Pub Date : 2024-10-01DOI: 10.1016/j.ijrobp.2024.07.068
S. Ma, M. Wu, D. Chen, J. Yu
<div><h3>Purpose/Objective(s)</h3><div>Tamoxifen has been commonly used for the treatment of ER+ breast cancer with nanomolar affinity for the estrogen receptor. In recent years, the immunomodulatory effects of tamoxifen at micromolar concentration have gradually been discovered. However, its immunomodulatory action on anti-tumor was still ambiguous. Radiotherapy (RT) still faces primary and secondary radiation resistance which partially originates from the accumulation of tumor-associated macrophages (TAMs) with the M2 phenotype. Regulating the immune system may be an effective way to overcome radiotherapy tolerance. To date, the clinical effect of combining tamoxifen with RT has not been clearly defined. Our study aimed to uncover the synergistic effect of tamoxifen with RT and provide basic support for clinical applications.</div></div><div><h3>Materials/Methods</h3><div>Subcutaneous tumor models with three cell lines were adopted for certificating the synergistic effect of tamoxifen with RT. The infiltration status and function of immune cells among tumors are detected by flow cytometry. The tumor cell conditioned medium (CM) and CM after radiotherapy (RTCM) with or without tamoxifen were applied for stimulating bone marrow-derived macrophages (BMDMs) and RAW264.7 to TAMs. We performed RNA sequencing to detect the mechanism of the synergistic effect and completed the validation.</div></div><div><h3>Results</h3><div>In vivo experiments, it was gratifying that the anti-tumor effect of radiotherapy was all boosted in the combination group of RT and tamoxifen. In comparison, the synergistic action disappeared in immunodeficiency models. The infiltration of CD8+ T cells and CD86+ M1 TAMs was statistically higher in the combination group than the alone treatment group, while the CD206+M2 TAMs did not vary obviously. The proportion of Gzmb+ and TNF-α+ TAMs dramatically improved in the combination group. Furthermore, the proportion of activated CD8+ T cells and cytotoxic CD8+ T cells both remarkably increased in the combination group. After depleting TAMs with clodronate liposomes, the synergistic effect of RT with tamoxifen vanished. In vitro, the highest level of M1-related markers and the highest level of CD86+ macrophages both appeared in the combination group demonstrating the excellent combination effect of inducing TAMs M1 polarization. The RNA sequencing results revealed the mechanism by which RT combined with tamoxifen polarized TAMs to M1-type by activating the JNK/c-Jun pathway. The addition of JNK-IN-8, an inhibitor of JNK, supports the pivotal role of the JNK/c-Jun pathway in the process of M1 polarization induced by tamoxifen combined with RT.</div></div><div><h3>Conclusion</h3><div>All in all, we found RT combined with high-dose tamoxifen could significantly activate the JNK/c-Jun pathway, and then modulate the immune microenvironment, finally resulting in a stronger antitumor effect in vivo. The immunomodulatory function may open a ne
{"title":"Exploring the Combined Effects of Tamoxifen and Radiotherapy, Regardless of Estrogen Receptor Status","authors":"S. Ma, M. Wu, D. Chen, J. Yu","doi":"10.1016/j.ijrobp.2024.07.068","DOIUrl":"10.1016/j.ijrobp.2024.07.068","url":null,"abstract":"<div><h3>Purpose/Objective(s)</h3><div>Tamoxifen has been commonly used for the treatment of ER+ breast cancer with nanomolar affinity for the estrogen receptor. In recent years, the immunomodulatory effects of tamoxifen at micromolar concentration have gradually been discovered. However, its immunomodulatory action on anti-tumor was still ambiguous. Radiotherapy (RT) still faces primary and secondary radiation resistance which partially originates from the accumulation of tumor-associated macrophages (TAMs) with the M2 phenotype. Regulating the immune system may be an effective way to overcome radiotherapy tolerance. To date, the clinical effect of combining tamoxifen with RT has not been clearly defined. Our study aimed to uncover the synergistic effect of tamoxifen with RT and provide basic support for clinical applications.</div></div><div><h3>Materials/Methods</h3><div>Subcutaneous tumor models with three cell lines were adopted for certificating the synergistic effect of tamoxifen with RT. The infiltration status and function of immune cells among tumors are detected by flow cytometry. The tumor cell conditioned medium (CM) and CM after radiotherapy (RTCM) with or without tamoxifen were applied for stimulating bone marrow-derived macrophages (BMDMs) and RAW264.7 to TAMs. We performed RNA sequencing to detect the mechanism of the synergistic effect and completed the validation.</div></div><div><h3>Results</h3><div>In vivo experiments, it was gratifying that the anti-tumor effect of radiotherapy was all boosted in the combination group of RT and tamoxifen. In comparison, the synergistic action disappeared in immunodeficiency models. The infiltration of CD8+ T cells and CD86+ M1 TAMs was statistically higher in the combination group than the alone treatment group, while the CD206+M2 TAMs did not vary obviously. The proportion of Gzmb+ and TNF-α+ TAMs dramatically improved in the combination group. Furthermore, the proportion of activated CD8+ T cells and cytotoxic CD8+ T cells both remarkably increased in the combination group. After depleting TAMs with clodronate liposomes, the synergistic effect of RT with tamoxifen vanished. In vitro, the highest level of M1-related markers and the highest level of CD86+ macrophages both appeared in the combination group demonstrating the excellent combination effect of inducing TAMs M1 polarization. The RNA sequencing results revealed the mechanism by which RT combined with tamoxifen polarized TAMs to M1-type by activating the JNK/c-Jun pathway. The addition of JNK-IN-8, an inhibitor of JNK, supports the pivotal role of the JNK/c-Jun pathway in the process of M1 polarization induced by tamoxifen combined with RT.</div></div><div><h3>Conclusion</h3><div>All in all, we found RT combined with high-dose tamoxifen could significantly activate the JNK/c-Jun pathway, and then modulate the immune microenvironment, finally resulting in a stronger antitumor effect in vivo. The immunomodulatory function may open a ne","PeriodicalId":14215,"journal":{"name":"International Journal of Radiation Oncology Biology Physics","volume":"120 2","pages":"Pages S44-S45"},"PeriodicalIF":6.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142359496","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-01DOI: 10.1016/j.ijrobp.2024.07.046
C. Cai , J. Xiao , R. Cai , J. Chen , H. Xu
Purpose/Objective(s)
To investigate the early prediction value of dynamic magnetic resonance imaging (MRI)-based radiomics acquired at baseline and during treatment for progression and prognosis in locally advanced cervical cancer (LACC) patients treated with concurrent chemoradiotherapy (CCRT).
