Pub Date : 2024-10-11DOI: 10.1016/j.radonc.2024.110573
O. Kaidar-Person , I Ratosa , P. Franco , V. Masiello , F. Marazzi , S. Pedretti , A. Ciabattoni , M.C. Leonardi , T. Tramm , CE Coles , I Meattini , M. Arenas , B.V. Offersen , L.J. Boersma , V. Valentini , D. Dodwell , P. Poortmans , C. Aristei
The “Assisi Think Tank Meeting” (ATTM) on Breast Cancer, endorsed by the European Society for Radiotherapy & Oncology (ESTRO) and the Italian Association of Radiotherapy and Clinical Oncology (AIRO), and conducted under the auspices of the European Society of Breast Cancer Specialists (EUSOMA), is a bi-annual meeting aiming to identify major clinical challenges in breast cancer radiation therapy (RT) and proposing clinical trials to address them. The topics discussed at the meeting are pre-selected by the steering committee. At the meeting, these topics are discussed in different working groups (WG), after preparation of the meeting by performing a systematic review of existing data and of ongoing trials. Prior to the meeting, each WG designs a survey on the topic to be discussed to reflect current clinical practice and to identify areas requiring further research. Herein, we present the work done by the Assisi WG focusing on lobular carcinoma and the RT perspectives in its treatment, including providing recommendations for locoregional therapy, mainly RT for patients with non-metastatic lobular breast cancer.
{"title":"The Assisi think tank focus review on postoperative radiation for lobular breast cancer","authors":"O. Kaidar-Person , I Ratosa , P. Franco , V. Masiello , F. Marazzi , S. Pedretti , A. Ciabattoni , M.C. Leonardi , T. Tramm , CE Coles , I Meattini , M. Arenas , B.V. Offersen , L.J. Boersma , V. Valentini , D. Dodwell , P. Poortmans , C. Aristei","doi":"10.1016/j.radonc.2024.110573","DOIUrl":"10.1016/j.radonc.2024.110573","url":null,"abstract":"<div><div>The “Assisi Think Tank Meeting” (ATTM) on Breast Cancer, endorsed by the European Society for Radiotherapy & Oncology (ESTRO) and the Italian Association of Radiotherapy and Clinical Oncology (AIRO), and conducted under the auspices of the European Society of Breast Cancer Specialists (EUSOMA), is a bi-annual meeting aiming to identify major clinical challenges in breast cancer radiation therapy (RT) and proposing clinical trials to address them. The topics discussed at the meeting are pre-selected by the steering committee. At the meeting, these topics are discussed in different working groups (WG), after preparation of the meeting by performing a systematic review of existing data and of ongoing trials. Prior to the meeting, each WG designs a survey on the topic to be discussed to reflect current clinical practice and to identify areas requiring further research. Herein, we present the work done by the Assisi WG focusing on lobular carcinoma and the RT perspectives in its treatment, including providing recommendations for locoregional therapy, mainly RT for patients with non-metastatic lobular breast cancer.</div></div>","PeriodicalId":21041,"journal":{"name":"Radiotherapy and Oncology","volume":"201 ","pages":"Article 110573"},"PeriodicalIF":4.9,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142473436","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 : 2024-10-11DOI: 10.1016/j.radonc.2024.110576
Till Tobias Böhlen , Michele Zeverino , Jean‐François Germond , Rémy Kinj , Luis Schiappacasse , François Bochud , Fernanda Herrera , Jean Bourhis , Raphaël Moeckli
Purpose
This study explores the dosimetric feasibility and plan quality of hybrid ultra-high dose rate (UHDR) electron and conventional dose rate (CDR) photon (HUC) radiotherapy for treating deep-seated tumours with FLASH-RT.
Methods
HUC treatment planning was conducted optimizing a broad UHDR electron beam (between 20–250 MeV) combined with a CDR VMAT for a glioblastoma, a pancreatic cancer, and a prostate cancer case. HUC plans were based on clinical prescription and fractionation schemes and compared against clinically delivered plans. Considering a HUC boost treatment for the glioblastoma consisting of a 15-Gy-single-fraction UHDR electron boost supplemented with VMAT, two scenarios for FLASH sparing were assessed using FLASH-modifying-factor-weighted doses.
Results
For all three patient cases, HUC treatment plans demonstrated comparable dosimetric quality to clinical plans, with similar PTV coverage (V95% within 0.5 %), homogeneity, and critical OAR-sparing. At the same time, HUC plans delivered a substantial portion of the dose to the PTV (Dmedian of 50–69 %) and surrounding tissues at UHDR. For the HUC boost treatment of the glioblastoma, the first FLASH sparing scenario showed a moderate FLASH sparing magnitude (10 % for D2%,PTV) for the 15-Gy UHDR electron boost, while the second scenario indicated a more substantial sparing of brain tissues inside and outside the PTV (32 % for D2%,PTV, 31 % for D2%,Brain).
Conclusions
From a planning perspective, HUC treatments represent a feasible approach for delivering dosimetrically conformal UHDR treatments, potentially mitigating technical challenges associated with delivering conformal FLASH-RT for deep-seated tumours. While further research is needed to optimize HUC fractionation and delivery schemes for specific patient cohorts, HUC treatments offer a promising avenue for the clinical transfer of FLASH-RT.
