Decision-making among experts in advanced Hodgkin Lymphoma.

BACKGROUND In the treatment of advanced Hodgkin Lymphoma (aHL), based on guidelines a multitude of treatment options are available. The availability of PET guided decision-making and new therapeutic agents increase the complexity of the decision-making process. METHODS Thirteen experts of Swiss university and cantonal hospitals in Switzerland were asked to describe their institutional decision-making practice in aHL. Variables influencing the decision-making process were identified, standardized and converted into decision trees for analysis of consent and discrepancies. The algorithms of all participating experts were analyzed with the objective consensus methodology. RESULTS Four decision criteria (age, fertility preservation, fitness, interim PET) and 12 unique treatment regimens were identified. Consensus for the treatment of aHL for young and fit, as well as for older patients without comorbidity was found. Large heterogeneity was identified with use of a variety of different regimens for unfit patients with aHL and for young female patients with a desire of fertility preservation. CONCLUSION Four major decision criteria were identified allowing the representation of expert's approach to first-line treatment of aHL. Among Swiss experts, consensus for a PET guided curative treatment of aHL was identified. The use of a multitude of treatment regimens was observed for older and comorbid (unfit) aHL patients, highlighting the need for clinical trials and recommendations for this group of patients

Team functioning across different tumour types: Insights from a Swiss cancer center using qualitative and quantitative methods.

BACKGROUND: Multidisciplinary care is pivotal in cancer centres and the interaction of all cancer disease specialists in decision making processes is state-of-the-art. AIM: To describe differences of MDTMs by tumour type. METHODS: Twelve multidisciplinary team meetings (MDTMs) with participation of different cancer disease specialists at a tertiary hospital were assessed by an exploratory sequential mixed method approach with interviews, observations and a survey to address the following five topics: organisational structure and supporting technology; leadership; teamwork; decision-making, perceived value and motivation. Thirteen persons with different tumour specialities and levels of seniority were interviewed. The 12 MDTMs were observed twice by uninvolved persons and evaluated by the participating physicians with a survey. RESULTS: There were no systematic differences between MDTMs for different tumour types with the exception of the non-disease specific type MDTM, which was the only one for which the organisational structure was not driven by an electronic tool. However, several factors could be identified that generally influenced the functioning of the MDTMs. In particular, the quality of decision-making was highly dependent on the availability of case-based information and the presence of relevant cancer disease specialists. Leadership and teamwork were rated as important and were comparable across the MDTM. Team participants' motivation and perceived value of MDTMs was high across all meetings. CONCLUSION: MDTM at a single institution did not demonstrate disease specific characteristics. An effective MDTM, irrespective of the tumour type, can be successfully structured by technical means and a chairperson coordinating the interaction of cancer disease specialists to improve the decision-making process

The SAKK cancer-specific geriatric assessment (C-SGA): a pilot study of a brief tool for clinical decision-making in older cancer patients

