observed within the extended wildtype group, even when selecting only left-sided tumors (PFS HR 0.96, p = 0.7775). However, compared to the original trial an increase of 6.5 months was seen for patients with both extended wildtype and left-sided tumors (median OS 28.6 months). CONCLUSION: Adding cetuximab to CAPOX and bevacizumab does not provide clinical benefit in patients with mCRC, even in the extended wildtype group with left-sided tumors. However, in the extended wildtype group we did observe clinically relevant higher survival compared to the initial trial report, indicating that it is important to analyze a broader panel of RAS and BRAF variants using more recent sequencing techniques when assessing survival benefit after anti-EGFR therapy.

Clinical Value of Consensus Molecular Subtypes in Colorectal Cancer: A Systematic Review and Meta-Analysis.

BACKGROUND: The consensus molecular subtypes (CMSs) of colorectal cancer (CRC) capture tumor heterogeneity at the gene-expression level. Currently, a restricted number of molecular features are used to guide treatment for CRC. We summarize the evidence on the clinical value of the CMSs. METHODS: We systematically identified studies in Medline and Embase that evaluated the prognostic and predictive value of CMSs in CRC patients. A random-effect meta-analysis was performed on prognostic data. Predictive data were summarized. RESULTS: In local disease, CMS4 tumors were associated with worse overall survival (OS) compared with CMS1 (hazard ratio [HR] = 3.28, 95% confidence interval = 1.27 to 8.47) and CMS2 cancers (HR = 2.60, 95% confidence interval = 1.93 to 3.50). In metastatic disease, CMS1 consistently had worse survival than CMS2-4 (OS HR range = 0.33-0.55; progression-free survival HR range = 0.53-0.89). Adjuvant chemotherapy in stage II and III CRC was most beneficial for OS in CMS2 and CMS3 (HR range = 0.16-0.45) and not effective in CMS4 tumors. In metastatic CMS4 cancers, an irinotecan-based regimen improved outcome compared with oxaliplatin (HR range = 0.31-0.72). The addition of bevacizumab seemed beneficial in CMS1, and anti-epidermal growth factor receptor therapy improved outcome for KRAS wild-type CMS2 patients. CONCLUSIONS: The CMS classification holds clear potential for clinical use in predicting both prognosis and response to systemic therapy, which seems to be independent of the classifier used. Prospective studies are warranted to support implementation of the CMS taxonomy in clinical practice.