{"title":"Hybrid ultra-high and conventional dose rate treatments with electrons and photons for the clinical transfer of FLASH-RT to deep-seated targets: A treatment planning study","authors":"Till Tobias Böhlen , Michele Zeverino , Jean‐François Germond , Rémy Kinj , Luis Schiappacasse , François Bochud , Fernanda Herrera , Jean Bourhis , Raphaël Moeckli","doi":"10.1016/j.radonc.2024.110576","DOIUrl":"10.1016/j.radonc.2024.110576","url":null,"abstract":"<div><h3>Purpose</h3><div>This study explores the dosimetric feasibility and plan quality of hybrid ultra-high dose rate (UHDR) electron and conventional dose rate (CDR) photon (HUC) radiotherapy for treating deep-seated tumours with FLASH-RT.</div></div><div><h3>Methods</h3><div>HUC treatment planning was conducted optimizing a broad UHDR electron beam (between 20–250 MeV) combined with a CDR VMAT for a glioblastoma, a pancreatic cancer, and a prostate cancer case. HUC plans were based on clinical prescription and fractionation schemes and compared against clinically delivered plans. Considering a HUC boost treatment for the glioblastoma consisting of a 15-Gy-single-fraction UHDR electron boost supplemented with VMAT, two scenarios for FLASH sparing were assessed using FLASH-modifying-factor-weighted doses.</div></div><div><h3>Results</h3><div>For all three patient cases, HUC treatment plans demonstrated comparable dosimetric quality to clinical plans, with similar PTV coverage (V<sub>95%</sub> within 0.5 %), homogeneity, and critical OAR-sparing. At the same time, HUC plans delivered a substantial portion of the dose to the PTV (D<sub>median</sub> of 50–69 %) and surrounding tissues at UHDR. For the HUC boost treatment of the glioblastoma, the first FLASH sparing scenario showed a moderate FLASH sparing magnitude (10 % for D<sub>2%,PTV</sub>) for the 15-Gy UHDR electron boost, while the second scenario indicated a more substantial sparing of brain tissues inside and outside the PTV (32 % for D<sub>2%,PTV</sub>, 31 % for D<sub>2%,Brain</sub>).</div></div><div><h3>Conclusions</h3><div>From a planning perspective, HUC treatments represent a feasible approach for delivering dosimetrically conformal UHDR treatments, potentially mitigating technical challenges associated with delivering conformal FLASH-RT for deep-seated tumours. While further research is needed to optimize HUC fractionation and delivery schemes for specific patient cohorts, HUC treatments offer a promising avenue for the clinical transfer of FLASH-RT.</div></div>","PeriodicalId":21041,"journal":{"name":"Radiotherapy and Oncology","volume":"201 ","pages":"Article 110576"},"PeriodicalIF":4.9,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142446945","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-10DOI: 10.1016/j.radonc.2024.110577
Sarah Potiron , Lorea Iturri , Marjorie Juchaux , Julie Espenon , Cristèle Gilbert , Josie McGarrigle , Ramon Ortiz Catalan , Alfredo Fernandez-Rodriguez , Catherine Sebrié , Laurène Jourdain , Ludovic De Marzi , Gilles Créhange , Yolanda Prezado
Background and purpose
Proton Minibeam Radiation Therapy (pMBRT) is an unconventional radiation technique based on a strong modulation of the dose deposition. Due to its specific pattern, pMBRT involves several dosimetry (peak and valley doses, peak-to-valley dose ratio (PVDR)) and geometrical parameters (beam width, spacing) that can influence the biological response. This study aims at contributing to the efforts to deepen the comprehension of how the various parameters relate to central biological mechanisms, particularly anti-tumor immunity, and how these correlations affect treatment outcomes with the goal to fully unleash the potential of pMBRT. We also evaluated the effects of X-ray MBRT to further elucidate the influence of peak dose and dose heterogeneity.
Methods and Materials
An orthotopic rat model of glioblastoma underwent several pMBRT configurations. The impact of different dosimetric parameters on survival and on the modulation of crucial mechanisms for pMBRT, such as immune response, was investigated. The latter was assessed by immunohistochemistry and flow cytometry at 7 days post-irradiation.
Results
Survival was improved across the various pMBRT regimens via maintaining a minimum valley dose as well as a higher dose heterogeneity, which is driven by peak dose. While the mean dose did not impact immune infiltration, a higher PVDR promoted a less immunosuppressive microenvironment.
Conclusions
Our results suggest that both tumor eradication, and immune infiltration are associated with higher dose heterogeneity. Higher dose heterogeneity was achieved by optimizing the peak dose, as well as maintaining a minimum valley dose. These parameters contributed to direct tumor eradication as well as reduction of immunosuppression, which is a departure from the more immunosuppressive tumor environment found in conventional proton therapy that delivers uniform dose distributions.
