[Whole genome sequencing to find the primary tumour in cancer of unknown primary origin]. / Onbekende primaire tumor opsporen met 'whole genome sequencing'.

Cancer of unknown primary origin (CUP) remains a serious problem. The incidence in the Netherlands is stable, 1-2 percent of all new cancer cases. In general, patients undergo a long diagnostic trajectory and only a minority receive a tumour directed treatment. More than half of the patients die within two months after the diagnosis. A complete analysis of the DNA of a tumour specimen by means of whole genome sequencing may be helpful in finding the primary tumour. Dutch medical oncologists and pathologists set up a protocol for CUP patients, in which WGS may be implemented in the diagnostic procedure.

Blended online learning for oncologists to improve skills in shared decision making about palliative chemotherapy: a pre-posttest evaluation.

PURPOSE: To improve shared decision making (SDM) with advanced cancer patients, communication skills training for oncologists is needed. The purpose was to examine the effects of a blended online learning (i.e. e-learning and online training session) for oncologists about SDM in palliative oncological care and to compare this blended format with a more extensive, fully in-person face-to-face training format. METHODS: A one-group pre-posttest design was adopted. Before (T0) and after (T2) training, participants conducted simulated consultations (SPAs) and surveys; after the e-learning (T1), an additional survey was filled out. The primary outcome was observed SDM (OPTION12 and 4SDM). Secondary outcomes included observed SDM per stage, SPA duration and decision made as well as oncologists' self-reported knowledge, clinical behavioural intentions, satisfaction with the communication and evaluation of the training. Additionally, outcomes of the blended learning were compared with those of the face-to-face training cohort. Analyses were conducted in SPSS by linear mixed models. RESULTS: Oncologists (n = 17) showed significantly higher SDM scores after the blended online learning. The individual stages of SDM and the number of times the decision was postponed as well as oncologists' beliefs about capabilities, knowledge and satisfaction increased after the blended learning. Consultation duration was unchanged. The training was evaluated as satisfactory. When compared with the face-to-face training, the blended learning effects were smaller. CONCLUSION: Blended online SDM training for oncologists was effective. However, the effects were smaller compared to face-to-face training. The availability of different training formats provides opportunities for tailoring training to the wishes and needs of learners.

First-line trifluridine/tipiracil + bevacizumab in patients with unresectable metastatic colorectal cancer: final survival analysis in the TASCO1 study.

BACKGROUND: Therapeutic options are limited in patients with unresectable metastatic colorectal cancer (mCRC) ineligible for intensive chemotherapy. The use of trifluridine/tipiracil plus bevacizumab (TT-B) in this setting was evaluated in the TASCO1 trial; here, we present the final overall survival (OS) results. METHODS: TASCO1 was an open-label, non-comparative phase II trial. Patients (n = 153) were randomised 1:1 to TT-B (trifluridine/tipiracil 35 mg/m2 orally twice daily on days 1-5 and 8-12, and bevacizumab intravenously 5 mg/kg on days 1 and 15 of each 28-day cycle) or capecitabine plus bevacizumab (C-B; capecitabine, 1250 mg/m2 orally twice daily on days 1-14 and bevacizumab 7.5 mg/kg intravenously on day 1 of each 21-day cycle). Final OS was analysed when all patients had either died or withdrawn from the study. Adjusted multivariate regression was used to investigate the effects of pre-specified variables on OS. RESULTS: At 1 September 2020, median OS was 22.3 months (95% CI: 18.0-23.7) with TT-B and 17.7 months (95% CI: 12.6-19.8) with C-B (adjusted HR 0.78; 95% CI: 0.55-1.10). No variables negatively affected OS with TT-B. Safety results were consistent with prior findings. CONCLUSIONS: TT-B is a promising therapeutic regimen in mCRC patients ineligible for intensive chemotherapy. CLINICAL TRIAL INFORMATION: NCT02743221 (clinicaltrials.gov).

Associations between the Geriatric-8 and 4-meter gait speed test and subsequent delivery of adjuvant chemotherapy in older patients with colon cancer.

