Phase III: What has to be Considered When Global Policy Networks Produce Long-term Outputs?

The possibilities and results of multimodal treatment in rectal cancer were reviewed with respect to the results of surgical treatment only. Based on the results of 4 studies, reducing local relapse rates and increasing long term survival rates significantly, postoperative radiochemotherapy (RCT) + chemotherapy (CT) should remain the recommended standard for R0 resected UICC II and III rectal cancers. The addition of RT to adjuvant CT reduces local relapses without significant impact on survival (NSABP R-02). Vice versa, the addition of CT to RT or an improved CT in the RCT-concept prolongs survival. Preoperative neoadjuvant radiotherapy (RT) reduced local relapse rates in 9 studies, and extended survival in one study that evaluated all eligible patients. Preoperative RT reduced local relapse rates in addition to total mesorectal excision (TME) but did not extend survival. The preoperative RCT + CT downstages resectable and nonresectable tumors and induces a higher sphincter preservation rate. Phase III data justifying its routine use in all UICC II + III stages are not yet available. This treatment may be routinely applied in nonresectable primary tumors or local relapses. Preoperative RCT (or RT) may evolve as standard, if the patient selection is improved and postoperative morbidity and long term toxicity reduced. Intraoperative RT could be added to this concept or be used together with preoperative/postoperative RT at the same indications. Postoperative adjuvant RT reduced local relapses significantly in a single trial, and no impact on survival time is reported. Since postoperative RT is inferior to preoperative RT, this treatment cannot be recommended, if RT is chosen as a single treatment modality in adjunction to surgery. The results of local tumor excisions may be improved with pre- or postoperative RCT + CT. In the future, multimodal treatment of rectal cancer might be more effective, if individualized according to prognostic factors.

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Treatment and secondary prevention of venous thromboembolism in cancer patients

Onkologische Welt ◽

10.1055/s-0038-1630173 ◽

2012 ◽

Vol 03 (03) ◽

pp. 121-125

Author(s):

I. Pabinger ◽

C. Ay

Keyword(s):

Clinical Trials ◽

Venous Thromboembolism ◽

Cancer Patients ◽

Oral Anticoagulants ◽

Factor Xa ◽

New Oral Anticoagulants ◽

Phase Iii ◽

Patients With Cancer ◽

Potential Use

SummaryCancer is a major and independent risk factor of venous thromboembolism (VTE). In clinical practice, a high number of VTE events occurs in patients with cancer, and treatment of cancerassociated VTE differs in several aspects from treatment of VTE in the general population. However, treatment in cancer patients remains a major challenge, as the risk of recurrence of VTE as well as the risk of major bleeding during anticoagulation is substantially higher in patients with cancer than in those without cancer. In several clinical trials, different anticoagulants and regimens have been investigated for treatment of acute VTE and secondary prophylaxis in cancer patients to prevent recurrence. Based on the results of these trials, anticoagulant therapy with low-molecular-weight heparins (LMWH) has become the treatment of choice in cancer patients with acute VTE in the initial period and for extended and long-term anticoagulation for 3-6 months. New oral anticoagulants directly inhibiting thrombin or factor Xa, have been developed in the past decade and studied in large phase III clinical trials. Results from currently completed trials are promising and indicate their potential use for treatment of VTE. However, the role of the new oral thrombin and factor Xa inhibitors for VTE treatment in cancer patients still has to be clarified in further studies specifically focusing on cancer-associated VTE. This brief review will summarize the current strategies of initial and long-term VTE treatment in patients with cancer and discuss the potential use of the new oral anticoagulants.

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K-924 Phase III 52 Weeks Long Term Study

Case Medical Research ◽

10.31525/ct1-nct04289662 ◽

2020 ◽

Author(s):

Keyword(s):

Phase Iii ◽

Term Study ◽

Long Term Study

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COVID-19 era in long-term cardiac rehabilitation programs: how was muscle strenght and lean mass affected in cardiovascular patients?

