Clinical and Translational Radiation Oncology最新文献

{"title":"NANO-GBM trial of AGuIX nanoparticles with radiotherapy and temozolomide in the treatment of newly diagnosed Glioblastoma: Phase 1b outcomes and MRI-based biodistribution","authors":"J. Biau ,&nbsp;X. Durando ,&nbsp;F. Boux ,&nbsp;I. Molnar ,&nbsp;J. Moreau ,&nbsp;B. Leyrat ,&nbsp;F. Guillemin ,&nbsp;A. Lavielle ,&nbsp;Y. Cremillieux ,&nbsp;K. Seddik ,&nbsp;S. Dufort ,&nbsp;O. De Beaumont ,&nbsp;E. Thivat ,&nbsp;G. Le Duc","doi":"10.1016/j.ctro.2024.100833","DOIUrl":"10.1016/j.ctro.2024.100833","url":null,"abstract":"<div><h3>Background</h3><p>In glioblastoma (GBM), tumor progression occurs mainly within the irradiated tumor volume. To address this challenge, a radiosensitization strategy with intravenous gadolinium-based theranostic nanoparticles (AGuIX) is being explored in the NANO-GBM phase1b/2R trial (NCT04881032). Here, we present the results of the phase 1b part, which is the first-in-human use of these nanoparticles with radiotherapy and chemotherapy for the treatment of newly diagnosed GBM.</p></div><div><h3>Material and Methods</h3><p>Eligible patients were aged 18 to 75 years with newly diagnosed and histologically confirmed GBM, with incomplete resection (biopsy or partial surgery). The phase 1b part was a dose escalation approach (Time-to-event Continuous Reassessment Method) with three dose levels: 50, 75, and 100 mg/kg. Patients were treated with RT (60 Gy), and concomitant and adjuvant TMZ, and 4 injections of AGuIX (D-3/-7, D1, D8, and D15). Dose-limiting-toxicity (DLT) was defined as any grade 3–4 adverse event (CTCAE v5.0), excluding alopecia, nausea, and rapidly controlled vomiting. Pharmacokinetic (PK), and biodistribution based on MRI were evaluated.</p></div><div><h3>Results</h3><p>Between March 2022 and March 2023, eight patients were enrolled: 1 at 50 mg/kg, 1 at 75 mg/kg, and 6 at 100 mg/kg. All patients received the four AGuIX injections. Only one patient experienced a DLT (at 100 mg/kg): a grade 3 lymphopenia (related to TMZ). The RP2D of AGuIX was determined as 100 mg/kg. AGuIX mean AUC increased with dose. Regions of GBM with moderate (36–123 µM), and high (123–291 µM) or very high (&gt;291 µM) AGuIX concentrations accounted in average for 38.7 and 26.8 %, respectively.</p></div><div><h3>Conclusion</h3><p>These results confirm the lack of AGuIX-related toxicity and the widespread dispersion of nanoparticles throughout GBM. This supports progression to the randomized phase 2 part, utilizing an RP2D of AGuIX of 100 mg/kg (4 injections).</p></div>","PeriodicalId":10342,"journal":{"name":"Clinical and Translational Radiation Oncology","volume":"48 ","pages":"Article 100833"},"PeriodicalIF":2.7,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2405630824001101/pdfft?md5=9cecb89af5e46aac662262b95623999b&pid=1-s2.0-S2405630824001101-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141961993","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acute toxicities in proton therapy for head and neck cancer – A matched analysis of the DAHANCA 35 feasibility study","authors":"K. Nowicka-Matus ,&nbsp;J. Friborg ,&nbsp;C.R. Hansen ,&nbsp;M. Bernsdorf ,&nbsp;U.V. Elstrøm ,&nbsp;M. Farhadi ,&nbsp;C. Grau ,&nbsp;J.G. Eriksen ,&nbsp;J. Johansen ,&nbsp;M.S. Nielsen ,&nbsp;A. Holm ,&nbsp;E. Samsøe ,&nbsp;P. Sibolt ,&nbsp;B. Smulders ,&nbsp;K. Jensen","doi":"10.1016/j.ctro.2024.100835","DOIUrl":"10.1016/j.ctro.2024.100835","url":null,"abstract":"<div><h3>Background and purpose</h3><p>As preparation for a national randomized study comparing proton radiotherapy to photon radiotherapy, DAHANCA 35, we performed a non-randomized pilot study to investigate patient selection, logistics, planning, and treatment delivery. With the present study, as a comprehensive safety analysis, we want to compare toxicity during and up to two months after therapy to a historically matched group of patients treated with photon radiotherapy.