Pub Date : 2024-12-25DOI: 10.1016/j.radonc.2024.110700
Monica Maria Vincenzi, Alessandro Cicchetti, Roberta Castriconi, Paola Mangili, Maria Giulia Ubeira-Gabellini, Anna Chiara, Chiara Deantoni, Martina Mori, Marcella Pasetti, Gabriele Palazzo, Roberta Tummineri, Tiziana Rancati, Nadia Gisella Di Muzio, Antonella Del Vecchio, Andrei Fodor, Claudio Fiorino
Purpose: The aim is to train and validate a multivariable Normal Tissue Complication Probability (NTCP) model predicting acute skin reactions in patients with breast cancer receiving adjuvant Radiotherapy (RT).
Methods and materials: We retrospectively reviewed 1570 single-institute patients with breast cancer treated with whole breast irradiation (40 Gy/15fr). The patients were divided into training (n = 878, treated with 3d-CRT, from 2009 to 2017) and validation cohorts (n = 692, treated from 2017 to 2021, including advanced RT techniques). In the validation cohort, patients were classified according to the delivery techniques into static (n = 404) and arc techniques (n = 288). Several clinical/technical information and DVHs of the "skin" (5 mm inner expansion from the body contour) were available. Skin toxicity was assessed during follow-up using the RTOG scale criteria. A multivariable logistic regression model was generated combining skin DVH and clinical parameters, using cross-validation methods that ensured high internal consistency and robustness. The performance of the model was tested in the validation cohort.
Results: 14.0 %/17.4 % of patients developed ≥ G2 toxicity, in the training/validation cohorts, respectively. The resulting multivariable logistic model included axillary lymph node dissection (OR = 1.58, 95 %CI = 1.01-2.48, p = 0.045), hypertension (OR = 1.54, 95 %CI = 1.04-2.27, p = 0.030) and skin V20Gy (OR = 1.008, 95 %CI = 1.004-1.013, p < 0.0001). The AUC of the model was 0.64/0.59 in training/validation, with better performance in the validation cohort if considering only V20Gy (0.62). The model showed satisfactory agreement between predicted and observed toxicity rates: in the validation group, the slope of the calibration plot was 0.96 (R2 = 0.6) with excellent goodness-of-fit (Hosmer-Lemeshow p-value = 0.99). Looking at each of the three predictors individually, only the role of V20Gy was confirmed in the validation group. Results were similar when considering patients treated with static or arc techniques.
Conclusion: An NTCP model for acute toxicity after moderately hypofractionated breast RT was trained. The model underwent temporal validation even for patients treated with advanced delivery techniques. Despite clinical differences and techniques, the confirmation of the dosimetry parameter in the validation cohort highlights its robustness and corroborates the hypothesis that skin DVH may assess the risk with the potential for improving plan optimisation.
{"title":"Training and temporally validating an NTCP model of acute toxicity after whole breast radiotherapy, including the impact of advanced delivery techniques.","authors":"Monica Maria Vincenzi, Alessandro Cicchetti, Roberta Castriconi, Paola Mangili, Maria Giulia Ubeira-Gabellini, Anna Chiara, Chiara Deantoni, Martina Mori, Marcella Pasetti, Gabriele Palazzo, Roberta Tummineri, Tiziana Rancati, Nadia Gisella Di Muzio, Antonella Del Vecchio, Andrei Fodor, Claudio Fiorino","doi":"10.1016/j.radonc.2024.110700","DOIUrl":"10.1016/j.radonc.2024.110700","url":null,"abstract":"<p><strong>Purpose: </strong>The aim is to train and validate a multivariable Normal Tissue Complication Probability (NTCP) model predicting acute skin reactions in patients with breast cancer receiving adjuvant Radiotherapy (RT).</p><p><strong>Methods and materials: </strong>We retrospectively reviewed 1570 single-institute patients with breast cancer treated with whole breast irradiation (40 Gy/15fr). The patients were divided into training (n = 878, treated with 3d-CRT, from 2009 to 2017) and validation cohorts (n = 692, treated from 2017 to 2021, including advanced RT techniques). In the validation cohort, patients were classified according to the delivery techniques into static (n = 404) and arc techniques (n = 288). Several clinical/technical information and DVHs of the \"skin\" (5 mm inner expansion from the body contour) were available. Skin toxicity was assessed during follow-up using the RTOG scale criteria. A multivariable logistic regression model was generated combining skin DVH and clinical parameters, using cross-validation methods that ensured high internal consistency and robustness. The performance of the model was tested in the validation cohort.</p><p><strong>Results: </strong>14.0 %/17.4 % of patients developed ≥ G2 toxicity, in the training/validation cohorts, respectively. The resulting multivariable logistic model included axillary lymph node dissection (OR = 1.58, 95 %CI = 1.01-2.48, p = 0.045), hypertension (OR = 1.54, 95 %CI = 1.04-2.27, p = 0.030) and skin V20Gy (OR = 1.008, 95 %CI = 1.004-1.013, p < 0.0001). The AUC of the model was 0.64/0.59 in training/validation, with better performance in the validation cohort if considering only V20Gy (0.62). The model showed satisfactory agreement between predicted and observed toxicity rates: in the validation group, the slope of the calibration plot was 0.96 (R<sup>2</sup> = 0.6) with excellent goodness-of-fit (Hosmer-Lemeshow p-value = 0.99). Looking at each of the three predictors individually, only the role of V20Gy was confirmed in the validation group. Results were similar when considering patients treated with static or arc techniques.</p><p><strong>Conclusion: </strong>An NTCP model for acute toxicity after moderately hypofractionated breast RT was trained. The model underwent temporal validation even for patients treated with advanced delivery techniques. Despite clinical differences and techniques, the confirmation of the dosimetry parameter in the validation cohort highlights its robustness and corroborates the hypothesis that skin DVH may assess the risk with the potential for improving plan optimisation.</p>","PeriodicalId":21041,"journal":{"name":"Radiotherapy and Oncology","volume":" ","pages":"110700"},"PeriodicalIF":4.9,"publicationDate":"2024-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142897182","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 : 2024-12-25DOI: 10.1016/j.radonc.2024.110705
Lasse Refsgaard, Marie Louise Holm Milo, Emma Skarsø Buhl, Jesper Møller Jensen, Else Maae, Martin Berg, Ingelise Jensen, Mette Holck Nielsen, Ebbe Laugaard Lorenzen, Lise Bech Jellesmark Thorsen, Stine Sofia Korreman, Birgitte Vrou Offersen
Background and purpose: Radiotherapy improves outcomes for breast cancer. However, prior studies have correlated the risk of coronary artery disease (CAD) to the mean heart dose (MHD), mean dose to the left anterior descending artery (LAD_mean) and the left ventricle V5Gy (LV5). Other studies showed an increased risk of CAD for patients with pronounced coronary artery calcification (CAC) at the time of radiotherapy.