OBJECTIVES: Feasible screening methods are important to identify older patients who might benefit from adjuvant chemotherapy. The aim of this study was to investigate the associations between the outcomes of screening for frailty with the Geriatric-8 questionnaire (G8) and the 4-meter gait speed test (4MGST) and subsequent delivery of adjuvant chemotherapy and treatment tolerance in older patients with colon cancer. MATERIAL AND METHODS: This retrospective multicentre study included all patients aged ≥70 with primary colon carcinoma who underwent elective surgery between May 2016 and December 2018 and for whom adjuvant chemotherapy was indicated. Data were analysed using multivariate regression models. RESULTS: 97 (73.5%) of 132 eligible patients were screened by the G8 and 85 (64.4%) by the 4MGST. In univariate analyses, patients who scored indicative for frailty on both the G8 (≤14) and the 4MGST (>4 s) significantly more often did not proceed with adjuvant chemotherapy than patients who scored fit on both instruments (OR = 5.10, p = 0.01). After adjustment for gender, stage, and postoperative complications, the OR decreased to 4.22 (p = 0.04). Tolerance of treatment was very high (93%) and did not differ between screening groups. CONCLUSION: Although patients who scored indicative for frailty on both the G8 and the 4MGST significantly more often did not proceed with adjuvant chemotherapy, it is still unknown whether the G8 and the 4MGST are reliable tools for identifying patients who are at high risk for severe chemotoxicity. Nonetheless, this study shows that current selection for adjuvant chemotherapy among older patients with colon cancer is safe with low rates of severe chemotoxicity.

Extensive diagnostic work-up for patients with carcinoma of unknown primary.

Patients with carcinoma of unknown primary (CUP) present with metastatic disease without an identified primary tumour. The unknown site of origin makes the diagnostic work-up and treatment challenging. Since little information is available regarding diagnostic work-up and treatment in daily practice, we collected and analysed these in a patient cohort with regard to the recommendations of the national CUP guideline. Data of 161 patients diagnosed with CUP in 2014 or 2015 were extracted from the Netherlands Cancer Registry (NCR) and supplemented with diagnostic work-up information from patient files and analysed. Patients underwent an average of five imaging studies during the diagnostic phase (range 1-17). From the tests as recommended in the national guideline on CUP, a chest X-ray was most commonly performed (73%), whereas a PET-CT was done in one out of four patients (24%). Biopsies were taken in 86% of the study population, with Cytokeratin 7 being the most frequently tested histopathological marker (73%). Less than half of patients received therapy (42%). CUP patients undergo extensive diagnostic work-up. The performance status did not influence the extent of the diagnostic work-up in CUP patients, but it was an important factor for receiving treatment.

Trifluridine/tipiracil plus bevacizumab in patients with untreated metastatic colorectal cancer ineligible for intensive therapy: the randomized TASCO1 study.

BACKGROUND: We designed an open-label, noncomparative phase II study to assess the safety and efficacy of first-line treatment with trifluridine/tipiracil plus bevacizumab (TT-B) and capecitabine plus bevacizumab (C-B) in untreated patients with unresectable metastatic colorectal cancer (mCRC) who were not candidates for combination with cytotoxic chemotherapies. PATIENTS AND METHODS: From 29 April 2016 to 29 March 2017, 153 patients were randomly assigned (1:1) to either TT-B (N = 77) or C-B (N = 76). The primary end point was progression-free survival (PFS). The primary PFS analysis was performed after 100 events (radiological progression or death) were observed. Secondary end points included overall survival (OS), quality of life (QoL; QLQ-C30 and QLQ-CR29 questionnaires), and safety. RESULTS: Median (range) duration of treatment was 7.8 (6.0-9.7) months and 6.2 (4.1-9.1) months in the TT-B and C-B groups, respectively. Median (range) PFS was 9.2 (7.6-11.6) and 7.8 (5.5-10.1) months, respectively. Median (range) OS was 18 (15.2 to NA) and 16.2 (12.5 to NA) months, respectively. QoL questionnaires showed no relevant changes over time for either treatment. Therapies were well tolerated. Patients receiving TT-B had more grade ≥3 neutropenia (47% versus 5% with C-B). Patients receiving C-B had more grade ≥3 hand-foot syndrome (12% versus 0% with TT-B) and grade ≥3 diarrhea (8% versus 1% with TT-B), consistent with the known safety profiles of these agents. CONCLUSION: TT-B treatment showed promising clinical activity in untreated patients with unresectable mCRC ineligible for intensive therapy, with an acceptable safety profile and no clinically relevant changes in QoL. CLINICAL TRIAL INFORMATION: NCT02743221 (ClinicalTrials.gov).

