[Aspirin and cancer: evidence of a prophylactic effect]. / Acetylsalicylzuur en kanker: aanwijzingen voor een preventief effect.

Due to increased life expectancy, the number of new patients diagnosed with cancer is also increasing; this requires effective and inexpensive strategies for preventing cancer. The concept of chemoprevention involves taking medication to reduce cancer risk. By re-assessing aspirin trials that were originally conducted to determine its effect on cardiovascular disease, it appeared that aspirin was associated with a reduction in the incidence of cancer as well as cancer-related mortality. The vascular benefits and risks associated with aspirin are only clinically relevant in the short term; its beneficial effects on cancer risk only become apparent after three years. Aspirin probably has a preventive effect on metastasis. These findings from randomised trials are consistent with results from methodologically rigorous observational studies. Until now, primary prevention in vascular disease has only proven to be cost-effective in certain risk groups. In future cost-effectiveness analyses, the beneficial effect of aspirin on cancer risk needs to be taken into account.

[Pregnancy-associated breast cancer: current opinions on diagnosis and treatment]. / Mammacarcinoom tijdens de zwangerschap: huidige inzichten in diagnostiek en behandeling.

Because of the trend to postpone childbirth until later in life we will be increasingly confronted with pregnancy-associated breast cancer. We report on two patients with pregnancy-associated breast cancer. Complete treatment of this condition during pregnancy by means of surgery, radiotherapy and chemotherapy is possible without any known damage to the foetus, even if the breast cancer is diagnosed early in pregnancy. Treatment should be multidisciplinary and preferably centralized. Pregnancy does not seem to influence the prognosis of breast cancer. All patients with pregnancy-associated breast cancer should be registered in a registration study.

[Re-irradiation of painful bone metastases]. / Herbestraling van pijnlijke botmetastasen: te weinig kennis over effect.

Little is known about what the best treatment is for patients returning with painful bone metastases after their first radiotherapy. Treatment should be individualized and should depend on the histology of the primary tumour, the general condition of the patient, systemic treatment options and prognosis. The precise effect of re-irradiation of painful bone metastases has scarcely been studied. A recent meta-analysis published in the Dutch Journal of Medicine sheds only some light on this subject; the meta-analysis provided only some indications as to the effects of re-irradiation, but did not provide any evidence. The studies included were, methodologically speaking, not very strong, as much data were derived from very small numbers of patients. In addition, re-irradiation was never the primary object of study. An international, prospective, randomized clinical trial into the effects of re-irradiation of bone metastases has recently achieved its patient-inclusion target. The first results will be available by the end of 2012; these results will hopefully fill the current gaps in our knowledge.

[Scalp cooling for chemotherapy-induced alopecia]. / Hoofdhuidkoeling tegen alopecia door chemotherapie.

Alopecia is a very common side effect of cytostatic therapy and is considered one of the most emotionally distressing effects. To prevent alopecia scalp cooling is currently used in some indications in medical oncology in 59 hospitals in the Netherlands. The success of scalp cooling depends on various factors such as type of chemotherapy, dose, infusion time, number of treatment cycles and combinations of drugs. In general, scalp cooling is well tolerated. The reported side-effects are headache, coldness, dizziness and sometimes claustrophobia. An increase in the risk of scalp metastases has not been demonstrated. Proceeding from the South Netherlands Comprehensive Cancer Centre a national working group is put together in order to draw up a national guideline for chemotherapy-induced alopecia.

[Allow scalp cooling during adjuvant chemotherapy in patients with breast cancer; scalp metastases rarely occur]. / Hoofdhuidkoeling toelaten bij adjuvante chemotherapie van borstkankerpatiënten; incidentie hoofdhuidmetastasen zeer gering.

OBJECTIVE: To investigate the incidence of scalp metastases in high-risk breast cancer patients in order to assess whether caution is warranted with scalp cooling during adjuvant therapy. DESIGN: Observational study. METHODS: The incidence of scalp metastases and the disease course were studied in 885 very well evaluated high-risk breast cancer patients. These patients, who had at least four positive axillary lymph nodes, were treated in a randomised study with either classical chemotherapy, or the same chemotherapy followed by high-dose chemotherapy and autologous stem cell transplantation (the so-called N4+ study). RESULTS: After a median follow up of 110 months, 403 of the 885 patients (46%) had relapsed or developed metastases. 25 patients (3%) had developed skin metastasis; 4 of these patients (0.5%) had developed hairy scalp metastasis. The scalp metastases always occurred at the same time as or later than metastases elsewhere. CONCLUSION: Scalp metastases occur with a very low frequency and not as the first sign of metastatic disease. It is therefore unlikely that scalp cooling (to prevent baldness) decreases the local working of chemotherapy to such an extent that the risk of scalp metastases increases.

