scholarly journals Combined Retro- and Prospective Analysis of Adherence to Guidelines and Patient-Tailored Therapeutic Recommendations in Patients with Myelodysplastic Syndromes (MDS) at a Tertiary Care Centre

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4250-4250
Author(s):  
Annika Kasprzak ◽  
Kathrin Nachtkamp ◽  
Mustafa Kondakci ◽  
Thomas Schroeder ◽  
Guido Kobbe ◽  
...  
Keyword(s):  
Financial Support ◽  
Survival Benefit ◽  
Research Funding ◽  
Iron Chelation ◽  
Treatment Recommendations ◽  
Matched Pair ◽  
Intensive Chemotherapy ◽  
Adherence To Treatment ◽  
Significant Survival Benefit ◽  
Significant Survival

Introduction The effect of adherence to treatment guidelines has not yet been evaluated in myelodysplastic syndromes (MDS). Based on the large Düsseldorf MDS Registry, we explored adherence to European LeukemiaNet (ELN) guidelines as well as MDS expert recommendations in clinical routine. Methods In a preliminary retrospective analysis of 1658 patients documented in the Düsseldorf MDS registry, we reviewed if treatment was in accordance with the published ELN guidelines from 2014. The following treatments were considered: erythropoiesis stimulating agents (ESA), iron chelation, Lenalidomide, hypomethylating agents (HMA), intensive chemotherapy, and allogeneic stem cell transplantation (alloSCT). Since patients were diagnosed between 1982 and 2018, clinical decision-making could not be exclusively based on current guidelines. Therefore, we also performed a prospective analysis of 381 patients who received patient-tailored treatment recommendations, considering, IPSS-R, MDS-CI, HCT-CI, distance to our center, and ELN guidelines, with special attention to the above-mentioned treatment options. In addition, we conducted a matched-pair analysis, comparing patients who received a certain treatment with patients who, though eligible, did not receive it. Information regarding adherence to treatment recommendations was obtained by searching medical files and contacting primary care physicians. Probability of survival was estimated using the Kaplan-Meier method. Results The retrospective cohort was followed for a median of 22 months (1-500 months). Patients treated in accordance with the ELN guideline did not gain a significant survival benefit in the subgroups treated with ESA, iron chelation, Lenalidomide, HMA, and intensive chemotherapy, compared to patients who were eligible for the respective treatment but did not receive it. Solely the group of patients undergoing alloSCT derived a significant survival benefit compared to patients not receiving alloSCT despite qualifying for this treatment according to ELN criteria (30 vs 18 months, p=0.011, 95% CI 16.86; 25.14, fig. 1). The prospective cohort was followed for a median of 14 months (1-195 months). A median of four months elapsed before treatment was started. Non-adherence to patient-tailored therapeutic recommendations was found in 33% of the patients. The proportion of non-adherence was higher for intensive chemotherapy (47%) and lowest for patients receiving supportive treatment (13%) like ESA and chelation therapy. In the prospective group, the matched-pair study showed again that patients receiving ESA, iron chelation, Lenalidomide, HMA or intensive chemotherapy did not gain a significant survival benefit from adherence to the respective treatment recommendations. Again, survival only differed between patients adhering to and patients not adhering to a recommendation for alloSCT (median survival of 74 vs 28 months; 95% CI 7.5; 48.5, p=0.015). Conclusions According to current ELN guidelines, 33% of patients did not receive the treatment they were eligible for. Non-adherence to patient-tailored treatment recommendations from our tertiary referral center was found in 33% of the patients. Based on our two patient cohorts, supportive care regimens, Lenalidomide, HMA, as well as intensive chemotherapy do not appear to improve overall survival, whereas allogeneic stem cell transplantation provided a significant survival benefit in both groups. In summary, while adherence to MDS treatment guidelines and expert recommendations may influence survival in some of the patients, the overall effect appears to be limited, owing to the limited efficacy of the available treatment options, with the notable exception of alloSCT. However, we cannot exclude that adherence to treatment recommendations has an effect on other relevant outcomes such as quality of life or frequency of hospitalisations due to infections, bleeding and cardiovascular events. Finally, a systematic and standardized assessment of guideline-adherence, reasons for non-adherence, and impact on relevant outcomes would be desirable because it would support us in monitoring the quality of care of MDS patients and would allow comparisons to be made between different health economic environments. Disclosures Nachtkamp: Jazz Pharmaceuticals: Honoraria; Celgene: Other: Travel Support. Schroeder:Celgene Corporation: Consultancy, Honoraria, Research Funding. Kobbe:Amgen: Honoraria, Other: Travel support, Research Funding; Neovii: Honoraria, Other: Travel support; Abbvie: Honoraria, Other: Travel support; Roche: Honoraria, Other: Travel support; Biotest: Honoraria, Other: Travel support; Celgene: Honoraria, Other: Travel support, Research Funding; Pfizer: Honoraria, Other: Travel support; Jazz: Honoraria, Other: Travel support; Takeda: Honoraria, Other: Travel support; Medac: Honoraria, Other: Travel support; MSD: Honoraria, Other: Travel support; Novartis: Honoraria, Other: Travel support. Kündgen:Otsuka: Honoraria; Takeda: Honoraria, Other: Travel Support; Novartis: Honoraria. Kaivers:Jazz Pharmaceuticals: Other: Travel Support. Rautenberg:Jazz Pharmaceuticals: Other: Travel Support; Celgene: Honoraria, Other: Travel Support. Gattermann:Novartis: Honoraria; Alexion: Research Funding; Takeda: Research Funding. Bonadies:Novartis: Other: financial support for travel, Research Funding; Roche: Other: financial support for travel, Research Funding; Amgen: Other: financial support for travel; Celgene: Other: financial support for travel, Research Funding; Sanofi Genzyme: Other: financial support for travel; Janssen: Other: financial support for travel. Germing:Celgene: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Jazz Pharmaceuticals: Honoraria; Amgen: Honoraria.