European Journal of Preventive Cardiology ◽

10.1093/eurjpc/zwab061.362 ◽

2021 ◽

Vol 28 (Supplement_1) ◽

Author(s):

M Borges ◽

M Lemos Pires ◽

R Pinto ◽

G De Sa ◽

I Ricardo ◽

...

Keyword(s):

Muscle Strength ◽

Cardiac Rehabilitation ◽

Lean Mass ◽

Lower Limb ◽

Lower Limbs ◽

Phase Iii ◽

Face To Face ◽

Home Based ◽

Lower Limb Strength

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Exercise prescription is one of the main components of phase III Cardiac Rehabilitation (CR) programs due to its documented prognostic benefits. It has been well established that, when added to aerobic training, resistance training (RT) leads to greater improvements in peripheral muscle strength and muscle mass in patients with cardiovascular disease (CVD). With COVID-19, most centre-based CR programs had to be suspended and CR patients had to readjust their RT program to a home-based model where weight training was more difficult to perform. How COVID-19 Era impacted lean mass and muscle strength in trained CVD patients who were attending long-term CR programs has yet to be discussed. Purpose To assess upper and lower limb muscle strength and lean mass in CVD patients who had their centre-based CR program suspended due to COVID-19 and compare it with previous assessments. Methods 87 CVD patients (mean age 62.9 ± 9.1, 82.8% male), before COVID-19, were attending a phase III centre-based CR program 3x/week and were evaluated annually. After 7 months of suspension, 57.5% (n = 50) patients returned to the face-to-face CR program. Despite all constraints caused by COVID-19, body composition and muscle strength of 35 participants (mean age 64.7 ± 7.9, 88.6% male) were assessed. We compared this assessment with previous years and established three assessment time points: M1) one year before COVID-19 (2018); M2) last assessment before COVID-19 (2019); M3) the assessment 7 months after CR program suspension (last trimester of 2020). Upper limbs strength was measured using a JAMAR dynamometer, 30 second chair stand test (number of repetitions – reps) was used to measure lower limbs strength and dual energy x-ray absorptiometry was used to measure upper and lower limbs lean mass. Repeated measures ANOVA were used. Results Intention to treat analysis showed that upper and lower limbs lean mass did not change from M1 to M2 but decreased significantly from M2 to M3 (arms lean mass in M2: 5.68 ± 1.00kg vs M3: 5.52 ± 1.06kg, p = 0.004; legs lean mass in M2: 17.40 ± 2.46kg vs M3: 16.77 ± 2.61kg, p = 0.040). Lower limb strength also decreased significantly from M2 to M3 (M2: 23.31 ± 5.76 reps vs M3: 21.11 ± 5.31 reps, p = 0.014) after remaining stable in the year prior to COVID-19. Upper limb strength improved significantly from M1 to M2 (M1: 39.00 ± 8.64kg vs M2: 40.53 ± 8.77kg, p = 0.034) but did not change significantly from M2 to M3 (M2 vs M3: 41.29 ± 9.13kg, p = 0.517). Conclusion After CR centre-based suspension due to COVID-19, we observed a decrease in upper and lower limbs lean mass and lower limb strength in previously trained CVD patients. These results should emphasize the need to promote all efforts to maintain physical activity and RT through alternative effective home-based CR programs when face-to-face models are not available or possible to be implemented.

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Body composition, lipid profile and mediterranean diet adherence in cardiovascular disease patients attending a long-term exercise-based cardiac rehabilitation program during COVID-19 pandemic

European Journal of Preventive Cardiology ◽

10.1093/eurjpc/zwab061.187 ◽

2021 ◽

Vol 28 (Supplement_1) ◽

Author(s):

M Linan Pinto ◽

R Pinto ◽

S Charneca ◽

J Vasques ◽

M Lemos Pires ◽

...