Materials and methods: This cohort study included 3355 high-risk breast cancer patients treated in Western Denmark (2008-2016). We analysed CT scans, treatment plans, and dose distributions. CAC was measured using the Agatston score (AS). We examined the dose-response relationship between MHD, LV5 and LAD_mean and CAD, and the effect of CAC presence at radiotherapy. Secondary analysis assessed overall survival.
Results: Of 3355 patients, 45 (1.2 %) developed CAD during follow-up. AS was a strong predictor of CAD risk with a hazard ratio of 9.51(CI95:5.16-17.53) for AS ≥ 100 versus AS < 100 and a 6.7 % difference in absolute cumulative CAD risk at ten years (7.7 % vs 1 %). For AS < 100 (97 % of patients) CAD risk increased with MHD, hazard ratio 1.25 (CI95:1.01-1.56) per Gy. ForAS ≥ 100, CAD risk was driven by CAC rather than radiation dose. CAC was associated with poorer overall survival. Median MHD for the whole cohort was 1.25 Gy (IQR:1.01-1.56).
Conclusion: AS from planning CT-scans predicted CAD risk and overall survival in breast cancer patients receiving radiotherapy. The MHD remained the strongest predictor in patients with low CAC. For patients with high CAC, the high baseline risk from CAC was a stronger risk factor than the dose-related risk.
{"title":"The effect of coronary artery calcifications and radiotherapy on the risk of coronary artery disease in high-risk breast cancer patients in the DBCG RT-Nation cohort.","authors":"Lasse Refsgaard, Marie Louise Holm Milo, Emma Skarsø Buhl, Jesper Møller Jensen, Else Maae, Martin Berg, Ingelise Jensen, Mette Holck Nielsen, Ebbe Laugaard Lorenzen, Lise Bech Jellesmark Thorsen, Stine Sofia Korreman, Birgitte Vrou Offersen","doi":"10.1016/j.radonc.2024.110705","DOIUrl":"10.1016/j.radonc.2024.110705","url":null,"abstract":"<p><strong>Background and purpose: </strong>Radiotherapy improves outcomes for breast cancer. However, prior studies have correlated the risk of coronary artery disease (CAD) to the mean heart dose (MHD), mean dose to the left anterior descending artery (LAD_mean) and the left ventricle V5Gy (LV5). Other studies showed an increased risk of CAD for patients with pronounced coronary artery calcification (CAC) at the time of radiotherapy.</p><p><strong>Materials and methods: </strong>This cohort study included 3355 high-risk breast cancer patients treated in Western Denmark (2008-2016). We analysed CT scans, treatment plans, and dose distributions. CAC was measured using the Agatston score (AS). We examined the dose-response relationship between MHD, LV5 and LAD_mean and CAD, and the effect of CAC presence at radiotherapy. Secondary analysis assessed overall survival.</p><p><strong>Results: </strong>Of 3355 patients, 45 (1.2 %) developed CAD during follow-up. AS was a strong predictor of CAD risk with a hazard ratio of 9.51(CI95:5.16-17.53) for AS ≥ 100 versus AS < 100 and a 6.7 % difference in absolute cumulative CAD risk at ten years (7.7 % vs 1 %). For AS < 100 (97 % of patients) CAD risk increased with MHD, hazard ratio 1.25 (CI95:1.01-1.56) per Gy. ForAS ≥ 100, CAD risk was driven by CAC rather than radiation dose. CAC was associated with poorer overall survival. Median MHD for the whole cohort was 1.25 Gy (IQR:1.01-1.56).</p><p><strong>Conclusion: </strong>AS from planning CT-scans predicted CAD risk and overall survival in breast cancer patients receiving radiotherapy. The MHD remained the strongest predictor in patients with low CAC. For patients with high CAC, the high baseline risk from CAC was a stronger risk factor than the dose-related risk.</p>","PeriodicalId":21041,"journal":{"name":"Radiotherapy and Oncology","volume":" ","pages":"110705"},"PeriodicalIF":4.9,"publicationDate":"2024-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142897175","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 : 2024-12-24DOI: 10.1016/j.radonc.2024.110697
Alexander Rühle, Maria Weymann, Max Behrens, Johannes Olbrich, Carmen Kut, Sebastian N Marschner, Marlen Haderlein, Alexander Fabian, Carolin Senger, Benjamin P Bakst, Johannes Kraft, Jens von der Grün, Esmée Lauren Looman, Eric Chen, Justus Domschikowski, Alev Altay-Langguth, Goda Kalinauskaite, Victor Lewitzki, Marcelo Bonomi, Dukagjin Blakaj, Sachin R Jhawar, Sujith Baliga, Ahmed N Elguindy, Konstantinos Ferentinos, Constantinos Zamboglou, Jörg Andreas Müller, Chris Leucht, Daniel R Dickstein, Sören Schnellhardt, Erik Haehl, Peter Hambsch, Thomas Kuhnt, Clemens Seidel, Claus Belka, Arnulf Mayer, Heinz Schmidberger, Anca-Ligia Grosu, Panagiotis Balermpas, Carmen Stromberger, Harald Binder, Harry Quon, Nils H Nicolay
Purpose: Cumulative cisplatin doses of ≥ 200 mg/m2 improve survival in adults with head-and-neck squamous cell carcinoma (HNSCC) undergoing chemoradiation, but many older adults with HNSCC cannot receive this prognostically relevant dose due to toxicities. This study aims to develop predictive models to assess the likelihood of older adults with HNSCC receiving ≥ 200 mg/m2 cisplatin during chemoradiation.
Methods: 366 patients from the SENIOR database, an international cohort of adults ≥ 65 years with HNSCC, received definitive chemoradiation with single-agent cisplatin and were analyzed. A Generalized Linear Model (GLM), Support Vector Machine (SVM), and Random Forest Model (RFM) were trained and compared for their performance in predicting a cumulative cisplatin dose of ≥ 200 mg/m2.
Results: 195 (53 %) patients achieved a cumulative cisplatin dose of ≥ 200 mg/m2. In the GLM, laryngeal carcinoma (β = 1.37, p = 0.01), tumoral p16 positivity (β = 0.69, p = 0.04), higher hemoglobin levels (β = 0.26, p = 0.002), elevated C-reactive protein (CRP) concentration (β = 0.02, p = 0.003), and increased estimated glomerular filtration rate (eGFR) (β = 0.02, p = 0.008) were associated with a higher probability of reaching ≥ 200 mg/m2 cisplatin. Hemoglobin, CRP, eGFR, and p16 status constituted the most important features in the SVM and RFM. AUC values for the GLM, SVM, and RFM were 0.70 (95 % CI, 0.67-0.73), 0.71 (95 % CI, 0.68-0.73), and 0.73 (95 % CI, 0.71-0.75), respectively.
Conclusions: We developed predictive models to support clinicians in identifying older adults with HNSCC capable of tolerating ≥ 200 mg/m2 cumulative cisplatin during chemoradiation. Once validated, these models could improve personalized treatments and enhance shared decision-making in older adults with HNSCC.
{"title":"Predicting cisplatin tolerability in older adults with head and neck cancer - Insights for improved chemoradiation outcomes.","authors":"Alexander Rühle, Maria Weymann, Max Behrens, Johannes Olbrich, Carmen Kut, Sebastian N Marschner, Marlen Haderlein, Alexander Fabian, Carolin Senger, Benjamin P Bakst, Johannes Kraft, Jens von der Grün, Esmée Lauren Looman, Eric Chen, Justus Domschikowski, Alev Altay-Langguth, Goda Kalinauskaite, Victor Lewitzki, Marcelo Bonomi, Dukagjin Blakaj, Sachin R Jhawar, Sujith Baliga, Ahmed N Elguindy, Konstantinos Ferentinos, Constantinos Zamboglou, Jörg Andreas Müller, Chris Leucht, Daniel R Dickstein, Sören Schnellhardt, Erik Haehl, Peter Hambsch, Thomas Kuhnt, Clemens Seidel, Claus Belka, Arnulf Mayer, Heinz Schmidberger, Anca-Ligia Grosu, Panagiotis Balermpas, Carmen Stromberger, Harald Binder, Harry Quon, Nils H Nicolay","doi":"10.1016/j.radonc.2024.110697","DOIUrl":"10.1016/j.radonc.2024.110697","url":null,"abstract":"<p><strong>Purpose: </strong>Cumulative cisplatin doses of ≥ 200 mg/m<sup>2</sup> improve survival in adults with head-and-neck squamous cell carcinoma (HNSCC) undergoing chemoradiation, but many older adults with HNSCC cannot receive this prognostically relevant dose due to toxicities. This study aims to develop predictive models to assess the likelihood of older adults with HNSCC receiving ≥ 200 mg/m<sup>2</sup> cisplatin during chemoradiation.</p><p><strong>Methods: </strong>366 patients from the SENIOR database, an international cohort of adults ≥ 65 years with HNSCC, received definitive chemoradiation with single-agent cisplatin and were analyzed. A Generalized Linear Model (GLM), Support Vector Machine (SVM), and Random Forest Model (RFM) were trained and compared for their performance in predicting a cumulative cisplatin dose of ≥ 200 mg/m<sup>2</sup>.</p><p><strong>Results: </strong>195 (53 %) patients achieved a cumulative cisplatin dose of ≥ 200 mg/m<sup>2</sup>. In the GLM, laryngeal carcinoma (β = 1.37, p = 0.01), tumoral p16 positivity (β = 0.69, p = 0.04), higher hemoglobin levels (β = 0.26, p = 0.002), elevated C-reactive protein (CRP) concentration (β = 0.02, p = 0.003), and increased estimated glomerular filtration rate (eGFR) (β = 0.02, p = 0.008) were associated with a higher probability of reaching ≥ 200 mg/m<sup>2</sup> cisplatin. Hemoglobin, CRP, eGFR, and p16 status constituted the most important features in the SVM and RFM. AUC values for the GLM, SVM, and RFM were 0.70 (95 % CI, 0.67-0.73), 0.71 (95 % CI, 0.68-0.73), and 0.73 (95 % CI, 0.71-0.75), respectively.</p><p><strong>Conclusions: </strong>We developed predictive models to support clinicians in identifying older adults with HNSCC capable of tolerating ≥ 200 mg/m<sup>2</sup> cumulative cisplatin during chemoradiation. Once validated, these models could improve personalized treatments and enhance shared decision-making in older adults with HNSCC.</p>","PeriodicalId":21041,"journal":{"name":"Radiotherapy and Oncology","volume":" ","pages":"110697"},"PeriodicalIF":4.9,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142897168","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}
Background and purpose: Knowledge-based planning (KBP) can consistently and efficiently create high-quality Volumetric Arc Therapy (VMAT) plans for cervix cancer. This study describes the cross-validation of two KBP models on geographically distinct populations and their comparison to manual plans from 67 centers. The purpose was to determine the universal applicability of a generic KBP model.
Materials and methods: Based on the EMBRACE-II protocol, two KBP models were developed at Tata Memorial Centre, India and Aarhus University Hospital, Denmark using respective patient plans. The KBP models were exchanged between three institutions with different geo-ethnic populations and validated on reference manual plans of 20 node-positive and 20 node-negative patients. Additionally, one patient case was manually planned by 67 centres. These manual treatment plans were compared to the two KBP model plans using a score out of 80, based on 20 DVH parameters.
Results: The manual and the KBP plans adhered to the EMBRACE II protocol. OAR sparing in KBP plans was similar or slightly improved as compared to the manual plans. The differences between the medians of manual and either KBP model plans were significant for 8 parameters among node positive patients, and 4 parameters among node negative patients. The comparison between the Tata and Aarhus KBP model plans to manual plans from 67 institutions showed that the two KPBs had superior plan quality in 88-99% of instances.
Conclusion: KBP has the potential to generate high-quality plans across institutions and geo-ethnic populations by reducing inter-planner variation, thereby facilitating the global standardisation of radiotherapy for cervical cancer.
{"title":"Can knowledge-based planning models validated on ethnically diverse patients lead to global standardisation of external beam radiation therapy for locally advanced cervix cancer?","authors":"Jeevanshu Jain, Monica Serban, Marianne Sanggaard Assenholt, Varsha Hande, Jamema Swamidas, Yvette Seppenwoolde, Joanne Alfieri, Kari Tanderup, Supriya Chopra","doi":"10.1016/j.radonc.2024.110694","DOIUrl":"10.1016/j.radonc.2024.110694","url":null,"abstract":"<p><strong>Background and purpose: </strong>Knowledge-based planning (KBP) can consistently and efficiently create high-quality Volumetric Arc Therapy (VMAT) plans for cervix cancer. This study describes the cross-validation of two KBP models on geographically distinct populations and their comparison to manual plans from 67 centers. The purpose was to determine the universal applicability of a generic KBP model.</p><p><strong>Materials and methods: </strong>Based on the EMBRACE-II protocol, two KBP models were developed at Tata Memorial Centre, India and Aarhus University Hospital, Denmark using respective patient plans. The KBP models were exchanged between three institutions with different geo-ethnic populations and validated on reference manual plans of 20 node-positive and 20 node-negative patients. Additionally, one patient case was manually planned by 67 centres. These manual treatment plans were compared to the two KBP model plans using a score out of 80, based on 20 DVH parameters.</p><p><strong>Results: </strong>The manual and the KBP plans adhered to the EMBRACE II protocol. OAR sparing in KBP plans was similar or slightly improved as compared to the manual plans. The differences between the medians of manual and either KBP model plans were significant for 8 parameters among node positive patients, and 4 parameters among node negative patients. The comparison between the Tata and Aarhus KBP model plans to manual plans from 67 institutions showed that the two KPBs had superior plan quality in 88-99% of instances.</p><p><strong>Conclusion: </strong>KBP has the potential to generate high-quality plans across institutions and geo-ethnic populations by reducing inter-planner variation, thereby facilitating the global standardisation of radiotherapy for cervical cancer.</p>","PeriodicalId":21041,"journal":{"name":"Radiotherapy and Oncology","volume":" ","pages":"110694"},"PeriodicalIF":4.9,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142872756","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 : 2024-11-28DOI: 10.1016/j.radonc.2024.110647
Louis Potters
{"title":"The indispensable role of peer review in modern radiation oncology","authors":"Louis Potters","doi":"10.1016/j.radonc.2024.110647","DOIUrl":"10.1016/j.radonc.2024.110647","url":null,"abstract":"","PeriodicalId":21041,"journal":{"name":"Radiotherapy and Oncology","volume":"202 ","pages":"Article 110647"},"PeriodicalIF":4.9,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142755361","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 : 2024-11-27DOI: 10.1016/j.radonc.2024.110654
Tom Marchant , Joseph Wood , Kathryn Banfill , Alan McWilliam , Gareth Price , Corinne Faivre-Finn
Background
Minimising heart exposure during lung radiotherapy (RT) is important due to association between increased cardiac dose and adverse outcomes such as cardiac toxicity and reduced overall survival. This study evaluated the impact of incorporating a cardiac avoidance area (CAA) located at the base of the heart on the dose received by cardiac subregions and thoracic organs at risk.