Posaconazole vs Standard Azole (FLU/ITRA) Therapy for Prophylaxis of Invasive Fungal Infections (IFIs) among High-Risk Neutropenic Patients: Results of a Randomized, Multicenter Trial.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1844-1844 ◽  
Author(s):  
O. Cornely ◽  
J. Maertens ◽  
D. Winston ◽  
J. Perfect ◽  
D. Helfgott ◽  
...  
Keyword(s):  
High Risk ◽  
Survival Benefit ◽  
Study Drug ◽  
Treatment Phase ◽  
Myelogenous Leukemia ◽  
P Value ◽  
Intensive Chemotherapy ◽  
Significant Survival Benefit ◽  
Significant Survival ◽  
Neutropenic Patients

Abstract Background: Patients with severe and prolonged neutropenia are at high-risk of developing life-threatening IFIs. Despite current treatment option, IFIs are difficult to treat and frequently associated with high mortality rates. Antifungal prophylaxis has shown benefits in high-risk populations and is a standard practice in many institutions. We compared Posaconazole (POS), a new broad-spectrum triazole, vs Standard Azoles for the prevention of IFIs in patients with a new diagnosis or first relapse of acute myelogenous leukemia (AML) or myelodysplastic syndrome (MDS) being treated with intensive chemotherapy. Methods: Patients in this randomized, evaluator-blinded, active controlled, multi-center study received oral POS (200mg tid) or oral Standard Azoles (either Fluconazole [FLU 400mg qd] or Itraconazole solution [ITRA 200mg bid]) with each cycle of chemotherapy until complete remission or for up to a maximum of 12 weeks. The primary efficacy end point was the comparison of the incidence of IFIs during the treatment phase (7 days after last dose) as adjudicated by the blinded expert panel based on EORTC/MSG criteria. The incidence of IFIs 100 days after randomization and the clinical outcome at the end of the treatment phase were also compared. Treatment failure was defined as presence of proven or probable IFIs, use of >3 days of empirical systemic antifungal treatment, use of >3 consecutive days or a total of 10 or more days of IV study drug (or alternative formulation for POS), discontinuation due to an adverse event related to study drug or lost to follow-up during treatment. Results: 602 patients were enrolled (304 POS, 298 Standard Azole [240 FLU, 58 ITRA]). The incidence of proven/probable IFIs was lower with POS prophylaxis (see table). The overall mortality was 49 (16%) vs 67 (22%) for patients in the POS and Standard Azoles arms respectively. Analysis of time to death (all cause mortality) within 100 days post randomization yielded a P-value of 0.035, indicating a significant survival benefit in favor of POS. Twenty-one (21) deaths due to IFIs occurred during the study (POS 5, Standard Azoles 16, P = 0.012). Treatment failures were fewer in the POS arm vs Standard Azoles arm (36% vs 46%, P = 0.0091). Safety and tolerability were comparable. Conclusions: In this study, POS was superior to the use of a Standard Azoles (FLU or ITRA) in preventing IFIs and in preventing aspergillosis, in high-risk neutropenic patients with AML or MDS undergoing intensive chemotherapy. Patients receiving POS experienced a significant survival benefit. POS N=304 FLU/ITRA N=298 Proven/Probable IFIs n (%) n (%) P-value All IFIs during Treatment Phase 7 (2) 25 (8) 0.0009 Aspergillus during Treatment Phase 2 (1) 20 (7) 0.0001 All IFIs within 100 days post-randomization 14 (5) 33 (11) 0.0031

