Patients with indolent lymphomas are at high risk of infections: experience from a German outpatient clinic.

BACKGROUND: Patients with indolent B-cell non-Hodgkin lymphomas (B-NHLs) have an increased risk of infections which is caused by pathomechanisms of the diseases itself but also as a result of anti-tumor therapy. Especially the effects of anti-CD20 antibodies are well understood as these lead to decreased antibody production. Most studies regarding immunodeficiency in B-NHLs were conducted with multiple myeloma and chronic lymphocytic leukemia patients. As these studies not always represent the general population we collected and analyzed real world data from patients with indolent lymphomas and a control group (CG). RESULTS: Patients with B-NHLs undergoing therapy or who were regularly monitored in a watch and wait approach had, over the time of one year, an increased rate of infections compared to the CG of 145 healthy volunteers (mean: 11.66 vs. 7.13 infections per 1000 days). Consistent with this finding B-NHL patients received more antibiotic treatment (mean: 11.17 vs. 6.27 days) and were more often hospitalized than persons from the CG (mean: 5.19 vs. 0.99 days per 1000 days). Lymphoma patients without immunodeficiency had a lower infection rate than patients with non-symptomatic and symptomatic immunodeficiency (mean: 10.91 vs. 12.07 and 12.36 per 1000 days). The number of infections differed statistically significant for the subgroups and CG (7.13 per 1000 days). Patients with symptomatic immunodeficiency were mostly treated with regular immunoglobulin substitutions and infection rates were comparable to those of patients with asymptomatic immunodeficiency. CONCLUSIONS: Our data suggest the use of an approach with regular immune monitoring including the measurement of immunoglobulin levels and regular appointments for clinical assessment of all indolent lymphoma patients in order to identify patients with increased risk of infections. It also raises the question if patients with immunodeficiency should be treated more often with regular immunoglobulin substitution, but so far more studies are necessary to answer this question.

Shared decision-making in routine breast cancer care in Germany-A cross-sectional study.

OBJECTIVE: Many preference-sensitive decisions have to be made in breast cancer care and little is known about the decision-making processes between breast cancer patients and the different health care professionals engaged in their treatment. METHODS: All female breast cancer patients who underwent surgery in four German breast centers between 07/2016 and 12/2018 were invited to fill in a survey. The decision-making process was evaluated using the 9-item Shared Decision Making Questionnaire (SDM-Q-9) and a German measure to assess satisfaction with care (ZAPA). The higher the total score (0-100), the higher the experienced degree of participation and satisfaction, respectively. Participants were asked to separately rate consultations with their inpatient hospital doctors, outpatient gynecologists, outpatient oncologists and primary care providers. An overall mean score for the degree of participation and the satisfaction with care was calculated for each patient across all consultations assessed. Differences between the 4 treating physician groups were analyzed as well. RESULTS: Of 1068 approached patients, 563 with a mean age of 62 and a standard deviation (SD) of 12.2 years filled in the survey (response rate: 53%). The overall SDM-Q-9 score was 73.8 (SD: 20.8). Older patients stated a higher level of participation than younger, different physician groups were rated quite similarly. Overall satisfaction with care was 87.4 (SD: 15.5). CONCLUSIONS: Overall, patients reported to have experienced a high level of shared decision-making (SDM) and were quite satisfied with their treatment. However, we do not know whether non-responders might have had different experiences.

Health status and infections in patients with symptomatic primary and secondary immunoglobulin G (IgG) deficiencies receiving intravenous IgG replacement.

BACKGROUND: The effects of intravenous immunoglobulin G replacement on perceived health and infection susceptibility of patients suffering from immunoglobulin G (IgG) deficiencies should be evaluated in a prospective analysis. METHODS: Patients with symptomatic primary or secondary IgG deficiencies were interviewed prior to the first IgG infusion (t0) and over the course of their treatment (t1 - t6). The respondents rated their current health using a 100 point scale (EQ-5D-5L), ranging from 0 ('worst imaginable health') to 100 ('best imaginable health'). The patients also provided information on the frequency of infections and of infections requiring antibiotics in the past 8 weeks. A healthy control group (CG) without oncologic diseases answered the questions once. RESULTS: One hundred six patients with a median age of 65 years (21-85 years) were investigated. The median serum IgG concentration changed from 500 mg/dl (t0) to 772 mg/dl (t6). The mean number of infections and of infections requiring antibiotics decreased during IgG replacement significantly. Current health according to EQ-5D-5L improved from 57 (t0) to 68 (t6), compared to 73 in the CG. CONCLUSION: During the course of IgG replacement patients reported fewer and less severe infections. Their health assessment improved but still was inferior to the healthy CG.