Materials/Methods
A total of 111 LACC patients (FIGO 2018 stages ⅡA- IVA) who received CCRT followed by brachytherapy between March 2017 and December 2021 were retrospectively enrolled in this study. The dynamic MRI images were acquired at baseline (MRIpre) before brachytherapy delivered (MRIpost) and at each follow-up visit. Clinical characteristics, 2-year progression-free survival (PFS), and 2-year overall survival (OS) were recorded during follow-up. To build the prognostic model, 88 patients were randomly divided into a training set, and the rest 23 patients reserved for the test set. The least absolute shrinkage and selection operator (LASSO) method was applied to extract features from MRI images as well as from clinical characteristics. Vector Machine (SVM) model was trained using 5-Fold cross-validation on the training set and then evaluated on the test set.
Results
The median follow-up was 4.3 years (IQR = 3.1-5.0), 2-year PFS was 73.9%, and 2-year OS was 82.9%. A total of 842 radiomics features were extracted from both original and wavelet-filtered images. Multi-sequence models using T1 contrast and DWI-sequence MRI exhibited superior performance, achieving higher AUC scores on the test set compared to single-sequence models (Table). Models built by the radiomics features from MRIpre, MRIpost and theΔMRI (variations in radiomics features from MRIpre and MRIpost) achieves AUC scores of 0.723,0.750 and 0.759 for 2-year PFS, and 0.711, 0.737, and 0.716 for 2-year OS on the test set. When combined with the clinical characteristics, the predictive model using ΔMRI features achieved higher AUC scores than MRIpre or MRIpost model, with AUC of 0.812 for the progression and 0.816 for the survival.
Conclusion
In this study, we built machine learning models from dynamic features in longitudinal images, finding the models using variations in radiomics features (ΔMRI) from multi-sequence MRI images hold significant promise for predicting the prognosis of LACC patients. The integrated models with clinical characteristics further enhanced the predictive performance.
{"title":"Longitudinal Dynamic MRI Radiomic Models for Early Prediction of Prognosis in Locally Advanced Cervical Cancer Treated with Concurrent Chemoradiotherapy","authors":"C. Cai , J. Xiao , R. Cai , J. Chen , H. Xu","doi":"10.1016/j.ijrobp.2024.07.046","DOIUrl":"10.1016/j.ijrobp.2024.07.046","url":null,"abstract":"<div><h3>Purpose/Objective(s)</h3><div>To investigate the early prediction value of dynamic magnetic resonance imaging (MRI)-based radiomics acquired at baseline and during treatment for progression and prognosis in locally advanced cervical cancer (LACC) patients treated with concurrent chemoradiotherapy (CCRT).</div></div><div><h3>Materials/Methods</h3><div>A total of 111 LACC patients (FIGO 2018 stages ⅡA- IVA) who received CCRT followed by brachytherapy between March 2017 and December 2021 were retrospectively enrolled in this study. The dynamic MRI images were acquired at baseline (MRI<sub>pre</sub>) before brachytherapy delivered (MRI<sub>post</sub>) and at each follow-up visit. Clinical characteristics, 2-year progression-free survival (PFS), and 2-year overall survival (OS) were recorded during follow-up. To build the prognostic model, 88 patients were randomly divided into a training set, and the rest 23 patients reserved for the test set. The least absolute shrinkage and selection operator (LASSO) method was applied to extract features from MRI images as well as from clinical characteristics. Vector Machine (SVM) model was trained using 5-Fold cross-validation on the training set and then evaluated on the test set.</div></div><div><h3>Results</h3><div>The median follow-up was 4.3 years (IQR = 3.1-5.0), 2-year PFS was 73.9%, and 2-year OS was 82.9%. A total of 842 radiomics features were extracted from both original and wavelet-filtered images. Multi-sequence models using T1 contrast and DWI-sequence MRI exhibited superior performance, achieving higher AUC scores on the test set compared to single-sequence models (Table). Models built by the radiomics features from MRI<sub>pre</sub>, MRI<sub>post</sub> and theΔMRI (variations in radiomics features from MRI<sub>pre</sub> and MRI<sub>post</sub>) achieves AUC scores of 0.723,0.750 and 0.759 for 2-year PFS, and 0.711, 0.737, and 0.716 for 2-year OS on the test set. When combined with the clinical characteristics, the predictive model using ΔMRI features achieved higher AUC scores than MRI<sub>pre</sub> or MRI<sub>post</sub> model, with AUC of 0.812 for the progression and 0.816 for the survival.</div></div><div><h3>Conclusion</h3><div>In this study, we built machine learning models from dynamic features in longitudinal images, finding the models using variations in radiomics features (ΔMRI) from multi-sequence MRI images hold significant promise for predicting the prognosis of LACC patients. The integrated models with clinical characteristics further enhanced the predictive performance.</div></div>","PeriodicalId":14215,"journal":{"name":"International Journal of Radiation Oncology Biology Physics","volume":"120 2","pages":"Page S33"},"PeriodicalIF":6.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142358668","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-01DOI: 10.1016/j.ijrobp.2024.07.030
X. Yang , Z. Gao , J. Fu
Purpose/Objective(s)
Kangfuxin liquid is derived from the desiccated bodies of American cockroaches and is recognized for its notable anti-ulcerative properties. This study aimed to elucidate the therapeutic efficacy and underlying mechanism of action of Kangfuxin liquid retention enema in mitigating radiation-induced proctitis (RP) in cervical cancer patients.