A randomized phase III trial of active symptom control (ASC) with or without chemotherapy in the treatment of patients with malignant pleural mesothelioma: First results of the Medical Research Council (MRC) / British Thoracic Society (BTS) MS01 trial

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. LBA7525-LBA7525 ◽  
Author(s):  
M. Muers ◽  
P. Fisher ◽  
M. Snee ◽  
E. Lowry ◽  
M. O'Brien ◽  
...  
Keyword(s):  
Randomized Trial ◽  
Median Survival ◽  
Malignant Pleural Mesothelioma ◽  
Survival Benefit ◽  
Phase Iii ◽  
Pleural Mesothelioma ◽  
Significant Survival Benefit ◽  
Significant Survival ◽  
Symptom Palliation ◽  
Weekly Cycles

LBA7525 Background: Although chemotherapy is widely used in the treatment of mesothelioma it has never been compared in a randomized trial with ASC alone. Two chemotherapy regimens that had shown good symptom palliation in phase II studies were chosen for investigation. Methods: Patients with malignant pleural mesothelioma were randomized to ASC alone (regular follow-up in a specialist clinic, and treatment could include steroids, analgesics, bronchodilators, palliative radiotherapy, etc), ASC+MVP (4 × 3-weekly cycles of mitomycin 6g/m2, vinblastine 6mg/m2, and cisplatin 50mg/m2), or ASC+N (12 weekly injections of vinorelbine 30mg/m2). 420 patients were required to detect a 3-month improvement in median survival with ASC+CT (both chemotherapy arms combined). Quality of Life (QL) was assessed using the EORTC QLQ-C30. Results: 409 patients were accrued (136 ASC, 137 ASC+MVP, 136 ASC+N). Median age: 65 years, male: 91%, Performance status 0: 23%, Epithelial histology: 73%, Stage III: 33%, Stage IV: 48%. In the ASC+MVP group 61% received all 4 cycles, and in the ASC+N group 49% received at least 10 weekly cycles. Good symptom palliation (defined as prevention, control or improvement) was achieved in all 3 groups, and no between-group differences were observed in 4 pre-defined QL subscales (physical functioning, dyspnoea, pain and global QL). A small (not conventionally significant) survival benefit was seen for ASC+CT (349 deaths, HR 0.89, 95%CI 0.72, 1.12, p=0.32). Median survival: ASC: 7.6 months, ASC+CT: 8.5 months. Exploratory analyses suggested a survival advantage for vinorelbine compared to ASC alone (HR 0.81, 95%CI 0.63, 1.05, p=0.11), with a median survival of 9.4 months, but no evidence of a benefit with MVP (HR 0.98, 95%CI 0.76, 1.28), p=0.91). Conclusions: This is the 2nd largest ever randomized trial in mesothelioma and the first to compare ASC with or without chemotherapy. Although the addition of chemotherapy to ASC did not result in a conventionally significant survival benefit, there was an indication that vinorelbine should be investigated further, and that MVP probably has no role in this disease. [Table: see text]

scholarly journals RARE-09. CYSTIC GLIOBLASTOMA PRESENTATION AS A BENEFICIAL PROGNOSTIC INDICATOR FOR OVERALL SURVIVAL

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi223-vi223
Author(s):  
Lee Curtin ◽  
Paula Whitmire ◽  
Cassandra Rickertsen ◽  
Peter D Canoll ◽  
Maciej Mrugala ◽  
...  
Keyword(s):  
Overall Survival ◽  
Survival Benefit ◽  
Standard Of Care ◽  
Prognostic Impact ◽  
Current Standard ◽  
Significant Survival Benefit ◽  
Care Treatment ◽  
Significant Survival ◽  
Cystic Component ◽  
Standard Of Care Treatment