[DNVF Memorandum Health Services Research in Oncology]. / DNVF-Memorandum Versorgungsforschung in der Onkologie.

Health services research in oncology deals with all situations which cancer patients face. It looks at the different phases of care, i. e. prevention / early detection, prehabilitation, diagnostics, therapy, rehabilitation and palliative care as well as the various actors, including those affected, the carers and self-help. It deals with healthy people (e. g. in the context of prevention / early detection), patients and cancer survivors. Due to the nature of cancer and the existing care structures, there are a number of specific contents for health services research in oncology compared to general health services research while the methods remain essentially identical. This memorandum describes the subject, illustrates the care structures and identifies areas of health services research in oncology. This memorandum has been prepared by the Oncology Section of the German Network for Health Services Research and is the result of intensive discussions.

High adherence of patients with multiple myeloma who receive treatment with immunomodulatory drugs (IMIDS) in hematology/oncology group practices in Germany.

PURPOSE: Immunomodulatory drugs (IMIDS) have changed the treatment and outcome of patients suffering from multiple myeloma. However, with the oral administration adherence becomes an issue. Since there is no "gold standard" in measuring adherence, we assessed the adherence of myeloma patients with the help of different data sources. METHODS: All patients who have been receiving IMIDS for at least 3 months were eligible. Computer assisted personal interviews of patients and, if possible, their caregivers were carried out. Attending oncologists evaluated the patient's adherence with the help of a standardized questionnaire. In addition, a retrospective analysis of prescription data was conducted. All data were analyzed statistically using SPSS. RESULTS: One hundred myeloma patients, 35% female, 65% male, with a median age of 70 years (37-86) were interviewed. Prescription data could be evaluated in terms of adherence in 78 patients (78%), 56 caregivers could be questioned (56%). Ninety-seven percent of patients rated themselves as adherent in taking IMIDS. Data from treating oncologists, caregivers and prescriptions supported this result. IMID therapies were rated as very effective and significant, toxicities were acceptable and dosing regimens simple/uncomplicated. CONCLUSIONS: Myeloma patients seem to be highly adherent to IMID treatments.

Metastatic Breast Cancer: Prolonging Life in Routine Oncology Care.

Overall survival (OS) of patients with metastatic breast cancer (MBC) has improved within controlled clinical trials. Whether these advances translate into improved OS in routine care is controversial. We therefore analyzed retrospectively unselected female patients from five oncology group practices and one university outpatient clinic, whose initial diagnosis of MBC was between 1995 and 2022. A total of 1610 patients with a median age of 63 years (23-100) were evaluated. In all, 82.9% had hormone-receptor-positive disease, and 23.8% were HER2-positive. Evaluation in time cohorts by initial MBC diagnosis date showed a continuous prolongation of median OS from 31.6 months (0.5-237.3+) (1995-2000) to 48.4 months (0.4-61.1+) (2018-2022) (p = 0.003). Univariable analyses showed a significant dependence on the time cohort of diagnosis, metastatic status at initial diagnosis, age at metastasis, hormone and HER2 status, general condition, metastasis localization, and the number of affected organs. A multivariable analysis revealed a significant dependence of survival probability on receptor status, general condition, and number of metastatic sites, as well as the time between initial breast cancer diagnosis and the diagnosis date of MBC in months. In sum, OS of patients with MBC has improved continuously and significantly in routine care over the last 27 years.

Curricular course for medical students at a hematology and oncology specialty practice, 2010-2022.