Methods
A comparative analysis was conducted on patients treated with lung RT at a single centre before and after the CAA was introduced as an anatomical region at risk (ARR) in April 2023. Two patient cohorts were analysed: those treated prior to CAA implementation (April 2021-March 2023, 923 patients) and those treated post implementation (April 2023-March 2024, 477 patients). For the second group, plans were optimised to keep CAA maximum dose to 1 cc below 19.5 Gy in 20 fractions (or equivalent biologically effective dose). Key dose metrics for the CAA, heart, lungs, oesophagus, and spinal canal were compared between the cohorts.
Results
The introduction of the CAA as an ARR resulted in significant reductions in CAA and overall heart dose, with median CAA maximum dose (EQD2) decreasing from 32.0 Gy3 to 16.9 Gy3 (p < 0.001). No significant increases in dose were observed for other thoracic organs at risk.
Conclusions
Implementing a cardiac avoidance area in lung RT planning significantly reduces doses to critical heart regions without compromising the safety of other organs. This approach holds promise for reducing cardiac-related adverse events and improving overall survival in patients with lung cancer undergoing RT.
{"title":"Dosimetric impact of sparing base of heart on organ at risk doses during lung radiotherapy","authors":"Tom Marchant , Joseph Wood , Kathryn Banfill , Alan McWilliam , Gareth Price , Corinne Faivre-Finn","doi":"10.1016/j.radonc.2024.110654","DOIUrl":"10.1016/j.radonc.2024.110654","url":null,"abstract":"<div><h3>Background</h3><div>Minimising heart exposure during lung radiotherapy (RT) is important due to association between increased cardiac dose and adverse outcomes such as cardiac toxicity and reduced overall survival. This study evaluated the impact of incorporating a cardiac avoidance area (CAA) located at the base of the heart on the dose received by cardiac subregions and thoracic organs at risk.</div></div><div><h3>Methods</h3><div>A comparative analysis was conducted on patients treated with lung RT at a single centre before and after the CAA was introduced as an anatomical region at risk (ARR) in April 2023. Two patient cohorts were analysed: those treated prior to CAA implementation (April 2021-March 2023, 923 patients) and those treated post implementation (April 2023-March 2024, 477 patients). For the second group, plans were optimised to keep CAA maximum dose to 1 cc below 19.5 <!--> <!-->Gy in 20 fractions (or equivalent biologically effective dose). Key dose metrics for the CAA, heart, lungs, oesophagus, and spinal canal were compared between the cohorts.</div></div><div><h3>Results</h3><div>The introduction of the CAA as an ARR resulted in significant reductions in CAA and overall heart dose, with median CAA maximum dose (EQD2) decreasing from 32.0 <!--> <!-->Gy<sub>3</sub> to 16.9 <!--> <!-->Gy<sub>3</sub> (p < 0.001). No significant increases in dose were observed for other thoracic organs at risk.</div></div><div><h3>Conclusions</h3><div>Implementing a cardiac avoidance area in lung RT planning significantly reduces doses to critical heart regions without compromising the safety of other organs. This approach holds promise for reducing cardiac-related adverse events and improving overall survival in patients with lung cancer undergoing RT.</div></div>","PeriodicalId":21041,"journal":{"name":"Radiotherapy and Oncology","volume":"202 ","pages":"Article 110654"},"PeriodicalIF":4.9,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142745817","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 : 2024-11-26DOI: 10.1016/j.radonc.2024.110653
Dirk Wagenaar , Steven J.M. Habraken , Ilaria Rinaldi , Daniëlle B.P. Eekers , Miranda Kramer , Jaap P.M. Jaspers , Dik van Gent , Lara Barazzuol , Yvonne L.B. Klaver , Jaap Zindler , Ida Coremans , Inge Compter , Daniel Scandurra , Hiska L. van der Weide , Stefan Both , Mischa Hoogeman , Mirko Unipan , Alejandra Méndez Romero
Background and purpose
With proton therapy, the relative biological effectiveness (RBE) accounts for increased DNA damage caused by higher linear energy transfer (LET) compared to photons. However, the LET and hence the RBE varies along the proton range, particularly at the Bragg peak, introducing challenges in proton treatment planning for brain tumors. The aim of this paper is to standardize evaluating and reporting LET and RBE in proton therapy for patients with grade 2 and 3 IDH mutant gliomas among the Dutch proton therapy centers.
Materials and methods
A working group, comprising experts from three Dutch proton therapy centers, conducted nine meetings between 2020 and 2023. A joint literature review supported the standardized evaluation and reporting of LET and RBE. Questionnaires sent out to the three Dutch proton centers in 2020 and 2023 provided input for discussions on clinical practices. Three clinical examples were chosen to illustrate the application of the recommended methodology in treatment planning.
Results
Following the literature review, a guideline on evaluation and reporting using the dose averaged LET (LETd) of primary and secondary protons calculated in water normalized to unit density was established. The McNamara variable RBE model with an α/β value of 2 Gy was selected for reporting.
Conclusion
The study presents a harmonization of approaches to evaluating and reporting LET and variable RBE in a guideline for the three Dutch proton therapy centers, providing clarity for future clinical interpretation. Having chosen a single variable RBE model offers practicality, although its accuracy remains a topic of ongoing research.
背景和目的与光子相比，质子治疗的线性能量传递（LET）更高，导致 DNA 损伤增加，因此质子治疗的相对生物有效性（RBE）也随之增加。然而，质子的线性能量传递（LET）和相对生物有效性（RBE）在质子范围内各不相同，尤其是在布拉格峰，这给脑肿瘤的质子治疗规划带来了挑战。本文旨在统一荷兰质子治疗中心对 2 级和 3 级 IDH 突变胶质瘤患者进行质子治疗时的 LET 和 RBE 的评估和报告。联合文献综述为 LET 和 RBE 的标准化评估和报告提供了支持。2020 年和 2023 年向三家荷兰质子中心发出的调查问卷为临床实践的讨论提供了信息。结果根据文献综述，制定了使用剂量平均 LET（LETd）进行评估和报告的指南，LETd 是在水中计算的一级质子和二级质子的剂量平均值，归一化为单位密度。该研究在荷兰三家质子治疗中心的指南中统一了 LET 和可变 RBE 的评估和报告方法，为今后的临床解释提供了清晰的思路。选择单一的可变 RBE 模型具有实用性，但其准确性仍是一个持续研究的课题。
{"title":"Evaluating and reporting LET and RBE-weighted dose in proton therapy for glioma – The Dutch approach","authors":"Dirk Wagenaar , Steven J.M. Habraken , Ilaria Rinaldi , Daniëlle B.P. Eekers , Miranda Kramer , Jaap P.M. Jaspers , Dik van Gent , Lara Barazzuol , Yvonne L.B. Klaver , Jaap Zindler , Ida Coremans , Inge Compter , Daniel Scandurra , Hiska L. van der Weide , Stefan Both , Mischa Hoogeman , Mirko Unipan , Alejandra Méndez Romero","doi":"10.1016/j.radonc.2024.110653","DOIUrl":"10.1016/j.radonc.2024.110653","url":null,"abstract":"<div><h3>Background and purpose</h3><div>With proton therapy, the relative biological effectiveness (RBE) accounts for increased DNA damage caused by higher linear energy transfer (LET) compared to photons. However, the LET and hence the RBE varies along the proton range, particularly at the Bragg peak, introducing challenges in proton treatment planning for brain tumors. The aim of this paper is to standardize evaluating and reporting LET and RBE in proton therapy for patients with grade 2 and 3 IDH mutant gliomas among the Dutch proton therapy centers.</div></div><div><h3>Materials and methods</h3><div>A working group, comprising experts from three Dutch proton therapy centers, conducted nine meetings between 2020 and 2023. A joint literature review supported the standardized evaluation and reporting of LET and RBE. Questionnaires sent out to the three Dutch proton centers in 2020 and 2023 provided input for discussions on clinical practices. Three clinical examples were chosen to illustrate the application of the recommended methodology in treatment planning.</div></div><div><h3>Results</h3><div>Following the literature review, a guideline on evaluation and reporting using the dose averaged LET (LET<sub>d</sub>) of primary and secondary protons calculated in water normalized to unit density was established. The McNamara variable RBE model with an α/β value of 2 Gy was selected for reporting.</div></div><div><h3>Conclusion</h3><div>The study presents a harmonization of approaches to evaluating and reporting LET and variable RBE in a guideline for the three Dutch proton therapy centers, providing clarity for future clinical interpretation. Having chosen a single variable RBE model offers practicality, although its accuracy remains a topic of ongoing research.</div></div>","PeriodicalId":21041,"journal":{"name":"Radiotherapy and Oncology","volume":"202 ","pages":"Article 110653"},"PeriodicalIF":4.9,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142722616","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 : 2024-11-24DOI: 10.1016/j.radonc.2024.110649
Pablo Jiménez-Labaig , Claudia Aymerich , Antonio Rullan , Jon Cacicedo , Irene Braña , Christopher Nutting , Kate Newbold , Kevin J. Harrington , Ana Catalan
Background and purpose
Patients with head and neck cancer (HNC) are particularly vulnerable to mental health concerns. Radiotherapy (RT) remains a key treatment modality for these malignancies, offering high chances of cure. However, the effects on mental health are not well defined. We aim to characterize longitudinally the prevalence and risk of depressive and anxiety symptoms over the course of RT in patients with HNC.
Material and methods
A literature search was performed from database inception until November 1st, 2024. PROSPERO/MOOSE-compliant and pre-registered (PROSPERO:CRD42023441432) systematic review identified studies longitudinally reporting in patients with HNC undergoing curative intent RT. Pooled prevalence and odds ratio of clinically significant anxiety and depressive symptoms between different treatment timepoints were estimated using random-effects meta-analysis.
Results
18 studies (total sample 1,920, mean age 59.9[SD = 3.17], 22.2 % female, 93.0 % white ethnicity) were included. Before RT, a pooled prevalence of depressive symptoms of 18.1 % (95 % confidence intervals [CI] = 13.1 %-24.4 %) was found. Short-term after completing RT (≤3 months), the prevalence of depressive symptoms peaked to 26.1 % (95 %CI = 18.9 %-35.0 %), decreasing in long-term (≥6 months) assessments to 16.4 % (95 %CI = 12.6 %-21.0 %). Anxiety symptoms continuously decreased from baseline (pooled prevalence 29.9 % [95 %CI = 27.3 %–32.7 %]) to 17.4 % (95 %CI = 12.1 %-24.5 %) in the long-term. Female and married patients showed higher prevalence of depressive symptoms. Those who underwent surgery showed a lower prevalence of anxiety symptoms.
Conclusions
High prevalence of clinically significant depressive and anxiety symptoms were found in patients with HNC undergoing RT, from baseline to long-term follow-up. The weeks following completion of RT are key, as depressive symptoms increase in this period. Screening and interventions prior to, during, and especially immediately post-RT would be beneficial.