Materials/Methods
A cohort of 86 cervical cancer patients, undergoing radiotherapy between June 2021 and January 2023, were enrolled. These participants were stratified into two groups based on their treatment modalities, each comprising 43 patients. Those in the control group did not receive any prophylactic Kangfuxin solution during the onset of their treatment. Conversely, the observation group underwent daily retention enemas containing the Kangfuxin solution from the commencement of their radiotherapy. Parameters, such as the incidence, onset, categorization of both acute and chronic RP, were meticulously documented for each group. Additionally, using flow cytometry, the expression levels of neutrophils, CD3, CD4, and CD8 were gauged pre- and post-treatment. Concurrently, C-reactive protein (CRP) levels were assessed before and after treatment via fluorescence assay.
Results
The observation group exhibited a markedly reduced incidence of acute RP post-radiotherapy, at 20.93%, in contrast to the control group, which presented a 41.86% incidence. Furthermore, the mean time to onset of RP in the observation group was significantly protracted relative to the control group, with the differences attaining statistical significance (P < 0.05). The incidence of moderate to severe radiation enteritis was considerably diminished in the observation group at 2.33%, as compared to 18.60% in the control group. Additionally, the incidences of grade 1-2 and grade 3-4 RP, as well as the cumulative incidence of both acute and chronic RP, were substantially lower in the observation group, demonstrating statistical significance (P < 0.05). Post-radiotherapy, the observation group displayed elevated levels of CD3 and CD4, and a reduction in CD8 levels, relative to the control group. Concurrently, the levels of neutrophils and CRP in the observation group were found to be lower than those in the control group, with the differences being statistically significant (P < 0.05).
Conclusion
The administration of Kangfuxin liquid retention enema demonstrates efficacy in both delaying the onset and diminishing the prevalence of radiation proctitis, subsequently ameliorating the clinical manifestations observed in cervical cancer patients post-radiotherapy. This therapeutic efficacy may be attributed to the enhancement of immune functionality coupled with a reduction in pro-inflammatory mediators (ChiCTR2200055355).
{"title":"Efficacy of Kangfuxin Liquid Retention Enema in Preventing and Treating Radiation-Induced Proctitis in Cervical Cancer Patients: A Randomized, Open-Label, Phase III Study","authors":"X. Yang , Z. Gao , J. Fu","doi":"10.1016/j.ijrobp.2024.07.030","DOIUrl":"10.1016/j.ijrobp.2024.07.030","url":null,"abstract":"<div><h3>Purpose/Objective(s)</h3><div>Kangfuxin liquid is derived from the desiccated bodies of American cockroaches and is recognized for its notable anti-ulcerative properties. This study aimed to elucidate the therapeutic efficacy and underlying mechanism of action of Kangfuxin liquid retention enema in mitigating radiation-induced proctitis (RP) in cervical cancer patients.</div></div><div><h3>Materials/Methods</h3><div>A cohort of 86 cervical cancer patients, undergoing radiotherapy between June 2021 and January 2023, were enrolled. These participants were stratified into two groups based on their treatment modalities, each comprising 43 patients. Those in the control group did not receive any prophylactic Kangfuxin solution during the onset of their treatment. Conversely, the observation group underwent daily retention enemas containing the Kangfuxin solution from the commencement of their radiotherapy. Parameters, such as the incidence, onset, categorization of both acute and chronic RP, were meticulously documented for each group. Additionally, using flow cytometry, the expression levels of neutrophils, CD3, CD4, and CD8 were gauged pre- and post-treatment. Concurrently, C-reactive protein (CRP) levels were assessed before and after treatment via fluorescence assay.</div></div><div><h3>Results</h3><div>The observation group exhibited a markedly reduced incidence of acute RP post-radiotherapy, at 20.93%, in contrast to the control group, which presented a 41.86% incidence. Furthermore, the mean time to onset of RP in the observation group was significantly protracted relative to the control group, with the differences attaining statistical significance (<em>P</em> < 0.05). The incidence of moderate to severe radiation enteritis was considerably diminished in the observation group at 2.33%, as compared to 18.60% in the control group. Additionally, the incidences of grade 1-2 and grade 3-4 RP, as well as the cumulative incidence of both acute and chronic RP, were substantially lower in the observation group, demonstrating statistical significance (<em>P</em> < 0.05). Post-radiotherapy, the observation group displayed elevated levels of CD3 and CD4, and a reduction in CD8 levels, relative to the control group. Concurrently, the levels of neutrophils and CRP in the observation group were found to be lower than those in the control group, with the differences being statistically significant (<em>P</em> < 0.05).</div></div><div><h3>Conclusion</h3><div>The administration of Kangfuxin liquid retention enema demonstrates efficacy in both delaying the onset and diminishing the prevalence of radiation proctitis, subsequently ameliorating the clinical manifestations observed in cervical cancer patients post-radiotherapy. This therapeutic efficacy may be attributed to the enhancement of immune functionality coupled with a reduction in pro-inflammatory mediators (ChiCTR2200055355).</div></div>","PeriodicalId":14215,"journal":{"name":"International Journal of Radiation Oncology Biology Physics","volume":"120 2","pages":"Page S25"},"PeriodicalIF":6.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142358676","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-01DOI: 10.1016/j.ijrobp.2024.07.010
S. Zheng , M. Dong , J. Jiang , J. Zhang , Y. Shi , L. Gan , B. Yu , J. Chen , L. Cao
Purpose/Objective(s)
The Phase 3 FAST-Forward trial showed that 26 Gy in 5 fractions over 1 week for whole breast irradiation (WBI) was safe and efficacy for early breast cancer patients, in which a sequential tumor bed boost was allowed (10 Gy or 16 Gy in 2-Gy fractions). Current trial delivers 26 Gy in 5 fractions over 1 week for WBI and 10.4 Gy in 2 fractions once daily for sequential tumor bed boost, to keep the total duration of radiotherapy (RT) to no more than 1.5 weeks if tumor bed boost is required. Here we report the early safety of this ultra-hypofractionation regimen.
