Patient experiences with patient-led, home-based follow-up after curative treatment for colorectal cancer: a qualitative study.

OBJECTIVES: The number of patients with colorectal cancer (CRC) in need of oncological follow-up is growing. As a response, patient-led, home-based follow-up (PHFU) was developed, implemented and assessed. The aim of this study was to investigate how patients experienced PHFU. DESIGN: A qualitative study with individual semistructured interviews. Interviews were transcribed verbatim, and thematically analysed through an inductive, double-coding approach. SETTING: A university medical centre in the Netherlands. PARTICIPANTS: 12 curatively treated patients with CRC who received PHFU were included after purposive sampling. RESULTS: Overall, participants (N=12) were satisfied with PHFU. The time and cost-saving aspects for patient and hospital were evidently valued. PHFU was experienced as a shared effort, but patients felt like the primary responsibility remained in the hospital. Patients mentioned a decreased personal interaction with their healthcare provider (HCP) and felt a higher threshold to ask for help. However, all major questions were still addressed. Patients felt sufficiently competent to interpret their individual test results but experienced difficulty in interpreting repeated increases in carcinoembryonic antigen levels within the normal range. Educational status, age and a complicated disease course were seen as factors limiting the applicability of PHFU, and it was expressed that PHFU should be offered as an alternative instead of a novel standard of care. CONCLUSIONS: According to patients, PHFU has great potential. However, PHFU may not be suitable for every CRC patient, and factors such as educational status, age and disease course should be taken into consideration. Patient and HCP have a shared responsibility to help successfully organise PHFU in practice.

Primary care physicians' knowledge and confidence in providing cancer survivorship care: a systematic review.

PURPOSE: To systematically review existing literature on knowledge and confidence of primary care physicians (PCPs) in cancer survivorship care. METHODS: PubMed, Ovid MEDLINE, CINAHL, Embase, and PsycINFO were searched from inception to July 2022 for quantitative and qualitative studies. Two reviewers independently assessed studies for eligibility and quality. Outcomes were characterized by domains of quality cancer survivorship care. RESULTS: Thirty-three papers were included, representing 28 unique studies; 22 cross-sectional surveys, 8 qualitative, and 3 mixed-methods studies. Most studies were conducted in North America (n = 23) and Europe (n = 8). For surveys, sample sizes ranged between 29 and 1124 PCPs. Knowledge and confidence in management of physical (n = 19) and psychosocial effects (n = 12), and surveillance for recurrences (n = 14) were described most often. Generally, a greater proportion of PCPs reported confidence in managing psychosocial effects (24-47% of PCPs, n= 5 studies) than physical effects (10-37%, n = 8). PCPs generally thought they had the necessary knowledge to detect recurrences (62-78%, n = 5), but reported limited confidence to do so (6-40%, n = 5). There was a commonly perceived need for education on long-term and late physical effects (n = 6), and cancer surveillance guidelines (n = 9). CONCLUSIONS: PCPs' knowledge and confidence in cancer survivorship care varies across care domains. Suboptimal outcomes were identified in managing physical effects and recurrences after cancer. IMPLICATIONS FOR CANCER SURVIVORS: These results provide insights into the potential role of PCPs in cancer survivorship care, medical education, and development of targeted interventions.

Cost-effectiveness of general practitioner- versus surgeon-led colon cancer survivorship care: an economic evaluation alongside a randomised controlled trial.

PURPOSE: The aim of this study is to assess cost-effectiveness of general practitioner (GP) versus surgeon-led colon cancer survivorship care from a societal perspective. METHODS: We performed an economic evaluation alongside the I CARE study, which included 303 cancer patients (stages I-III) who were randomised to survivorship care by a GP or surgeon. Questionnaires were administered at baseline, 3-, 6-, 12-, 24- and 36-months. Costs included healthcare costs (measured by iMTA MCQ) and lost productivity costs (SF-HLQ). Disease-specific quality of life (QoL) was measured using EORTC QLQ-C30 summary score and general QoL using EQ-5D-3L quality-adjusted life years (QALYs). Missing data were imputed. Incremental cost-effectiveness ratios (ICERs) were calculated to relate costs to effects on QoL. Statistical uncertainty was estimated using bootstrapping. RESULTS: Total societal costs of GP-led care were significantly lower compared to surgeon-led care (mean difference of - €3895; 95% CI - €6113; - €1712). Lost productivity was the main contributor to the difference in societal costs (- €3305; 95% CI - €5028; - €1739). The difference in QLQ-C30 summary score over time between groups was 1.33 (95% CI - 0.049; 3.15). The ICER for QLQ-C30 was - 2073, indicating that GP-led care is dominant over surgeon-led care. The difference in QALYs was - 0.021 (95% CI - 0.083; 0.040) resulting in an ICER of 129,164. CONCLUSIONS: GP-led care is likely to be cost-effective for disease-specific QoL, but not for general QoL. IMPLICATIONS FOR CANCER SURVIVORS: With a growing number of cancer survivors, GP-led survivorship care could help to alleviate some of the burden on more expensive secondary healthcare services.

