[How long are medical oncology patients in The Netherlands willing to travel for their cancer care?] / Hoe lang zijn patiënten bereid te reizen voor medisch-oncologische zorg?

BACKGROUND: The number of people with cancer will increase in the Netherlands. Further concentration and network care is pursued. The aim of this study was to explore how long medical oncology patients are willing to travel for their cancer care. METHOD: A flashmob study into patients' willingness to travel for cancer care was conducted in 65 Dutch hospitals. Patients completed a questionnaire about willingness to travel and any experienced issues with traveling. RESULTS: A total of 4337 medical oncology patients completed the questionnaire. Of the patients, 20% were willing to travel more than 1 hour (one-way) for their current treatment, and more willing to travel for treatment in a hospital more experienced in their specific type of cancer (44% more than 1 hour). Willingness to travel longer was higher among patientsagedv40 years or younger, those with higher education, with better physical functioning and with a rare cancer. Willingness to travel longer was lowest among patients aged 75 or older. Approximately 30% of all patients experienced issues with traveling, especially those with comorbidities or with decreased physical functioning. CONCLUSION: In this flashmob study, 15% of patients were willing to travel up to 30 minutes (one-way) and 44% more than 1 hour for treatment and follow-up in a hospital more experienced in their specific type of cancer. Patients aged 75 years or older were less willing to travel longer. Thirty percent of patients experienced issues with travelling. It is important to take this into account in the future organization of cancer care.

[Assessment of new oncological drugs]. / De beoordeling van oncologische middelen.

As the number of cancer patients increases and new (mostly expensive) treatment options are evolving rapidly, a critical evaluation of the value of new treatments is required in order to maintain access to new drugs and affordable cancer care. In the Netherlands, the Dutch Society of Medical Oncology- CieBOM (NVMO CieBOM) has an unique role in assessment of the value and use of new oncological drugs, next to the National Committee of Health Insurance (cieBAG) and the Dutch Health Care Institute. CieBOM developed transparent criteria for approval of oncological drugs in several settings, and recently also criteria for drugs only tested in non-randomised studies have been developed.

Limiting systemic endocrine overtreatment in postmenopausal breast cancer patients with an ultralow classification of the 70-gene signature.

PURPOSE: Guidelines recommend endocrine treatment for estrogen receptor-positive (ER+) breast cancers for up to 10 years. Earlier data suggest that the 70-gene signature (MammaPrint) has potential to select patients that have an excellent survival without chemotherapy and limited or no tamoxifen treatment. The aim was to validate the 70-gene signature ultralow-risk classification for endocrine therapy decision making. METHODS: In the IKA trial, postmenopausal patients with non-metastatic breast cancer had been randomized between no or limited adjuvant tamoxifen treatment without receiving chemotherapy. For this secondary analysis, FFPE tumor material was obtained of ER+HER2- patients with 0-3 positive lymph nodes and tested for the 70-gene signature. Distant recurrence-free interval (DRFI) long-term follow-up data were collected. Kaplan-Meier curves were used to estimate DRFI, stratified by lymph node status, for the three predefined 70-gene signature risk groups. RESULTS: A reliable 70-gene signature could be obtained for 135 patients. Of the node-negative and node-positive patients, respectively, 20% and 13% had an ultralow-risk classification. No DRFI events were observed for node-negative patients with an ultralow-risk score in the first 10 years. The 10-year DRFI was 90% and 66% in the low-risk (but not ultralow) and high-risk classified node-negative patients, respectively. CONCLUSION: These survival analyses indicate that the postmenopausal node-negative ER+HER2- patients with an ultralow-risk 70-gene signature score have an excellent 10-year DRFI after surgery with a median of 1 year of endocrine treatment. This is in line with published results of the STO-3-randomized clinical trial and supports the concept that it is possible to reduce the duration of endocrine treatment in selected patients.

Informal caregiver well-being during and after patients' treatment with adjuvant chemotherapy for colon cancer: a prospective, exploratory study.

INTRODUCTION: Caring for a significant other during cancer treatment can be demanding. Little is known about the well-being of informal caregivers of patients with colon cancer. This study aims to examine informal caregiver well-being during adjuvant chemotherapy for colon cancer. MATERIAL AND METHODS: This exploratory longitudinal, prospective study measured the course of informal caregiver burden (Self-Perceived Pressure of Informal Care), distress (Hospital Anxiety and Depression Scale), health-related quality of life (RAND-36), marital satisfaction (Maudsley Marital Questionnaire), social support (Social Support List - Discrepancies), fatigue (Abbreviated Fatigue Questionnaire), and self-esteem (Caregiver Reaction Assessment) before (T0), during (T1), and after (T2) patients' treatment. RESULTS: Baseline data of 60 out of 76 eligible dyads (79%) were analyzed. Mean levels of informal caregiver burden and distress improved significantly over time, as did their health-related quality of life and perceived social support. At baseline, 30% and 26.7% of informal caregivers reported moderate-to-high levels of burden and clinically relevant levels of distress, respectively, which changed to 20% and 18.8% at T2. Informal caregiver burden and distress at baseline were the strongest predictors of informal caregiver burden and distress during and following patients' treatment, respectively. CONCLUSION: When informal caregivers and patients experience problems before start of adjuvant chemotherapy, problems seem to improve over time. Approximately 20% of informal caregivers remain burdened and distressed after patients' end of treatment. Paying attention to baseline distress and burden seems indicated, as these were strong predictors of informal caregivers' well-being during and after treatment.

Prospective practice survey of management of cetuximab-related skin reactions.

PURPOSE: Evidence-based guidelines on how to prevent or treat cetuximab-related skin reactions are lacking and multiple care and management strategies are used. The main purpose of the present study is to gain information about the different skincare products being used against skin reactions in metastatic colorectal cancer (mCRC) and recurrent/metastatic (R/M) or locally advanced (LA) squamous cell cancer of the head and neck (SCCHN) patients treated with cetuximab. METHODS: An open-label, prospective observational study conducted in the Netherlands. The occurrence of skin reactions and the care and management options taken were documented for 16 weeks, starting from the first administration of cetuximab. RESULTS: A total of 103 patients were included in 7 hospitals. 38 patients (37%) developed a grade ≥ 2 skin reaction. Eighty-six patients could be analysed for the primary endpoint (73.3% males, mean age 62.4 years, n = 44 LA SCCHN, n = 16 R/M SCCHN, n = 26 mCRC). The most frequently used skin products at some point during the observation period were moisturizing products (70%), systemic antibiotics (64%), topical antibiotics (58%), lipid-regenerating (28%) and other topical products (28%). The overall use of products gradually increased from baseline to week 6-10, reducing by week 16. Hospital protocols were the primary reason (> 50%) for choice of the skincare products and medications. CONCLUSION: A variety of skin care products and antibiotics were commonly used. Only few patients developed severe cutaneous reactions. For patients, the occurrence of skin reactions did not influence their willingness to continue cetuximab therapy.

Caregivers of patients receiving long-term treatment with a tyrosine kinase inhibitor (TKI) for gastrointestinal stromal tumour (GIST): a cross-sectional assessment of their distress and burden.

BACKGROUND: TKIs are a long-term treatment for GIST, and may have an impact on caregivers. MATERIAL AND METHODS: For this cross-sectional study, patients and caregivers were both included when patients had been treated with TKIs for at least six months. Caregivers completed questionnaires including demographics, distress (Hospital Anxiety and Depression scale), burden (Self-Perceived Pressure from Informal Care) general health (RAND-36), comorbidity (Self-administered Comorbidity Questionnaire), social support (Social Support List - Discrepancies) and marital satisfaction (Maudsley Marital Questionnaire). Patients completed similar questionnaires, without 'burden'. We conducted analyses to explore differences between caregivers with low/moderate versus high levels of burden and low versus high levels of distress. RESULTS: Sixty-one out of seventy-one eligible couples (84%) were included in the analysis. The median age of the caregivers was 60 years; 66% were female and 78% were the patients' spouse. The median age of the patients was 66 years; 43% were female. Caregivers experienced high levels of burden and distress in 10% and 23%, respectively. Caregivers with high levels of burden perceived significantly lower mental health, less vitality, lower general health and high levels of distress. Significantly higher levels of burden were found in non-spouses, caregivers of patients with more treatment-related side-effects, caregivers who spent more hours caring, and those caring for more than one person. For distress, caregivers with high levels of distress perceived significantly more burden, lower social functioning, more role physical and emotional problems, lower mental health, less vitality and lower general health. Furthermore, high levels of distress were found in caregivers of more dependent patients and those caring for more than one person. CONCLUSIONS: Caregivers of the patients with GIST treated with TKI are managing well. There is a small, vulnerable group of caregivers with high levels of burden and/or distress, show more health-related problems, both physical and mental, and require adequate support.

