With the great improvement in the prognosis and survival of breast cancer patients, coupled with the widespread use of cardiotoxic drugs, the cardiotoxicity caused by radiation-induced heart disease (RIHD) partially offsets the overall survival benefits of breast cancer patients. Heart damage occurs in many structures, such as left and right coronary arteries, the cardiac conduction system, the pericardium, and heart valves. RIHD has a long incubation period, most of which occur more than 10 years after radiotherapy, and the clinical manifestations become prominent with the extension of time. Advanced modern radiotherapy concepts such as respiratory gating, image-guided radiotherapy, conformal intensity-modulated radiotherapy, and intensity-modulated proton therapy can effectively reduce the radiation dose of breast cancer radiotherapy-related heart and left anterior descending coronary artery. The study of precise radiotherapy protection technology for the heart and large vessels is expected to reduce non-tumor-related death and achieve long-term survival in patients with breast cancer. The important direction in the future is to study the mechanism of RIHD, to find the best cardiac dose reference point, and to define the ideal dose-response relations. Combined with hematological markers, auxiliary examination parameters and cardiovascular risk factors, a predictive model will be established to estimate the probability of radiation-related cardiotoxicity in patients with breast cancer. As the radiation-related cardiotoxicity of breast cancer has become increasingly prominent, the purpose of this article is to summarize the related studies of RIHD in order to improve the long-term survival rate and quality of life of these sufferers.

With the great improvement in the prognosis and survival of breast cancer patients, coupled with the widespread use of cardiotoxic drugs, the cardiotoxicity caused by radiation-induced heart disease (RIHD) partially offsets the overall survival benefits of breast cancer patients. Heart damage occurs in many structures, such as left and right coronary arteries, the cardiac conduction system, the pericardium, and heart valves. RIHD has a long incubation period, most of which occur more than 10 years after radiotherapy, and the clinical manifestations become prominent with the extension of time. Advanced modern radiotherapy concepts such as respiratory gating, image-guided radiotherapy, conformal intensity-modulated radiotherapy, and intensity-modulated proton therapy can effectively reduce the radiation dose of breast cancer radiotherapy-related heart and left anterior descending coronary artery. The study of precise radiotherapy protection technology for the heart and large vessels is expected to reduce non-tumor-related death and achieve long-term survival in patients with breast cancer. The important direction in the future is to study the mechanism of RIHD, to find the best cardiac dose reference point, and to define the ideal dose-response relations. Combined with hematological markers, auxiliary examination parameters and cardiovascular risk factors, a predictive model will be established to estimate the probability of radiation-related cardiotoxicity in patients with breast cancer. As the radiation-related cardiotoxicity of breast cancer has become increasingly prominent, the purpose of this article is to summarize the related studies of RIHD in order to improve the long-term survival rate and quality of life of these sufferers.

Deficient mismatch repair(dMMR)is currently recognized as a biomarker for predicting the efficacy of immune checkpoint inhib-itors(ICIs),and domestic and foreign guidelines recommend first-line immunotherapy for patients with solid dMMR tumors.For rectal can-cer,only 5%of patients are classified as dMMR/microsatellite instability-high(MSI-H),and most have"immune desert type"or mismatch re-pair proficient(pMMR)/microsatellite stabilization(MSS)diseases,which respond poorly to ICIs.Therefore,recently,the synergistic effect of immune drugs and neoadjuvant chemoradiotherapy has been the focus of basic and clinical research.An increasing number of clinical trials of phase Ⅱ/Ⅲ immuno-total neoadjuvant therapy(iTNT)have emerged,and the management of locally advanced rectal cancer(LARC)has begun to enter the non-operative treatment era.Furthermore,an increasing number of studies support the efficacy of neoadjuvant immun-otherapy in patients with dMMR/MSI-H LARC,which exempts such patients from surgery and chemoradiotherapy as follow-up treatment and results in a pivot in the treatment paradigm of a watch-and-wait strategy.Regarding the LARC with pMMR/MSS,the preliminary iTNT findings support ICIs as a shift from an initial posterior-line palliative scheme to a first-line selection strategy and the continuation of large-scale clinical trials.However,no definitive conclusion has been reached regarding the best iTNT application for LARC.Recent studies have shown that short-course radiotherapy and sequential neoadjuvant chemotherapy,combined with immunotherapy,can achieve good short-term outcomes.Finally,identifying other new biomarkers may facilitate the identification of patients with pMMR/MSS who are sensitive to immune drugs(especially for low rectal cancer).In the future,the treatment strategy of LARC should be combined with the stratification of clinical recurrence risk and patient willingness for organ retention to achieve stratified and accurate treatment.This article will review the re-lated research background,basic and clinical research progress and existing problems of iTNT in LARC.