Dataset Information

Expression of HGF, pMet, and pAkt is related to benefit of radiotherapy after breast-conserving surgery: a long-term follow-up of the SweBCG91-RT randomised trial.

ABSTRACT: Experimental studies suggest that hepatocyte growth factor (HGF) and its transmembrane tyrosine kinase receptor, Met, in part also relying on Akt kinase activity, mediate radioresistance. We investigated the importance of these biomarkers for the risk of ipsilateral breast tumour recurrence (IBTR) after adjuvant radiotherapy (RT) in primary breast cancer. HGF, phosphorylated Met (pMet) and phosphorylated Akt (pAkt) were evaluated immunohistochemically on tissue microarrays from 1004 patients in the SweBCG91-RT trial, which randomly assigned patients to breast-conserving therapy, with or without adjuvant RT. HGF was evaluated in the stroma (HGF_str ); pMet in the membrane (pMet_mem ); HGF, pMet and pAkt in the cytoplasm (HGF_cyt , pMet_cyt , pAkt_cyt ); and pAkt in the nucleus (pAkt_nuc ). The prognostic and treatment predictive effects were evaluated to primary endpoint IBTR as first event during the first 5 years. Patients with tumours expressing low levels of HGF_cyt and pMet_cyt and high levels of pAkt_nuc derived a larger benefit from RT [hazard ratio (HR): 0.11 (0.037-0.30), 0.066 (0.016-0.28) and 0.094 (0.028-0.31), respectively] compared to patients with high expression of HGF_cyt and pMet_cyt , and low pAkt_nuc [HR: 0.36 (0.19-0.67), 0.35 (0.20-0.64) and 0.47 (0.32-0.71), respectively; interaction analyses: P = 0.052, 0.035 and 0.013, respectively]. These differences remained in multivariable analysis when adjusting for patient age, tumour size, histological grade, St Gallen subtype and systemic treatment (interaction analysis, P-values: 0.085, 0.027, and 0.023, respectively). This study suggests that patients with immunohistochemically low HGF_cyt , low pMet_cyt and high pAkt_nuc may derive an increased benefit from RT after breast-conserving surgery concerning the risk of developing IBTR.

SUBMITTER: Sjostrom M

PROVIDER: S-EPMC7607179 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Expression of HGF, pMet, and pAkt is related to benefit of radiotherapy after breast-conserving surgery: a long-term follow-up of the SweBCG91-RT randomised trial.

Sjöström Martin M Veenstra Cynthia C Holmberg Erik E Karlsson Per P Killander Fredrika F Malmström Per P Niméus Emma E Fernö Mårten M Stål Olle O

Molecular oncology 20200928 11

Experimental studies suggest that hepatocyte growth factor (HGF) and its transmembrane tyrosine kinase receptor, Met, in part also relying on Akt kinase activity, mediate radioresistance. We investigated the importance of these biomarkers for the risk of ipsilateral breast tumour recurrence (IBTR) after adjuvant radiotherapy (RT) in primary breast cancer. HGF, phosphorylated Met (pMet) and phosphorylated Akt (pAkt) were evaluated immunohistochemically on tissue microarrays from 1004 patients in ...[more]