Keyword(s):

Cardiovascular Disease ◽

Body Composition ◽

Lipid Profile ◽

Mediterranean Diet ◽

Dietary Patterns ◽

Nutritional Intervention ◽

Phase Iii ◽

Body Composition Assessment ◽

Metabolic Complications

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Cardiovascular disease (CVD) is recognized as a major public health issue and remains the leading cause of mortality worldwide. There is a clear association between adiposity, blood lipid profile, and adherence to the Mediterranean diet (MD) with the risk of CVD. However, the assessment of body composition parameters, dietary patterns and nutritional intervention in CVD patients undergoing a cardiovascular rehabilitation (CR) program remains insufficient. Purpose to characterize body composition, lipid profile and MD adherence in patients with CVD who were attending an exercise-based CR program during COVID-19 era. Methods The study was developed between October 2020 and January 2021 in a phase III centre-based CR program. Body composition was assessed by dual energy x-ray absorptiometry Hologic Explorer-W. Adherence to the MD was assessed by the 14-item MD questionnaire. Fasting blood sample was taken for measurement of lipid profile. Results A sample of 41 patients (mean age 64.4 ± 7.9 years, 87.8% male) was evaluated. The most prevalent CVD were coronary artery disease (89.5%) and heart failure (21.1%). The main CVD risk factors at admission in the CR program were dyslipidaemia (71.1%), hypertension (68.4%), physical inactivity (26.3%) and diabetes mellitus (21.0%). In our sample the mean body mass index was 28 ± 3.8 kg/m2, being most patients overweight (75.6%), and having a substantially increased risk of metabolic complications (85.3%) accordingly to waist-hip ratio. Body composition assessment showed that 14.6% of the patients had a body fat mass index above 90th percentile. Although only 9.8% of the patients had reduced fat free mass, 17.1% showed appendicular lean mass below the reference value. In addition, less than one third of the patients (31.7%) revealed a high adherence to the MD pattern. A sub-analysis on blood lipids (n = 26) showed that most patients had levels of LDL cholesterol (76.9%) and non-HDL cholesterol (65.4%) above the therapeutic target and 15.4% had triglycerides higher than 150 mg/dl. Conclusion Body composition, lipid profile and dietary patterns, play a major role in CVD secondary prevention. Our findings showed that a substantial number of CVD patients, in COVID-19 era, did not have optimal body composition, were above lipid profile targets, and had a low/medium adherence to the MD. Thus, this study highlights the relevance of nutrition on cardiometabolic status and demonstrates the crucial role of nutritional intervention as an integrated part of a long-term phase III CR program. Moreover, further research about nutritional intervention in patients undergoing CR is warranted.

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CTNI-01. EFFECT OF STEREOTACTIC RADIOSURGERY COMPARED TO WHOLE-BRAIN RADIOTHERAPY FOR LIMITED BRAIN METASTASIS ON LONG TERM COGNITION AND QUALITY OF LIFE: A POOLED ANALYSIS OF RANDOMIZED CLINICAL TRIALS

Neuro-Oncology ◽

10.1093/neuonc/noaa215.168 ◽

2020 ◽

Vol 22 (Supplement_2) ◽

pp. ii40-ii41

Author(s):

Joshua Palmer ◽

Brett Klamer ◽

Karla Ballman ◽

Paul Brown ◽

Jane Cerhan ◽

...