Cognitive behavioral therapy or graded exercise therapy compared with usual care for severe fatigue in patients with advanced cancer during treatment: a randomized controlled trial.

BACKGROUND: Cancer-related fatigue remains a prevalent and burdensome symptom experienced by patients with advanced cancer. Our aim was to assess the effects of cognitive behavioral therapy (CBT) or graded exercise therapy (GET) on fatigue in patients with advanced cancer during treatment with palliative intent. PATIENTS AND METHODS: A randomized controlled trial was conducted from 1 January 2013 to 1 September 2017. Adult patients with locally advanced or metastatic cancer who reported severe fatigue during treatment [Checklist Individual Strength, subscale fatigue severity (CIS-fatigue) ≥35] were accrued across nine centers in The Netherlands. Patients were randomly assigned to either 12 weeks of CBT or GET, or usual care (1 : 1: 1, computer-generated sequence). Primary outcome was CIS-fatigue at 14 weeks. Secondary outcomes included fatigue measured with the European Organisation for Research and Treatment of Cancer-Quality of Life Questionnaire (EORTC-QLQ-C30), quality of life, emotional functioning, physical functioning, and functional impairments at baseline, 14, 18, and 26 weeks. RESULTS: Among 134 participants randomized, the mean age was 63 (standard deviation 9) years and 77 (57%) were women. Common diagnoses included: breast (41%), colorectal (28%), and prostate cancer (17%). A total of 126 participants completed assessment at 14 weeks. Compared with usual care, CBT significantly reduced fatigue [difference -7.2, 97.5% confidence interval (CI) -12.7 to -1.7; P = 0.003, d = 0.7], whereas GET did not (-4.7, 97.5% CI -10.2 to 0.9; P = 0.057, d = 0.4). CBT significantly reduced EORTC-QLQ-C30 fatigue (-13.1, 95% CI -22.1 to -4.0; P = 0.005) and improved quality of life (10.2, 95% CI 2.4 to 17.9; P = 0.011) and physical functioning (7.1, 95% CI 0.5 to 13.7; P = 0.036) compared with usual care. Improvement in emotional functioning and decrease in functional impairments failed to reach significance. GET did not improve secondary outcomes compared with usual care. CONCLUSIONS: Among advanced cancer patients with severe fatigue during treatment, a CBT intervention was more effective than usual care for reducing fatigue. Following GET, patients reported lower fatigue, but results were not significant, probably due to a smaller sample size and lower adherence than anticipated. TRIAL REGISTRATION: Netherlands National Trial Register, identifier: NTR3812.

The relative effectiveness of eribulin for advanced breast cancer treatment: a study of the southeast Netherlands advanced breast cancer registry.

Background: Eribulin provided significant overall survival (OS) benefit in heavily pretreated advanced breast cancer patients in the EMBRACE trial. We investigated the use of eribulin in daily clinical practice, the relative effectiveness of eribulin versus non-eribulin chemotherapy, and the safety of eribulin in real-world patients included in the SOutheast Netherlands Advanced BREast cancer (SONABRE) registry.Material and methods: Patients treated with eribulin and eligible patients for eribulin who received a different chemotherapy (i.e., non-eribulin group) in ten hospitals in 2013-2017 were included. A multivariate matching algorithm was applied to correct for differences in baseline characteristics between the groups, including the number of previous treatment lines. Progression-free survival (PFS) and OS of eribulin were compared with the matched non-eribulin group through Kaplan-Meier curves and multivariate Cox proportional hazard models. The occurrence of dose delay and reduction was described.Results: Forty-five patients received eribulin according to its registration criteria and 74 patients were eligible for eribulin but received non-eribulin chemotherapy. Matching increased the similarity in baseline characteristics between the eribulin and non-eribulin groups. Median PFS was 3.5 months (95% confidence interval (CI): 2.7-5.5) in the eribulin group and 3.2 months (95% CI: 2.0-4.8) in the matched non-eribulin group (adjusted hazard ratio (HR): 0.83, 95% CI: 0.49-1.38). Median OS was 5.9 months (95% CI: 4.6-11.0) and 5.2 months (95% CI: 4.6-9.5) in the eribulin and non-eribulin groups, respectively (adjusted HR: 0.66, 95% CI: 0.38-1.13). Dose delay or reduction occurred in 14 patients (31%) receiving eribulin.Conclusions: No difference in PFS and OS was observed between eribulin and non-eribulin treated patients. Eribulin had a manageable toxicity profile.