Abstract Glioblastoma (GBM) is the most aggressive primary brain tumor with a median overall survival of 15 months with standard-of-care treatment. GBM patients sometimes present with a cystic component, which can be identified through magnetic resonance imaging (MRI). Previous studies suggest that cysts occur in 7–22% of GBM patients and have reported mixed results regarding whether cystic GBM have a survival benefit compared to noncystic GBM. Using our large retrospective cohort of 493 first-diagnosis GBM patients, we aim to elucidate this link between cystic GBM and survival. Within this cohort, 88 patients had a significant cystic component at presentation as identified on MRI. Compared to noncystic GBM (n=405), cystic GBM patients had significantly better overall survival (15 vs 22 months median, log-rank, p=0.001) and were significantly younger at the time of presentation (t-test, p=0.002). However, within patients that received current standard-of-care treatment (n=184), cystic GBM (n=40) was not as beneficial for outcome (22 vs 25 months, log-rank, p=0.3). We also did not observe a significant survival benefit when comparing this standard-of-care cystic cohort to cystic GBM patients diagnosed before the standard was established (n=19, 25 vs 23 months, log-rank, p=0.3), but the analogous result for noncystic GBM patients gives a sizeable benefit, as expected (n=144, n=111, respectively, 22 vs 12 months, log-rank p < 0.0001). Together, these results on current standard-of-care may explain later studies that note no significant survival benefit for cystic GBM patients receiving current standard-of-care. We also report differences in the absolute and relative sizes of imaging abnormalities on MRI and in prognostic impact of cysts based on sex. We discuss current hypotheses for these observed differences, including the possibility that the presence of a cyst could be indicative of a less aggressive tumor.

scholarly journals 51 Timing of adjuvant treatments on glioblastoma survival: A retrospective cohort analysis based on the national cancer database

2018 ◽  
Vol 45 (S3) ◽  
pp. S11-S12
Author(s):  
Ping Zhu ◽  
Xianglin L. Du ◽  
Yoshua Esquenazi ◽  
Jay-Jiguang Zhu
Keyword(s):  
Adjuvant Treatment ◽  
Survival Benefit ◽  
Cohort Analysis ◽  
Cox Proportional Hazards ◽  
High Dose ◽  
National Cancer Database ◽  
Risk Of Death ◽  
Significant Survival Benefit ◽  
Significant Survival ◽  
The Impact

Few studies investigated the associations between intervention modalities, timing, and survival in glioblastoma (GBM) patients. A total of 20511 eligible GBM patients underwent biopsy and craniotomy surgeries followed by adjuvant treatments (2005-2014) were derived from the National Cancer Database (NCDB). The time intervals (days) from the date of diagnosis to the initiation date of adjuvant treatment [radiation therapy only (RT), chemotherapy only, concurrent chemoradiation (CRT), or non-concurrent RT and chemotherapy] were categorized into quartiles (Q1-Q4). Kaplan-Meier method and Cox proportional hazards regression were applied for survival analysis. Multivariate logistic regression was performed to compare differences in treatment timing, intervention modalities, and secondary outcomes. The patients underwent biopsy obtained significant survival benefit by having delayed adjuvant treatment [comparing to Q1, Q2: HR (hazard ratio), 0.88, Q3: HR, 0.86]. For patients underwent resection, the prolonged waiting time of adjuvant treatment had 5-6% reduced risk of death [comparing to Q1, Q2: HR, 0.95; Q3: HR, 0.94]. Patients received more RT fractions [comparing to 10-29 fractions, 30-33 fractions: HR: 0.62 (biopsy), 0.62 (resection); ≥34 fractions: HR: 0.53 (biopsy), 0.62 (resection)] and high-dose RT [comparing to 34-46 Gy, 50-60 Gy: HR: 0.91 (biopsy), 0.95 (resection); ≥ 60 Gy: HR: 0.77 (biopsy), 0.88 (resection)] experienced significantly superior survival in both biopsy and resection groups. The impact of timing to adjuvant treatment on GBM survival varied by surgery procedures. Having adjuvant treatment initiated within 21 days for both biopsy and craniotomy groups may not guarantee a significant survival benefit. More RT fractions and high-dose RT are associated with better GBM survival.