{"title":"The significance of dose heterogeneity on the anti-tumor response of minibeam radiation therapy","authors":"Sarah Potiron , Lorea Iturri , Marjorie Juchaux , Julie Espenon , Cristèle Gilbert , Josie McGarrigle , Ramon Ortiz Catalan , Alfredo Fernandez-Rodriguez , Catherine Sebrié , Laurène Jourdain , Ludovic De Marzi , Gilles Créhange , Yolanda Prezado","doi":"10.1016/j.radonc.2024.110577","DOIUrl":"10.1016/j.radonc.2024.110577","url":null,"abstract":"<div><h3>Background and purpose</h3><div>Proton Minibeam Radiation Therapy (pMBRT) is an unconventional radiation technique based on a strong modulation of the dose deposition. Due to its specific pattern, pMBRT involves several dosimetry (peak and valley doses, peak-to-valley dose ratio (PVDR)) and geometrical parameters (beam width, spacing) that can influence the biological response. This study aims at contributing to the efforts to deepen the comprehension of how the various parameters relate to central biological mechanisms, particularly anti-tumor immunity, and how these correlations affect treatment outcomes with the goal to fully unleash the potential of pMBRT. We also evaluated the effects of X-ray MBRT to further elucidate the influence of peak dose and dose heterogeneity.</div></div><div><h3>Methods and Materials</h3><div>An orthotopic rat model of glioblastoma underwent several pMBRT configurations. The impact of different dosimetric parameters on survival and on the modulation of crucial mechanisms for pMBRT, such as immune response, was investigated. The latter was assessed by immunohistochemistry and flow cytometry at 7 days post-irradiation.</div></div><div><h3>Results</h3><div>Survival was improved across the various pMBRT regimens via maintaining a minimum valley dose as well as a higher dose heterogeneity, which is driven by peak dose. While the mean dose did not impact immune infiltration, a higher PVDR promoted a less immunosuppressive microenvironment.</div></div><div><h3>Conclusions</h3><div>Our results suggest that both tumor eradication, and immune infiltration are associated with higher dose heterogeneity. Higher dose heterogeneity was achieved by optimizing the peak dose, as well as maintaining a minimum valley dose. These parameters contributed to direct tumor eradication as well as reduction of immunosuppression, which is a departure from the more immunosuppressive tumor environment found in conventional proton therapy that delivers uniform dose distributions.</div></div>","PeriodicalId":21041,"journal":{"name":"Radiotherapy and Oncology","volume":"201 ","pages":"Article 110577"},"PeriodicalIF":4.9,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142406738","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-10DOI: 10.1016/j.radonc.2024.110575
Zan Hou , Xiaoping Lin , Baiqiang Dong , Zaishan Lin , Yuan Zhang , Xu Liu , Chenfei Wu , Qingqing Xu , Ying Wang , Keying Chen , Qiwen Li , Ming Chen
Background and purpose
Metastasis of non-metastatic non-small cell lung cancer (NMNSCLC) to contralateral hilar lymph nodes (CHLN) eliminates the opportunity for radical therapy. This study aims to analyze whether CHLN metastasis in NMNSCLC is commonly overestimated in clinical practice and to establish a predictive model for enhanced precision.
Methods and materials
We conducted a retrospective analysis of 834 pathologically confirmed NMNSCLC patients. Monitoring of treatment responses and regular ≥ 1 year CT follow-up was used to determine the nature of CHLN. Lasso regression was used to select predictive factors, and a multivariate binary logistic regression model (HAM) was constructed. Internal validation was performed using ten-fold cross-validation.
Results
The CHLN metastasis rate was 4.4% among the NMNSCLC patients. The positive predictive value (PPV) and sensitivity for PET-CT diagnosis were 36.8% and 67.5%, while for CT they are 44.8% and 70.2%, respectively. The five optimal predictive factors (emphysema or bullae, central-type lung cancer, short diameter of CHLN, calcification and SUVmax) were used to develop the HAM model. The Area under curve (AUC) values for PET-CT, CT, and HAM model were 0.81, 0.83, and 0.96, respectively. The F1 scores for PET-CT and CT were 0.48 and 0.55, respectively, while the maximum F1 score of our model was 0.73, with corresponding PPV and sensitivity of 66.7%, and 81.1%, respectively.
Conclusions
CHLN metastasis is rare in NMNSCLC patients. PET-CT diagnosis significantly overestimates CHLN metastasis and the HAM model improves clinical decision-making in this study. Prospective studies are needed to confirm these conclusions.
{"title":"Overestimation of contralateral hilar lymph node metastasis in non-metastatic non-small cell lung cancer and its predictive model: HAM","authors":"Zan Hou , Xiaoping Lin , Baiqiang Dong , Zaishan Lin , Yuan Zhang , Xu Liu , Chenfei Wu , Qingqing Xu , Ying Wang , Keying Chen , Qiwen Li , Ming Chen","doi":"10.1016/j.radonc.2024.110575","DOIUrl":"10.1016/j.radonc.2024.110575","url":null,"abstract":"<div><h3>Background and purpose</h3><div>Metastasis of non-metastatic non-small cell lung cancer (NMNSCLC) to contralateral hilar lymph nodes (CHLN) eliminates the opportunity for radical therapy. This study aims to analyze whether CHLN metastasis in NMNSCLC is commonly overestimated in clinical practice and to establish a predictive model for enhanced precision.</div></div><div><h3>Methods and materials</h3><div>We conducted a retrospective analysis of 834 pathologically confirmed NMNSCLC patients. Monitoring of treatment responses and regular ≥ 1 year CT follow-up was used to determine the nature of CHLN. Lasso regression was used to select predictive factors, and a multivariate binary logistic regression model (HAM) was constructed. Internal validation was performed using ten-fold cross-validation.</div></div><div><h3>Results</h3><div>The CHLN metastasis rate was 4.4% among the NMNSCLC patients. The positive predictive value (PPV) and sensitivity for PET-CT diagnosis were 36.8% and 67.5%, while for CT they are 44.8% and 70.2%, respectively. The five optimal predictive factors (emphysema or bullae, central-type lung cancer, short diameter of CHLN, calcification and SUVmax) were used to develop the HAM model. The Area under curve (AUC) values for PET-CT, CT, and HAM model were 0.81, 0.83, and 0.96, respectively. The F1 scores for PET-CT and CT were 0.48 and 0.55, respectively, while the maximum F1 score of our model was 0.73, with corresponding PPV and sensitivity of 66.7%, and 81.1%, respectively.</div></div><div><h3>Conclusions</h3><div>CHLN metastasis is rare in NMNSCLC patients. PET-CT diagnosis significantly overestimates CHLN metastasis and the HAM model improves clinical decision-making in this study. Prospective studies are needed to confirm these conclusions.</div></div>","PeriodicalId":21041,"journal":{"name":"Radiotherapy and Oncology","volume":"201 ","pages":"Article 110575"},"PeriodicalIF":4.9,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142442711","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 : 2024-10-10DOI: 10.1016/j.radonc.2024.110572
J. Feldman , A. Pryanichnikov , D. Shwartz , Y. Hillman , M. Wygoda , P. Blumenfeld , M. Marash , A. Popovtzer
Purpose
To evaluate the patient’s positioning reproducibility during upright treatment with image-guided adaptive proton therapy (IGAPT) for head and neck cancers.