BACKGROUND Recommendations from international task forces on geriatric assessment emphasize the need for research including validation of cancer-specific geriatric assessment (C-SGA) tools in oncological settings. The objective of this study was to evaluate the feasibility of the SAKK Cancer-Specific Geriatric Assessment (C-SGA) in clinical practice. METHODS A cross sectional study of cancer patients >=65 years old (N = 51) with pathologically confirmed cancer presenting for initiation of chemotherapy treatment (07/01/2009-03/31/2011) at two oncology departments in Swiss canton hospitals: Kantonsspital Graubunden (KSGR N = 25), Kantonsspital St. Gallen (KSSG N = 26). Data was collected using three instruments, the SAKK C-SGA plus physician and patient evaluation forms. The SAKK C-SGA includes six measures covering five geriatric assessment domains (comorbidity, function, psychosocial, nutrition, cognition) using a mix of medical record abstraction (MRA) and patient interview. Five individual domains and one overall SAKK C-SGA score were calculated and dichotomized as below/above literature-based cut-offs. The SAKK C-SGA was evaluated by: patient and physician estimated time to complete, ease of completing, and difficult or unanswered questions. RESULTS Time to complete the patient questionnaire was considered acceptable by almost all (>=96%) patients and physicians. Patients reported slightly shorter times to complete the questionnaire than physicians (17.33 +/- 7.34 vs. 20.59 +/- 6.53 minutes, p = 0.02). Both groups rated the patient questionnaire as easy/fairly easy to complete (91% vs. 84% respectively, p = 0.14) with few difficult or unanswered questions. The MRA took on average 8.32 +/- 4.72 minutes to complete. Physicians (100%) considered time to complete MRA acceptable, 96% rated it as easy/fairly easy to complete. Individual study site populations differed on health-related characteristics (excellent/good physician-rated general health KSGR 71% vs. KSSG 32%, p = 0.007). The overall mean C-SGA score was 2.4 +/- 1.12. Patients at KSGR had lower C-SGA scores (2.00 +/- 1.19 vs. 2.81 +/- 0.90, p = 0.009) and a smaller proportion (28% vs.65%, p = 0.008) was above the C-SGA cut-off score compared to KSSG. CONCLUSIONS These results suggest the SAKK C-SGA is a feasible practical tool for use in clinical practice. It demonstrated discriminative ability based on objective geriatric assessment measures, but additional investigations on use for clinical decision-making are warranted. The SAKK C-SGA also provides important usable domain information for intervention to optimize outcomes in older cancer patients

Cancer-specific geriatric assessment and quality of life: important factors in caring for older patients with aggressive B-cell lymphoma.

PURPOSE To evaluate the efficacy and tolerability of chemotherapy, a geriatric assessment is recommended in elderly patients with cancer. We aimed to characterize and compare patients with aggressive lymphoma by objective response and survival status based on pre-treatment cancer-specific geriatric (C-SGA) and quality of life (QoL) assessments. METHODS Patients not eligible for anthracycline-based first-line therapy or intensive salvage regimens completed C-SGA and QoL assessment before and after a rituximab-bendamustine-lenalidomide (R-BL) treatment in a phase II clinical trial. Clinical outcomes were compared based on pre-treatment individual and summary C-SGA measures, their cutoff-based subcategories and QoL indicators, using Wilcoxon rank sum or chi-square tests. RESULTS A total of 57 patients (41 included in the clinical trial) completed a C-SGA. Participants with pre-treatment impaired functional status (Vulnerable Elders Survey-13 score ≥3) were more likely to experience worse outcomes: a higher proportion were non-responders, died before the median follow-up of 31.6 months (interquartile range (IQR) 27.9-37.9) or died during treatment. Non-responders were patients categorized as having possible depression (Geriatric Depression Scale-5 score ≥2) and with worse QoL scores for functional performance. Patients with worse C-SGA summary scores and with greater tiredness were more likely to die during treatment. CONCLUSION A pre-treatment impaired functional status is an important factor with respect to clinical outcomes in patients receiving an R-BL regimen. Individual geriatric and related QoL domains showed similar associations with clinical outcomes. Whether interventions targeting specific geriatric dimensions also translate in better symptom- or domain-specific QoL warrants further research

A phase I trial of inotuzumab ozogamicin in combination with temsirolimus in patients with relapsed or refractory CD22-positive B-cell non-Hodgkin lymphomas.

This phase I trial evaluated the safety, tolerability, and preliminary activity of inotuzumab ozogamicin in combination with temsirolimus in patients with relapsed/refractory CD22 positive B-cell non-Hodgkin lymphomas. Nineteen patients received at least one dose of both study drugs. Dose-limiting toxicities consisted of thrombocytopenia, hypertriglyceridemia, oral mucositis, clinical deterioration, and the inability to receive at least three doses of temsirolimus during cycle 1. The most common grade ≥3 treatment-related adverse events were thrombocytopenia (n = 8), neutropenia (n = 5), and two patients each hyperphosphatemia, lymphopenia, and hypertriglyceridemia. The recommended phase II dose was inotuzumab ozogamicin 0.8 mg/m2 on day 1 in combination with temsirolimus 10 mg on days 8, 15, and 22 every 28 days. Among 18 patients evaluable, seven (39%) with follicular lymphoma had a partial remission. This drug combination is not possible within a therapeutically useful range of doses due to toxicities. Antitumor activity was observed in heavily pretreated patients (ClinicalTrials.gov, Identifier NCT01535989)

Predictive value of baseline metabolic tumor volume in early-stage favorable Hodgkin Lymphoma - Data from the prospective, multicenter phase III HD16 trial

Background: F-18 -fluorodeoxyglucose (FDG) positron emission tomography (PET) plays an important role in the staging and response assessment of lymphoma patients. Our aim was to explore the predictive relevance of metabolic tumor volume (MTV) and total lesion glycolysis (TLG) in patients with early stage Hodgkin lymphoma treated within the German Hodgkin Study Group HD16 trial. Methods: F-18-FDG PET/CT images were available for MTV and TLG analysis in 107 cases from the HD16 trial. We calculated MTV and TLG using three different threshold methods (SUV4.0,SUV(41% )and SUV140%L), and then performed receiver-operating-characteristic analysis to assess the predictive impact of these parameters in predicting an adequate therapy response with PET negativity after 2 cycles of chemotherapy. Results: All three threshold methods analyzed for MTV and TLG calculation showed a positive correlation with the PET response after 2 cycles chemotherapy. The largest area under the curve (AUC) was observed using the fixed threshold of SUV4.0 for MTV- calculation (AUC 0.69 [95% CI 0.55-0.83]) and for TLG-calculation (AUC 0.69 [0.55-0.82]). The calculations for MTV and TLG with a relative threshold showed a lower AUC: using SUV140%L AUCs of 0.66 [0.53-0.80] for MTV and 0.67 for TLG [0.54-0.81]) were observed, while with SUV41% an AUC of 0.61 [0.45-0.76] for MTV, and an AUC 0.64 [0.49-0.80]) for TLG were seen. Conclusions: MTV and TLG do have a predictive value after two cycles ABVD in early stage Hodgkin lymphoma, particularly when using the fixed threshold of SUV4.0 for MTV and TLG calculation

Bleomycin in older early-stage favorable Hodgkin lymphoma patients: analysis of the German Hodgkin Study Group (GHSG) HD10 and HD13 trials

Doxorubicin, bleomycin, vinblastine sulfate, and dacarbazine (ABVD) is associated with severe toxicity in older patients, particularly from bleomycin-induced lung toxicity (BLT). Therefore, using bleomycin has been questioned in older Hodgkin lymphoma (HL) patients, especially in early-stage HL. We therefore analyzed feasibility, toxicity, and efficacy of ABVD or AVD in 287 older early-stage favorable HL patients. We included patients >= 60 years of age in the German Hodgkin Study Group HD10 and HD13 trials randomized to either 2 cycles of ABVD (2xABVD; n=137) or AVD (2xAVD; n=82), each followed by involved-field radiotherapy (IF-RT), with patients randomized to 4xABVD+IF-RT (n=68). Patients' median age was 65 years (range, 60-75) with comparable patient and disease characteristics. Grade III-IV adverse event rates were similar in patients receiving 2xAVD and 2xABVD (40% and 39%, respectively), but considerably higher in patients receiving 4xABVD (65%). Similarly, BLT was rare in patients receiving 2xABVD/AVD, but occurred in 7/69 (10%) of patients randomized to 4xABVD, with 3 lethal events. In conclusion, no effects of bleomycin on toxicity rates were detectable in older patients receiving 2 cycles of chemotherapy. However, we found a high risk of severe toxicity of bleomycin in older HL patients receiving more than 2 cycles of ABVD. These trials are registered at www.clinicaltrials.gov and www.isrctn.com as #NCT00265018 (HD10) and #ISRCTN63474366 (HD13)