Efficacy of adjuvant chemotherapy with S-1 in patients with positive peritoneal cytology (CY1) who underwent R1 surgery.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 84-84
Author(s):  
M. Terashima ◽  
E. Bando ◽  
M. Tokunaga ◽  
Y. Tanizawa ◽  
T. Kawamura ◽  
...  
Keyword(s):  
Lymph Node ◽  
Adjuvant Chemotherapy ◽  
Lymph Node Dissection ◽  
Survival Benefit ◽  
Residual Tumor ◽  
Peritoneal Cytology ◽  
Node Dissection ◽  
Significant Survival Benefit ◽  
Significant Survival ◽  
Positive Peritoneal Cytology

84 Background: In recent TNM classification, positive peritoneal cytology (CY1) is regarded as M1 disease and classified into stage IV. However, the prognosis of the CY1 patients underwent R1 surgery (microscopic residual tumor) is considered to be relatively better than those underwent R2 surgery (macroscopic residual tumor). Adjuvant chemotherapy with S-1 had demonstrated significant survival benefit in stage II and III gastric cancer in Japan. However, the efficacy of adjuvant S-1 in patients with relatively more advanced stage had not been investigated. Therefore, we investigated the efficacy of adjuvant chemotherapy with S-1 in CY1 patients underwent R1 surgery. Methods: Among the 2,202 patients with gastric cancer treated at our department between September 2002 and July 2009, a total of 105 patients with CY1 and underwent R1 surgery were included in this study. Clinocopathological features and survival were retrospectively analyzed using prospectively registered data base system. Results: There were 64 male and 41 female patients. The median age was 61 years old. Eighty-five patients had T4a or T4b tumor and 96 patients had lymph node metastasis. Seventy-eight patients had undifferentiated type of tumor. In 83 patients, adjuvant chemotherapy with S-1 had been performed. In the uni-variate analysis, only the extent of lymph node dissection (D2) and the adjuvant chemotherapy with S-1 demonstrated significant survival benefit. In multi-variable analysis using Cox proportional hazarded model, N-factor, extent of lymph node dissection (D2 vs D1), and adjuvant chemotherapy with S-1 were selected as independent prognostic factors. The median survival time and 5-year survival rate in patients underwent R1 resection with D2 lymphadenectomy and adjuvant S-1 treatment were 42 months and 46%, respectively. Conclusions: In patients with CY1 and underwent R1 surgery, adjuvant chemotherapy with S-1 demonstrated significant survival benefit. In patients with positive peritoneal cytology without other non-curative factors, D2 lymph node dissection and adjuvant chemotherapy using S-1 is recommended. No significant financial relationships to disclose.

Low molecular weight heparin (LMWH) usage for cancer patients under palliative care.

2017 ◽  
Vol 35 (31_suppl) ◽  
pp. 1-1
Author(s):  
Ahmed Ali ◽  
Amani Zayir ◽  
Adel Hamody ◽  
Shakeel Ahmed
Keyword(s):  
Molecular Weight ◽  
Palliative Care ◽  
Cancer Patients ◽  
Survival Benefit ◽  
Low Molecular Weight Heparin ◽  
Low Molecular Weight ◽  
Care Hospital ◽  
Significant Survival Benefit ◽  
Significant Survival ◽  
Clinically Significant

1 Background: Cancer patients are at increased risk of thromboembolic complications. Studies show that prophylactic low molecular weight heparin (LMWH) can successfully reduce incidence of venous thromboembolic events; however, a survival benefit for patients with advanced cancer who receive LMWH in a palliative setting has not been confirmed. Methods: We evaluated the survival of cancer patients undergoing palliative treatment in a tertiary care hospital in Saudi Arabia during 2016. Patients were followed from the day of palliative care initiation until the day of death, and we compared the survival of patients who received LMWH (enoxaparin) with those who did not. Gender, diagnosis (site of cancer), and date of diagnosis were considered for subgroup analysis. Results: Of the 209 patients included in this study, enoxaparin was administered to 91(about 44%), while 117 (about 56%) did not receive any LMWH, and the treatment of one patient was not clearly defined. Male and female patients are equally distributed (104 and 105 patients, respectively). Cancer sites included breast, brain, gastrointestinal, genitourinary, lung, hematological malignancies, bone, and others. Although there was generally no statistical difference in survival time between treated and untreated groups (approximately 48 days each), subgroup analyses showed a statistically significant but not clinically significant survival benefit for patients with genitourinary cancers, such as uterine, urinary bladder, ovarian, or prostatic carcinomas who received LMWH (14.15 to 63.85 Days, P=0.0046). Conclusions: Prophylactic treatment with LMWH provided no clinically significant survival benefit to terminally ill cancer patients when administered in conjunction with other medications. Further prospective trials are warranted. Clinical trial information: ONC0329.

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