Materials and methods
10 head and neck (H&N) patients were treated with gantry-less IGAPT, which includes daily 3D computed tomography (CT) and two 2D kilovoltage radiographs before treatment and weekly 3DCT immediately after irradiation. All procedures were performed in the carbon chair on the 6 degrees of freedom robotic positioner.
Results
Prior to treatment we registered shifts in patient positioning using 3D/3D registration at the imaging isocenter: X = -0.1 ± 3.9 (mean ± standard deviation) mm, Y = −3.7 ± 3.5 mm, Z = 0.5 ± 6.2 mm. The corresponding vector was applied to the robotic positioner to compensate for the registered shifts, after which the patients were moved to the treatment isocenter and the following shifts were obtained there using 2D/3D registration: X = -0.31 ± 1.37 mm, Y = −0.02 ± 1.33 mm, Z = 0.59 ± 1.55 mm. Finally, the weekly follow-up 3D/3D registration showed X = -0.2 ± 1.2 mm, Y = −0.0 ± 1.4 mm, Z = 2.3 ± 2.0 mm.
Conclusions
A novel image-guided gantry-less PT facility showed reliable results in terms of patient positioning for H&N cases during clinical trials. This fact confirmed the suitability of using gantry-less PT for H&N treatment. A small, systematic shift in the vertical direction was detected in the follow-up 3D/3D registration. The effect of this shift will be investigated in further studies with pre/post treatment 2D/3D registration. The next phase of the clinical trial of this facility is dedicated to the thorax region.
{"title":"Study of upright patient positioning reproducibility in image-guided proton therapy for head and neck cancers","authors":"J. Feldman , A. Pryanichnikov , D. Shwartz , Y. Hillman , M. Wygoda , P. Blumenfeld , M. Marash , A. Popovtzer","doi":"10.1016/j.radonc.2024.110572","DOIUrl":"10.1016/j.radonc.2024.110572","url":null,"abstract":"<div><h3>Purpose</h3><div>To evaluate the patient’s positioning reproducibility during upright treatment with image-guided adaptive proton therapy (IGAPT) for head and neck cancers.</div></div><div><h3>Materials and methods</h3><div>10 head and neck (H&N) patients were treated with gantry-less IGAPT, which includes daily 3D computed tomography (CT) and two 2D kilovoltage radiographs before treatment and weekly 3DCT immediately after irradiation. All procedures were performed in the carbon chair on the 6 degrees of freedom robotic positioner.</div></div><div><h3>Results</h3><div>Prior to treatment we registered shifts in patient positioning using 3D/3D registration at the imaging isocenter: X = -0.1 ± 3.9 (mean ± standard deviation) mm, Y = −3.7 ± 3.5 mm, Z = 0.5 ± 6.2 mm. The corresponding vector was applied to the robotic positioner to compensate for the registered shifts, after which the patients were moved to the treatment isocenter and the following shifts were obtained there using 2D/3D registration: X = -0.31 ± 1.37 mm, Y = −0.02 ± 1.33 mm, Z = 0.59 ± 1.55 mm. Finally, the weekly follow-up 3D/3D registration showed X = -0.2 ± 1.2 mm, Y = −0.0 ± 1.4 mm, Z = 2.3 ± 2.0 mm.</div></div><div><h3>Conclusions</h3><div>A novel image-guided gantry-less PT facility showed reliable results in terms of patient positioning for H&N cases during clinical trials. This fact confirmed the suitability of using gantry-less PT for H&N treatment. A small, systematic shift in the vertical direction was detected in the follow-up 3D/3D registration. The effect of this shift will be investigated in further studies with pre/post treatment 2D/3D registration. The next phase of the clinical trial of this facility is dedicated to the thorax region.</div></div>","PeriodicalId":21041,"journal":{"name":"Radiotherapy and Oncology","volume":"201 ","pages":"Article 110572"},"PeriodicalIF":4.9,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142442775","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-10DOI: 10.1016/j.radonc.2024.110578
Ruichen Li , Yang Zhao , Kangting Wu, Huiqing Li, Xinru Lin, Liting Zhu, Yi Zhu, Xiaoshen Wang
Purpose
To identify whether p16 status or response to induction chemotherapy (IC) predicts the radiotherapy (RT) response and survival outcomes in Chinese oropharyngeal squamous cell carcinoma (OPSCC).
Methods
A total of 211 patients, including 128 p16-positive and 83 p16-negative were analyzed. All patients underwent IC followed by definitive RT or concurrent chemoradiotherapy (CCRT). Propensity score matching (PSM) was used to eliminate the baseline variations.