Materials/Methods
This is a multicenter, single-arm, phase 2 trial carried out at 4 tertiary hospitals in China. Patients aged at least 18 years with invasive breast carcinoma (pT1-3, N0-1mic, M0) or ductal carcinoma in situ (DCIS) after lumpectomy were eligible. All enrolled patients underwent WBI of 26 Gy in 5 fractions over 5 days. A sequential tumor bed boost of 10.4 Gy in 2 fractions over 2 days was at the discretion of radiation oncologist. The primary endpoint was acute radiation-induced toxicity within 6 months after RT, aiming for a 10% non-inferiority margin based on a projected 50% baseline incidence of ≥Grade 2 (G2) acute toxicity. Acute toxicity was assessed using CTCAE v5.0 at 1 week and 2 weeks during RT, and at 1 month and 6 months after RT completion. This trial is registered at ClinicalTrials.gov (NCT04926766).
Results
Between January 2021, and July 2023, recruitment of 217 patients has been completed, of whom 210 received tumor bed boost. Within 6 months after RT, 157 (72.4%) patients experienced G1 acute toxicity only, 16 (7.4%) patients experienced G2 acute toxicity, with no G3 events observed. No toxicity event was reported in 44 (20.3%) patients. Detailed assessments at each time point are presented in Table 1. Of the 122 patients who had chest CT for evaluation at 6 months after RT, 26 (21%) experienced G1 radiation pneumonitis. No significant changes in echocardiography or cardiac biomarkers after RT were found. At a median follow-up of 16.3 months (interquartile range [IQR] = 7.3 to 37.6), no severe toxicities were found, and no locoregional recurrence, distant metastasis or death occurred. A second primary cancer of urothelial carcinoma was reported in a patient with germline BRCA1/2 mutation.
Conclusion
Ultra-hypofractionated RT of WBI and sequential tumor bed boost administrated within 1.5 weeks using 5.2 Gy per fraction is well-tolerated in early breast cancer patients. Further follow-up is needed in order to assess late toxicity and long-term efficacy.
{"title":"Early Safety of Ultra-Hypofractionated Whole Breast Irradiation and Sequential Tumor Bed Boost for Early Breast Cancer (SHIFT): A Multicenter, Phase 2 Trial","authors":"S. Zheng , M. Dong , J. Jiang , J. Zhang , Y. Shi , L. Gan , B. Yu , J. Chen , L. Cao","doi":"10.1016/j.ijrobp.2024.07.010","DOIUrl":"10.1016/j.ijrobp.2024.07.010","url":null,"abstract":"<div><h3>Purpose/Objective(s)</h3><div>The Phase 3 FAST-Forward trial showed that 26 Gy in 5 fractions over 1 week for whole breast irradiation (WBI) was safe and efficacy for early breast cancer patients, in which a sequential tumor bed boost was allowed (10 Gy or 16 Gy in 2-Gy fractions). Current trial delivers 26 Gy in 5 fractions over 1 week for WBI and 10.4 Gy in 2 fractions once daily for sequential tumor bed boost, to keep the total duration of radiotherapy (RT) to no more than 1.5 weeks if tumor bed boost is required. Here we report the early safety of this ultra-hypofractionation regimen.</div></div><div><h3>Materials/Methods</h3><div>This is a multicenter, single-arm, phase 2 trial carried out at 4 tertiary hospitals in China. Patients aged at least 18 years with invasive breast carcinoma (pT1-3, N0-1mic, M0) or ductal carcinoma in situ (DCIS) after lumpectomy were eligible. All enrolled patients underwent WBI of 26 Gy in 5 fractions over 5 days. A sequential tumor bed boost of 10.4 Gy in 2 fractions over 2 days was at the discretion of radiation oncologist. The primary endpoint was acute radiation-induced toxicity within 6 months after RT, aiming for a 10% non-inferiority margin based on a projected 50% baseline incidence of ≥Grade 2 (G2) acute toxicity. Acute toxicity was assessed using CTCAE v5.0 at 1 week and 2 weeks during RT, and at 1 month and 6 months after RT completion. This trial is registered at ClinicalTrials.gov (NCT04926766).</div></div><div><h3>Results</h3><div>Between January 2021, and July 2023, recruitment of 217 patients has been completed, of whom 210 received tumor bed boost. Within 6 months after RT, 157 (72.4%) patients experienced G1 acute toxicity only, 16 (7.4%) patients experienced G2 acute toxicity, with no G3 events observed. No toxicity event was reported in 44 (20.3%) patients. Detailed assessments at each time point are presented in Table 1. Of the 122 patients who had chest CT for evaluation at 6 months after RT, 26 (21%) experienced G1 radiation pneumonitis. No significant changes in echocardiography or cardiac biomarkers after RT were found. At a median follow-up of 16.3 months (interquartile range [IQR] = 7.3 to 37.6), no severe toxicities were found, and no locoregional recurrence, distant metastasis or death occurred. A second primary cancer of urothelial carcinoma was reported in a patient with germline BRCA1/2 mutation.</div></div><div><h3>Conclusion</h3><div>Ultra-hypofractionated RT of WBI and sequential tumor bed boost administrated within 1.5 weeks using 5.2 Gy per fraction is well-tolerated in early breast cancer patients. Further follow-up is needed in order to assess late toxicity and long-term efficacy.</div></div>","PeriodicalId":14215,"journal":{"name":"International Journal of Radiation Oncology Biology Physics","volume":"120 2","pages":"Page S16"},"PeriodicalIF":6.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142359554","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-01DOI: 10.1016/j.ijrobp.2024.07.013
A.G. Wernicke , B. Gui , M.M. Shalamov , L. Ottensoser , B. Parashar , L. Potters
Purpose/Objective(s)
Radiotherapy (RT) causes toxicity and outcomes of treatment may not be known for months post-therapy. Early identification of response with a ctDNA blood draw may provide a non-invasive way to predict response to treatment. In this study, we used ctDNA to assess response to RT in patients with GYN cancers as early as mid-way during treatment.
