30 research outputs found
PRECYCLE: multicenter, randomized phase IV intergroup trial to evaluate the impact of eHealth-based patient-reported outcome (PRO) assessment on quality of life in patients with hormone receptor positive, HER2 negative locally advanced or metastatic breast cancer treated with palbociclib and an aromatase inhibitor or palbociclib and fulvestrant
Background
Efficacy and quality of life (QoL) are key criteria for therapy selection in metastatic breast cancer (MBC). In hormone receptor positive (HR +) human epidermal growth factor receptor 2 negative (HER2 −) MBC, addition of targeted oral agents such as everolimus or a cycline-dependent kinase 4/6 (CDK 4/6) inhibitor (e.g., palbociclib, ribociclib, abemaciclib) to endocrine therapy substantially prolongs progression-free survival and in the case of a CDK 4/6i also overall survival. However, the prerequisite is adherence to therapy over the entire course of treatment. However, particularly with new oral drugs, adherence presents a challenge to disease management. In this context, factors influencing adherence include maintaining patients’ satisfaction and early detection/management of side effects. New strategies for continuous support of oncological patients are needed. An eHealth-based platform can help to support therapy management and physician–patient interaction.
Methods
PreCycle is a multicenter, randomized, phase IV trial in HR + HER2 − MBC. All patients (n = 960) receive the CDK 4/6 inhibitor palbociclib either in first (62.5%) or later line (37.5%) together with endocrine therapy (AI, fulvestrant) according to national guidelines. PreCycle evaluates and compares the time to deterioration (TTD) of QoL in patients supported by eHealth systems with substantially different functionality: CANKADO active vs. inform. CANKADO active is the fully functional CANKADO-based eHealth treatment support system. CANKADO inform is a CANKADO-based eHealth service with a personal login, documentation of daily drug intake, but no further functions. To evaluate QoL, the FACT-B questionnaire is completed at every visit. As little is known about relationships between behavior (e.g., adherence), genetic background, and drug efficacy, the trial includes both patient-reported outcome and biomarker screening for discovery of forecast models for adherence, symptoms, QoL, progression free survival (PFS), and overall survival (OS).
Discussion
The primary objective of PreCycle is to test the hypothesis of superiority for time to deterioration (TTD) in terms of DQoL = “Deterioration of quality of life” (FACT-G scale) in patients supported by an eHealth therapy management system (CANKADO active) versus in patients merely receiving eHealth-based information (CANKADO inform).
EudraCT Number: 2016–004191-2
Split Course Hyperfractionated Accelerated Radio-Chemotherapy (SCHARC) for patients with advanced head and neck cancer: Influence of protocol deviations and hemoglobin on overall survival, a retrospective analysis
BACKGROUND: The advantage of hyperfractionated accelerated radiation therapy for advanced head and neck cancer has been reported. Furthermore, randomized trials and meta-analyses have confirmed the survival benefit of additional chemotherapy to radiotherapy. We retrospectively analyzed the efficiency and toxicity of the Regensburg standard therapy protocol "SCHARC" and the overall survival of our patients. METHODS: From 1997 to 2004, 64 patients suffering from advanced head and neck cancer (88 % stage IV, 12 % stage III) were assigned to receive the SCHARC protocol. Around half of the patients were diagnosed with oro-hypopharynx carcinoma (52 %), one third with tongue and floor of mouth tumors (29 %) and one fifth (19 %) suffered from H & N cancer at other sites. The schedule consisted of one therapy block with 30 Gy in 20 fractions over a two week period with concomitant chemotherapy (d 1–5: 20 mg/m(2)/d DDP + 750–1000 mg/m(2)/d 5FU (cont. infusion). This therapy block was repeated after a fortnight break up to a cumulative dose of 60 Gy and followed by a boost up to 70 Gy (69–70.5 Gy). All patients assigned to this scheme were included in the survival evaluation. RESULTS: Forty patients (63 %) received both radiation and chemotherapy according to the protocol. The mean follow up was 2.3 years (829 d) and the median follow up was 1.9 years (678 d), respectively. The analysis of survival revealed an estimated 3 year overall survival rate of 57 %. No patient died of complications, 52 patients (80 %) had acute grade 2–3 mucositis, and 33 patients (58 %) suffered from acute grade 3 skin toxicity. Leucopenia was no major problem (mean nadir 3.4 g/nl, no patient < 1.0 g/nl) and the mean hemoglobin value decreased from 13.2 to 10.5 g/dl. Univariate analysis of survival showed a better outcome for patients with a hemoglobin nadir >10.5 g/dl and for patients who completed the protocol. CONCLUSION: The SCHARC protocol was effective in patients diagnosed with advanced head and neck cancer. It led to long-term disease control and survival in about 50 % of the patients with significant but acceptable toxicity. Most patients were not anemic at beginning of therapy. Therefore, we could assess the influence of pre-treatment hemoglobin on survival. However, a low hemoglobin nadir was associated with poor outcome. This result suggests an influence of anemia during therapy on prognosis