[Oncology is not waiting for "shared decision-making" Patients and doctors generally reach consensus]. / Oncologie roept niet om keuzehulp.

In recent times, the importance of shared decision-making (SDM) when making medical decisions has been emphasised. In general, SDM is seen as a consultative communication style, mainly used in reaching important, preference-sensitive decisions when multiple options are available, each with advantages and disadvantages. SDM is particularly advocated in palliative cancer treatments, as patients have different goals for treatment and different trade-offs for side effects. Decision-support tools might facilitate the process of SDM, but might also fill a needs' gap only in a minority of patients. As cancer treatment increasingly becomes more personalised, cancer patients also deserve personalised guidance; sometimes this means sharing decision-making but sometimes paternalistic advice is actually required. It is questionable whether general decision-making tools will have significant impact on patient satisfaction in medical decision-making.

Willingness to accept chemotherapy and attitudes towards costs of cancer treatment; A multisite survey study in the Netherlands.

BACKGROUND: In the past years, interest in patient treatment preferences is growing. Our objectives were: (1) to assess and compare the minimal required benefit for patients with cancer, patients without cancer and healthcare professionals to make chemotherapy acceptable and (2) to obtain insight into attitudes towards societal costs of cancer treatment. PATIENTS AND METHODS: We performed a prospective survey consisting of hypothetical scenarios among patients with cancer, patients without cancer and healthcare professionals. Participants were asked to indicate the minimal desired benefit in terms of chance of cure, life prolongation and symptom relief which would make intensive and mild chemotherapy regimens acceptable. In two other scenarios, attitudes towards monthly costs for chemotherapy treatment were examined. RESULTS: The minimal benefit required to make chemotherapy acceptable did not differ between cancer and non-cancer patients, with respect to chance of cure (mean 57%), life prolongation (median 24 months) and symptom relief (mean 50%); healthcare providers were likely to accept the same chemotherapy regimen at lower thresholds (p < 0.01). Education level was an important explanatory variable and the differences between patients and healthcare professionals disappeared when corrected for education level. Opinions about the maximum acceptable costs for chemotherapy displayed a large spread between the groups. CONCLUSIONS: Minimal benefits to accept chemotherapy were not different between cancer and non-cancer patients, but are beyond what can generally can be achieved. Healthcare professionals were willing to accept chemotherapy for less benefit. This difference may be attributed to a difference in education level between the groups. Healthcare professionals rated the maximum acceptable societal cost for chemotherapy lower than patients.

Phase I and pharmacological trial of lapatinib in combination with gemcitabine in patients with advanced breast cancer.