Aim: For several years now, medical students have also been taught general practice at academic medical teaching practices. Specialty practices have not yet been included in the curricular education. Since 1998, we have conducted a block seminar in hematology twice per semester for eighth-semester medical students. This block seminar was offered from 1998-2001 to students at the Philipps University in Marburg and since 2001 to students at the Johannes Gutenberg University in Mainz. Since 2010 our block seminar has been part of the curriculum at the Johannes Gutenberg University. Method: Standardized course evaluation by students who had attended our block seminar between January 2010 and March 2022. Courses that were held virtually due to corona were not included in the analysis. The questionnaire used to evaluate courses in the medical degree program at the Johannes Gutenberg University served as the evaluation instrument. Results: Since 1998 more than 1,000 students have attended our seminar. The systematic evaluation of the course by 500 students who participated in the curricular, classroom-based seminar sessions since 2010 shows that the highest ratings possible are given for practical relevance, learning atmosphere, teaching and effectiveness. Conclusion: High quality in teaching curricular courses to medical students at a specialty practice is possible. Insights into the possibilities connected with working in the outpatient setting at a medical practice broadens students' experience. This teaching format facilitates external university instructors in terms of teaching and, at the same time, relieves the university in terms of staff and financial budget.

Survival improvement of patients with chronic lymphocytic leukemia (CLL) in routine care 1995-2017.

Seven hundred and twenty-four CLL-outpatients with a median age of 67 (35-92) were analyzed. Four hundred and twenty-seven (59%) were male, 297 (41%) female. At diagnosis 556 (77%) were in Binet stage A, 91 (13%) stage B and 36 (5%) stage C. Forty-six percent received treatment during the evaluation period. Treatment consisted of purine analogs in 38%, alkylating agents in 96%, chemoimmunotherapy with anti-CD20 monoclonal antibodies in 63%, ibrutinib in 9%, venetoclax in 1% and idelalisib in 3%. 3% received allogeneic hematopoietic stem cell transplantation. Overall survival (OS) according to Binet stage was: A 13.9 years (0.1-37.4), B 9.2 years (1.4-29.3) and C 7.9 years (0.5-19.4) respectively. Median OS from the start of therapy improved over time; 1995-2001: 5.8 years, 2002-2008: 6.1 years and 2009-2017: median not reached. Survival of patients with CLL has improved in routine care and was strongly related to active disease, disease stage, performance status and whether therapy included an anti-CD20 monoclonal antibody.

Successful Evidence-Based Treatment of Patients with Advanced Pancreatic Cancer in Community-Based Oncology Group Practices.

BACKGROUND: Randomized clinical trials do not reflect the day-to-day reality of patient care; hence, the treatment of patients with advanced pancreatic cancer in oncology group practices was evaluated. PATIENTS AND METHODS: All consecutive patients with advanced pancreatic cancer who were treated between 01/2012 and 12/2015 in 4 oncology group practices were analyzed retrospectively using SPSS software. RESULTS: 324 patients with a median age of 70 years (range 32-94 years) were analyzed. The majority were male (56%) and had distant metastases (74%). Chemotherapy was the major modality of treatment (86%) with a median overall survival (OS) of 33.3 weeks (range 1.7-245.4 weeks). Chemotherapy significantly (p < 0.001) improved OS in comparison to best supportive care only (37.6 vs. 13.9 weeks). Patients with locally advanced disease had a better prognosis compared to patients with metastases (median OS 49.6 vs. 30.4 weeks; p < 0.001). An age-adjusted Charlson comorbidity score of ≥ 9 was found to influence the OS significantly (p = 0.004). CONCLUSION: Chemotherapy remains the main modality of treatment for patients with advanced pancreatic cancer with an OS comparable to prospective randomized trials. The OS of this patient cohort has remained the same over the last 20 years despite advances in treatment modalities.

Adherence assessment of patients with metastatic solid tumors who are treated in an oncology group practice.