Materials/Methods
After IRB approval, patients with vulvar, cervical, and recurrent endometrial cancer were treated with RT at our institution between 2022 and 2024. The ctDNA was obtained using personalized molecular residual disease assay pre-RT, mid-way through RT, pre-boost with brachytherapy or SBRT, at the end and in follow-up at 1, 3, 6, and every 6 months -post RT, respectively. A detectable value of ctDNA was defined as any level above 0.00 mean tumor molecules (MTM)/mL, whereas 0.00MTM/mL was undetectable. During and after RT, ctDNA of 0.00MTM/mL was defined as complete metabolic response (cMR) but a reduction without achieving the value 0.00MTM/mL in ctDNA was deemed partial metabolic response (pMR). Correlation between ctDNA levels and imaging (PET-CT, MRI, and CT) was also assessed. Statistical analyses used were descriptive statistics, t-test, Chi-square test and a spearman-rank correlation coefficient (ρ).
Results
A total of 105 serial ctDNA blood draws were obtained from 21 patients with 8 (38%) vulvar, 7 (33%) cervical, 2 (10%) neuroendocrine, and 3 (19%) recurrent endometrial cancers (reEMCa). Median age was 59 years (range = 35-90 years). Median number of ctDNA draws per patient was 6 (range = 1-9). Median radiation dose was 5900 cGy (range = 4500-7000 cGy), brachy boost of 28 Gy/4 fx T&O and SBRT 30 Gy/5 fx for 7 cervix cases, and SBRT boost 2750 cGy/5 fx for reEMCa. There was 100% reduction in ctDNA values (metabolic response) from pre-to post-RT (mean = 2.04 vs. 0, P = 0.03): 75% cMR and 25% pMR. In patients who sustained response to RT, mid- and end-RT ctDNA draw exhibited 0.00MT/ml (undetectable), which continued in follow-up. A strong correlation was observed between elevated ctDNA and SUV/measurable disease on imaging pre-treatment (ρ = 0.64, P = 0.01), as well as undetectable ctDNA and decline of SUV/complete resolution of SUV at 3-6 months following RT (P = 0.045).
Conclusion
The ctDNA in patients with gynecological malignancies drawn at pre-, mid- and post-RT sustained metabolic response and correlated with response to treatment by imaging and clinical examinations. Our early findings suggest that a mid-treatment ctDNA test identified responders to RT and thus may serve as an early predictive biomarker of response. A larger prospective evaluation is warranted.
{"title":"Early Assessment of Response Using ctDNA as a Non-Invasive Biomarker in Patients with Gynecologic Malignancies Undergoing Radiotherapy","authors":"A.G. Wernicke , B. Gui , M.M. Shalamov , L. Ottensoser , B. Parashar , L. Potters","doi":"10.1016/j.ijrobp.2024.07.013","DOIUrl":"10.1016/j.ijrobp.2024.07.013","url":null,"abstract":"<div><h3>Purpose/Objective(s)</h3><div>Radiotherapy (RT) causes toxicity and outcomes of treatment may not be known for months post-therapy. Early identification of response with a ctDNA blood draw may provide a non-invasive way to predict response to treatment. In this study, we used ctDNA to assess response to RT in patients with GYN cancers as early as mid-way during treatment.</div></div><div><h3>Materials/Methods</h3><div>After IRB approval, patients with vulvar, cervical, and recurrent endometrial cancer were treated with RT at our institution between 2022 and 2024. The ctDNA was obtained using personalized molecular residual disease assay pre-RT, mid-way through RT, pre-boost with brachytherapy or SBRT, at the end and in follow-up at 1, 3, 6, and every 6 months -post RT, respectively. A detectable value of ctDNA was defined as any level above 0.00 mean tumor molecules (MTM)/mL, whereas 0.00MTM/mL was undetectable. During and after RT, ctDNA of 0.00MTM/mL was defined as complete metabolic response (cMR) but a reduction without achieving the value 0.00MTM/mL in ctDNA was deemed partial metabolic response (pMR). Correlation between ctDNA levels and imaging (PET-CT, MRI, and CT) was also assessed. Statistical analyses used were descriptive statistics, t-test, Chi-square test and a spearman-rank correlation coefficient (ρ).</div></div><div><h3>Results</h3><div>A total of 105 serial ctDNA blood draws were obtained from 21 patients with 8 (38%) vulvar, 7 (33%) cervical, 2 (10%) neuroendocrine, and 3 (19%) recurrent endometrial cancers (reEMCa). Median age was 59 years (range = 35-90 years). Median number of ctDNA draws per patient was 6 (range = 1-9). Median radiation dose was 5900 cGy (range = 4500-7000 cGy), brachy boost of 28 Gy/4 fx T&O and SBRT 30 Gy/5 fx for 7 cervix cases, and SBRT boost 2750 cGy/5 fx for reEMCa. There was 100% reduction in ctDNA values (metabolic response) from pre-to post-RT (mean = 2.04 vs. 0, <em>P</em> = 0.03): 75% cMR and 25% pMR. In patients who sustained response to RT, mid- and end-RT ctDNA draw exhibited 0.00MT/ml (undetectable), which continued in follow-up. A strong correlation was observed between elevated ctDNA and SUV/measurable disease on imaging pre-treatment (ρ = 0.64, <em>P</em> = 0.01), as well as undetectable ctDNA and decline of SUV/complete resolution of SUV at 3-6 months following RT (<em>P</em> = 0.045).</div></div><div><h3>Conclusion</h3><div>The ctDNA in patients with gynecological malignancies drawn at pre-, mid- and post-RT sustained metabolic response and correlated with response to treatment by imaging and clinical examinations. Our early findings suggest that a mid-treatment ctDNA test identified responders to RT and thus may serve as an early predictive biomarker of response. A larger prospective evaluation is warranted.</div></div>","PeriodicalId":14215,"journal":{"name":"International Journal of Radiation Oncology Biology Physics","volume":"120 2","pages":"Page S17"},"PeriodicalIF":6.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142359557","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-01DOI: 10.1016/j.ijrobp.2024.07.044
