Personalization in Modern Radiation Oncology: Methods, Results and Pitfalls. Personalized Interventions and Breast Cancer

Aristei, Cynthia; Perrucci, Elisabetta; Alì, Emanuele; Marazzi, Fabio; Masiello, Valeria; Saldi, Simonetta; Ingrosso, Gianluca

doi:10.3389/fonc.2021.616042

Cited by 11 publications

(7 citation statements)

References 99 publications

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“…Genomic profiling continues to show promise as an aid in diagnosis, prognosis, and guidance for treatment in a variety of cancers. These practices can be further utilized to enhance precision medicine and tailor treatments more specifically to the patient’s needs [ 103 , 104 , 105 ]. One phase II clinical trial was conducted to assess whether a genomic predictor for platinum sensitivity can guide treatment decisions in stage IIIB/IV NSCLC patients.…”

Section: Predictive Markers Of Cisplatin Resistancementioning

confidence: 99%

Targeting DNA Damage Response and Repair to Enhance Therapeutic Index in Cisplatin-Based Cancer Treatment

Kiss

Xia

Acklin

2021

IJMS

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Platinum-based chemotherapies, such as cisplatin, play a large role in cancer treatment. The development of resistance and treatment toxicity creates substantial barriers to disease control, yet. To enhance the therapeutic index of cisplatin-based chemotherapy, it is imperative to circumvent resistance and toxicity while optimizing tumor sensitization. One of the primary mechanisms by which cancer cells develop resistance to cisplatin is through upregulation of DNA repair pathways. In this review, we discuss the DNA damage response in the context of cisplatin-induced DNA damage. We describe the proteins involved in the pathways and their roles in resistance development. Common biomarkers for cisplatin resistance and their utilization to improve patient risk stratification and treatment personalization are addressed. Finally, we discuss some of the current treatments and future strategies to circumvent the development of cisplatin resistance.

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Section: Predictive Markers Of Cisplatin Resistancementioning

confidence: 99%

Targeting DNA Damage Response and Repair to Enhance Therapeutic Index in Cisplatin-Based Cancer Treatment

Kiss

Xia

Acklin

2021

IJMS

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“… 7 – 9 A strong interest in designing personalized treatments based on the molecular subtypes has been advocated. 10 , 11 Although molecular subtypes and histotypes are often regarded as essential when making treatment decisions, the biomolecular dynamics for each subtype and histotype remain unclear and challenging to track in response to treatment. Developing a tool to identify and monitor biomarkers that can be used as targets in cancer treatment (e.g., to develop radiosensitizers) is necessary.…”

Section: Introductionmentioning

confidence: 99%

Group and Basis Restricted Non-Negative Matrix Factorization and Random Forest for Molecular Histotype Classification and Raman Biomarker Monitoring in Breast Cancer

et al. 2021

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Raman spectroscopy is a non-invasive optical technique that can be used to investigate biochemical information embedded in cells and tissues exposed to ionizing radiation used in cancer therapy. Raman spectroscopy could potentially be incorporated in personalized radiation treatment design as a tool to monitor radiation response in at the metabolic level. However, tracking biochemical dynamics remains challenging for Raman spectroscopy. Here we developed a novel analytical framework by combining group and basis restricted non-negative matrix factorization and random forest (GBR-NMF-RF). This framework can monitor radiation response profiles in different molecular histotypes and biochemical dynamics in irradiated breast cancer cells. Five subtypes of; human breast cancer (MCF-7, BT-474, MDA-MB-230, and SK-BR-3) and normal cells derived from human breast tissue (MCF10A) which had been exposed to ionizing radiation were tested in this framework. Reference Raman spectra of 20 biochemicals were collected and used as the constrained Raman biomarkers in the GBR-NMF-RF framework. We obtained scores for individual biochemicals corresponding to the contribution of each Raman reference spectrum to each spectrum obtained from the five cell types. A random forest classifier was then fitted to the chemical scores for performing molecular histotype classifications (HER2, PR, ER, Ki67, and cancer versus non-cancer) and assessing the importance of the Raman biochemical basis spectra for each classification test. Overall, the GBR-NMF-RF framework yields classification results with high accuracy (>97%), high sensitivity (>97%), and high specificity (>97%). Variable importance calculated in the random forest model indicated high contributions from glycogen and lipids (cholesterol, phosphatidylserine, and stearic acid) in molecular histotype classifications.

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“…Finally, we estimated the ratio of survival attributable to RT versus CV mortality. As explained, RT was associated with a 4.9% survival benefit, and this corresponds to a number needed to treat (NNT) of 20 (16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26) to prevent one death from BC in this population. The increase in the absolute risk of CV mortality was 0.23% (0.17-0.29), and this corresponds to a number needed to harm (NNH) for CV mortality associated with RT of 434 (344-588).…”

Section: Resultsmentioning

confidence: 95%

Oncological Benefit versus Cardiovascular Risk in Breast Cancer Patients Treated with Modern Radiotherapy

Acevedo

Orellana

et al. 2022

JCM

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Radiotherapy (RT) is an essential part of breast cancer (BC) treatments. Unfortunately, heart exposure to radiation can also impair the long-term survival of patients. Our study aimed to quantify the oncological benefit and the cardiovascular (CV) risk associated with modern RT in a real-world cohort of BC patients. Our descriptive study enrolled BC patients who received adjuvant RT. Ten-year overall survival (OS) was estimated using Predict® version 2.1 (National Health Service, London, UK). The basal risk of CV events was estimated using the American Heart Association (ACC/AHA) CV score. Treatment volumes and mean cardiac doses were obtained from RT treatment plan records. The increased risk of CV events due to RT was estimated using a model proposed by Darby. The risk of acute myocardial infarction or stroke mortality was estimated using HeartScore® (European Society of Cardiology, Brussels, Belgium). A total of 256 BC patients were included in the study. The average age of patients was 57 years old (range: 25–91); 49.6% had left BC. The mean cardiac dose was 166 cGy (interquartile range (IQR) 94–273); the estimated hazard ratio (HR) for CV disease was HR 1.12 (confidence interval (CI) 1.04–1.24). The estimated baseline 10-year CV risk was 5.6% (0.2 to 51.2); CV risk increased by 0.9% (range 0.02–35.47%) after RT. The absolute risk of 10-year mortality from CV disease was 2.5% (0.1–9); RT was associated with an estimated 4.9% survival benefit (3.73–6.07) against BC death and a 0.23% (0.17–0.29) estimated increase in CV mortality. Modern RT decreased 10-year BC mortality by 4% but increased CV mortality by 0.2% in this cohort. Our findings encourage the implementation of personalized adjuvant RT treatments that balance risks and benefits to improve long-term BC patient survival.

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Personalization in Modern Radiation Oncology: Methods, Results and Pitfalls. Personalized Interventions and Breast Cancer

Cited by 11 publications

References 99 publications

Targeting DNA Damage Response and Repair to Enhance Therapeutic Index in Cisplatin-Based Cancer Treatment

Targeting DNA Damage Response and Repair to Enhance Therapeutic Index in Cisplatin-Based Cancer Treatment

Group and Basis Restricted Non-Negative Matrix Factorization and Random Forest for Molecular Histotype Classification and Raman Biomarker Monitoring in Breast Cancer

Oncological Benefit versus Cardiovascular Risk in Breast Cancer Patients Treated with Modern Radiotherapy

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