Due to the increase of oral agents nonadherence is an emerging challenge in cancer care. We evaluated how well different assessments match and how adherence could be measured in routine care. For this purpose patients suffering from metastatic solid tumors who were treated with oral anticancer drugs in an oncology group practice were surveyed. Attending oncologists answered a questionnaire, too, and a retrospective analysis of prescription data was conducted. Caregivers who were eligible for an interview were surveyed additionally. 128 patients (70 % female) with a median age of 69 years (36-88) took part, 95 % of all approached patients. 56 % suffered from metastatic breast cancer, 44 % from other metastatic solid tumors. 65 caregivers (60 % female) with a median age of 62 years (21-82) were interviewed as well. Patients were assessed in 84 % as very reliable in medication-taking by their oncologists. This high adherence rate was supported by patients, caregivers and prescription data. However, concordance between assessments of patients, caregivers and oncologists was not substantial. Our method of considering different perspectives to assess adherence has to be improved and validated but could help to evaluate adherence with oral cancer therapy in routine care.

Outpatient Management of Patients with Immune Thrombocytopenia (ITP) by Hematologists 1995-2014.

BACKGROUND: The aim of this study was to evaluate the treatment reality for outpatients with immune thrombocytopenia (ITP) managed by hematologists in routine care. PATIENTS AND METHODS: All patients with ITP diagnosed between 06/1995 and 12/2014 in a community-based oncology group practice in Germany were retrospectively analyzed. RESULTS: 422 patients with a median age of 55 years (range 7-91 years) were evaluated. 57% were female and 43% male. Only 198 (47%) patients needed therapy. First-line therapy (n = 198) consisted of steroids in 81%, intravenous immunoglobulins (IVIG) in 12%, and IVIG plus steroids in 6%. Patients received a median of 2 (range 1-10) lines of therapy. The most frequently used treatment modalities were steroids in 93%, IVIG in 55%, splenectomy in 21%, and other immunosuppressive agents (OISA) in 23% of patients. Rituximab and thrombopoietin receptor agonists (TRAs) were used in 10% and 6% only. 9 (2%) patients needed hospitalization due to bleeding complications. 72% of patients achieved a durable remission after their last line of therapy. 1 (0.2%) patient died due to bleeding complications. CONCLUSION: The treatment modalities most frequently used are steroids, immunoglobulins, splenectomy, and OISA. Rituximab and TRAs are only used infrequently. 72% of ITP patients achieve durable remissions. The rate of hospital admissions due to bleeding complications and the ITP-related mortality are low. The majority of ITP patients can be safely managed by hematologists on an outpatient basis.

Breast cancer morbidity: questionnaire survey of patients on the long term effects of disease and adjuvant therapy.

BACKGROUND: Many women have symptoms of various kinds after being treated for breast cancer. It is unclear how frequently these different side effects of treatment arise. METHOD: All women who underwent surgery for breast cancer and subsequently received adjuvant systemic treatment in a single certified breast-cancer center from 2006 to 2010 were asked to fill out a standardized questionnaire. Medical data were retrieved from their charts and statistically analyzed together with the questionnaire responses. The questionnaire was also given to an age-adjusted control group. RESULTS: 734 questionnaires were filled out and returned (response rate, 70%). The mean interval from the diagnosis of breast cancer to the time of response to the questionnaire was 38 months. The median age at time of response to the questionnaire was 65 years (range, 30 to 91 years). The distribution of UICC stages at the time of initial diagnosis was as follows: I 46%, II 42%, III 12%. 78% of the patients underwent breat conserving surgery, 85% had radio - therapy, 85% had antihormonal treatment, and 49% had chemotherapy. 91% were satisfied or very satisfied with the outcome of surgery. 34% reported operation site pain; 35% reported limitations of shoulder or arm function. Younger patients suffered from emotional sequelae more than older ones did. 25% reported a change in their relationship with their spouse. Before being diagnosed with breast cancer, 9% had consulted a psychiatrist or psychotherapist; after the diagnosis, 19% did. 14% had taken psychoactive medication before the diagnosis, and 26% did afterward. CONCLUSION: Treatment for breast cancer has negative physical, emotional, and social effects on many patients. They suffer these effects to varying degrees depending on age, type of surgery, and systemic treatment.

Metastatic breast cancer: prolongation of survival in routine care is restricted to hormone-receptor- and Her2-positive tumors.