[Favourable course of cancer of unknown primary]. / Gunstig beloop bij een onbekende primaire tumor.

Favourable course of cancer of unknown primary Background Most patients with cancer of unknown primary have a very poor prognosis. Case description A 61-year-old woman was diagnosed with a cancer of unknown primary that had metastasised to the lymph nodes in the right axilla and the peritoneum. Because she could not be allocated to a treatable sub-group, she was eligible for treatment as part of a clinical trial. Prior to commencing treatment, molecular testing was conducted, the result of which suggested the primary tumour was a melanoma. We subsequently treated the patient with ipilimumab. Four years after diagnosis, there is no evidence of active disease and the patient remains in an excellent state of health. Conclusion Molecular and genetic testing can improve diagnosis and treatment options in patients with CUP. In the near future, PET-CT diagnostics and whole genome sequencing will probably suffice to identify the primary tumour.

A real-life study on the implementation and effectiveness of exemestane plus everolimus per hospital type in patients with advanced breast cancer. A study of the Southeast Netherlands Advanced Breast Cancer registry.

PURPOSE: We aimed to assess the implementation and effectiveness of exemestane plus everolimus treatment per hospital type in real-life, shortly after approval of everolimus. METHODS: Advanced breast cancer patients treated with exemestane plus everolimus in 2012-2014 were included from the SONABRE registry. Progression-free survival (PFS) and a 12-week conditional PFS (post-hoc) were estimated by Kaplan-Meier method. The multivariable Cox proportional hazards model was performed by type of hospital and adjusted for patient, tumour and treatment characteristics. RESULTS: We included 122 patients, comprising 48 patients treated in academic (N = 1), 56 in teaching (N = 4), and 18 in non-teaching (N = 2) hospitals. The median PFS was 6.3 months (95% Confidence Interval (CI) 4.0-8.6) overall, and 8.5 months (95% CI 7.7-9.3), 4.2 months (95% CI 2.0-6.3), and 5.5 months (95% CI 4.2-6.7) for the patients treated in academic, teaching and non-teaching hospitals, respectively. The adjusted Hazard Ratio (HR) for PFS-events was 1.5 (95% CI 1.0-2.2) and 1.0 (95% CI 0.5-1.9) respectively for patients treated at teaching and non-teaching hospitals versus the academic hospital. The adjusted HR for 12-week conditional PFS-events was not different between hospital types. In the first 12-week treatment period, treatment was discontinued due to early progression in one out of 48 patients in the academic versus nine out of 74 patients in the non-academic hospitals, confirmed by imaging in one and two patients, respectively. CONCLUSIONS: In our study, the median PFS was borderline significantly different between hospital types, possibly the result of a different assessment approach in the first 12-week treatment period.

Unknown primary carcinoma in the Netherlands: decrease in incidence and survival times remain poor between 2000 and 2012.

BACKGROUND/AIM: Unknown primary tumour (UPT) is the term applied to metastatic cancer, the origin of which remains unidentified. Since cancer treatment is primarily based on the tumour site of origin, treatment of UPT patients is challenging. The number of reports on incidence, treatment and survival of UPT is limited. We hereby report data on patients (2000-2012) with UPT in the Netherlands. METHODS: The age-standardised rate (ASR) of 'other and unspecified' malignancies in the Netherlands was compared with other European countries. Patients diagnosed with UPT between 2000 and 2012 were selected from the Netherlands Cancer Registry (NCR) to calculate incidence rates. Patient characteristics, treatment and survival rates were assessed. RESULTS: The ASR of 'other and unspecified' malignancies in the Netherlands did not differ from the European average ASRs (2008-2012). A total of 29,784 patients with an unknown primary tumour were selected from the NCR (2000-2012). The incidence decreased from 14 per 100,000 person years (European standardised rate) in 2000 to 7.0 in 2012. The most common metastatic sites were liver, lymph nodes, bone and lung (42%, 22%, 16% and 14%, respectively), and approximately two-thirds of patients were diagnosed with metastases at a single site. One-third of the patients were treated; these were mainly younger patients. The overall median survival for all patients was 1.7 months. The median survival of untreated patients was 1.0 month and of treated patients 6.3 months. CONCLUSION: The incidence of UPT between 2000 and 2012 is decreasing in the Netherlands, and one-third of these patients received treatment. Survival after diagnosis is limited to months rather than years.