[The quality indicator 'tumour positive surgical margin following breast-conserving surgery' does not provide transparent insight into care]. / De prestatie-indicator 'irradicaliteit na borstsparende operatie': geen zuiver zicht op goede zorg.

OBJECTIVE: To determine whether the quality indicator 'tumour positive surgical margin following breast-conserving surgery, consistently measured the quality of breast-cancer surgery independently of the different definitions used and differences in case mix, taking statistical random variation into account. DESIGN: Descriptive study. METHODS: Data was collected from 762 patients who underwent breast-conserving surgery for invasive or in situ carcinoma of the breast, in the period 1 July 2007 - 30 June 2008 in 1 of the 9 hospitals in the region of the Comprehensive Cancer Centre West in the Netherlands. We compared 3 definitions for 'tumour positive surgical margin': the one used by the Health Care Inspectorate, the one used by the organisation 'Zichtbare Zorg' ('transparent care') and the percentage of re-resection. For case mix correction we identified risk factors for tumour margin positivity with logistic regression. The results were presented in a funnel plot, using 95% confidence interval (CI) around the national standard of 20%. RESULTS: Depending on the definition used, the tumour positive surgical margin rate of the total group varied from 11 to 21%. Individual hospital rates varied by up to 19%. In situ carcinoma was associated with higher tumour positive surgical margin rates. Results differed significantly between hospitals for all 3 definitions. However, the funnel plot showed that results for most hospitals fell within the 95% CI of the standard. Whether a hospital fell within the 95% CI of the standard depended upon on the definition used and case mix correction. CONCLUSION: The lack of a single definition for the quality indicator 'tumour positive surgical margin following breast-conserving surgery' and the lack of case-mix correction undermine the validity of the indicator. Standardisation of definitions, uniform registration and the use of funnel plots can provide a more transparent insight into the quality of care.

Minimal GVHD following in-vitro T cell-depleted allogeneic stem cell transplantation with reduced-intensity conditioning allowing subsequent infusions of donor lymphocytes in patients with hematological malignancies and solid tumors.

OBJECTIVE: Allogeneic stem cell transplantation (alloSCT) following reduced-intensity conditioning offers a relatively nontoxic regimen while preserving rapid and sustained engraftment. Acute and chronic graft-vs-host disease (GVHD) is, however, a significant cause of severe morbidity. To reduce the incidence of GVHD, we treated a group of high-risk patients with a reduced-intensity conditioning regimen followed by in vitro T-cell-depleted alloSCT using Campath 1-H incubation. PATIENTS AND METHODS: Eighteen patients were treated with fludarabine (6 x 30 mg/m(2)), busulphan (2 x 3.2 mg/kg), and ATG (4 x 10 mg/kg) followed by the infusion of high-dose T-cell-depleted peripheral stem cells from sibling donors. No posttransplant GVHD prophylaxis was administered. At 6 months after alloSCT, low-dose donor lymphocyte infusion (DLI) was administered. RESULTS: All patients had sustained engraftment of donor cells with a median of 95% donor cells at 3 months after alloSCT. Minimal acute and no chronic GVHD was observed after alloSCT. A high incidence of cytomegalovirus (CMV) reactivation but no CMV disease was observed. Eleven patients received DLI at a median of 6.5 months after alloSCT. Acute GVHD grade II-III developed in 6 patients. All patients showed improvement of donor chimerism after DLI. With a median follow-up of 211 days, 11 patients are alive. Particular in patients with chronic lymphocytic leukemia and acute myeloid leukemia, a significant graft-vs-tumor effect was observed. CONCLUSIONS: In vitro T-cell-depleted alloSCT following reduced-intensity conditioning leads to durable donor engraftment without GVHD. The high levels of donor chimerism allow the subsequent use of cellular immunotherapy to treat residual disease.