{"title":"Prevalence of depressive and anxiety symptoms in patients with head and neck cancer undergoing radiotherapy: A systematic review and meta-analysis of longitudinal studies","authors":"Pablo Jiménez-Labaig , Claudia Aymerich , Antonio Rullan , Jon Cacicedo , Irene Braña , Christopher Nutting , Kate Newbold , Kevin J. Harrington , Ana Catalan","doi":"10.1016/j.radonc.2024.110649","DOIUrl":"10.1016/j.radonc.2024.110649","url":null,"abstract":"<div><h3>Background and purpose</h3><div>Patients with head and neck cancer (HNC) are particularly vulnerable to mental health concerns. Radiotherapy (RT) remains a key treatment modality for these malignancies, offering high chances of cure. However, the effects on mental health are not well defined. We aim to characterize longitudinally the prevalence and risk of depressive and anxiety symptoms over the course of RT in patients with HNC.</div></div><div><h3>Material and methods</h3><div>A literature search was performed from database inception until November 1st, 2024. PROSPERO/MOOSE-compliant and pre-registered (PROSPERO:CRD42023441432) systematic review identified studies longitudinally reporting in patients with HNC undergoing curative intent RT. Pooled prevalence and odds ratio of clinically significant anxiety and depressive symptoms between different treatment timepoints were estimated using random-effects meta-analysis.</div></div><div><h3>Results</h3><div>18 studies (total sample 1,920, mean age 59.9[SD = 3.17], 22.2 % female, 93.0 % white ethnicity) were included. Before RT, a pooled prevalence of depressive symptoms of 18.1 % (95 % confidence intervals [CI] = 13.1 %-24.4 %) was found. Short-term after completing RT (≤3 months), the prevalence of depressive symptoms peaked to 26.1 % (95 %CI = 18.9 %-35.0 %), decreasing in long-term (≥6 months) assessments to 16.4 % (95 %CI = 12.6 %-21.0 %). Anxiety symptoms continuously decreased from baseline (pooled prevalence 29.9 % [95 %CI = 27.3 %–32.7 %]) to 17.4 % (95 %CI = 12.1 %-24.5 %) in the long-term. Female and married patients showed higher prevalence of depressive symptoms. Those who underwent surgery showed a lower prevalence of anxiety symptoms.</div></div><div><h3>Conclusions</h3><div>High prevalence of clinically significant depressive and anxiety symptoms were found in patients with HNC undergoing RT, from baseline to long-term follow-up. The weeks following completion of RT are key, as depressive symptoms increase in this period. Screening and interventions prior to, during, and especially immediately post-RT would be beneficial.</div></div>","PeriodicalId":21041,"journal":{"name":"Radiotherapy and Oncology","volume":"202 ","pages":"Article 110649"},"PeriodicalIF":4.9,"publicationDate":"2024-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142716739","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 : 2024-11-24DOI: 10.1016/j.radonc.2024.110652
Jakob Fenske , Claudius Steffen , Friedrich Mrosk , Philipp Lampert , Eirini Nikolaidou , Marcus Beck , Max Heiland , Kilian Kreutzer , Christian Doll , Steffen Koerdt , Carsten Rendenbach
Background and purpose
With standard radiotherapy protocols after R0 resection of advanced local oral squamous cell carcinoma (OSCC) and primary reconstruction of segmental defects, a high radiation dose is applied to healthy tissue in autologous microvascular free flaps. Considering the potential consequences of flap complications and associated surgeries for patients, data is lacking on whether postoperative radiotherapy (PORT) of the flap volume is indicated at all.
Materials and methods
Patients with segmental mandibular resection and immediate reconstruction with osseous free flaps due to advanced OSCC between 2012 and 2022 were analyzed retrospectively regarding overall (OS), disease-free survival (DFS), local failure-free survival (LFFS), the need for secondary surgeries as well as flap complications and compared between patients with and without PORT in a matched-pair approach with occurrence of flap complications as a primary endpoint.
Results
105 patients matched the inclusion criteria. The maximum follow-up period was 60 months. 68 patients received PORT. 74 patients were included in the final analysis. No case of disease recurrence inside the free flap was recorded. There were no significant differences in DFS (p = 0.21), OS (p = 0.33) and LFFS (p = 0.6) between both cohorts. Occurrence of osteoradionecrosis (p = 0.03) and bone exposure (p = 0.003) was higher in irradiated flaps. In patients with PORT, the demand for secondary surgeries due to flap complications was significantly higher (p = 0.009). Radiation doses were not increased in patients with flap ORN.
Conclusion
PORT is associated with higher flap complications and need for secondary surgeries in advanced stage OSCC. Given a recurrence rate of zero inside the flap without PORT and the improbability of recurrence within healthy transplanted tissue, the usefulness of applying high radiation doses to this vulnerable tissue is questioned. Further refinements of RT planning should be evaluated and tested in a RCT trial.
