Anne C. Regierer

Biomarkers of depression in cancer patients

Inflammation and perturbation of the hypothalamic‐pituitary‐adrenal (HPA) axis function appears to play a putative role in the etiology of depression. Patients with metastatic cancer demonstrate elevated prevalence rates for depression. The objective of the current study was to illustrate the efficacy of interleukin‐6 (IL‐6) and HPA axis function as adjuncts to support the diagnosis of depression in cancer patients.

A comparison of international breast cancer guidelines – Do the national guidelines differ in treatment recommendations?

AIM OF THE STUDY Clinical practice guidelines (CPG) are an appropriate method to optimise routine clinical care. Numerous CPGs for the diagnosis and treatment of breast cancer have been developed by national health institutions or medical societies. While a comparison of methodological criteria has been undertaken before, it is unknown whether these CPGs differ in their actual treatment recommendations. METHODS We included national breast cancer CPGs from the USA, Canada, Australia, the UK, and Germany that satisfy internationally recognised methodological criteria and are in widespread use in daily clinical care. Treatment recommendations for adjuvant invasive breast cancer including surgery, radiation, endocrine therapy, chemotherapy and anti-HER2-therapy were compared. RESULTS Recommendations for endocrine therapy show discordances regarding optimal usage of ovarian function suppression for premenopausal patients and aromatase inhibitors for postmenopausal patients. However, most other treatment recommendations exhibit a large degree of congruency. This reflects the fact that they rest on the same evidence base, and that many national guidelines are adopted from other guidelines so that well accepted guidelines are cited within other guidelines. CONCLUDING STATEMENT Considering that the development of guidelines is a very expensive and resource-intensive task the question arises whether the development of national guidelines in numerous countries is worth the effort since the recommendations differ only marginally.

An internally and externally validated prognostic score for metastatic breast cancer: analysis of 2269 patients

BACKGROUND The prognosis of metastatic breast cancer (MBC) is extremely heterogeneous. Although patients with MBC will uniformly die to their disease, survival may range from a few months to several years. This underscores the importance of defining prognostic factors to develop risk-adopted treatment strategies. Our aim has been to use simple measures to judge a patients prognosis when metastatic disease is diagnosed. PATIENTS AND METHODS We retrospectively analyzed 2269 patients from four clinical cancer registries. The prognostic score was calculated from the regression coefficients found in the Cox regression analysis. Based on the score, patients were classified into high-, intermediate-, and low-risk groups. Bootstrapping and time-dependent receiver operating characteristic curves were used for internal validation. Two independent datasets were used for external validation. RESULTS Metastatic-free interval, localization of metastases, and hormone receptor status were identified as significant prognostic factors in the multivariate analysis. The three prognostic groups showed highly significant differences regarding overall survival from the time of metastasis [intermediate compared with low risk: hazard ratio (HR) 1.76, 95% confidence interval (CI) 1.36-2.27, P < 0.001; high compared with low risk: HR 3.54, 95% CI 2.81-4.45, P < 0.001). The median overall survival in these three groups were 61, 38, and 22 months, respectively. The external validation showed congruent results. CONCLUSIONS We developed a prognostic score, based on routine parameters easily accessible in daily clinical care. Although major progress has been made, the optimal therapeutic management of the individual patient is still unknown. Besides elaborative molecular classification of tumors, simple clinical measures such as our model may be helpful to further individualize optimal breast cancer care.BACKGROUND The prognosis of metastatic breast cancer (MBC) is extremely heterogeneous. Although patients with MBC will uniformly die to their disease, survival may range from a few months to several years. This underscores the importance of defining prognostic factors to develop risk-adopted treatment strategies. Our aim has been to use simple measures to judge a patients prognosis when metastatic disease is diagnosed. PATIENTS AND METHODS We retrospectively analyzed 2269 patients from four clinical cancer registries. The prognostic score was calculated from the regression coefficients found in the Cox regression analysis. Based on the score, patients were classified into high-, intermediate-, and low-risk groups. Bootstrapping and time-dependent receiver operating characteristic curves were used for internal validation. Two independent datasets were used for external validation. RESULTS Metastatic-free interval, localization of metastases, and hormone receptor status were identified as significant prognostic factors in the multivariate analysis. The three prognostic groups showed highly significant differences regarding overall survival from the time of metastasis [intermediate compared with low risk: hazard ratio (HR) 1.76, 95% confidence interval (CI) 1.36-2.27, P < 0.001; high compared with low risk: HR 3.54, 95% CI 2.81-4.45, P < 0.001). The median overall survival in these three groups were 61, 38, and 22 months, respectively. The external validation showed congruent results. CONCLUSIONS We developed a prognostic score, based on routine parameters easily accessible in daily clinical care. Although major progress has been made, the optimal therapeutic management of the individual patient is still unknown. Besides elaborative molecular classification of tumors, simple clinical measures such as our model may be helpful to further individualize optimal breast cancer care.