Keyword(s):

Quality Of Life ◽

Randomized Clinical Trials ◽

Whole Brain Radiotherapy ◽

Pooled Analysis ◽

Cognitive Outcomes ◽

Phase Iii ◽

Brain Radiotherapy ◽

Over Time

Abstract PURPOSE We investigated the long term impact of SRS and WBRT in two large prospective phase III trials. METHODS Patients with 1–4 BMs +/- resection were randomized to SRS or WBRT. Cognitive deterioration was a drop of >1 standard deviation from baseline in >2/6 cognitive measures (CM). Quality of life (QOL) scores were scored 0–100 point scale. CM and QOL scores were modeled using baseline adjusted Linear Mixed Models (LMM) with uncorrelated random intercept for subject and random slopes for time. Differences over time between groups and the effect of >2 cognitive scores with >2 SD change from baseline were assessed. RESULTS 88 patients were included with median follow up of 24 months. We observed decreasing CM over time (SRS: 4/6; WBRT: 5/6). Mean CM was significantly higher in SRS for Total recall and Delayed Recall at 3, 6, 9, 12 months. More patients in WBRT arm declined 1 SD in >1 and >2 CM at the 3, 6, 9, and 12 months. A 1 SD decline in >3 CM at 1 year was 21% SRS vs 47% WBRT (p=0.02). SRS had fewer patients with a 2 SD decline in >1 CM at every time point. SRS had fewer patients with a 2 SD decline at >2 and >3 CM. WBRT had lower QOL at 3 months, but switched to SRS having lower QOL at 24 months for PWB, EWB, FWB, FactG, BR, and FactBR (p< 0.05). A 2 SD decline in cognition decreased mean FWB by 6.4 units (95% CI: -11, -1.75; p=0.007) and decreased QOL by 5.1 units (95% CI: -7.7, -2.5; p< 0.001). CONCLUSIONS We report the first pooled prospective study demonstrating the long term outcomes of patients with BMs after cranial radiation. WBRT was associated with worse cognitive outcomes. Impaired cognition is associated with worse QOL.

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Assessment of thrombotic risk during long-term treatment of immune thrombocytopenia with fostamatinib

Therapeutic Advances in Hematology ◽

10.1177/20406207211010875 ◽

2021 ◽

Vol 12 ◽

pp. 204062072110108

Author(s):

Nichola Cooper ◽

Ivy Altomare ◽

Mark R. Thomas ◽

Phillip L. R. Nicolson ◽

Steve P. Watson ◽

...

Keyword(s):

Immune Thrombocytopenia ◽

Term Treatment ◽

Phase Iii ◽

Thromboembolic Events ◽

Thrombotic Risk ◽

Long Term Treatment ◽

Heavily Pretreated ◽

The Usa ◽

Syk Inhibitor

Background: Patients with immune thrombocytopenia (ITP) are at risk of bleeding and, paradoxically, thromboembolic events (TEEs), irrespective of thrombocytopenia. The risk of thrombosis is increased by advanced age, obesity, and prothrombotic comorbidities: cancer, hyperlipidemia, diabetes, hypertension, coronary artery disease, and chronic kidney disease, among others. Certain ITP treatments further increase the risk of TEE, especially splenectomy and thrombopoietin receptor agonists. Spleen tyrosine kinase (SYK) is a key signaling molecule common to thromboembolic and hemostatic (in addition to inflammatory) pathways. Fostamatinib is an orally administered SYK inhibitor approved in the USA and Europe for treatment of chronic ITP in adults. Methods: The phase III and extension studies included heavily pretreated patients with long-standing ITP, many of whom had risk factors for thrombosis prior to initiating fostamatinib. This report describes long-term safety and efficacy of fostamatinib in 146 patients with up to 5 years of treatment, a total of 229 patient-years, and assesses the incidence of thromboembolic events (by standardized MedDRA query). Results: Platelet counts ⩾50,000/µL were achieved in 54% of patients and the safety profile was as described in the phase III clinical studies with no new toxicities observed over the 5 years of follow-up. The only TEE occurred in one patient (0.7%, or 0.44/100 patient-years), who experienced a mild transient ischemic attack. This is a much lower rate than might be expected in ITP patients. Conclusion: This report demonstrates durable efficacy and a very low incidence of TEE in patients receiving long-term treatment of ITP with the SYK inhibitor fostamatinib. identifiers: NCT02076399, NCT02076412, and NCT02077192.

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