</p></div><div><h3>Materials and methods</h3><p>62 patients treated with protons were matched to 124 patients who received photon treatment outside a protocol. Available data were retrieved from the DAHANCA database. Patients were matched on treatment centre, concurrent chemotherapy, tumour site, stage, p16 status for oropharynx cancers. Selection of patients for proton therapy was based on comparative treatment plans with a NTCP reduction for dysphagia and xerostomia at six months.</p></div><div><h3>Results</h3><p>Baseline characteristics between groups were well balanced, except for the type of drug used concurrently; more photon patients received Carboplatin (21.2 % vs 5.8 %, p = 0.01). Proton therapy was associated with significantly less weight loss at the end of treatment, mean weight loss of 3 % for protons and 5 % for photons (p &lt; 0.001). There were more grade 3 skin reactions and grade 3 mucositis after proton treatment compared with photons at the end of treatment, Risk Ratio (RR) 1.9 (95 % CI: 1.01–3.5, p = 0.04) and RR 1.5 (95 % CI: 1.3–1.7, p &lt; 0.001), respectively. All differences resolved at follow up two months after treatment. There were no significant differences between groups on opioid use, use of feeding tubes, or hospitalization during the observation period.</p></div><div><h3>Conclusion</h3><p>Proton treatment resulted in excess objective mucositis and dermatitis, which was transient and did not seem to negatively influence weight or treatment compliance and intensity. Selection bias was likely especially since NTCP models were used for selection of proton treatment and photon treated patients were matched manually. We are currently including patients in a randomized controlled trial.</p></div>","PeriodicalId":10342,"journal":{"name":"Clinical and Translational Radiation Oncology","volume":"48 ","pages":"Article 100835"},"PeriodicalIF":2.7,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2405630824001125/pdfft?md5=1d748e857b70a7683da6bb4004a4d6cb&pid=1-s2.0-S2405630824001125-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141962004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The carbon footprint of external beam radiotherapy and its impact in health technology assessment","authors":"Chloé Dupraz ,&nbsp;Coline Ducrot ,&nbsp;Benoit Allignet ,&nbsp;Gregory Delpon ,&nbsp;Anthony Alexis ,&nbsp;Ariane Lapierre ,&nbsp;Stéphane Supiot ,&nbsp;David Ali ,&nbsp;Max Piffoux","doi":"10.1016/j.ctro.2024.100834","DOIUrl":"10.1016/j.ctro.2024.100834","url":null,"abstract":"<div><h3>Background</h3><p>The major drivers of carbon dioxide (CO₂eq) emissions of external beam radiation therapy (EBRT) are not well known and limit our ability to initiate mitigation strategies.</p></div><div><h3>Material and methods</h3><p>We describe the carbon footprint of four typical centers. We explore direct EBRT associated factors such as the impact of fractionation and use of MRI-LINAC, as well as indirect factors (e.g. patient rides). Treatment strategy related CO₂eq emissions are included in a health technology assessment analysis that takes into account CO₂eq emissions.</p></div><div><h3>Results</h3><p>A typical EBRT treatment emits from 185 kgCO₂eq to 2066 kgCO₂eq. CO₂eq emissions are mostly driven by (i) accelerator acquisition and maintenance (37.8 %), (ii) patients and workers rides (32.7 %), (iii) drugs and medical devices (7.3 %), (iv) direct energy consumption (6.1 %), and (v) building and bunker construction (5.6 %) with a substantial heterogeneity among centers. Hypofractionation has a strong impact to mitigate emissions. MRI-LINAC is associated with a substantial increase in CO₂eq emissions per fraction and requires ultra hypofractionation in 5 fractions to achieve a similar carbon footprint compared to 20 fractions treatment schemes. The expected limited small increase in toxicities due to hypofractionation (when existing) are in the same range as avoided detrimental effects to future people’s health thanks to CO₂eq mitigation.