Autotransplant with and without induction chemotherapy in older multiple myeloma patients: long-term outcome of a randomized trial.

Autologous transplantation is controversial for older patients with multiple myeloma. The role of age-adjusted high-dose melphalan and the impact of induction chemotherapy cycles is still unclear. A total of 434 patients aged 60-70 years were randomly assigned to 4 cycles of standard anthracycline-based induction chemotherapy or no induction. For all patients, double autologous transplantation after melphalan 140 mg/m2 (MEL140) was planned. The primary end point was progression-free survival. Of 420 eligible patients, 85% received a first transplant and 69% completed double transplantation. Treatment duration was short with a median of 7.7 months with induction chemotherapy cycles and 4.6 months without induction. On an intention-to-treat basis, median progression-free survival with induction chemotherapy cycles (207 patients) was 21.4 months versus 20.0 months with no induction cycles (213 patients) (hazard ratio 1.04, 95% confidence interval 0.84-1.28; P=0.36). Per protocol, progression-free survival was 23.7 months versus 23.0 months (P=0.28). Patients aged 65 years or over (55%) did not have an inferior outcome. Patients with low-risk cytogenetics [absence of del17p13, t(4;14) and 1q21 gains] showed a favorable overall survival and included the patients with sustained first remission. MEL140 was associated with a low rate of severe mucositis (10%) and treatment-related deaths (1%). Based on hazard ratio, the short treatment arm consisting of mobilization chemotherapy and tandem MEL140 achieved 96% of the progression-free survival, demonstrating its value as an independent component of therapy in older patients with multiple myeloma who are considered fit for autologous transplantation. (clinicaltrials.gov identifier: 02288741).

Improved Risk Stratification for Breast Cancer Samples Based on the Expression Ratio of the Estrogen and Progesterone Receptor.

BACKGROUND: The receptors for estrogen (ESR1) and progesterone (PGR) are both part of the same signaling pathway and routinely used for breast cancer stratification. We tested the hypothesis if a coordinated analysis could add extra information for prognostic stratification. MATERIALS AND METHODS: ESR1 and PGR gene expression was first investigated by quantitative reverse transcription polymerase chain reaction in fresh-frozen invasive ductal breast cancer samples (Hamburg collective, case-control, n=317). Our results were then tested using two datasets generated by different technical approaches: i) a public DNA-chip data set (GSE3494, n=251) and ii) semiquantitative protein expression data based on immunohistochemistry (Stuttgart collective, n=18,528). RESULTS: The PGR/ESR1 gene-expression ratio was a prognostic indicator in those with ESR1/PGR-positive breast cancer (Hamburg collective), with a high PGR/ESR1 expression ratio indicating a favorable outcome. In all three collectives, the PGR/ESR1 mRNA ratio or its protein equivalent was a univariate prognostic factor and also a multivariate prognostic factor in the Hamburg and Stuttgart collectives. CONCLUSION: Calculation of the PGR/ESR1 gene-expression ratio and its immunohistochemical surrogate could be a useful and simple addition to routine breast cancer diagnostics. A high PGR/ESR1 ratio could be indicative of a favorable clinical outcome.

Tubular breast cancer. A retrospective study.

BACKGROUND: The well-characterized tubular-type of breast tumors is classified as low-risk breast cancer. PATIENTS AND METHODS: We report on the results of a retrospective analysis on clinical and biological features of 248 tubular breast tumors including follow-up and treatment data from two German series of 21,065 breast cancer cases. The majority of tumors were stage I or stage II, ER- and PR-positive and c-erbB2-negative with a 5-year survival-rate of 96.3%. 51.3% of patients received hormonal treatment, 75.5% had post-operative radiotherapy and 11.8% were treated with a chemotherapeutical regimen. CONCLUSION: Our retrospective analysis showed no treatment benefit for either anti-hormonal or chemotherapeutical regimens. Post-operative radiotherapy, however, improved the survival rate of patients with tubular carcinoma (log-rank=5, p=0.025). Our data suggest that post-operative radiotherapy is an important treatment to prolong survival for patients suffering from tubular breast cancer.

[Benchmarking: how to measure outcome quality at the comprehensive oncology centre in Stuttgart]. / Benchmarking der Ergebnisqualität am Onkologischen Schwerpunkt Stuttgart.

BACKGROUND: Quality-controlled documentation and evaluation of long-term course of disease is essential for measuring the outcome quality in the care of cancer patients. This project, based on the ongoing clinical cancer registry of the Comprehensive Oncology Centre (COC) Stuttgart, was aimed to integrate a long-term follow-up documentation and to compare outcome quality between centres of the OCC. METHODS: In a prospective, non-randomised, multi-centred, registry-based cohort study overall survival, disease free survival and quality of life were evaluated as indicators of outcome quality. The study included all patients suffering from breast, colon or rectum cancer, who were treated with curative intent in one of the centres of the OCC between Sep 30, 2003, and Dec 31, 2008. Cox regressions were used for the statistical evaluation of differences between centres. RESULTS: Patients suffering from breast cancer (n=3,213), colon cancer (n=1,216) and rectum cancer (n=847) were eligible for the analysis. They were treated in 10 of 13 centres of the OCC. Statistically significant differences in the overall survival could be demonstrated between centres. DISCUSSION: This project initiated a regular comparative evaluation of the outcome quality and showed that there are statistically significant differences between centres. Based on these findings, the benchmarking process will have to be further developed and elaborated.