PMID: 32946618

Similar Datasets

Project description:BackgroundBehavioural support via mobile health (mHealth) is emerging. This study aimed to assess the feasibility, acceptability, cost, and potential effect on weight of a mHealth follow-up program in bariatric surgery.MethodsThis was a non-randomised feasibility study describing intervention development and proof in the concept of a mHealth follow-up program in bariatric surgery. The study compares a prospective cohort with a historical control group and was conducted in a tertiary bariatric surgery service in Australia. The intervention group included individuals who had bariatric surgery (2019-2021) and owned a smart device, and the historical control group received usual postoperative care (2018). The intervention involved usual care plus codesigned biweekly text messages, monthly email newsletters, and online resources/videos over a 6-month period. The primary outcome measures included feasibility (via recruitment and retention rate), acceptability (via mixed methods), marginal costs, and weight 12 months postoperatively. Quantitative analysis was performed, including descriptive statistics and inferential and regression analysis. Multivariate linear regression and mixed-effects models were undertaken to test the potential intervention effect. Qualitative analysis was performed using inductive content analysis.ResultsThe study included 176 participants (n = 129 historical control, n = 47 intervention group; mean age 56 years). Of the 50 eligible patients, 48 consented to participate (96% recruitment rate). One participant opted out of the mHealth program entirely without disclosing their reason (98% retention rate). The survey response rate was low (n = 16/47, 34%). Participants agreed/strongly agreed that text messages supported new behaviours (n = 13/15, 87%); however, few agreed/strongly agreed that the messages motivated goal setting and self-monitoring (n = 8/15, 53%), dietary change (n = 6/15, 40%), or physical activity (n = 5/15, 33%). Interviews generated four main themes (n = 12): 'motivators and expectations', 'preferences and relevance', 'reinforced information", and 'wanting social support'. The intervention reinforced information, email newsletters were lengthy/challenging to read, and text messages were favoured, yet tailoring was recommended. The intervention cost AUD 11.04 per person. The mean 12-month weight was 86 ± 16 kg and 90 ± 16 kg (intervention and historical control) with no statistically significant difference. Intervention recipients enrolled at 3 months postoperatively demonstrated a statistically significant difference in 12-month weight (p = 0.014).ConclusionAlthough this study observed high rates of recruitment and retention, findings should be considered with caution as mHealth may have been embraced more by the intervention cohort as a result of the 2019 coronavirus pandemic. Of the various digital strategies developed and tested, the text message approach was the most acceptable; however, future intervention iterations could be strengthened through tailoring information when possible. The use of email newsletters and online resources/videos requires further testing of effectiveness to determine their value for continued use in bariatric surgery services.

Project description:PurposeThis study aimed to evaluate the robustness with respect to the positional variations of five planning strategies in free-breathing breast hypofractionated radiotherapy (HFRT) for patients after breast-conserving surgery.MethodsTwenty patients who received breast HFRT with 42.72 Gy in 16 fractions were retrospectively analyzed. Five treatment planning strategies were utilized for each patient, including 1) intensity-modulated radiation therapy (IMRT) planning (IMRTpure); 2) IMRT planning with skin flash tool extending and filling the fluence outside the skin by 2 cm (IMRTflash); 3) IMRT planning with planning target volume (PTV) extended outside the skin by 2 cm in the computed tomography dataset (IMRTePTV); 4) hybrid planning, i.e., 2 Gy/fraction three-dimensional conformal radiation therapy combined with 0.67 Gy/fraction IMRT (IMRThybrid); and 5) hybrid planning with skin flash (IMRThybrid-flash). All plans were normalized to 95% PTV receiving 100% of the prescription dose. Six additional plans were created with different isocenter shifts for each plan, which were 1 mm, 2 mm, 3 mm, 5 mm, 7 mm, and 10 mm distally in the X (left-right) and Y (anterior-posterior) directions, namely, (X,Y), to assess their robustness, and the corresponding doses were recalculated. Variation of dosimetric parameters with increasing isocenter shift was evaluated.ResultsAll plans were clinically acceptable. In terms of robustness to isocenter shifts, the five planning strategies followed the pattern IMRTePTV, IMRThybrid-flash, IMRTflash, IMRThybrid, and IMRTpure in descending order. V 95% of IMRTePTV maintained at 99.6% ± 0.3% with a (5,5) shift, which further reduced to 98.2% ± 2.0% with a (10,10) shift. IMRThybrid-flash yielded the robustness second to IMRTePTV with less risk from dose hotspots, and the corresponding V 95% maintained >95% up until (5,5).ConclusionConsidering the dosimetric distribution and robustness in breast radiotherapy, IMRTePTV performed best at maintaining high target coverage with increasing isocenter shift, while IMRThybrid-flash would be adequate with positional uncertainty<5 mm.

Dataset Information

Expression of HGF, pMet, and pAkt is related to benefit of radiotherapy after breast-conserving surgery: a long-term follow-up of the SweBCG91-RT randomised trial.

Publications

Expression of HGF, pMet, and pAkt is related to benefit of radiotherapy after breast-conserving surgery: a long-term follow-up of the SweBCG91-RT randomised trial.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets