Radiotherapie Groep

Adjuvant chemotherapy in the treatment of endometrial cancer can be difficult to tolerate for older women. This study examined age-related differences in patient preferences for chemotherapy in women with high-risk endometrial cancer. We re-analyzed data from the cross-sectional patient preference study PRETEC-2 to determine the difference between three age groups in minimally desired survival benefit of chemotherapy. For this, patients with high-risk endometrial cancer treated with adjuvant pelvic radiotherapy with or without chemotherapy completed a treatment trade-off questionnaire. Patients also rated the importance they attributed to treatment duration and acute and late side-effects for their decision on chemotherapy, which we analyzed by age group. A total of 171 patients (23% <60years, 40% 60-69years and 37% ≥70years) were included in the analysis. Older patients had a significantly higher median minimally desired survival benefit for preferring chemoradiotherapy (5% for <60years, 8% for 60-69years and 15% for patients ≥70years; (p<0.001)), and had the largest variability in minimally desired survival benefit. For a real-life five-year survival benefit of 5%, fewer older patients preferred the addition of chemotherapy to their treatment regimen (61.5% for <60years, 45.6% for 60-69years and 21.9% for ≥70years; p<0.001). Furthermore, older patients rated both treatment duration (p=0.001) and long-term tingling or numbness (p=0.005) as significantly more important than their younger counterparts. There is more heterogeneity in the desired benefit of chemotherapy among patients aged 70years or more compared to younger patients. This underlines the importance of recognizing individual differences and the need for shared decision-making.

BackgroundEvidence for effectiveness of radiotherapy for Ledderhose disease was demonstrated in the LedRad-study. However, the health economic impact of Ledderhose disease is unclear. Therefore, an economic evaluation alongside the LedRad-study was planned. MethodsThe economic evaluation was performed as a cost-effectiveness and cost-utility analysis from the societal perspective. Primary outcome parameters were pain burden and Quality Adjusted Life Years (QALY), until 12 months after the end of treatment. Secondary analyses were performed with outcomes until 18 months. Incremental cost-effectiveness (ICER) and cost-utility ratios (ICUR) were calculated to express costs per unit improvement in pain burden and costs per QALY gained, for radiotherapy compared to sham-radiotherapy. Bootstrap replication was used to assess uncertainty surrounding the ratios and to construct cost-effectiveness acceptability curves for QALY gain. ResultsPrevious analysis showed a statistically significant improvement in pain- and QoL scores in favour of radiotherapy at 12 and 18 months. At these timepoints and excluding treatment costs, cumulative total costs were considerably lower in the radiotherapy group. The ICER until 12 months after treatment was 4987 euro per unit of pain burden reduction. The ICUR was 14249 euro per QALY gained. Most of the bootstrap replications were in the upper right quadrant, indicating that health gain can be achieved at higher costs. At increasing levels of willingness to pay for a gain in QALY, the probability of cost-utility gradually increased to approximately 85%. ConclusionsIn patients with symptomatic Ledderhose disease, radiotherapy, at a moderate threshold for willingness to pay, is cost-effective in terms of QoL gain.

&lt;div&gt;Abstract&lt;p&gt;&lt;b&gt;Purpose:&lt;/b&gt; A gene expression signature, predictive for local recurrence after breast-conserving treatment, has previously been identified from a series of 165 young patients with breast cancer. We evaluated this signature on both another platform and an independent series, compared its performance with other published gene-sets, and investigated the gene expression profile of a larger data set.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Experimental Design:&lt;/b&gt; Gene expression tumor profiles were obtained on 148 of the initial 165 Dutch patients and on an independent validation series of 195 French patients. Both unsupervised and supervised classifications were used to study the gene expression profile of the 343 breast cancers and to identify subgroups that differ for their risk of local recurrence.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Results:&lt;/b&gt; The previous local recurrence signature was validated across platforms. However, when applied to the French patients, the signature did not reproduce its reported performance and did not better classify the patients than other published gene sets. Hierarchical clustering of all 343 breast cancers did not show any grouping reflecting local recurrence status. Genes related to proliferation were found differentially expressed between patients with or without local recurrence only in triple-negative tumors. Supervised classification revealed no significant gene set predictive for local recurrence or able to outperform classification based on clinical variables.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Conclusions:&lt;/b&gt; Although the previously identified local recurrence signature was robust on another platform, we were neither able to validate it on an independent data set, nor able to define a strong gene expression classifier for local recurrence using a larger data set. We conclude that there are no significant differences in gene expression pattern in tumors from patients with and without local recurrence after breast-conserving treatment. &lt;i&gt;Clin Cancer Res; 18(6); 1704–15. ©2012 AACR&lt;/i&gt;.&lt;/p&gt;&lt;/div&gt;

Figure 1: Doxorubicin dose-response plot. Dose-response curve for continuous doxorubicin dose and breast cancer risk, adjusted for age at HL treatment, chest radiotherapy and gonadotoxic treatment. Adjusted HRs for doxorubicin dose categories are added. Background: Female Hodgkin lymphoma (HL) survivors treated with chest radiotherapy at a young age have a strongly increased risk of breast cancer (BC). Recent studies in childhood cancer survivors have shown that doxorubicin may also increase BC risk. So far, the association between doxorubicin and BC risk has not been examined in cancer survivors treated at adolescent/adult ages. Methods: We assessed BC risk in a cohort of 1964 female five year HL survivors, treated at ages 15–50 years in 20 Dutch hospitals between 1975 and 2008. Cumulative BC incidence was estimated in the presence of death as a competing risk. Treatment factors were time-dependently included in the multivariable Cox regression analysis, focusing on the effect of doxorubicin exposure on BC risk. Results: HL survivors were treated at a median age of 27.8 years (interquartile range (IQR) 21.9–35.2 years). After a median follow-up of 18.3 years (IQR 12.9–24.7) years, 200 women had developed invasive BC (n=190) and/or ductal carcinoma in situ (n=49). The 30-year cumulative incidence was 19.4% (95% confidence Interval (CI) 16.6–22.3%). Among patients treated with chemotherapy (n=1113), receipt of doxorubicin-containing chemotherapy increased from 32.6% in 1975–1986 to 84.5% in 1998–2008. In multivariable analysis a cumulative dose of >200 mg/m2 was associated with increased BC risk (HR 1.7; 95% CI 1.1–2.4), compared to patients not treated with doxorubicin. BC risk increased 19% (HR 1.19; 95% CI 1.1–1.3) per additional 100 mg/m2 doxorubicine (ptrend=0.003). Receipt of mantle or axillary field irradiation or gonadotoxic therapy did not modify the association between doxorubicin and BC risk. Among patients who received >200 mg/m2 doxorubicin, the HR was 1.6 (95% CI 1.1–2.5) for patients treated with and 2.0 (95% CI 0.9–4.2) for patients treated without mantle or axillary field irradiation (Pinteraction=0.35). Gonadotoxic treatment (>8.4 g/m2 procarbazine or pelvic irradiation) significantly decreased the risk of BC. Conclusion: This study shows that doxorubicin is associated with an increased BC risk among adolescent and adult HL survivors. Now that radiotherapy doses and volumes have decreased and doxorubicin increasingly forms the backbone of HL treatment, the potential association of doxorubicin with increased BC risk is an important issue.