Results
Age, sex, smoking history, alcohol history, and primary site were unbalanced between different p16 status subgroups. Before PSM, the objective response rates to IC between p16-positive and p16-negative groups were 80.5 % and 85.5 % (p = 0.344). After RT, the complete response (CR) rates were 73.4 % and 66.3 %, respectively (p = 0.264). IC-sensitive (IC-s) subgroups had a higher percentage of RT-CR rate than the IC-resistant (IC-r) subgroups in both p16-positive and p16-negative patients. IC-s showed significant improvement in cancer-specific survival (CSS) (92.9 % vs. 53.6 %, p < 0.0001), progression-free survival (PFS) (p < 0.0001), locoregional relapse-free survival (LRFS) (p < 0.0001) and distant metastasis-free survival (DMFS) (p = 0.025). After PSM, the CR rates among different p16 groups remained comparable following RT (71.2 % vs. 65.8 %, p = 0.476). Before or after PSM, CSS, PFS, LRFS, and DMFS were similar between different p16 status either in IC-s or IC-r subgroups (p > 0.05). IC-r was independently associated with shorter PFS (HR = 2.661, p = 0.002) and LRFS (HR = 2.876, p = 0.002; HR = 2.78, p = 0.018).
Conclusions
Response to IC is an important predictor of prognosis in Chinese OPSCC treated with definitive RT. Poor response to IC is associated with unsatisfactory outcomes either in p16-positive or p16-negative OPSCC.
{"title":"p16 status or response to induction chemotherapy, which predicts survival outcomes in Chinese oropharyngeal cancer treated with definitive radiotherapy?","authors":"Ruichen Li , Yang Zhao , Kangting Wu, Huiqing Li, Xinru Lin, Liting Zhu, Yi Zhu, Xiaoshen Wang","doi":"10.1016/j.radonc.2024.110578","DOIUrl":"10.1016/j.radonc.2024.110578","url":null,"abstract":"<div><h3>Purpose</h3><div>To identify whether p16 status or response to induction chemotherapy (IC) predicts the radiotherapy (RT) response and survival outcomes in Chinese oropharyngeal squamous cell carcinoma (OPSCC).</div></div><div><h3>Methods</h3><div>A total of 211 patients, including 128 p16-positive and 83 p16-negative were analyzed. All patients underwent IC followed by definitive RT or concurrent chemoradiotherapy (CCRT). Propensity score matching (PSM) was used to eliminate the baseline variations.</div></div><div><h3>Results</h3><div>Age, sex, smoking history, alcohol history, and primary site were unbalanced between different p16 status subgroups. Before PSM, the objective response rates to IC between p16-positive and p16-negative groups were 80.5 % and 85.5 % (p = 0.344). After RT, the complete response (CR) rates were 73.4 % and 66.3 %, respectively (p = 0.264). IC-sensitive (IC-s) subgroups had a higher percentage of RT-CR rate than the IC-resistant (IC-r) subgroups in both p16-positive and p16-negative patients. IC-s showed significant improvement in cancer-specific survival (CSS) (92.9 % vs. 53.6 %, p < 0.0001), progression-free survival (PFS) (p < 0.0001), locoregional relapse-free survival (LRFS) (p < 0.0001) and distant metastasis-free survival (DMFS) (p = 0.025). After PSM, the CR rates among different p16 groups remained comparable following RT (71.2 % vs. 65.8 %, p = 0.476). Before or after PSM, CSS, PFS, LRFS, and DMFS were similar between different p16 status either in IC-s or IC-r subgroups (p > 0.05). IC-r was independently associated with shorter PFS (HR = 2.661, p = 0.002) and LRFS (HR = 2.876, p = 0.002; HR = 2.78, p = 0.018).</div></div><div><h3>Conclusions</h3><div>Response to IC is an important predictor of prognosis in Chinese OPSCC treated with definitive RT. Poor response to IC is associated with unsatisfactory outcomes either in p16-positive or p16-negative OPSCC.</div></div>","PeriodicalId":21041,"journal":{"name":"Radiotherapy and Oncology","volume":"201 ","pages":"Article 110578"},"PeriodicalIF":4.9,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142442777","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 : 2024-10-10DOI: 10.1016/j.radonc.2024.110574
Mette S. Thomsen , Jan Alsner , Christina M. Lutz , Martin Berg , Ingelise Jensen , Ebbe L. Lorenzen , Hanne M. Nielsen , Erik H. Jakobsen , Lars Stenbygaard , Mette H. Nielsen , Maj-Britt Jensen , Jens Overgaard , Birgitte V. Offersen , on behalf of the DBCG RT Committee
Purpose
To investigate the association between irradiated breast volume and grade 2–3 breast induration three years after radiotherapy in the phase III Danish Breast Cancer Group HYPO trial randomizing patients ≥ 41 years to whole breast irradiation (WBI) with 40 Gy/15fr versus 50 Gy/25fr.
Methods
Treatment plans were available for all Danish patients. Associations between frequency of induration and irradiated volume, age, smoking status, and boost were assessed by logistic regression. A sequential boost was given to patients < 50 years or in case of a narrow (<2 mm) resection margin.
Results
RT plans from 1,333 patients were analyzed with 178 (13 %) having grade 2–3 induration. 1135 patients had only WBI. For this group, induration was correlated with irradiated breast volume for patients ≥ 65 years (n = 343, 10 %/22 % for small/large irradiated volumes, p = 0.005) but not for patients aged 50–64 years (n = 792, 11 % for both small and large volumes, p = 0.82). Smoking doubled the frequency irrespective of irradiated volume and age. All patients < 50 years (n = 156) had a boost. A volume effect was found for this group (5 %/21 % induration for small/large volume, p = 0.002). 42 patients ≥ 50 years had a boost and 14 (33 %) had grade 2–3 induration, however, with a p-value > 0.05 due to the few numbers of patients.
Conclusion
A relationship between irradiated breast volume and 3-year frequency of breast induration was found for patients ≥ 65 years, whilst not for patients aged 50–64 years. Smoking doubled the risk of induration irrespective of volume and age. A dose-induration relationship was seen for boost patients < 50 years.
{"title":"Breast induration and irradiated volume in the DBCG HYPO trial: The impact of age, smoking, and boost","authors":"Mette S. Thomsen , Jan Alsner , Christina M. Lutz , Martin Berg , Ingelise Jensen , Ebbe L. Lorenzen , Hanne M. Nielsen , Erik H. Jakobsen , Lars Stenbygaard , Mette H. Nielsen , Maj-Britt Jensen , Jens Overgaard , Birgitte V. Offersen , on behalf of the DBCG RT Committee","doi":"10.1016/j.radonc.2024.110574","DOIUrl":"10.1016/j.radonc.2024.110574","url":null,"abstract":"<div><h3>Purpose</h3><div>To investigate the association between irradiated breast volume and grade 2–3 breast induration three years after radiotherapy in the phase III Danish Breast Cancer Group HYPO trial randomizing patients ≥ 41 years to whole breast irradiation (WBI) with 40 Gy/15fr versus 50 Gy/25fr.</div></div><div><h3>Methods</h3><div>Treatment plans were available for all Danish patients. Associations between frequency of induration and irradiated volume, age, smoking status, and boost were assessed by logistic regression. A sequential boost was given to patients < 50 years or in case of a narrow (<2 mm) resection margin.</div></div><div><h3>Results</h3><div>RT plans from 1,333 patients were analyzed with 178 (13 %) having grade 2–3 induration. 1135 patients had only WBI. For this group, induration was correlated with irradiated breast volume for patients ≥ 65 years (n = 343, 10 %/22 % for small/large irradiated volumes, p = 0.005) but not for patients aged 50–64 years (n = 792, 11 % for both small and large volumes, p = 0.82). Smoking doubled the frequency irrespective of irradiated volume and age. All patients < 50 years (n = 156) had a boost. A volume effect was found for this group (5 %/21 % induration for small/large volume, p = 0.002). 42 patients ≥ 50 years had a boost and 14 (33 %) had grade 2–3 induration, however, with a p-value > 0.05 due to the few numbers of patients.</div></div><div><h3>Conclusion</h3><div>A relationship between irradiated breast volume and 3-year frequency of breast induration was found for patients ≥ 65 years, whilst not for patients aged 50–64 years. Smoking doubled the risk of induration irrespective of volume and age. A dose-induration relationship was seen for boost patients < 50 years.</div></div>","PeriodicalId":21041,"journal":{"name":"Radiotherapy and Oncology","volume":"201 ","pages":"Article 110574"},"PeriodicalIF":4.9,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142442776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Transit-Guided Radiation Therapy (TGRT) is a novel technique that uses the transit portal images (TPIs) acquired with Electronic Portal Image Devices (EPID) to quantify patient position errors during the treatment. It has been validated using anthropomorphic phantoms but a validation in a clinical setting was lacking. A pilot clinical study is presented to confirm our previous results.
Materials and methods
A prospective study was conducted between June and December 2022 with patients who received whole-brain or breast radiotherapy treatments. The selected treatments were composed of radiation fields using skin-flash, where the body contour projected a sharp edge on the EPID which has been used as a surrogate of the true patient position. Daily imaging procedures were applied as scheduled before running the one- and two-parameter model (1PM and 2PM) of the TGRT formalism on the acquired TPIs to independently estimate the patient position errors.
Results
43 patients and 1015 TPIs have been assessed. The 2PM showed a better correlation with the true position errors (R2 = 0.76 vs. 0.73), a lower detection threshold (0.77 mm vs. 1.24 mm), and a lower overcorrection risk above the detection threshold (7.0 % vs. 11.1 %) than the 1PM. Overall, the 2PM would have significantly reduced the true position errors by a factor of 0.58 (0.49 – 1.27) (p < 0.0001).
Conclusion
The TGRT technique has confirmed the ability to reduce the position errors in a clinical setting, demonstrating the potential to enhance the patient position monitoring without increasing treatment time or patient dose.