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Report on computational assessment of Tumor Infiltrating Lymphocytes from the International Immuno-Oncology Biomarker Working Group
Funder: U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)Funder: National Center for Research Resources under award number 1 C06 RR12463-01, VA Merit Review Award IBX004121A from the United States Department of Veterans Affairs Biomedical Laboratory Research and Development Service, the DOD Prostate Cancer Idea Development Award (W81XWH-15-1-0558), the DOD Lung Cancer Investigator-Initiated Translational Research Award (W81XWH-18-1-0440), the DOD Peer Reviewed Cancer Research Program (W81XWH-16-1-0329), the Ohio Third Frontier Technology Validation Fund, the Wallace H. Coulter Foundation Program in the Department of Biomedical Engineering and the Clinical and Translational Science Award Program (CTSA) at Case Western Reserve University.Funder: Susan G Komen Foundation (CCR CCR18547966) and a Young Investigator Grant from the Breast Cancer Alliance.Funder: The Canadian Cancer SocietyFunder: Breast Cancer Research Foundation (BCRF), Grant No. 17-194Abstract: Assessment of tumor-infiltrating lymphocytes (TILs) is increasingly recognized as an integral part of the prognostic workflow in triple-negative (TNBC) and HER2-positive breast cancer, as well as many other solid tumors. This recognition has come about thanks to standardized visual reporting guidelines, which helped to reduce inter-reader variability. Now, there are ripe opportunities to employ computational methods that extract spatio-morphologic predictive features, enabling computer-aided diagnostics. We detail the benefits of computational TILs assessment, the readiness of TILs scoring for computational assessment, and outline considerations for overcoming key barriers to clinical translation in this arena. Specifically, we discuss: 1. ensuring computational workflows closely capture visual guidelines and standards; 2. challenges and thoughts standards for assessment of algorithms including training, preanalytical, analytical, and clinical validation; 3. perspectives on how to realize the potential of machine learning models and to overcome the perceptual and practical limits of visual scoring
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Pitfalls in assessing stromal tumor infiltrating lymphocytes (sTILs) in breast cancer
Abstract: Stromal tumor-infiltrating lymphocytes (sTILs) are important prognostic and predictive biomarkers in triple-negative (TNBC) and HER2-positive breast cancer. Incorporating sTILs into clinical practice necessitates reproducible assessment. Previously developed standardized scoring guidelines have been widely embraced by the clinical and research communities. We evaluated sources of variability in sTIL assessment by pathologists in three previous sTIL ring studies. We identify common challenges and evaluate impact of discrepancies on outcome estimates in early TNBC using a newly-developed prognostic tool. Discordant sTIL assessment is driven by heterogeneity in lymphocyte distribution. Additional factors include: technical slide-related issues; scoring outside the tumor boundary; tumors with minimal assessable stroma; including lymphocytes associated with other structures; and including other inflammatory cells. Small variations in sTIL assessment modestly alter risk estimation in early TNBC but have the potential to affect treatment selection if cutpoints are employed. Scoring and averaging multiple areas, as well as use of reference images, improve consistency of sTIL evaluation. Moreover, to assist in avoiding the pitfalls identified in this analysis, we developed an educational resource available at www.tilsinbreastcancer.org/pitfalls
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Application of a risk-management framework for integration of stromal tumor-infiltrating lymphocytes in clinical trials
Funder: Breast Cancer Research Foundation (BCRF); doi: https://doi.org/10.13039/100001006Abstract: Stromal tumor-infiltrating lymphocytes (sTILs) are a potential predictive biomarker for immunotherapy response in metastatic triple-negative breast cancer (TNBC). To incorporate sTILs into clinical trials and diagnostics, reliable assessment is essential. In this review, we propose a new concept, namely the implementation of a risk-management framework that enables the use of sTILs as a stratification factor in clinical trials. We present the design of a biomarker risk-mitigation workflow that can be applied to any biomarker incorporation in clinical trials. We demonstrate the implementation of this concept using sTILs as an integral biomarker in a single-center phase II immunotherapy trial for metastatic TNBC (TONIC trial, NCT02499367), using this workflow to mitigate risks of suboptimal inclusion of sTILs in this specific trial. In this review, we demonstrate that a web-based scoring platform can mitigate potential risk factors when including sTILs in clinical trials, and we argue that this framework can be applied for any future biomarker-driven clinical trial setting
Contour changes of peri-implant tissues are minimal and similar for a one- and a two-piece implant system over 12 years
OBJECTIVES: To assess contour changes of peri-implant tissues comparing a one- and a two-piece dental implant system over 12 years.