</p></div><div><h3>Conclusion</h3><p>Carbon footprint of EBRT is not neglectable and could be mitigated. When safely feasible, hypofractionation is one of the main factors to decrease this impact. Taking into account CO₂eq emissions has a substantial impact on the health technology assessment of EBRT, favoring hypofractionated regimens.</p></div>","PeriodicalId":10342,"journal":{"name":"Clinical and Translational Radiation Oncology","volume":"48 ","pages":"Article 100834"},"PeriodicalIF":2.7,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2405630824001113/pdfft?md5=78a826fcf8ab77c942ddbe7a8447cb15&pid=1-s2.0-S2405630824001113-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141962920","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Incidental dose distribution to contralateral internal mammary nodes in breast cancer patients undergoing adjuvant radiotherapy","authors":"Sophie T. Behzadi ,&nbsp;Mathias Duesberg ,&nbsp;Rebecca Moser ,&nbsp;Marciana-Nona Duma ,&nbsp;Markus Oechsner ,&nbsp;Sophia Kiesl ,&nbsp;Jana Nano ,&nbsp;Stephanie E. Combs ,&nbsp;Kai J. Borm","doi":"10.1016/j.ctro.2024.100831","DOIUrl":"10.1016/j.ctro.2024.100831","url":null,"abstract":"<div><h3>Background and purpose</h3><p>In a relevant number of primary breast cancer patients, lymphatic drainage to the contralateral internal mammary nodes (cIMN) is being observed. Nevertheless, so far lymphatic drainage pathway to the cIMN is largely neglected during adjuvant radiotherapy.</p></div><div><h3>Materials and methods</h3><p>This study evaluated the incidental dose to the cIMN for 120 volumetric modulated arc therapy (VMAT) treatment plans for node positive breast in dependence of internal mammary node irradiation (IMNI) and deep inspiration breath hold (DIBH). Additionally, incidental dose distribution to the cIMN based on the field design in the MA20, EORTC22922/10925 and AMAROS trials was assessed.</p></div><div><h3>Results</h3><p>The incidental dose (Dmean ± SD) to the cIMN-CTV was 13.0 (±4.7) Gy with a maximum dose of &lt; 30 Gy in 113/120 cases. If IMNI was included (n = 80), the Dmean to the cIMN-CTV was significantly higher compared to no IMNI, but still comparably low (n = 40; 14.3 Gy vs. 9.6 Gy; p = 0.0001). Furthermore, the dose in the cIMN during free breathing (n = 80) was higher compared to DIBH (n = 40; 13.9 Gy vs. 11.2 Gy; p = 0.002).</p><p>Simulated treatment plans based on the randomized RNI trials revealed neglectable dose coverage of the cIMN (Dmean 1.0–1.8 Gy) for all protocols.</p></div><div><h3>Conclusion</h3><p>Neither in the randomized RNI trials nor during contemporary treatment techniques clinically relevant dose distribution to the cIMN was observed. Further studies are warranted to assess the potential impact of intended irradiation of cIMN in high-risk patients.</p></div>","PeriodicalId":10342,"journal":{"name":"Clinical and Translational Radiation Oncology","volume":"48 ","pages":"Article 100831"},"PeriodicalIF":2.7,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2405630824001083/pdfft?md5=0e607623ee6962268087664721d4d66f&pid=1-s2.0-S2405630824001083-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141962919","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adaptive bridging radiation therapy for relapsed/refractory B-cell lymphoma patient undergoing CAR T-cell therapy: Case report","authors":"Hazim S. Ababneh ,&nbsp;P. Connor Johnson ,&nbsp;Jennifer