{"title":"Transit-guided radiation therapy: a novel patient monitoring approach","authors":"Artur Latorre-Musoll , Gabriela Oses , Gabriela Antelo , Sergi Serrano-Rueda , Meritxell Mollà , Josep Sempau , Núria Jornet","doi":"10.1016/j.radonc.2024.110580","DOIUrl":"10.1016/j.radonc.2024.110580","url":null,"abstract":"<div><h3>Background and purpose</h3><div>Transit-Guided Radiation Therapy (TGRT) is a novel technique that uses the transit portal images (TPIs) acquired with Electronic Portal Image Devices (EPID) to quantify patient position errors during the treatment. It has been validated using anthropomorphic phantoms but a validation in a clinical setting was lacking. A pilot clinical study is presented to confirm our previous results.</div></div><div><h3>Materials and methods</h3><div>A prospective study was conducted between June and December 2022 with patients who received whole-brain or breast radiotherapy treatments. The selected treatments were composed of radiation fields using skin-flash, where the body contour projected a sharp edge on the EPID which has been used as a surrogate of the true patient position. Daily imaging procedures were applied as scheduled before running the one- and two-parameter model (1PM and 2PM) of the TGRT formalism on the acquired TPIs to independently estimate the patient position errors.</div></div><div><h3>Results</h3><div>43 patients and 1015 TPIs have been assessed. The 2PM showed a better correlation with the true position errors (<em>R</em><sup>2</sup> = 0.76 vs. 0.73), a lower detection threshold (0.77 mm vs. 1.24 mm), and a lower overcorrection risk above the detection threshold (7.0 % vs. 11.1 %) than the 1PM. Overall, the 2PM would have significantly reduced the true position errors by a factor of 0.58 (0.49 – 1.27) (<em>p</em> < 0.0001).</div></div><div><h3>Conclusion</h3><div>The TGRT technique has confirmed the ability to reduce the position errors in a clinical setting, demonstrating the potential to enhance the patient position monitoring without increasing treatment time or patient dose.</div></div>","PeriodicalId":21041,"journal":{"name":"Radiotherapy and Oncology","volume":"201 ","pages":"Article 110580"},"PeriodicalIF":4.9,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142446946","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 : 2024-10-10DOI: 10.1016/j.radonc.2024.110579
H. Sallem , S. Harrabi , E. Traneus , K. Herfarth , J. Debus , J. Bauer
Purpose
Late-occurring contrast-enhancing brain lesions (CEBLs) have been observed on MRI follow-up in low-grade glioma (LGG) patients post-proton therapy. Predictive risk-models for this endpoint identified a dose-averaged linear energy transfer (LETd)-dependent proton relative biological effectiveness (RBE) effect on CEBL occurrence and increased radiosensitivity of the cerebral periventricular region (VP4mm). This work aimed to design a stable risk-minimizing treatment planning (TP) concept addressing these intertwined risk factors through a classically formulated optimization problem.
Material and methods
The concept was developed in RayStation-research 11B IonPG featuring a variable-RBE-based optimizer involving 20 LGG patients with varying target volume localizations and risk-factor contributions. Classical cost functions penalizing dose, dose-volume-histogram points, and equivalent uniform dose were used to formulate the optimization problem, and a new set of structures was introduced to actively spare the VP4mm, control high LETd regions, and de-escalate the dose outside the gross tumor volume. Target volume coverage and organ-at-risk sparing were robustly evaluated, and Normal Tissue Complication Probabilities (NTCP) for CEBL occurrence were quantified.
Results
The concept yielded stable optimization outcomes for all considered subjects. Risk hot spots were successfully mitigated, and an NTCP reduction of up to 79 % was observed compared to conventional TP while maintaining target coverage, demonstrating the feasibility of the chosen model-based approach.
Conclusion
With the proposed TP protocol, we close the gap between predictive risk-modeling and practical risk-mitigation in the clinic and provide a concept for CEBL avoidance with the potential to advance treatment precision for LGG patients.
{"title":"A model-based risk-minimizing proton treatment planning concept for brain injury prevention in low-grade glioma patients","authors":"H. Sallem , S. Harrabi , E. Traneus , K. Herfarth , J. Debus , J. Bauer","doi":"10.1016/j.radonc.2024.110579","DOIUrl":"10.1016/j.radonc.2024.110579","url":null,"abstract":"<div><h3>Purpose</h3><div>Late-occurring contrast-enhancing brain lesions (CEBLs) have been observed on MRI follow-up in low-grade glioma (LGG) patients post-proton therapy. Predictive risk-models for this endpoint identified a dose-averaged linear energy transfer (LET<sub>d</sub>)-dependent proton relative biological effectiveness (RBE) effect on CEBL occurrence and increased radiosensitivity of the cerebral periventricular region (VP<sub>4mm</sub>). This work aimed to design a stable risk-minimizing treatment planning (TP) concept addressing these intertwined risk factors through a classically formulated optimization problem.</div></div><div><h3>Material and methods</h3><div>The concept was developed in RayStation-research 11B IonPG featuring a variable-RBE-based optimizer involving 20 LGG patients with varying target volume localizations and risk-factor contributions. Classical cost functions penalizing dose, dose-volume-histogram points, and equivalent uniform dose were used to formulate the optimization problem, and a new set of structures was introduced to actively spare the VP<sub>4mm</sub>, control high LET<sub>d</sub> regions, and de-escalate the dose outside the gross tumor volume. Target volume coverage and organ-at-risk sparing were robustly evaluated, and Normal Tissue Complication Probabilities (NTCP) for CEBL occurrence were quantified.</div></div><div><h3>Results</h3><div>The concept yielded stable optimization outcomes for all considered subjects. Risk hot spots were successfully mitigated, and an NTCP reduction of up to 79 % was observed compared to conventional TP while maintaining target coverage, demonstrating the feasibility of the chosen model-based approach.</div></div><div><h3>Conclusion</h3><div>With the proposed TP protocol, we close the gap between predictive risk-modeling and practical risk-mitigation in the clinic and provide a concept for CEBL avoidance with the potential to advance treatment precision for LGG patients.</div></div>","PeriodicalId":21041,"journal":{"name":"Radiotherapy and Oncology","volume":"201 ","pages":"Article 110579"},"PeriodicalIF":4.9,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142406726","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-10DOI: 10.1016/j.radonc.2024.110571
Zhiying Liang , Chao Luo , Shuqi Li , Yuliang Zhu , Wenjie Huang , Di Cao , Yifei Liu , Guangying Ruan , Shaobo Liang , Xi Chen , Kit-Ian Kou , Guoyi Zhang , Lizhi Liu , Haojiang Li
Background and purpose
Induction chemotherapy (IC) before concurrent chemoradiotherapy does not universally improve long-term overall survival (OS) in locoregionally advanced nasopharyngeal carcinoma (LANPC). Conventional risk stratification often yields suboptimal IC decisions. Our study introduces a ternary classification of predicted individual treatment effect (PITE) to guide personalized IC decisions.