Randomized phase III trial of S-1 versus capecitabine in the first-line treatment of metastatic colorectal cancer: SALTO study by the Dutch Colorectal Cancer Group.

BACKGROUND: Hand-foot syndrome (HFS) is a common side-effect of capecitabine. S-1 is an oral fluoropyrimidine with comparable efficacy to capecitabine in gastrointestinal cancers but associated with a lower incidence of HFS in Asian patients. This study compares the incidence of HFS between S-1 and capecitabine as first-line treatment in Western metastatic colorectal cancer (mCRC) patients. PATIENTS AND METHODS: Patients with previously untreated mCRC and planned treatment with fluoropyrimidine monochemotherapy were randomized 1 : 1 to receive either capecitabine (1250 mg/m2 orally for patients <70 years; 1000 mg/m2 for patients ≥70 years, twice daily on days 1-14) or S-1 (30 mg/m2 orally twice daily on days 1-14) in 3-weekly cycles, with bevacizumab optional in both groups. The primary endpoint was the incidence of any grade HFS, as assessed by both physicians and patients (diaries). Secondary endpoints included grade 3 HFS, other toxicities, relative dose intensity, progression-free survival, response rate and overall survival. RESULTS: A total of 161 patients were randomized in 27 centres. The incidence of any grade HFS as assessed by physicians was 73% in the capecitabine group (n = 80) and 45% in the S-1 group (n = 80) [odds ratio (95% confidence interval) 0.31 (0.16-0.60), P = 0.0005]. The incidence of grade 3 HFS was 21% and 4% (P = 0.003), respectively. Patient-assessed any grade HFS was 84% and 58%, respectively (P = 0.004). Grade 3 anorexia was more common in the S-1 group (3% versus 13%, P = 0.03). Median relative dose intensity was 88% in the capecitabine group and 95% in the S-1 group (P = 0.026). There were no statistically significant differences in median progression-free survival, response rate and overall survival rates. CONCLUSION: Treatment with S-1 in Western mCRC patients is associated with a significantly lower incidence of HFS compared with capecitabine, with comparable efficacy. CLINICALTRIALS.GOV REGISTRATION NUMBER: NCT01918852.

Real-world and trial-based cost-effectiveness analysis of bevacizumab in HER2-negative metastatic breast cancer patients: a study of the Southeast Netherlands Breast Cancer Consortium.

INTRODUCTION: The aim of our analysis was to assess the real-world cost-effectiveness of bevacizumab in addition to taxane treatment versus taxane monotherapy for HER2-negative metastatic breast cancer compared with the cost-effectiveness based on the efficacy results from a trial. METHODS: A state transition model was built to estimate costs, life years (LYs) and quality-adjusted life years (QALYs) for both treatments. Two scenarios were examined: a real-world scenario and a trial-based scenario in which transition probabilities were primarily based on a real-world cohort study and the E2100 trial, respectively. In both scenarios, costs and utility parameter estimates were extracted from the real-world cohort study. Moreover, the Dutch health care perspective was adopted. RESULTS: In both the real-world and trial scenarios, bevacizumab-taxane is more expensive (incremental costs of €56,213 and €52,750, respectively) and more effective (incremental QALYs of 0.362 and 0.189, respectively) than taxane monotherapy. In the real-world scenario, bevacizumab-taxane compared to taxane monotherapy led to an incremental cost-effectiveness ratio (ICER) of €155,261 per QALY gained. In the trial scenario, the ICER amounted to €278,711 per QALY gained. CONCLUSION: According to the Dutch informal threshold, bevacizumab in addition to taxane treatment was not considered cost-effective for HER2-negative metastatic breast cancer both in a real-world and in a trial scenario.

In real life, one-quarter of patients with hormone receptor-positive metastatic breast cancer receive chemotherapy as initial palliative therapy: a study of the Southeast Netherlands Breast Cancer Consortium.