Z. Sherwani , S. Damast , E.C. Fields , S. Shah , S. Beriwal , Z.D. Horne , E. Parks , E.A. Kidd , E.W. Leung , L. Waleed Khoja , N.K. Taunk , J.P. Chino , C.C. Huang , A.L. Russo , M.A.A. Dyer , K.V. Albuquerque , L. Hathout
<div><h3>Purpose/Objective(s)</h3><div>To examine the impact of MLH1 promoter hypermethylation (MLH1ph) on prognosis and recurrence patterns in stage I-II endometroid endometrial cancer (EEC) treated with adjuvant radiotherapy.</div></div><div><h3>Materials/Methods</h3><div>In a retrospective multi-institutional cohort study, patients with stage I-II EEC status post-surgical resection with known mismatch repair (MMR) status were included. Tumors with MSH2, MSH6, MLH1 or PMS2 mutations were classified as somatic deficient MMR (sdMMR), while tumors with epigenetic silencing of the MLH1 promoter were classified as MLH1ph. Recurrences were classified into 3 categories: vaginal, pelvic or distant (including para-aortic lymph nodes). Recurrence-free survival (RFS) and overall survival (OS) were calculated by the Kaplan Meier method. Univariate and multivariate analyses (UVA/MVA) were performed via Cox proportional hazard models. Statistical analyses were conducted using statistical software.</div></div><div><h3>Results</h3><div>A total of 823 patients were included with a median age at diagnosis of 65 (IQR = 58-71). Most patients had grade 2-3 disease (59.5%), ≥ 50% depth of myometrial invasion (56.4%), absence of lympho-vascular space invasion (57.5%), and no cervical stromal involvement (77.5%). Vaginal brachytherapy (VBT) was the most common adjuvant radiation modality for 643 (78.1%) patients, while 180 (21.9%) patients received external beam radiation (EBRT) +/- VBT. After a median follow up (MFU) of 38.2 months, OS and RFS for the entire cohort were 93.8% and 87.5%, respectively. MMR was proficient in 550 (66.8%) patients and deficient in 273 (33.2%) patients, most of which were MLH1ph (<em>n</em> = 171, 62.6%), while 93 (34.1%) were sdMMR; 9 could not be classified. The following prognostic factors were associated with decreased RFS on UVA and maintained significance on MVA: age ≥ 65 (<em>P</em> = 0.008, HR = 1.7), grade 2-3 (<em>P</em> = 0.046, HR = 1.6), and MMR status (<em>P</em> < 0.001, HR = 2.1). At MFU, patients with MLH1ph had inferior RFS compared to sdMMR and pMMR (73.5% vs 86% vs 92%, respectively, <em>P</em> < 0.001), but there was no difference in OS (92%, 92%, and 96%, respectively, <em>P</em> = 0.57). Of the 117 recurrences overall, the most common site of recurrence was distant regardless of MMR status, with overall breakdown as follows: 20 (2.4%) vaginal, 19 (2.3%) pelvic, and 78 (9.5%) distant. Patients with MLH1ph had a higher proportion of pelvic (28.2%) and vaginal (20.5%) recurrences, with only 51.3% distant recurrences compared to pMMR (73.2%) and sdMMR (76.5%) (<em>P</em> = 0.04).</div></div><div><h3>Conclusion</h3><div>This large multi-institutional study highlights the importance of MLH1 promoter hypermethylation testing when analyzing MMR status for patients with early-stage EEC treated with adjuvant radiotherapy. While MMR status did not impact OS, patients with MLH1ph dMMR had worse RFS and a higher proportion
{"title":"The Prognostic Impact of MLH1 Promoter Hypermethylation in Stage I-II Endometrial Cancer Treated with Adjuvant Radiotherapy","authors":"Z. Sherwani , S. Damast , E.C. Fields , S. Shah , S. Beriwal , Z.D. Horne , E. Parks , E.A. Kidd , E.W. Leung , L. Waleed Khoja , N.K. Taunk , J.P. Chino , C.C. Huang , A.L. Russo , M.A.A. Dyer , K.V. Albuquerque , L. Hathout","doi":"10.1016/j.ijrobp.2024.07.044","DOIUrl":"10.1016/j.ijrobp.2024.07.044","url":null,"abstract":"<div><h3>Purpose/Objective(s)</h3><div>To examine the impact of MLH1 promoter hypermethylation (MLH1ph) on prognosis and recurrence patterns in stage I-II endometroid endometrial cancer (EEC) treated with adjuvant radiotherapy.</div></div><div><h3>Materials/Methods</h3><div>In a retrospective multi-institutional cohort study, patients with stage I-II EEC status post-surgical resection with known mismatch repair (MMR) status were included. Tumors with MSH2, MSH6, MLH1 or PMS2 mutations were classified as somatic deficient MMR (sdMMR), while tumors with epigenetic silencing of the MLH1 promoter were classified as MLH1ph. Recurrences were classified into 3 categories: vaginal, pelvic or distant (including para-aortic lymph nodes). Recurrence-free survival (RFS) and overall survival (OS) were calculated by the Kaplan Meier method. Univariate and multivariate analyses (UVA/MVA) were performed via Cox proportional hazard models. Statistical analyses were conducted using statistical software.