Breast Cancer-Associated Thrombotic Microangiopathy

Background: Thrombotic microangiopathy (TMA) is defined as thrombocytopenia and microangiopathic hemolytic anemia. Cancer-associated TMA, a rare but fatal condition, seems an entity distinct from classical thrombotic thrombocytopenic purpura (TTP)/hemolytic uremic syndrome (HUS). Patients and Methods: All patients with breast cancer-associated TMA treated at our institution between 2003 and 2008 were analyzed retrospectively. To elucidate pathophysiological mechanisms, we measured the serum activity of the metalloprotease ADAMTS13. Results: 8 patients were identified. All showed bone marrow infiltration of breast cancer as well as thrombocytopenia, schistocytes, and hemolytic anemia. ADAMTS13 activity was mildly decreased in 4/6 patients (20–108%, normal range 30–120%), but none showed severely low levels as is characteristic of classical TTP. 6 patients were treated with anthracycline-containing fractionated chemotherapy, 5/6 patients experienced partial response. Overall survival was 13 months. Fractionated chemotherapy was well tolerated. Conclusions: Cancer-associated TMA has an underlying mechanism different from classical TTP. While bone marrow infiltration might be of major relevance, ADAMTS13 deficiency seems to be an epiphenomenon. Fractionated chemotherapy resulted in higher remission rates and comparatively long survival.

Contrast-Enhancing Meningeal Lesions Are Associated with Longer Survival in Breast Cancer-Related Leptomeningeal Metastasis.

Background: Leptomeningeal metastasis (LM) is a devastating complication of advanced cancer. Despite aggressive therapy survival is very poor. Methods: Data of all breast cancer patients with LM were retrospectively analyzed (n = 27). Results: Median survival was 9 weeks. Patients with contrast-enhancing meningeal lesions (n = 11) detected by MRI had a median survival of 33 weeks versus 8 weeks for patients without contrast-enhancing lesions (n = 9; p = 0.0407). Patients who received systemic chemotherapy (n = 18) had a median survival of 15 weeks versus 7 weeks (n = 9; p = 0.0106). Patients undergoing radiotherapy (n = 8) had a median survival of 17 weeks as compared to 5 weeks for patients without radiotherapy (n = 18; p = 0.0188). In a multiple Cox regression analysis, lack of systemic therapy (hazard ratio, HR 89.5; p = 0.002) and negative hormone receptor status (HR 4.2; p = 0.027) emerged as significant main risk factors, together with contrast-enhancing lesion as effect modifier for systemic therapy (p = 0.03). Conclusion: Contrast-enhancing meningeal lesions, systemic therapy, and radiotherapy were significantly associated with longer survival. Patients with contrast-enhancing lesions who were treated systemically had the longest survival. Evidence is increasing that systemic therapy plays an important role and should be applied in breast cancer patients with LM.

The Role of Intra-cerebrospinal Fluid Treatment and Prophylaxis in Patients With Solid Tumors

Metastasis to the central nervous system (CNS), including neoplastic meningitis (NM), is a devastating complication of systemic cancer. With the improved survival of cancer patients, the incidence of CNS metastasis is rising, especially among those with breast or lung carcinoma. New therapies that effectively treat these primary tumors outside of the CNS have underscored the significance of CNS metastases; they have become a significant clinical issue and a therapeutic challenge. This review discusses clinical situations in which treatment or chemoprophylaxis of CNS metastases and NM from breast or lung cancer may play an important role. Potential clinical trials to assess these assumptions also will be proposed.

5FU Continuous Infusion in Heavily Pretreated Advanced Breast Cancer Patients

Background: Despite advances in the first- and secondline treatment of advanced breast cancer, optimal therapy thereafter remains controversial. Treatment of heavily pretreated patients is not standardized, often of low efficacy, and limited by comorbidity. In these patients, an effective treatment with low toxicity is needed. Patients and Methods: We retrospectively analyzed all metastatic breast cancer patients treated with 5-fluorouracil as continuous infusion (CI-5FU) with daily doses of 150–300 mg/m2. Results: 43 patients were treated with CI-5FU until disease progression. The median number of metastatic sites was 3. Most patients were heavily pretreated with a median of 3 palliative chemotherapies (range 1–11). 42 patients were evaluable for objective response; among them 5 (12%) showed a partial response (PR) and 6 (15%) showed stable disease (SD) lasting at least 6 months, leading to a clinical benefit (CB) rate (complete response + PR + SD ≧ 6 months) of 27%. The median time to progression of patients with CB was 10 months (range 3–22). Overall survival of all patients from the start of CI-5FU was 8 months (range 1–75) and from the time of first metastases 42 months (range 9–281). Toxicity was low even in patients with hepatic insufficiency. Conclusion: CI-5FU showed a positive efficacy/toxicity ratio. Taking into account the high number of previous treatments, it results in a remarkable CB rate of 27%.