BACKGROUND: The objective of this study was to present initial systemic treatment choices and the outcome of hormone receptor-positive (HR+) metastatic breast cancer. PATIENTS AND METHODS: All the 815 consecutive patients diagnosed with metastatic breast cancer in 2007-2009 in eight participating hospitals were identified. From the 611 patients with HR+ disease, a total of 520 patients with HER2-negative (HER2-) breast cancer were included. Initial palliative systemic treatment was registered. Progression-free survival (PFS) and overall survival (OS) per initial palliative systemic therapy were obtained using the Kaplan-Meier method and compared using the log-rank test. RESULTS: From the total of 520 patients with HR+/HER2- metastatic breast cancer, 482 patients (93%) received any palliative systemic therapy. Patients that received initial chemotherapy (n = 116) were significantly younger, had less comorbidity, had received more prior adjuvant systemic therapy and were less likely to have bone metastasis only compared with patients that received initial endocrine therapy (n = 366). Median PFS of initial palliative chemotherapy was 5.3 months [95% confidence interval (CI) 4.2-6.2] and of initial endocrine therapy 13.3 months (95% CI 11.3-15.5), with a median OS of 16.1 and 36.9 months, respectively. Initial chemotherapy was also associated with worse outcome in terms of PFS and OS after adjustment for prognostic factors. CONCLUSIONS: A high percentage of patients with HR+ disease received initial palliative chemotherapy, which was associated with worse outcome, even after adjustment of relevant prognostic factors.

Prognosis of metastatic breast cancer: are there differences between patients with de novo and recurrent metastatic breast cancer?

BACKGROUND: We aimed to determine the prognostic impact of time between primary breast cancer and diagnosis of distant metastasis (metastatic-free interval, MFI) on the survival of metastatic breast cancer patients. METHODS: Consecutive patients diagnosed with metastatic breast cancer in 2007-2009 in eight hospitals in the Southeast of the Netherlands were included and categorised based on MFI. Survival curves were estimated using the Kaplan-Meier method. Cox proportional hazards model was used to determine the prognostic impact of de novo metastatic breast cancer vs recurrent metastatic breast cancer (MFI ⩽24 months and >24 months), adjusted for age, hormone receptor and HER2 status, initial site of metastasis and use of prior (neo)adjuvant systemic therapy. RESULTS: Eight hundred and fifteen patients were included and divided in three subgroups based on MFI; 154 patients with de novo metastatic breast cancer, 176 patients with MFI <24 months and 485 patients with MFI >24 months. Patients with de novo metastatic breast cancer had a prolonged survival compared with patients with recurrent metastatic breast cancer with MFI <24 months (median 29.4 vs 9.1 months, P<0.0001), but no difference in survival compared with patients with recurrent metastatic breast cancer with MFI >24 months (median, 29.4 vs 27.9 months, P=0.73). Adjusting for other prognostic factors, patients with MFI <24 months had increased mortality risk (hazard ratio 1.97, 95% CI 1.49-2.60, P<0.0001) compared with patients with de novo metastatic breast cancer. When comparing recurrent metastatic breast cancer with MFI >24 months with de novo metastatic breast cancer no significant difference in mortality risk was found. The association between MFI and survival was seen irrespective of use of (neo)adjuvant systemic therapy. CONCLUSION: Patients with de novo metastatic breast cancer had a significantly better outcome when compared with patients with MFI <24 months, irrespective of the use of prior adjuvant systemic therapy in the latter group. However, compared with patients with MFI >24 months, patients with de novo metastatic breast cancer had similar outcome.

Fracture incidence in pre- and postmenopausal women after completion of adjuvant hormonal therapy for breast cancer.

INTRODUCTION: Although the effect of hormonal therapy (HT) on fracture risk during treatment of breast cancer is established, information about fracture incidence after completion of HT is scarce. In this hospital based observational study we evaluated fracture rates after completion of HT in pre- and postmenopausal women with breast cancer. METHODS: All women diagnosed with breast cancer in the VieCuri Medical Center between 1998 and 2005 who started adjuvant HT with aromatase inhibitors or tamoxifen were included (n = 289). Data on fracture rate, fracture type and risk factors for fracture after completion of HT were collected. RESULTS: The overall fracture rate was 12% in pre- and 15% in postmenopausal women respectively during an average follow-up of 3.1 ± 2.9 years. The number of patients with at least one fracture was 41 (14%). There was no difference in fracture rates between different types of HT (P = 0.15). The most common types of fractures were toe/finger fractures in premenopausal- and hip and major fractures in postmenopausal women. Median time to first fracture was shorter in premenopausal women (1.4 years, IQR 0.2-3.5) than in postmenopausal women (2.4 years, IQR 0.7-5.1, P = 0.01). A history of previous fracture was a significant risk factor for fracture in postmenopausal women (HR 3.9, 95% CI 1.3-11.7). CONCLUSION: Fracture rates in the first years after cessation of HT for breast cancer were 12% and 15% for pre- and postmenopausal women respectively. The most common fractures in postmenopausal women were hip and major fractures.