Materials and methods
A two-center retrospective analysis of 1,213 patients with LANPC was conducted to develop and validate prognostic models integrating magnetic resonance imaging and clinical data to estimate individual 5-year OS probabilities for IC and non-IC treatments. Differences in these probabilities defined PITE, facilitating patient stratification into three IC recommendation categories. Model effectiveness was validated using Kaplan–Meier estimators, decision curve-like analysis, and evaluations of variable importance and distribution.
Results
The models exhibited strong predictive performance in both treatments across training and cross-validation sets, enabling accurate PITE calculations and patient classification. Compared with non-IC treatment, IC markedly improved OS in the IC-preferred group (HR = 0.62, p = 0.02), had no effect in the IC-neutral group (HR = 1.00, p = 0.70), and worsened OS in the IC-opposed group (HR = 2.00, p = 0.03). The ternary PITE classification effectively identified 41.7 % of high-risk patients not benefiting from IC, and yielded a 2.68 % higher mean 5-year OS probability over risk-based decisions. Significantly increasing distributions of key prognostic indicators, such as metastatic lymph node number and plasma Epstein–Barr virus DNA level from IC-opposed to IC-preferred groups, further validated the clinical relevance of PITE classification.
Conclusion
The ternary PITE classification offers an accurate and clinically advantageous approach to guide personalized IC decision-making in patients with LANPC.
背景和目的：对于局部区域性晚期鼻咽癌（LANPC），在同时进行化放疗之前先进行诱导化疗（IC）并不能普遍提高长期总生存率（OS）。传统的风险分层通常会产生次优化疗决策。我们的研究引入了预测个体治疗效果（PITE）的三元分类法，以指导个性化的IC决策：我们在两个中心对 1,213 名 LANPC 患者进行了回顾性分析，开发并验证了整合磁共振成像和临床数据的预后模型，以估计 IC 和非 IC 治疗的个体 5 年 OS 概率。这些概率的差异定义了 PITE，有助于将患者分为三个 IC 推荐类别。使用 Kaplan-Meier 估计器、决策曲线分析以及变量重要性和分布评估验证了模型的有效性：结果：在训练集和交叉验证集上，模型对两种治疗方法都表现出很强的预测能力，能够准确计算 PITE 和对患者进行分类。与非 IC 治疗相比，IC 首选组的 OS 明显改善（HR = 0.62，p = 0.02），IC 中立组无影响（HR = 1.00，p = 0.70），而 IC 反对组的 OS 则恶化（HR = 2.00，p = 0.03）。PITE 三元分类法能有效识别出 41.7% 的高危患者无法从 IC 中获益，其 5 年平均 OS 概率比基于风险的决策高出 2.68%。关键预后指标（如转移性淋巴结数量和血浆 Epstein-Barr 病毒 DNA 水平）的分布明显增加，进一步验证了 PITE 分类的临床相关性：结论：三元 PITE 分类为指导 LANPC 患者的个性化 IC 决策提供了一种准确且具有临床优势的方法。
{"title":"Guiding induction chemotherapy of locoregionally advanced nasopharyngeal carcinoma with ternary classification of predicted individual treatment effect","authors":"Zhiying Liang , Chao Luo , Shuqi Li , Yuliang Zhu , Wenjie Huang , Di Cao , Yifei Liu , Guangying Ruan , Shaobo Liang , Xi Chen , Kit-Ian Kou , Guoyi Zhang , Lizhi Liu , Haojiang Li","doi":"10.1016/j.radonc.2024.110571","DOIUrl":"10.1016/j.radonc.2024.110571","url":null,"abstract":"<div><h3>Background and purpose</h3><div>Induction chemotherapy (IC) before concurrent chemoradiotherapy does not universally improve long-term overall survival (OS) in locoregionally advanced nasopharyngeal carcinoma (LANPC). Conventional risk stratification often yields suboptimal IC decisions. Our study introduces a ternary classification of predicted individual treatment effect (PITE) to guide personalized IC decisions.</div></div><div><h3>Materials and methods</h3><div>A two-center retrospective analysis of 1,213 patients with LANPC was conducted to develop and validate prognostic models integrating magnetic resonance imaging and clinical data to estimate individual 5-year OS probabilities for IC and non-IC treatments. Differences in these probabilities defined PITE, facilitating patient stratification into three IC recommendation categories. Model effectiveness was validated using Kaplan–Meier estimators, decision curve-like analysis, and evaluations of variable importance and distribution.</div></div><div><h3>Results</h3><div>The models exhibited strong predictive performance in both treatments across training and cross-validation sets, enabling accurate PITE calculations and patient classification. Compared with non-IC treatment, IC markedly improved OS in the IC-preferred group (HR = 0.62, p = 0.02), had no effect in the IC-neutral group (HR = 1.00, p = 0.70), and worsened OS in the IC-opposed group (HR = 2.00, p = 0.03). The ternary PITE classification effectively identified 41.7 % of high-risk patients not benefiting from IC, and yielded a 2.68 % higher mean 5-year OS probability over risk-based decisions. Significantly increasing distributions of key prognostic indicators, such as metastatic lymph node number and plasma Epstein–Barr virus DNA level from IC-opposed to IC-preferred groups, further validated the clinical relevance of PITE classification.</div></div><div><h3>Conclusion</h3><div>The ternary PITE classification offers an accurate and clinically advantageous approach to guide personalized IC decision-making in patients with LANPC.</div></div>","PeriodicalId":21041,"journal":{"name":"Radiotherapy and Oncology","volume":"201 ","pages":"Article 110571"},"PeriodicalIF":4.9,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142406737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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