Vorwort zur 3. Auflage

Nur 6 Jahre nach dem ersten Erscheinen liegt hiermit bereits die 3. Auflage dieses Buches vor – aktualisiert, überarbeitet und um neue Aspekte erweitert. Dies zeigt uns das Interesse der Leser und den Bedarf an schmerzmedizinischen Informationen und Kenntnissen. Eine wichtige Neuerung erkennen Sie schon beim Blick auf den Einband: Herausgeber und Verlag haben sich zu einer Titeländerung entschlossen. Das vorliegende Buch heißt nun »Praktische Schmerzmedizin«. Dieser Begriff hat sich in den letzten 2 Jahren in Deutschland mehr und mehr durchgesetzt und umfasst alle Aspekte um das Thema Schmerz: Grundlagen und Forschung, Diagnostik, Therapie, Aus-, Fortund Weiterbildung, Versorgungsaspekte, Gutachtenwesen. Der Begriff trägt der Tatsache Rechnung, dass nicht nur die Therapie entscheidend ist. Voraussetzung für eine gute Therapie ist die Forschung und Weiterentwicklung, die Kenntnis von Grundlagen sowie eine umfassende Diagnostik, die alle Facetten der Schmerzentstehung und -chronifizierung erfasst und in der Therapie berücksichtigt. Voraussetzung für eine gute Versorgung der Patienten ist auch die Verankerung der Schmerzmedizin in der Lehre sowie eine breit gefächerte Fortund Weiterbildung. Der Begriff Schmerzmedizin beinhaltet insbesondere Interdisziplinarität. Mittlerweile ist es eine alte Erkenntnis, dass eine monodisziplinäre Herangehensweise bei Patienten mit chronischen Schmerzen deutlich weniger effektiv ist als ein interdisziplinärer Ansatz, bei dem verschiedene Berufsgruppen – Ärzte, psychologische Psychotherapeuten, Physiotherapeuten, Sporttherapeuten, Ergotherapeuten, Pflegekräfte und andere – gemeinsam, abgestimmt, koordiniert und auf Augenhöhe in die Therapie eingebunden sind. Ganz besonderer Wert wurde bei dieser Auflage auch darauf gelegt, auf bestehende Leitlinien zu verweisen. Eine leitliniengerechte Therapie garantiert Qualität, verbessert das Therapieergebnis und hilft, den immer noch vorhandenen Defiziten in Behandlung und Versorgung von Patienten mit Schmerzen entgegenzutreten. Das Buch »Praktische Schmerzmedizin« will alle diese Aspekte berücksichtigen. Es ist mit dem Ziel konzipiert, eine interdisziplinäre, aktuelle, umfangreiche, aber leicht verständliche Umsetzung der neuen Erkenntnisse aus der Wissenschaft in die praktische Schmerzmedizin und die Versorgung der Patienten zu gewährleisten. Das Buch richtet sich an alle Berufsgruppen, die in der Schmerzmedizin tätig oder daran interessiert sind, also auch an Studierende. Wir hoffen, Ihnen etwas von der spannenden Schmerzmedizin mit Kenntnissen, evidenzbasierten Therapieansätzen und Ideen zur Behandlung Ihrer Patienten weiterzugeben und bedanken uns bei allen Autorinnen und Autoren, die sich nach nur 2 Jahren erneut der Aufgabe gestellt haben, ihre Kapitel auf den neuesten Stand der Schmerzmedizin zu bringen, die Erkenntnisse und Entwicklungen der letzten Jahre einzuarbeiten und die Literatur zu aktualisieren. Auch den neu hinzugekommenen Autorinnen und Autoren danken wir für ihre kompetente und instruktive Arbeit. Ein besonderer Dank gilt Frau Hartmann und Frau Schoeler vom Springer-Verlag, die sich erneut sehr für dieses Buch eingesetzt und uns bei der Entstehung der dritten Auflage intensiv begleitet haben.

Paradigmenwechsel hin zu einer chronischen Behandlung

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