MATERIALS AND METHODS: Patients seeking implant therapy were enrolled and randomly allocated to receive implants (a one-piece (STM) or a two-piece (BRA) system). Impressions were taken at the time of insertion of the final reconstruction (BL), after 1 year (FU-1), 5 years (FU-5), and at 12 years (FU-12). Thirty patients were included in the analysis (STM, 16; BRA, 14). Digital scans of casts were superimposed and analyzed in an image analysis program. Measurements included changes of the crown height, contour changes on the buccal side of the implants and the contralateral teeth (control).
RESULTS: Contour changes at implant sites revealed a loss of - 0.29 mm (STM) and - 0.46 mm (BRA) during an observation period of 12 years. Contour changes at the corresponding tooth sites amounted to - 0.06 mm (STM) and - 0.12 mm (BRA) during the same time period. The implant crown gained 0.25 mm (STM) and 0.08 mm (BRA) in height due to recession of the marginal mucosa. The corresponding gain in crown height at the contralateral tooth sites amounted to 0.36 mm (STM) and 0.10 mm (BRA). Interproximal marginal bone level changes measured - 0.28 mm (STM) and - 1.11 mm (BRA). The mean BOP amounted to 38.8% (STM) and 48.7% (BRA) at the 12-year follow-up (FU-12).
CONCLUSION: Minimal changes of the peri-implant soft tissue contour were observed at implant sites over the period of 12 years irrespective of the use of a one- or a two-piece implant system. The differences between the implant sites and corresponding teeth were clinically negligible.
CLINICAL RELEVANCE: Peri-implant soft tissue stability is of high clinical relevance when monitoring dental implant sites on the long run. Clinical data on the extent of soft tissue changes around different implant systems are scarce. The present RCTs demonstrate minimal changes of the peri-implant soft tissue contour 12 years after implant insertion independent of the use of a one- or a two-piece implant system
Neoadjuvant and adjuvant end-points in health technology assessment in oncology
Health technology assessment (HTA) of clinical and economic value of a new intervention is an integral step in providing the access of patients to innovative cancer care and treatment. Overall survival (OS) is the preferred criterion for demonstrating the therapeutic efficacy in HTA given its direct clinical and patient relevance. However, with often long life expectancy of patients with early cancer, analysis of OS becomes less practical. Partially due to this reason, pathological complete response (pCR) and time-to-event end-points like disease-free survival are frequently incorporated into the pivotal clinical trials in the neoadjuvant and adjuvant settings. However, there exists a discrepancy between different national HTA bodies regarding the acknowledgement of patient relevance of these end-points. In this article, we analysed the perspectives of patients on different aspects of end-points used in clinical trials in early cancer. Gathered evidence strongly suggests that complete tumour eradication and reduced risk of recurrence provide important psychological benefits thus signifying that pCR and time-to-event end-points are directly relevant to patients. Additionally, we reviewed opinions on patient relevance of neoadjuvant and adjuvant therapy end-points adopted by HTA bodies during the recent evaluations. We found that improvements in end-points used in the adjuvant setting were commonly considered as valuable to patients. In contrast, opinions on patient relevance of neoadjuvant therapy end-points varied between the national HTA bodies. Universal acknowledgement of patient relevance of therapeutic end-points for early cancer by HTA bodies is necessary to balance the inequality in uptake of innovative therapies into national healthcare systems. (C) 2021 Elsevier Ltd. All rights reserved
Protroca: A Noninterventional Study on Prophylactic Lipegfilgrastim against Chemotherapy-Induced Neutropenia in Nonselected Breast Cancer Patients
Background: Protroca evaluated the efficacy and safety of primary and secondary prophylaxis of neutropenia with lipegfilgrastim (Lonquex (R)) in breast cancer patients receiving neoadjuvant or adjuvant chemotherapy (CT). Patients and Methods: Of the 255 patients enrolled, 248 patients were evaluable for the intent-to-treat (ITT) and 194 patients for the per-protocol set. Primary and secondary end points after lipegfilgrastim treatment were assessed. Results: Nine patients of the ITT set receiving lipegfilgrastim as primary prophylaxis (n = 222) had febrile neutropenia of grade 3-4 (5 patients) or infection of grade 3-4 (4 patients); 1/26 of those receiving secondary prophylaxis had an event. Dose reductions were performed in 9.5% of the patients. Postponement of cancer CT cycles for >3 days occurred in <15% of patients; 10.8% (92/851 AEs) and 8% (2/25 SAEs) of documented adverse events and serious adverse events, respectively, were related to lipegfilgrastim. Conclusions: Application of lipegfilgrastim was effective as primary and secondary prophylaxis in the prevention of CT-induced neutropenia in breast cancer