Pursley ,&nbsp;Chirayu G. Patel","doi":"10.1016/j.ctro.2024.100832","DOIUrl":"10.1016/j.ctro.2024.100832","url":null,"abstract":"<div><p>Radiation therapy (RT) is utilized as a bridging strategy for patients with aggressive B-cell lymphoma prior to CD19-targeted chimeric antigen receptor (CAR T)-cell therapy. RT has been shown to provide local control without exacerbating the toxicities associated with subsequent CAR T-cell infusion. However, a consensus on the optimal radiation dose and fractionation for bridging purposes has yet to be established. We present a case of a patient with relapsed aggressive B-cell lymphoma who underwent bridging adaptive RT on a CT-linac prior to receiving CAR T-cell therapy. At month 6 post-CAR T infusion, the patient demonstrates no signs of disease recurrence or relapse, nor any unexpected toxicities attributable to the combined treatment. This underscores the feasibility and success of this innovative approach in treating lymphoma patients undergoing CAR T-cell therapy.</p></div>","PeriodicalId":10342,"journal":{"name":"Clinical and Translational Radiation Oncology","volume":"48 ","pages":"Article 100832"},"PeriodicalIF":2.7,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2405630824001095/pdfft?md5=e56356711d09d5aa012d9c4e9b1f66a2&pid=1-s2.0-S2405630824001095-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141961992","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spatially fractionated radiotherapy (Lattice SFRT) in the palliative treatment of locally advanced bulky unresectable head and neck cancer","authors":"Peng Xu,&nbsp;Shuo Wang,&nbsp;Jie Zhou,&nbsp;Ke Yuan,&nbsp;Xianliang Wang,&nbsp;Lintao Li,&nbsp;Jinyi Lang,&nbsp;Shun Lu","doi":"10.1016/j.ctro.2024.100830","DOIUrl":"10.1016/j.ctro.2024.100830","url":null,"abstract":"<div><h3>Objectives</h3><p>Locally advanced bulky unresectable head neck cancer causes significant tumor mass effects, leading to severe symptoms. This study aims to report the safety and outcomes in patients undergoing Lattice spatially fractionated radiotherapy (Lattice SFRT) for locally advanced bulky unresectable head and neck cancer.</p></div><div><h3>Methods</h3><p>Patients with bulky head and neck cancer received Lattice SFRT between June 2022 and June 2023. Lattice SFRT was administered in 2–3 fractions of 12 Gy (Gy) using 6-megavolt (MV) photon beams through a multileaf collimator (MLC) based on VMAT technology. The primary endpoints were symptomatic and tumor response rates. Secondary endpoints were overall survival, local control, and acute and late toxicity rates.</p></div><div><h3>Results</h3><p>19 consecutive patients meeting the study criteria were identified, predominantly with squamous cell carcinoma histology. The median patient age was 62 years (range 39–79 years), and the median tumor volume was 208 cc (cc) (range 48–701 cc). All patients completed radiotherapy. Among all investigated patients, 16 of 19 (84.2 %) patients achieved an objective response, including 10 individuals achieved a partial response (PR), with 3 of them exhibiting regression exceeding 75 %. 17 patients showed symptom improvement to varying degrees. Acute toxicity of Radiation Therapy Oncology Group (RTOG) grade 1 or higher occurred in 5 patients, while no grade 3 adverse events was observed.</p></div><div><h3>Conclusions</h3><p>Lattice SFRT proves to be a viable treatment option for the palliative management of bulky head and neck cancer. In the palliative setting, Lattice SFRT offers timely symptom relief, enhancing patient quality of life. Treatment toxicity remains within an acceptable range. Continued optimization of Lattice SFRT delivery and patient selection can benefit from further data on the feasibility and efficacy of this radiation modality.