18,000 women die due to metastatic breast cancer in Germany per year. Median survival is 20-28 months after diagnosis. The question we wanted to answer was whether survival has improved in routine care? For this purpose we conducted a retrospective analysis of all patients with metastatic breast cancer who were treated between 06/1995-06/2013 in a community-based oncology group practice in Germany. 716 patients were analyzed with a median age of 61 (31-93). Localizations of metastases were distributed as follows: 47% visceral, 36% bone, 9% lymphatic, 4% CNS, 4% others. 79% were hormone-receptor-positive, 20% Her2-positive, 9% triple-negative. Median overall survival was 34 months (95% Confidence Interval: 31-37), median disease-specific survival 36.8 months and disease-specific survival after 5 years 34%. Survival was significantly correlated with localizations of metastases, number of metastasized organs, disease free survival since initial diagnosis, hormone-receptor status and age. Patients with hormone-receptor-positive tumors had a median overall survival of 37 months, Her2-positive patients of 34 months and triple-negative patients of 13 months. 86% of hormone-receptor-positive patients received antihormonal therapy. 81% of Her2-positive patients received anti-Her2 therapy. In summary, longer survival is strongly restricted to hormone receptor- and Her2-positive tumors most likely due to targeted therapies directed against the estrogen-receptor and Her2.

Retreatment with bendamustine-containing regimens in patients with relapsed/refractory chronic lymphocytic leukemia and indolent B-cell lymphomas achieves high response rates and some long lasting remissions.

Bendamustine and bendamustine/rituximab combinations have shown high efficacy in relapsed/refractory chronic lymphocytic leukemia (CLL) and indolent B-cell malignancies (non-Hodgkin lymphoma, NHL). No data exist about bendamustine retreatment after relapse, concerning efficacy and toxicity in this patient population. Eighty-eight outpatients (57 patients with CLL, 31 patients with NHL) who had previously been treated with bendamustine were retreated with a bendamustine regimen. Treatment consisted of bendamustine (B) or bendamustine + mitoxantrone (BM) or bendamustine + rituximab (BR) or bendamustine + mitoxantrone + rituximab (BMR). Median age was 72 years (50-88). A reversible grade 3 or 4 leukocytopenia or thrombocytopenia was observed in 24% and 13%, respectively. The overall response rate (ORR) was 76% (7% complete remission [CR], 69% partial remission [PR]) with 77% (6% CR, 71% PR) in CLL and 71% (8% CR, 63% PR) in NHL. ORR according to regimen was as follows: B: 57% (14% CR, 43% PR), BM: 70% (4% CR, 66% PR), BR: 55% (10% CR, 45% PR), BMR: 84% (7% CR, 78% PR). Bendamustine retreatment is feasible and achieves high response rates and some long lasting remissions.

Standard of care of patients with Chronic Myeloid Leukemia (CML) treated in community based oncology group practices between 2001-2015 in Rhineland- Palatinate (Germany)

Background: The aim of this study was to assess retrospectively treatment and outcome of CML-patients in community based oncology practices in Germany and whether European LeukemiaNET (ELN) recommendations were followed. Method: All Ph+, BCR-ABL1+ CML-patients who were treated between 11/2001 and 12/2015 in nine oncology group practices were analyzed retrospectively. Results: Two hundred sixty patients with a median age of 60 (18­90) were analyzed. 254 (98%) were in chronic phase, 5 (2%) in accelerated and 1 (0.4%) in blast crisis. 248 patients (95%) received some form of TKI-therapy. 1st line TKI was imatinib in 197 patients (79%), 51 (21%) received a second generation TKI. 75% of TKI-therapies were monitored by PCR. Overall survival after 10 years according to Charlson comorbidity index (CCI) was: CCI 2: 100%; CCI 3­4: 83%; CCI 5­6: 52%; CCI ≥7: 39%. More patients died from comorbidities (8%) than from CML (5%). Whether patients died was strongly correlated to CCI at diagnosis: CCI 2: 3% of patients died, CCI 3­4: 16% of patients died, CCI 5­6: 38% of patients died, CCI ≥ 7: 42% of patients died. Conclusion: CML-patients treated in oncology group practices receive standard of care as recommended by ELN. Overall survival in routine care is comparable to international studies. Molecular monitoring should be improved (AU)