</div></div><div><h3>Results</h3><div>A total of 823 patients were included with a median age at diagnosis of 65 (IQR = 58-71). Most patients had grade 2-3 disease (59.5%), ≥ 50% depth of myometrial invasion (56.4%), absence of lympho-vascular space invasion (57.5%), and no cervical stromal involvement (77.5%). Vaginal brachytherapy (VBT) was the most common adjuvant radiation modality for 643 (78.1%) patients, while 180 (21.9%) patients received external beam radiation (EBRT) +/- VBT. After a median follow up (MFU) of 38.2 months, OS and RFS for the entire cohort were 93.8% and 87.5%, respectively. MMR was proficient in 550 (66.8%) patients and deficient in 273 (33.2%) patients, most of which were MLH1ph (<em>n</em> = 171, 62.6%), while 93 (34.1%) were sdMMR; 9 could not be classified. The following prognostic factors were associated with decreased RFS on UVA and maintained significance on MVA: age ≥ 65 (<em>P</em> = 0.008, HR = 1.7), grade 2-3 (<em>P</em> = 0.046, HR = 1.6), and MMR status (<em>P</em> < 0.001, HR = 2.1). At MFU, patients with MLH1ph had inferior RFS compared to sdMMR and pMMR (73.5% vs 86% vs 92%, respectively, <em>P</em> < 0.001), but there was no difference in OS (92%, 92%, and 96%, respectively, <em>P</em> = 0.57). Of the 117 recurrences overall, the most common site of recurrence was distant regardless of MMR status, with overall breakdown as follows: 20 (2.4%) vaginal, 19 (2.3%) pelvic, and 78 (9.5%) distant. Patients with MLH1ph had a higher proportion of pelvic (28.2%) and vaginal (20.5%) recurrences, with only 51.3% distant recurrences compared to pMMR (73.2%) and sdMMR (76.5%) (<em>P</em> = 0.04).</div></div><div><h3>Conclusion</h3><div>This large multi-institutional study highlights the importance of MLH1 promoter hypermethylation testing when analyzing MMR status for patients with early-stage EEC treated with adjuvant radiotherapy. While MMR status did not impact OS, patients with MLH1ph dMMR had worse RFS and a higher proportion ","PeriodicalId":14215,"journal":{"name":"International Journal of Radiation Oncology Biology Physics","volume":"120 2","pages":"Page S32"},"PeriodicalIF":6.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142358592","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-01DOI: 10.1016/j.ijrobp.2024.07.029
A. Raldow , P. Lee , S.G. Chun , J. Gilliland , J.V. Hegde , A.U. Kishan , A.A. Odwuor , S. Ramakrishnan , M. Tate , J. Underwood , M. Xiang , T. Atkinson , A.B. Chen
<div><h3>Purpose/Objective(s)</h3><div>While patient symptom self-reporting improves clinical outcomes in patients with metastatic cancer receiving outpatient chemotherapy, the effects are not well established in the setting of patients undergoing radiation therapy (RT). In this phase II multi-institutional study, we assessed the impact of patient symptom self-reporting using the mPROS mobile application during definitive chemoradiation on health-related quality of life (HRQOL).</div></div><div><h3>Materials/Methods</h3><div>Patients initiating definitive radiation therapy with concurrent chemotherapy for GI, GYN, lung, CNS, and H&N cancers were randomly assigned to symptom self-reporting with mPROS (experimental arm; EXP) or usual care (control arm, CON). In the EXP arm, participants were asked to report symptoms at least weekly; severe or worsening symptoms triggered alerts to the clinical team. Participants remained on study until 3 months after completion of RT. PROMIS-29, a validated questionnaire assessing HRQOL, was administered at baseline, completion of RT (EOT), and 3 months after RT completion. The primary endpoint was HRQOL at EOT. Patient assessment of the usefulness of mPROS was measured via a 24 question exit survey using a 7-point Likert scale.</div></div><div><h3>Results</h3><div>Fifty-nine (<em>n</em> = 30 experimental, and <em>n</em> = 29 control) patients (mean age 61.9 years. 51% male) were included, of which 46 (<em>n</em> = 22 experimental and <em>n</em> = 24 control) completed both baseline and EOT PROMIS-29 questionnaires. On average, EXP participants logged symptoms twice per week, with a mean of 15 severe attributes and 11 unique symptoms reported. There were no significant differences between mean changes to PROMIS physical (EXP, 52.31 to 46.12, ∆ -6.03 vs. CON 50.72 to 45.77, ∆ -4.04, <em>P</em> = 0.45) or mental (EXP 49.25 to 45.80, ∆ -2.82 vs. CON 50.82 to 47.52, ∆ -2.17, <em>P</em> = 0.78) function scores from baseline to EOT. Likewise, there were no significant differences between median changes to PROMIS physical (EXP 56.12 to 44.92, ∆ -3.87 vs. CON 49.14 to 44.87, ∆ -2.02, <em>P</em> = 0.29) or mental (EXP 49.79 to 43.82, ∆ -1.74 vs. CON 52.47 to 48.22, ∆ -1.39, <em>P</em> = 0.77) function scores from baseline to EOT. On multivariate linear regression adjusting for age, sex, race, ethnicity, and education, treatment arm was not a statistically significant predictor of changes in physical (2.11 (95% CI = -3.65 to -7.87), <em>P</em> value = 0.48) or mental scores 0.12 (95% CI = -5.14 to -5.38, <em>P</em> = 0.96) between baseline and EOT. On exit survey, mean scores for selected questions were as follows: care team understanding symptoms (6.27), feeling more involved in care (6.36), help with symptom tracking (6.18), and recommending mPROS to other patients (6.09).</div></div><div><h3>Conclusion</h3><div>Use of a mobile application to monitor symptoms, compared with usual care, did not result in statistically s