{"title":"A critical reflection of radiotherapy on osseous free flaps in mandibular segmental resection and immediate reconstruction in locally advanced oral squamous cell carcinoma: A cohort study","authors":"Jakob Fenske , Claudius Steffen , Friedrich Mrosk , Philipp Lampert , Eirini Nikolaidou , Marcus Beck , Max Heiland , Kilian Kreutzer , Christian Doll , Steffen Koerdt , Carsten Rendenbach","doi":"10.1016/j.radonc.2024.110652","DOIUrl":"10.1016/j.radonc.2024.110652","url":null,"abstract":"<div><h3>Background and purpose</h3><div>With standard radiotherapy protocols after R0 resection of advanced local oral squamous cell carcinoma (OSCC) and primary reconstruction of segmental defects, a high radiation dose is applied to healthy tissue in autologous microvascular free flaps. Considering the potential consequences of flap complications and associated surgeries for patients, data is lacking on whether postoperative radiotherapy (PORT) of the flap volume is indicated at all.</div></div><div><h3>Materials and methods</h3><div>Patients with segmental mandibular resection and immediate reconstruction with osseous free flaps due to advanced OSCC between 2012 and 2022 were analyzed retrospectively regarding overall (OS), disease-free survival (DFS), local failure-free survival (LFFS), the need for secondary surgeries as well as flap complications and compared between patients with and without PORT in a matched-pair approach with occurrence of flap complications as a primary endpoint.</div></div><div><h3>Results</h3><div>105 patients matched the inclusion criteria. The maximum follow-up period was 60 months. 68 patients received PORT. 74 patients were included in the final analysis. No case of disease recurrence inside the free flap was recorded. There were no significant differences in DFS (p = 0.21), OS (p = 0.33) and LFFS (p = 0.6) between both cohorts. Occurrence of osteoradionecrosis (p = 0.03) and bone exposure (p = 0.003) was higher in irradiated flaps. In patients with PORT, the demand for secondary surgeries due to flap complications was significantly higher (p = 0.009). Radiation doses were not increased in patients with flap ORN.</div></div><div><h3>Conclusion</h3><div>PORT is associated with higher flap complications and need for secondary surgeries in advanced stage OSCC. Given a recurrence rate of zero inside the flap without PORT and the improbability of recurrence within healthy transplanted tissue, the usefulness of applying high radiation doses to this vulnerable tissue is questioned. Further refinements of RT planning should be evaluated and tested in a RCT trial.</div></div>","PeriodicalId":21041,"journal":{"name":"Radiotherapy and Oncology","volume":"202 ","pages":"Article 110652"},"PeriodicalIF":4.9,"publicationDate":"2024-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142699909","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 : 2024-11-23DOI: 10.1016/j.radonc.2024.110650
Muyu Liu , Bo Pang , Shuoyan Chen , Yiling Zeng , Qi Zhang , Hong Quan , Yu Chang , Zhiyong Yang
Backgrounds
Intensity-modulated proton therapy (IMPT) is particularly susceptible to range and setup uncertainties, as well as anatomical changes.
Purpose
We present a framework for IMPT planning that employs a deep learning method for dose prediction based on multiple-CT (MCT). The extra CTs are created from cone-beam CT (CBCT) using deformable registration with the primary planning CT (PCT). Our method also includes a dose mimicking algorithm.
Methods
The MCT IMPT planning pipeline involves prediction of robust dose from input images using a deep learning model with a U-net architecture. Deliverable plans may then be created by solving a dose mimicking problem with the predictions as reference dose. Model training, dose prediction and plan generation are performed using a dataset of 55 patients with head and neck cancer in this retrospective study. Among them, 38 patients were used as training set, 7 patients were used as validation set, and 10 patients were reserved as test set for final evaluation.
Results
We demonstrated that the deliverable plans generated through subsequent MCT dose mimicking exhibited greater robustness than the robust plans produced by the PCT, as well as enhanced dose sparing for organs at risk. MCT plans had lower D2% (76.1 Gy vs. 82.4 Gy), better homogeneity index (7.7% vs. 16.4%) of CTV1 and better conformity index (70.5% vs. 61.5%) of CTV2 than the robust plans produced by the primary planning CT for all test patients.
Conclusions
We demonstrated the feasibility and advantages of incorporating daily CBCT images into MCT optimization. This approach improves plan robustness against anatomical changes and may reduce the need for plan adaptations in head and neck cancer treatments.
{"title":"Deep learning-based multiple-CT optimization: An adaptive treatment planning approach to account for anatomical changes in intensity-modulated proton therapy for head and neck cancers","authors":"Muyu Liu , Bo Pang , Shuoyan Chen , Yiling Zeng , Qi Zhang , Hong Quan , Yu Chang , Zhiyong Yang","doi":"10.1016/j.radonc.2024.110650","DOIUrl":"10.1016/j.radonc.2024.110650","url":null,"abstract":"<div><h3>Backgrounds</h3><div>Intensity-modulated proton therapy (IMPT) is particularly susceptible to range and setup uncertainties, as well as anatomical changes.</div></div><div><h3>Purpose</h3><div>We present a framework for IMPT planning that employs a deep learning method for dose prediction based on multiple-CT (MCT). The extra CTs are created from cone-beam CT (CBCT) using deformable registration with the primary planning CT (PCT). Our method also includes a dose mimicking algorithm.</div></div><div><h3>Methods</h3><div>The MCT IMPT planning pipeline involves prediction of robust dose from input images using a deep learning model with a U-net architecture. Deliverable plans may then be created by solving a dose mimicking problem with the predictions as reference dose. Model training, dose prediction and plan generation are performed using a dataset of 55 patients with head and neck cancer in this retrospective study. Among them, 38 patients were used as training set, 7 patients were used as validation set, and 10 patients were reserved as test set for final evaluation.</div></div><div><h3>Results</h3><div>We demonstrated that the deliverable plans generated through subsequent MCT dose mimicking exhibited greater robustness than the robust plans produced by the PCT, as well as enhanced dose sparing for organs at risk. MCT plans had lower D<sub>2%</sub> (76.1 Gy vs. 82.4 Gy), better homogeneity index (7.7% vs. 16.4%) of CTV1 and better conformity index (70.5% vs. 61.5%) of CTV2 than the robust plans produced by the primary planning CT for all test patients.</div></div><div><h3>Conclusions</h3><div>We demonstrated the feasibility and advantages of incorporating daily CBCT images into MCT optimization. This approach improves plan robustness against anatomical changes and may reduce the need for plan adaptations in head and neck cancer treatments.</div></div>","PeriodicalId":21041,"journal":{"name":"Radiotherapy and Oncology","volume":"202 ","pages":"Article 110650"},"PeriodicalIF":4.9,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142710914","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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