Detection of colon cancer recurrences during follow-up care by general practitioners vs surgeons.

BACKGROUND: In the I CARE study, colon cancer patients were randomly assigned to receive follow-up care from either a general practitioner (GP) or a surgeon. Here, we address a secondary outcome, namely, detection of recurrences and effect on time to detection of transferring care from surgeon to GP. METHODS: Pattern, stage, and treatment of recurrences were described after 3 years. Time to event was defined as date of surgery, until date of recurrence or last follow-up, with death as competing event. Effects on time to recurrence and death were estimated as hazard ratios (HRs) using Cox regression. Restricted mean survival times were estimated. RESULTS: Of 303 patients, 141 were randomly assigned to the GP and 162 to the surgeon. Patients were male (67%) with a mean age of 68.0 (8.4) years. During follow-up, 46 recurrences were detected; 18 (13%) in the GP vs 28 (17%) in the surgeon group. Most recurrences were detected via abnormal follow-up tests (74%) and treated with curative intent (59%). Hazard ratio for recurrence was 0.75 (95% confidence interval [CI] = 0.41 to 1.36) in GP vs surgeon group. Patients in the GP group remained in the disease-free state slightly longer (2.76 vs 2.71 years). Of the patients, 38 died during follow-up; 15 (11%) in the GP vs 23 (14%) in the surgeon group. Of these, 21 (55%) deaths were related to colon cancer. There were no differences in overall deaths between the groups (HR = 0.76, 95% CI = 0.39 to 1.46). CONCLUSION: Follow-up provided by GPs vs surgeons leads to similar detection of recurrences. Also, no differences in mortality were found.

Addressing colon cancer patients' needs during follow-up consultations at the outpatient clinic: a multicenter qualitative observational study.

PURPOSE: To describe colon cancer patients' needs and how healthcare providers respond to these needs during routine follow-up consultations in hospital. METHODS: A multicenter qualitative observational study, consisting of follow-up consultations by surgeons and specialized oncology nurses. Consultations were analyzed according to Verona Coding Definitions of Emotional Sequences. Patients' questions, cues, and concerns were derived from the data and categorized into supportive care domains. Responses of healthcare providers were defined as providing or reducing space for disclosure. Patient satisfaction with care was measured with a short questionnaire. RESULTS: Consultations with 30 patients were observed. Questions typically centered around the health system and information domain (i.e., follow-up schedule and test results; 92%). Cues and concerns were mostly associated with the physical and daily living domain (i.e., experiencing symptoms and difficulties resuming daily routine; 43%), followed by health system and information (i.e., miscommunication or lack of clarity about follow-up; 28%), and psychological domain (i.e., fear of recurrence and complications; 28%). Problems in the sexuality domain hardly ever arose (0%). Healthcare providers provided space to talk about half of the cues and concerns (54%). Responses to cancer-related versus unrelated problems were similar. Overall, the patients were satisfied with the information and communication received. CONCLUSIONS: Colon cancer patients express various needs during consultations. Healthcare providers respond to different types of needs in a similar fashion. We encourage clinicians to discuss all supportive care domains, including sexuality, and provide space for further disclosure. General practitioners are trained to provide holistic care and could play a greater role.

Delivering colon cancer survivorship care in primary care; a qualitative study on the experiences of general practitioners.

BACKGROUND: With more patients in need of oncological care, there is a growing interest to transfer survivorship care from specialist to general practitioner (GP). The ongoing I CARE study was initiated in 2015 in the Netherlands to compare (usual) surgeon- to GP-led survivorship care, with or without access to a supporting eHealth application (Oncokompas). METHODS: Semi-structured interviews were held at two separate points in time (i.e. after 1- and 5-years of care) to explore GPs' experiences with delivering this survivorship care intervention, and study its implementation into daily practice. Purposive sampling was used to recruit 17 GPs. Normalisation Process Theory (NPT) was used as a conceptual framework. RESULTS: Overall, delivering survivorship care was not deemed difficult and dealing with cancer repercussions was already considered part of a GPs' work. Though GPs readily identified advantages for patients, caregivers and society, differences were seen in GPs' commitment to the intervention and whether it felt right for them to be involved. Patients' initiative with respect to planning, absence of symptoms and regular check-ups due to other chronic care were considered to facilitate the delivery of care. Prominent barriers included GPs' lack of experience and routine, but also lack of clarity regarding roles and responsibilities for organising care. Need for a monitoring system was often mentioned to reduce the risk of non-compliance. GPs were reticent about a possible future transfer of survivorship care towards primary care due to increases in workload and financial constraints. GPs were not aware of their patients' use of eHealth. CONCLUSIONS: GPs' opinions and beliefs about a possible future role in colon cancer survivorship care vary. Though GPs recognize potential benefit, there is no consensus about transferring survivorship care to primary care on a permanent basis. Barriers and facilitators to implementation highlight the importance of both personal and system level factors. Conditions are put forth relating to time, reorganisation of infrastructure, extra personnel and financial compensation. TRIAL REGISTRATION: Netherlands Trial Register; NTR4860 . Registered on the 2nd of October 2014.

Recruitment challenges to the I CARE study: a randomised trial on general practitioner-led colon cancer survivorship care.

OBJECTIVES: The I CARE study (Improving Care After colon canceR treatment in the Netherlands) aims to compare surgeon-led to general practitioner (GP)-led colon cancer survivorship care. Recruitment to the trial took longer than expected. In this descriptive study, recruitment is critically reviewed. SETTING: Patients were recruited from eight Dutch medical centres. PARTICIPANTS: Patients treated with curative intent for stages I-III colon cancer. Target patient sample size was calculated at 300. INTERVENTIONS: Patients were randomised to surgeon-led (usual) versus GP-led care, with or without access to an eHealth application (Oncokompas). OUTCOME MEASURES: Baseline characteristics of (non-)participants, reasons for non-participation and strategies to improve recruitment were reviewed. RESULTS: Out of 1238 eligible patients, 353 patients were included. Of these, 50 patients dropped out shortly after randomisation and before start of the intervention, resulting in a participation rate of 25%. Participants were on average slightly younger (68.1 years vs 69.3 years) and more often male (67% vs 50%) in comparison to non-participants. A total of 806 patients declined participation for reasons most often relating to research (57%), including the wish to remain in specialist care (31%) and too much effort to participate (12%). Some patients mentioned health (9%) and confrontation with the disease (5%) as a reason. In 43 cases, GPs declined participation, often related to the study objective, need for financial compensation and time restraints. The generally low participation rate led to concerns about reaching the target sample size. Methods to overcome recruitment challenges included changes to the original recruitment procedure and the addition of new study centres. CONCLUSIONS: Challenges were faced in the recruitment to a randomised trial on GP-led colon cancer survivorship care. Research on the transition of care requires sufficient time, funding and support base among patients and healthcare professionals. These findings will help inform researchers and policy-makers on the development of future practices. TRIAL REGISTRATION NUMBER: NTR4860.

Effect of general practitioner-led versus surgeon-led colon cancer survivorship care, with or without eHealth support, on quality of life (I CARE): an interim analysis of 1-year results of a randomised, controlled trial.

BACKGROUND: Colon cancer is associated with an increased risk of physical and psychosocial morbidity, even after treatment. General practitioner (GP) care could be beneficial to help to reduce this morbidity. We aimed to assess quality of life (QOL) in patients who received GP-led survivorship care after treatment for colon cancer compared with those who received surgeon-led care. Furthermore, the effect of an eHealth app (Oncokompas) on QOL was assessed in both patient groups. METHODS: We did a pragmatic two-by-two factorial, open-label, randomised, controlled trial at eight hospitals in the Netherlands. Eligible patients were receiving primary surgical treatment for stage I-III colon cancer or rectosigmoid carcinoma and qualified for routine follow-up according to Dutch national guidelines. Patients were randomly assigned (1:1:1:1)-via computer-generated variable block randomisation stratified by age and tumour stage-to survivorship care overseen by a surgeon, survivorship care overseen by a surgeon with access to Oncokompas, survivorship care overseen by a GP, or survivorship care overseen by a GP with access to Oncokompas. Blinding of the trial was not possible. The primary endpoint of the trial was QOL at 5 years, as measured by the change from baseline in the European Organistion for Research and Treatment of Cancer QLQ-C30 summary score. Here, we report an unplanned interim analysis of QOL at the 12-month follow-up. Grouped comparisons were done (ie, both GP-led care groups were compared with both surgeon-led groups, and both Oncokompas groups were compared with both no Oncokompas groups). Differences in change of QOL between trial groups were estimated with linear mixed-effects models. A change of ten units was considered clinically meaningful. Analysis was by intention to treat. This trial is registered with the Netherlands Trial Register, NTR4860. FINDINGS: Between March 26, 2015, and Nov 21, 2018, 353 patients were enrolled and randomly assigned. There were 50 early withdrawals (27 patient decisions and 23 GP withdrawals). Of the remaining 303 participants, 79 were assigned to surgeon-led care, 83 to surgeon-led care with Oncokompas, 73 to GP-led care, and 68 to GP-led care with Oncokompas. Median follow-up was 12·2 months (IQR 12·0-13·0) in all groups. At baseline, QOL was high in all trial groups. At 12 months, there was no clinically meaningful difference in change from baseline in QOL between the GP-led care groups and the surgeon-led care groups (difference in summary score -2·3 [95% CI -5·0 to 0·4]) or between the Oncokompas and no Oncokompas groups (-0·1 [-2·8 to 2·6]). INTERPRETATION: In terms of QOL, GP-led survivorship care can be considered as an alternative to surgeon-led care within the first year after colon cancer treatment. Other outcomes, including patient and physician preferences, will be important for decisions about the type of survivorship care. FUNDING: Dutch Cancer Society (KWF).

The predictive ability of the 313 variant-based polygenic risk score for contralateral breast cancer risk prediction in women of European ancestry with a heterozygous BRCA1 or BRCA2 pathogenic variant.

PURPOSE: To evaluate the association between a previously published 313 variant-based breast cancer (BC) polygenic risk score (PRS313) and contralateral breast cancer (CBC) risk, in BRCA1 and BRCA2 pathogenic variant heterozygotes. METHODS: We included women of European ancestry with a prevalent first primary invasive BC (BRCA1 = 6,591 with 1,402 prevalent CBC cases; BRCA2 = 4,208 with 647 prevalent CBC cases) from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), a large international retrospective series. Cox regression analysis was performed to assess the association between overall and ER-specific PRS313 and CBC risk. RESULTS: For BRCA1 heterozygotes the estrogen receptor (ER)-negative PRS313 showed the largest association with CBC risk, hazard ratio (HR) per SD = 1.12, 95% confidence interval (CI) (1.06-1.18), C-index = 0.53; for BRCA2 heterozygotes, this was the ER-positive PRS313, HR = 1.15, 95% CI (1.07-1.25), C-index = 0.57. Adjusting for family history, age at diagnosis, treatment, or pathological characteristics for the first BC did not change association effect sizes. For women developing first BC < age 40 years, the cumulative PRS313 5th and 95th percentile 10-year CBC risks were 22% and 32% for BRCA1 and 13% and 23% for BRCA2 heterozygotes, respectively. CONCLUSION: The PRS313 can be used to refine individual CBC risks for BRCA1/2 heterozygotes of European ancestry, however the PRS313 needs to be considered in the context of a multifactorial risk model to evaluate whether it might influence clinical decision-making.

Biomarkers for Response of Melanoma Patients to Immune Checkpoint Inhibitors: A Systematic Review.

BACKGROUND: Immune checkpoint inhibitors (ICIs), targeting CTLA-4 or PD-1 molecules, have shown impressive therapeutic results. However, only 20-40% of advanced melanoma patients have durable responses to ICI, and these positive effects must be balanced against severe off-target immune toxicity and high costs. This urges the development of predictive biomarkers for ICI response to select patients with likely clinical benefit from treatment. Although many candidate biomarkers exist, a systematic overview of biomarkers and their usefulness is lacking. OBJECTIVES: Here, we systematically review the current literature of clinical data of ICI treatment to provide an overview of candidate predictive biomarkers for ICI in melanoma patients. METHODS: To identify studies on biomarkers for clinical response or survival to ICI therapy in melanoma patients, we performed a systematic search in OVID MEDLINE and retrieved 429 publications, of which 67 met the eligibility criteria. RESULTS: Blood and genomic biomarkers were mainly studied for CTLA-4 ICI, while tumor tissue markers were analyzed for both CTLA-4 and PD-1 ICI. Blood cytology and soluble factors correlated more frequently to overall survival (OS) than to response, indicating their prognostic rather than predictive nature. Systemic T-cell response and regulation markers correlated to response, but progression-free survival or OS were not analyzed. Tumor tissue analyses revealed response correlations with mutational load, neoantigen load, immune-related gene expression, and CD8+ T-cell infiltration at the invasive margin. The predictive value of PD-L1 varied, possibly due to the influence of T-cell infiltration on tumor PD-L1 expression. Genomic biomarker studies addressed CTLA-4 and other immune-related genes. CONCLUSION: This review outlines all published biomarkers for ICI therapy and highlights potential candidate markers for future research. To date, PD-L1 is the best studied biomarker for PD-1 ICI response. The most promising candidate predictive biomarkers for ICI response have not yet been identified. Variations in outcome parameters, statistical power, and analyses hampered summary of the results. Further investigation of biomarkers in larger patient cohorts using standardized objectives and outcome measures is recommended.