目的/目标：患者症状自我报告可改善接受门诊化疗的转移性癌症患者的临床预后，但在接受放疗（RT）的患者中，其效果尚未得到充分证实。在这项 II 期多机构研究中，我们评估了在确定性化疗期间使用 mPROS 移动应用进行患者症状自我报告对健康相关生活质量（HRQOL）的影响。材料/方法对开始接受确定性放疗并同时接受化疗的消化道、妇科、肺、中枢神经系统和 H&N 癌症患者随机分配到使用 mPROS 进行症状自我报告（实验组；EXP）或常规护理（对照组；CON）。在 EXP 试验组中，参与者被要求至少每周报告一次症状；症状严重或恶化时会向临床团队发出警报。参与者在完成 RT 治疗 3 个月后继续接受研究。PROMIS-29是一份评估HRQOL的有效问卷，在基线、RT完成（EOT）和RT完成后3个月进行问卷调查。主要终点是 EOT 时的 HRQOL。患者对 mPROS 实用性的评估通过 24 个问题的退出调查进行测量，采用 7 点李克特量表。结果59 名患者（实验组 30 人，对照组 29 人）（平均年龄 61.9 岁，51% 为男性）参与了研究，其中 46 人（实验组 22 人，对照组 24 人）完成了基线和 EOT PROMIS-29 问卷调查。EXP 参与者平均每周记录两次症状，平均报告了 15 个严重属性和 11 个独特症状。PROMIS 身体（EXP，52.31 至 46.12，∆ -6.03 vs. CON 50.72 至 45.77，∆ -4.04，P = 0.45）或精神（EXP 49.25 至 45.80，∆ -2.82 vs. CON 50.82 至 47.52，∆ -2.17，P = 0.78）功能评分从基线到 EOT 的平均变化无明显差异。同样，PROMIS 体力（EXP 56.12 至 44.92，∆ -3.87 vs. CON 49.14 至 44.87，∆ -2.02，P = 0.29）或精神（EXP 49.79 至 43.82，∆ -1.74 vs. CON 52.47 至 48.22，∆ -1.39，P = 0.77）功能评分从基线到 EOT 的中位数变化也无明显差异。在对年龄、性别、种族、民族和教育程度进行调整的多变量线性回归中，治疗组并不是基线与 EOT 之间身体（2.11 (95% CI = -3.65 to -7.87)，P 值 = 0.48）或精神（0.12 (95% CI = -5.14 to -5.38，P = 0.96)变化的显著预测因素。在退出调查中，选定问题的平均得分如下：护理团队了解症状（6.27）、感觉更多参与护理（6.36）、帮助追踪症状（6.18）以及向其他患者推荐 mPROS（6.09）。但是，实验组的患者对自我报告表示非常满意，觉得自己更愿意参与癌症护理，并有助于他们跟踪症状。
{"title":"Symptom Monitoring with Patient-Reported Outcomes during Definitive Radiation Treatment","authors":"A. Raldow , P. Lee , S.G. Chun , J. Gilliland , J.V. Hegde , A.U. Kishan , A.A. Odwuor , S. Ramakrishnan , M. Tate , J. Underwood , M. Xiang , T. Atkinson , A.B. Chen","doi":"10.1016/j.ijrobp.2024.07.029","DOIUrl":"10.1016/j.ijrobp.2024.07.029","url":null,"abstract":"<div><h3>Purpose/Objective(s)</h3><div>While patient symptom self-reporting improves clinical outcomes in patients with metastatic cancer receiving outpatient chemotherapy, the effects are not well established in the setting of patients undergoing radiation therapy (RT). In this phase II multi-institutional study, we assessed the impact of patient symptom self-reporting using the mPROS mobile application during definitive chemoradiation on health-related quality of life (HRQOL).</div></div><div><h3>Materials/Methods</h3><div>Patients initiating definitive radiation therapy with concurrent chemotherapy for GI, GYN, lung, CNS, and H&N cancers were randomly assigned to symptom self-reporting with mPROS (experimental arm; EXP) or usual care (control arm, CON). In the EXP arm, participants were asked to report symptoms at least weekly; severe or worsening symptoms triggered alerts to the clinical team. Participants remained on study until 3 months after completion of RT. PROMIS-29, a validated questionnaire assessing HRQOL, was administered at baseline, completion of RT (EOT), and 3 months after RT completion. The primary endpoint was HRQOL at EOT. Patient assessment of the usefulness of mPROS was measured via a 24 question exit survey using a 7-point Likert scale.</div></div><div><h3>Results</h3><div>Fifty-nine (<em>n</em> = 30 experimental, and <em>n</em> = 29 control) patients (mean age 61.9 years. 51% male) were included, of which 46 (<em>n</em> = 22 experimental and <em>n</em> = 24 control) completed both baseline and EOT PROMIS-29 questionnaires. On average, EXP participants logged symptoms twice per week, with a mean of 15 severe attributes and 11 unique symptoms reported. There were no significant differences between mean changes to PROMIS physical (EXP, 52.31 to 46.12, ∆ -6.03 vs. CON 50.72 to 45.77, ∆ -4.04, <em>P</em> = 0.45) or mental (EXP 49.25 to 45.80, ∆ -2.82 vs. CON 50.82 to 47.52, ∆ -2.17, <em>P</em> = 0.78) function scores from baseline to EOT. Likewise, there were no significant differences between median changes to PROMIS physical (EXP 56.12 to 44.92, ∆ -3.87 vs. CON 49.14 to 44.87, ∆ -2.02, <em>P</em> = 0.29) or mental (EXP 49.79 to 43.82, ∆ -1.74 vs. CON 52.47 to 48.22, ∆ -1.39, <em>P</em> = 0.77) function scores from baseline to EOT. On multivariate linear regression adjusting for age, sex, race, ethnicity, and education, treatment arm was not a statistically significant predictor of changes in physical (2.11 (95% CI = -3.65 to -7.87), <em>P</em> value = 0.48) or mental scores 0.12 (95% CI = -5.14 to -5.38, <em>P</em> = 0.96) between baseline and EOT. On exit survey, mean scores for selected questions were as follows: care team understanding symptoms (6.27), feeling more involved in care (6.36), help with symptom tracking (6.18), and recommending mPROS to other patients (6.09).</div></div><div><h3>Conclusion</h3><div>Use of a mobile application to monitor symptoms, compared with usual care, did not result in statistically s","PeriodicalId":14215,"journal":{"name":"International Journal of Radiation Oncology Biology Physics","volume":"120 2","pages":"Page S25"},"PeriodicalIF":6.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142358684","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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