Treatment and complications in elderly stage III colon cancer patients in the Netherlands.

BACKGROUND: We evaluated which patient factors were associated with treatment tolerance and outcome in elderly colon cancer patients. DESIGN: Population-based data from five regions included in the Netherlands Cancer Registry were used. Patients with resected stage III colon cancer aged ≥75 years diagnosed in 1997-2004 who received adjuvant chemotherapy (N = 216) were included as well as a random sample (N = 341) of patients who only underwent surgery. RESULTS: The most common motives for withholding adjuvant chemotherapy were a combination of high age, co-morbidity and poor performance status (PS, 43%) or refusal by the patient or family (17%). In 57% of patients receiving chemotherapy, adaptations were made in treatment regimens. Patients who received adjuvant chemotherapy developed more complications (52%) than those with surgery alone (41%). For the selection of patients who had survived the first year after surgery, receiving adjuvant chemotherapy resulted in better 5-year overall survival (52% versus 34%), even after adjustment for differences in age, co-morbidity and PS. CONCLUSION: Despite high toxicity rates and adjustments in treatment regimens, elderly patients who received chemotherapy seemed to have a better survival. Prospective studies are needed for evaluating which patient characteristics predict the risks and benefits of adjuvant chemotherapy in elderly colon cancer patients.

The unknown biology of the unknown primary tumour: a literature review.

The unknown primary tumour (UPT) is an intriguing clinical phenomenon found in approximately 5% of all newly diagnosed patients with cancer. It is unclear whether UPT forms a distinct biological entity with specific genetic and phenotypic characteristics, or whether it is merely a clinical presentation of metastases in patients in whom the primary tumour cannot be detected and does not result in any visible clinical signs. Understanding the basic biology of UPT may shed light on this issue and, moreover, may have a direct impact on clinical care. A review of the literature revealed only a limited number of publications describing the genetic and phenotypic features of UPT, most of which focus only on the potential of these markers to predict prognosis. The question as to whether the biology of UPT is different from tumours of known primaries therefore remains unanswered. Further insight into the molecular mechanisms underlying the oncogenesis of UPT, e.g. by applying newly available DNA and gene profiling microarray techniques, will be necessary to understand its specific biology and to develop more effective treatments.

Epidemiology of unknown primary tumours; incidence and population-based survival of 1285 patients in Southeast Netherlands, 1984-1992.

Patients with an unknown primary tumour (UPT) represent 5-10% of all new cancer patients. Data on survival and prognostic factors of UPTs are based on selected patient series from specialised institutions. Population-based data on incidence, histology and determinants of survival for patients with UPT are not available. All patients diagnosed with UPT between 1984 and 1992 and entered in the population-based Eindhoven Cancer Registry for Southeast Netherlands were included. Follow-up of vital status is complete up to 1999. 1285 patients were registered. In 1024 patients, the diagnosis was confirmed histopathologically: 479 (47%) had adenocarcinoma, 453 (44%) poorly differentiated carcinoma (PDC) or adenocarcinoma (PDA), 76 (7%) squamous cell carcinoma and 16 patients (2%) had an undifferentiated malignant neoplasm. In 26% of these patients with UPT, the tumour was already widely disseminated at presentation. The majority of patients (67%) received only supportive treatment. The median survival was 11 weeks and only 15% were still alive 1 year after diagnosis. Favourable subgroups comprised young patients and patients with metastases localised in lymph nodes. In 261 cases, the diagnosis was made clinically. These patients were evaluated separately. They were older than the biopsy-confirmed patients, received less cancer therapy and their prognosis was even worse (median survival of 7 weeks). In a comparison with data from a tertiary referral centre in the United States of America (USA), our patients were older, received less therapy and had a poorer prognosis. Demographics of our favourable subgroup resembled the patients from the American study. The differences were most likely caused by the differences in the patient populations. In conclusion, we have demonstrated in a population-based study that the prognosis for patients with UPT is more unfavourable than suggested in most clinical studies.