Symptom-oriented follow-up of early breast cancer is not inferior to conventional control. Results of a prospective multicentre study.

BACKGROUND: The homogeneity of the schemes for follow-up care after curative surgical treatment of early breast cancer is still a matter of debate in Germany. We investigated whether symptom-oriented follow-up is equivalent in terms of survival rates to conventional surveillance based on scheduled tests. PATIENTS AND METHODS: In a prospective, non-randomised, multicentre cohort study carried out between 1995 and 2000, 244 patients underwent a conventional follow-up (scheduled laboratory tests including CEA and CA 15-3, chest X-rays and liver ultrasound). 426 patients were monitored in a symptom-oriented manner (additional tests only in the case of symptoms indicating possible recurrence). Mammography, structured histories and physical examinations were done regularly in both branches. 1,108 patients did not participate in the project. They represent 'real world patients', unaffected by the implications of a study. RESULTS: The symptom-oriented follow- up group produced results not inferior to those of the intensive one (p < 0.05) in terms of overall and relapse-free survival. Furthermore, no difference was indicated in terms of overall survival between study participants and the 'real world patients' (p = 0.316). CONCLUSION: The results confirm that regular imaging and laboratory tests have no relevant effect on overall survival of patients after curative primary therapy of early breast cancer and support the implementation of a symptom-oriented routine follow-up.

Immunochemotherapy with rituximab and cyclophosphamide, doxorubicin, vincristine, and prednisone significantly improves response and time to treatment failure, but not long-term outcome in patients with previously untreated mantle cell lymphoma: results of a prospective randomized trial of the German Low Grade Lymphoma Study Group (GLSG).

PURPOSE: Mantle cell lymphoma (MCL) is characterized by a poor prognosis with a low to moderate sensitivity to chemotherapy and a median survival of only 3 to 4 years. In an attempt to improve outcome, the German Low Grade Lymphoma Study Group (GLSG) initiated a randomized trial comparing the combination of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) and rituximab (R-CHOP) with CHOP alone as first-line therapy for advanced-stage MCL. PATIENTS AND METHODS: One hundred twenty-two previously untreated patients with advanced-stage MCL were randomly assigned to six cycles of CHOP (n = 60) or R-CHOP (n = 62). Patients up to 65 years of age achieving a partial or complete remission underwent a second randomization to either myeloablative radiochemotherapy followed by autologous stem-cell transplantation or interferon alfa maintenance (IFNalpha). All patients older than 65 years received IFNalpha maintenance. RESULTS: R-CHOP was significantly superior to CHOP in terms of overall response rate (94% v 75%; P = .0054), complete remission rate (34% v 7%; P = .00024), and time to treatment failure (TTF; median, 21 v 14 months; P = .0131). No differences were observed for progression-free survival. Toxicity was acceptable, with no major differences between the two therapeutic groups. CONCLUSION: The combined immunochemotherapy with R-CHOP resulted in a significantly higher response rate and a prolongation of the TTF as compared with chemotherapy alone. Hence, R-CHOP may serve as a new baseline regimen for advanced stage MCL, but needs to be further improved by novel strategies in remission.

[Lead poisoning after ingestion of ayurvedic drugs]. / Bleiintoxikation durch Einnahme ayurvedischer Arzneimittel.

HISTORY AND CLINICAL FINDINGS: A 60-year-old woman suffering from rheumatoid arthritis and taking methotrexate was admitted with recurrent episodes of nausea, vomiting, constipation, loss of appetite, myalgia and backache, sternal chest pain, costal and jaw pain. On examination the epigastrium was tender to palpation and nonrigid. INVESTIGATIONS: Laboratory tests showed normocytic anemia (with a hemoglobin concentration of 8.6 g/dl), elevated blood urea and creatinine levels, hyponatremia, hypochloremia, hemolysis and polychromasia, anisocytosis, poikilocytosis and basophilic stippling of several red cells. On gastroscopy an ulcer was excluded, ultrasound scan of abdomen, X-ray of chest and pelvis showed no abnormalities. The electrocardiogram showed a right bundle branch block and left anterior hemiblock. DIAGNOSIS, TREATMENT, AND COURSE: In the differential diagnosis of anemia with basophilic stippling and abdominal discomfort, lead poisoning was found. Whole-blood lead concentration was markedly raised to 852 micro g/l (normal < 100 micro g/l). Lead poisoning was the result of the use of ayurvedic drugs during a period of 7.5 months prior to admission to the authors' hospital. CONCLUSION: Heavy metal poisoning, especially lead poisoning, should be considered in the differential diagnosis in patients with unspecific clinical symptoms taking traditional Indian remedies.