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Polyphenols as Potential Protectors against Radiation-Induced Adverse Effects in Patients with Thoracic Cancer.

ABSTRACT: Radiotherapy is one of the standard treatment approaches used against thoracic cancers, occasionally combined with chemotherapy, immunotherapy and molecular targeted therapy. However, these cancers are often not highly sensitive to standard of care treatments, making the use of high dose radiotherapy necessary, which is linked with high rates of radiation-induced adverse effects in healthy tissues of the thorax. These tissues remain therefore dose-limiting factors in radiation oncology despite recent technological advances in treatment planning and delivery of irradiation. Polyphenols are metabolites found in plants that have been suggested to improve the therapeutic window by sensitizing the tumor to radiotherapy, while simultaneously protecting normal cells from therapy-induced damage by preventing DNA damage, as well as having anti-oxidant, anti-inflammatory or immunomodulatory properties. This review focuses on the radioprotective effect of polyphenols and the molecular mechanisms underlying these effects in the normal tissue, especially in the lung, heart and esophagus.

SUBMITTER: Prades-Sagarra E

PROVIDER: S-EPMC10177176 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature

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Polyphenols as Potential Protectors against Radiation-Induced Adverse Effects in Patients with Thoracic Cancer.

Prades-Sagarra Èlia È Yaromina Ala A Dubois Ludwig J LJ

Cancers 20230422 9

Radiotherapy is one of the standard treatment approaches used against thoracic cancers, occasionally combined with chemotherapy, immunotherapy and molecular targeted therapy. However, these cancers are often not highly sensitive to standard of care treatments, making the use of high dose radiotherapy necessary, which is linked with high rates of radiation-induced adverse effects in healthy tissues of the thorax. These tissues remain therefore dose-limiting factors in radiation oncology despite r ...[more]

PMID: 37173877

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Project description:Cancer growth in host tissues features glutamine (gln) depletion over time, decreasing epithelial cells' optimal functioning. In addition, radiotherapy (RT) and/or chemotherapy (CT) cause damage to normal tissues, probably enhanced by this depletion. The present study prospectively examined the effect of gln supplementation on 72 patients with thoracic and upper aerodigestive malignancies (T&UAM) treated with sequential or concurrent RT-CT or RT alone. All patients received prophylactic gln powder 15 g bid for the full duration of treatment. The severity of acute radiation toxicities was graded according to the RT Oncology Group/European Organization for Research and Treatment of Cancer criteria. Primary endpoints were the incidence of grade >2 toxicities, weight loss and requirement for analgesics, and the secondary endpoint was the association of the length of irradiated esophagus from treatment planning with the use of opioids. The incidence of adverse effects was as follows: Grade >2 stomatitis, 25.0%; esophagitis, 60.5%; dysphagia, 54.2%; pain, 25.4%; mycosis, 40.8%. Stomatitis grade >2 was more frequent in patients with head and neck tumors (P<0.001) and in those with prior surgery (P<0.001). Esophagitis (P=0.020) and dysphagia (P=0.008) grade >2 were more frequent in patients with concurrent RT-CT. Regarding analgesics, 9.9% of patients received no pain treatment, 56.3% received simple analgesic therapy and 33.8% opioids. Patients on opioid therapy had a greater mean length of irradiated esophagus (P=0.024) or length >12 cm (P=0.018). In 54.2% of patients, weight loss was observed, particularly with concurrent RT-CT (P=0.007). Thus, the use of oral gln may have an important role in reducing acute radiation toxicities and weight loss, and in lowering the requirement for analgesics in patients with T&UAM. Further randomized trials are required to identify the appropriate gln dose, duration of treatment and precise radiation dosimetric parameters in this group of patients. The present clinical trial was retrospectively registered in the ClinicalTrials.gov Protocol Registration and Results System (registration no. NCT05054517/22-09-2021).

Project description:Introduction:Lung cancer is a disease which, despite the advancements in treatment, still has a very poor 5-year survival rate. Stereotactic ablative radiation therapy (SABR) is a highly advanced, sophisticated, and safe treatment which allows patients with early stage lung cancer to be treated effectively without invasive procedures and with excellent clinical outcomes. Avoiding surgery minimises morbidity and recovery time, bettering patients' quality of life. Furthermore, SABR allows patients unsuitable for surgery to still undergo curative treatment. Methods:We aimed to review SABR-related normal tissue toxicities reported in the literature. While many studies assess safety, clinical efficacy, and disease control of SABR for lung cancer, the number of comprehensive reviews that analyse SABR-related side-effects is scarce. This integrative review summarises the toxicities reported in literature based on published clinical trials and tumour location (central or peripheral tumours) for available SABR techniques. Given that the majority of the clinical studies did not report on the statistical significance (e.g., p-values and confidence intervals) of the toxicities experienced by patients, statistical analyses cannot be performed. As a result, adverse events are compiled from clinical reports; however, due to various techniques and nonstandard toxicity reports, no meta-analysis is possible at the current stage of reported data. Results:When comparing lobectomy and SABR in phase III trials, surgery resulted in increased procedure-related morbidity. In phase II trials, very few studies showed high grade toxicities/fatalities as a result of SABR for lung cancer. Gross target volume size was a significant predictor of toxicity. An ipsilateral mean lung dose larger than 9 Gy was significantly associated with radiation pneumonitis. Conclusions:Based on the studies reviewed SABR is a safe treatment technique for lung cancer; however, further well-designed phase III randomised clinical trials are required to produce timely conclusive results and to enable their comparison and statistical analysis.

Dataset Information

Polyphenols as Potential Protectors against Radiation-Induced Adverse Effects in Patients with Thoracic Cancer.

Publications

Polyphenols as Potential Protectors against Radiation-Induced Adverse Effects in Patients with Thoracic Cancer.

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