BACKGROUND: Lapatinib has proven efficacy as monotherapy and in combination with capecitabine in patients with metastatic breast cancer (MBC) overexpressing HER2 and/or EGFR. Gemcitabine also has anti-tumor activity in MBC and a favourable toxicity profile. In this phase I study lapatinib and gemcitabine were combined. METHODS: Female patients with advanced BC were given lapatinib once daily (QD) in 28-day cycles with gemcitabine administered on day 1, 8 and 15. Physical examinations, vital signs and blood sampling for hematology, clinical chemistry and pharmacokinetics (PK) and radiological assessments of disease were performed at regular intervals. RESULTS: In total, 33 patients were included. Six dose-limiting toxicities were observed, mostly grade 3 increases in liver function tests. Most common toxicities were fatigue (73%), nausea (70%), diarrhea (58%), increases in ALAT and ASAT (55 and 52%, respectively) and rash (46%). The maximum tolerated dose was lapatinib 1250 mg QD with gemcitabine 1000 mg/m(2). Lapatinib and gemcitabine PK did not appear to be influenced by each other. Anti-tumor activity was observed with one patient (4%) showing complete response and six (23%) partial response. CONCLUSION: Despite a slightly increased toxicity profile compared to their respective monotherapies, lapatinib and gemcitabine can be safely combined while showing signs of anti-tumor activity.

Baseline comprehensive geriatric assessment is associated with toxicity and survival in elderly metastatic breast cancer patients receiving single-agent chemotherapy: results from the OMEGA study of the Dutch breast cancer trialists' group.

AIM: To evaluate the association between baseline comprehensive geriatric assessment (CGA) or the Groningen Frailty Indicator (GFI) and toxicity in elderly metastatic breast cancer (MBC) patients treated with first-line palliative chemotherapy. PATIENTS AND METHODS: MBC patients (≥65 years) were randomized between pegylated liposomal doxorubicine or capecitabine. CGA included instrumental activities of daily living (IADL), cognition using the mini-mental state examination (MMSE), mood using the geriatric depression scale (GDS), comorbidity using the Charlson index, polypharmacy and nutritional status using the body mass index. Frailty on CGA was defined as one or more of the following: IADL ≤ 13, MMSE ≤ 23, GDS ≥ 5, BMI ≤ 20, ≥5 medications or Charlson ≥2. The cut-off for frailty on the GFI was ≥4. RESULTS: Of the randomized 78 patients (median age 75.5 years, range 65.8-86.8 years), 73 were evaluable for CGA; 52 (71%) had one or more geriatric conditions. Grade 3-4 chemotherapy-related toxicity was experienced by 19% of patients without geriatric conditions compared to 56% of patients with two geriatric conditions and 80% of those with three or more (p = 0.002). Polypharmacy was the only individual factor significantly associated with toxicity (p = 0.001). GFI had a sensitivity of 69% and a specificity of 76% for frailty on CGA, and was not significantly associated with survival or toxicity. CONCLUSION: In this study of elderly patients with MBC, the number of geriatric conditions correlated with grade 3-4 chemotherapy-related toxicity. Therefore, in elderly patients for whom chemotherapy is being considered, a CGA could be a useful addition to the decision-making process.

A randomized phase II study investigating the addition of the specific COX-2 inhibitor celecoxib to docetaxel plus carboplatin as first-line chemotherapy for stage IC to IV epithelial ovarian cancer, Fallopian tube or primary peritoneal carcinomas: the DoCaCel study.

BACKGROUND: In ovarian cancer, cyclooxygenase-2 (COX-2) overexpression is prognostic for poor survival. We investigated the efficacy of celecoxib (C), a selective COX-2 inhibitor, added to docetaxel (Taxotere)/carboplatin (DC) in advanced ovarian cancer. PATIENTS AND METHODS: In a phase II, randomized study, 400 mg celecoxib b.i.d. was added to first-line DC treatment (DCC). Celecoxib was to be continued after DC termination up to 3 years. Study end points were tolerability, progression-free survival (PFS) and overall survival (OS). RESULTS: 151 of 196 eligible patients were diagnosed with stage IIIC/IV disease. Median follow-up for patients alive was 32.3 months. Celecoxib was used during a mean of 8.5 months. Twenty-three of 97 DCC patients stopped celecoxib prematurely, mainly due to skin reactions. Complete biochemical response was achieved in 51/78 DC patients (65%) versus 57/78 DCC patients (75%, not significant). In both study arms, median PFS was 14.3 months and median OS 34 months. COX-2 was expressed in 82% of 120 tumor samples retrospectively recovered. The PFS and OS of patients with intermediate/high COX-2 expression were similar to that in the other patients. CONCLUSION: Celecoxib did not influence PFS and OS, but interpretation of results is hampered by premature celecoxib discontinuation.

Increased adjuvant treatment and improved survival in elderly stage III colon cancer patients in The Netherlands.

BACKGROUND: We determined to what extent patients with colon cancer stage III ≥ 75 years received adjuvant chemotherapy and the impact on overall and disease-specific survival. PATIENTS AND METHODS: Data from The Netherlands Cancer Registry on all 8051 patients with colon cancer stage III ≥ 75 years diagnosed in 1997-2009 were included. Trends in adjuvant chemotherapy administration were analysed and multivariable overall and disease-specific survival analyses were performed. RESULTS: The proportion of stage III colon cancer patients ≥ 75 years who received adjuvant chemotherapy increased from 12%in 1997-2000 to 23% in 2007-2009 (P < 0.0001), with a marked age gradient and large geographic variation. Five-year overall survival increased over time from 28% in 1997-2000 to 35% in 2004-2006 (P < 0.0001). Sixty percent of patients died of colorectal cancer. Adjuvant chemotherapy was the strongest positive predictor of survival in this retrospective study (hazard ratio = 0.5; 95% confidence interval: 0.4-0.5). CONCLUSION: There has been an increase in administration of adjuvant chemotherapy to elderly patients with stage III colon cancer in The Netherlands since 1997. Survival of elderly patients with stage III colon cancer increased over time, at least partly due to stage migration. The large effect of adjuvant chemotherapy on survival in this study is likely to be associated with the selection of fitter patients for adjuvant treatment.

Two sides of the medallion: poor treatment tolerance but better survival by standard chemotherapy in elderly patients with advanced-stage diffuse large B-cell lymphoma.

BACKGROUND: We investigated treatment of unselected elderly patients with diffuse large B-cell lymphoma (DLBCL) and its subsequent impact on treatment tolerance and survival. PATIENTS AND METHODS: Data from all 419 advanced-stage DLBCL patients, aged 75 or older and newly diagnosed between 1997 and 2004, were included from five regional population-based cancer registries in The Netherlands. Subsequent data on comorbidity, performance status, treatment, motives for adaptations or refraining from chemotherapy and toxic effects was collected from the medical records. Follow-up was completed until 1st January 2009. RESULTS: Only 46% of patients received the standard therapy [aggressive chemotherapy with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP)-like chemotherapy]. Motives for withholding chemotherapy were refusal by patient/family, poor performance status or estimated short life expectancy. Of all patients receiving CHOP-like chemotherapy, only 56% could complete at least six cycles. Grade 3 or 4 toxicity occurred in 67% of patients receiving standard therapy. The independent effect of therapy on survival remained after correction for the age-adjusted International Prognostic Index. CONCLUSIONS: Standard therapy was applied less often in elderly patients with a subsequent independent negative impact on survival. Furthermore, high toxicity rate and the impossibility of the majority of patients to complete treatment were seen. This implies that better treatment strategies should be devised including a proper selection of senior patients for this aggressive chemotherapy.

Quality of life, geriatric assessment and survival in elderly patients with non-small-cell lung cancer treated with carboplatin-gemcitabine or carboplatin-paclitaxel: NVALT-3 a phase III study.

BACKGROUND: Elderly patients with advanced non-small-cell lung cancer (NSCLC) may derive similar benefit from platinum-based chemotherapy as younger patients. Quality of life (QoL) and comprehensive geriatric assessment (CGA) is often advocated to assess benefits and risks. PATIENTS AND METHODS: A total of 181 chemotherapy-naive patients [≥70 years, performance score (PS) of 0-2] with stage III-IV NSCLC received carboplatin and gemcitabine (CG) (n = 90) or carboplatin and paclitaxel (CP) (n = 91) every 3 weeks for up to four cycles. Primary end point was change in global QoL from baseline compared with week 18. Pretreatment CGA and mini geriatric assessment during and after treatment were undertaken. A principal component (PC) analysis was carried out to determine the underlying dimensions of CGA and QoL and subsequently related to survival. RESULTS: There were no changes in QoL after treatment. The number of QoL responders (CG arm, 12%; CP arm, 5%) was not significantly different. CGA items were only associated with neuropsychiatric toxicity. Quality-adjusted survival was not different between treatment arms. The PC analysis derived from nine CGA, six QoL and one PS score indicated only one dominant dimension. This dimension was strongly prognostic, and physical and role functioning, Groningen Frailty Indicator and Geriatric Depression Scale were its largest contributors. CONCLUSIONS: Paclitaxel or gemcitabine added to carboplatin did not have a differential effect on global QoL. CGA was associated with toxic effects in a very limited manner. CGA and QoL items measure one underlying dimension, which is highly prognostic.

Soft tissue sarcoma: why not treated?

BACKGROUND: Soft tissue sarcomas (STS) are uncommon malignancies and elderly STS patients have been reported to receive less definitive treatment compared to young STS patients. The present study was performed to investigate whether withholding treatment was based on disease specific aspects, patients' general health condition, comorbidity or a combination of these. METHODS: Patients with primary STS, registered by the Comprehensive Cancer Center North-Netherlands (CCCN) from 1989 to 1999, were analyzed retrospectively with regard to the inclusion-criteria: no primary anti-tumor treatment. RESULTS: From 1989 to 1999, 620 patients (including 56 Kaposi sarcoma) were registered with primary STS. Seventy-six patients (13%) were registered as untreated. Nineteen patients were excluded. Records of 57 patients, median age 71 years (range 23-92, 40 patients > or =65 years, 17 patients < 65 years) were examined. The reasons for no treatment were irresectability of the sarcoma (65%), metastatic disease (11%), comorbidity (4%), poor general health (5%), death prior to therapy (7%) and refusal of therapy (3%) (motivation not documented in 5%). CONCLUSIONS: Thirteen percent of all STS patients within the CCCN region were not treated, 70% of these patients were elderly. Withholding treatment was mostly disease-related (76%), e.g. irresectable retroperitoneal STS or metastatic disease; for 19% of the patients, it was related to their poor general health. The decision to refrain from cancer treatment was justifiable in all these STS patients.

[Abdominal complaints and neurological symptoms as an early sign of lung cancer: a manifestation of the anti-Hu syndrome]. / Buikklachten en neurologische symptomen als vroege manifestatie van longkanker: een uiting van het anti-Hu-syndroom.

In two patients, women aged 73 and 46 years, gastrointestinal symptoms were initially not recognised as a paraneoplastic syndrome due to small-cell lung cancer. This led to redundant diagnostics as well as a delay in final diagnosis. The anti-Hu syndrome is characterised by the presence of anti-Hu antibodies and neurological symptoms. About a quarter of the patients with the anti-Hu syndrome will develop gastrointestinal motility disorders in the course of their illness. The primary tumour is usually a small-cell lung cancer. Whereas the presence of anti-Hu antibodies appears to be beneficial for the oncological prognosis, the neurological outcome is less favourable.

Quantification of oral mucositis due to radiotherapy by determining viability and maturation of epithelial cells.

BACKGROUND: An in-vitro assay has been developed for quantitative assessment of chemotherapy induced oral mucositis. In the present study this method was evaluated for assessment of irradiation mucositis at a cellular level. METHODS: Ten patients participated in this consecutive study. All patients were treated with conventional fractionated curative postoperative radiotherapy. Prior to, and weekly during, the irradiation course, oral washings were obtained to determine viability of epithelial cells by trypan blue dye exclusion. Maturation of epithelial cells was assessed from smears (Papanicolaou staining). The viability data were compared with the WHO-score for mucositis. RESULTS: Epithelial cell viability increased during the first three weeks of radiation (P = 0.04), and was seen earlier than the subjective mucosal changes with the WHO-score. Cell maturity shifted from immature and intermediate to mature (P = 0.03). CONCLUSIONS: The cell viability assay can be considered an objective method for following the development of irradiation mucositis, and seems to be more sensitive during the first three weeks of irradiation than the WHO-scoring method.