</p></div>","PeriodicalId":10342,"journal":{"name":"Clinical and Translational Radiation Oncology","volume":"48 ","pages":"Article 100830"},"PeriodicalIF":2.7,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2405630824001071/pdfft?md5=f7bcf32c2f2137c4c3c0fd38d00ff1ae&pid=1-s2.0-S2405630824001071-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141963639","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Utility of interim apparent diffusion coefficient value in predicting treatment response among patients with locally advanced cervical cancer treated with radiotherapy","authors":"Chunyu Liang ,&nbsp;Wei Wang ,&nbsp;Guohui Yang ,&nbsp;Zhiyuan Xu ,&nbsp;Jian Li ,&nbsp;Kusheng Wu ,&nbsp;Xinping Shen","doi":"10.1016/j.ctro.2024.100827","DOIUrl":"10.1016/j.ctro.2024.100827","url":null,"abstract":"<div><h3>Background</h3><p>For locally advanced cervical cancer (LACC), treatment response to radiotherapy (RT) can vary significantly even among those with the same stage classification of International Federation of Gynecology and Obstetrics (FIGO). This study investigated the value of ADC metric for forecasting end-of-treatment outcomes in LACC patients referred for RT.</p></div><div><h3>Methods</h3><p>Eighty patients with pathologically confirmed cervical squamous cell carcinoma with (SCC) were included in the research. Abdominal or pelvic MRI scans were conducted at least three times for all participants: before RT, three weeks after beginning of RT and approximately two months after RT was finalized. Calculated apparent diffusion coefficient (ADC) values of the LACC include: pre-ADC, interim-ADC, ΔADC and Δ%ADC. Based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1,<!--> <!-->subjects were calculated and subsequently categorized into good responders group (complete response) and poor responders group (progressive disease, stable disease or partial response).</p></div><div><h3>Results</h3><p>Compared to good-responders, subjects of poor-responder group showed significantly lower values of interim-ADC, ΔADC, and Δ%ADC (all <em>P</em> &lt; 0.05). To distinguish between good and poor responders, the optimal cutoff values of interim-ADC, ΔADC, and Δ%ADC were determined to be 1.067 × 10⁻³ mm²/sec, 0.209 × 10⁻³ mm²/sec, and 30.74 % using the ROC curve, with corresponding sensitivities of 83.78 %, 86.49 %, 75.68 %, and specificities of 88.37 %, 86.49 %, 75.68 %, respectively. Multivariate logistic regression revealed that the baseline tumor diameter and interim-ADC were significant prognostic factors for treatment response with an odds ratio (OR) of 0.105 (95 % confidence interval [95 % CI] 0.018–0.616) for baseline tumor diameter and 42.896 (95 % CI 8.205–224.262) for interim-ADC.</p></div><div><h3>Conclusion</h3><p>The interim-ADC value and baseline tumor diameter surfaced as possible indicative factors for predicting the response to RT in patients with LACC.</p></div>","PeriodicalId":10342,"journal":{"name":"Clinical and Translational Radiation Oncology","volume":"48 ","pages":"Article 100827"},"PeriodicalIF":2.7,"publicationDate":"2024-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2405630824001046/pdfft?md5=ec39cfd6558baadc2325795795d9f1e8&pid=1-s2.0-S2405630824001046-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141850863","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reply to: Comment on “Repeated HyperArc radiosurgery for recurrent intracranial metastases and dosimetric analysis of recurrence pattern to account for diffuse dose effect on microscopical disease”","authors":"Luca Nicosia ,&nbsp;Andrea Gaetano Allegra ,&nbsp;Filippo Alongi","doi":"10.1016/j.ctro.2024.100826","DOIUrl":"10.1016/j.ctro.2024.100826","url":null,"abstract":"","PeriodicalId":10342,"journal":{"name":"Clinical and Translational Radiation Oncology","volume":"48 ","pages":"Article 100826"},"PeriodicalIF":2.7,"publicationDate":"2024-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2405630824001034/pdfft?md5=ae6e28950ad1dd848f0afe452564e23a&pid=1-s2.0-S2405630824001034-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141851522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Radiation response assessment of organoids derived from patients with pancreatic cancer","authors":"Iris W.J.M. van Goor ,&nbsp;Leon Raymakers ,&nbsp;Daan S.H. Andel ,&nbsp;Lodewijk A.A. Brosens ,&nbsp;Onno Kranenburg ,&nbsp;Jeanette H.W. Leusen ,&nbsp;Gert J. Meijer ,&nbsp;I. Quintus Molenaar ,&nbsp;Hjalmar C. van Santvoort ,&nbsp;J.H. Wilfred de Vries ,&nbsp;Andre J.M. Wopereis ,&nbsp;Martijn P.W. Intven ,&nbsp;Lois A. Daamen","doi":"10.1016/j.ctro.2024.100829","DOIUrl":"10.1016/j.ctro.2024.100829","url":null,"abstract":"<div><h3>Background</h3><p>The effectiveness of radiotherapy for pancreatic cancer is debated. Patient-derived organoids (PDOs) already mimicked clinical radiation response in other cancer types, which could be valuable in pancreatic cancer as well. This study aimed to investigate whether PDOs can be used to model RT response in pancreatic cancer and to explore the presence of a dose–response correlation.</p></div><div><h3>Methods</h3><p>PDOs derived from two pancreatic cancer patients (HUB-08-B2-022A and HUB-08-B2-026B) were irradiated with doses ranging from 0 to 40 Gray. Viability assessments were conducted after seven and 10 days by measuring ATP-levels. Results were normalized, defining the viability at 0 Gray as 100 % and an absolute viability of 0 as 0 %. The relative area under the curve (rAUC) was calculated (0 = total sensitivity, 1 = total resistance).</p></div><div><h3>Results</h3><p>With a readout time of seven days, both HUB-08-B2-022A and HUB-08-B2-026B exhibited viability above 50 % at the highest dose of 12 Gy (rAUC of 0.79 and 0.69, respectively). With a readout time of 10 days, both PDOs showed a dose–response relation although HUB-08-B2-022A was more sensitive than HUB-08-B2-026B (rAUC of 0.37 and 0.51, respectively). Increasing the radiation dose to 40 Gy did not further affect viability, but the dose–response relation remained present (rAUC of 0.13 and 0.26, respectively). In the final experiment with a readout time of 10 days and a maximum dose of 14 Gy, the dose–response correlation was paramount in both PDOs (rAUC 0.28 and 0.45, respectively), with HUB-08-B2-022A being most sensitive.</p></div><div><h3>Conclusions</h3><p>In this setup, both pancreatic cancer PDOs showed an irradiation dose–response correlation. These preliminary findings suggest that pancreatic cancer PDOs are suitable for assessing radiation response <em>in vitro</em>. Further experiments are needed to eventually simulate treatment responses to personalized treatment strategies.</p></div>","PeriodicalId":10342,"journal":{"name":"Clinical and Translational Radiation Oncology","volume":"48 ","pages":"Article 100829"},"PeriodicalIF":2.7,"publicationDate":"2024-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S240563082400106X/pdfft?md5=12c334bbe015de6fbdffd5493ffdfc43&pid=1-s2.0-S240563082400106X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141847766","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Local relapse patterns after preoperative radiotherapy of limb and trunk wall soft tissue sarcomas: Prognostic role of imaging and pathologic response factors","authors":"M. Cuenin ,&nbsp;A. Levy ,&nbsp;D. Peiffert ,&nbsp;MP. Sunyach ,&nbsp;A. Ducassou ,&nbsp;A. Cordoba ,&nbsp;P. Gillon ,&nbsp;D. Thibouw ,&nbsp;M. Lapeyre ,&nbsp;D. Lerouge ,&nbsp;S. Helfre ,&nbsp;A. Leroux ,&nbsp;J. Salleron ,&nbsp;F. Sirveaux ,&nbsp;F. Marchal ,&nbsp;P.Teixeira ,&nbsp;PA. Debordes ,&nbsp;G.Vogin","doi":"10.1016/j.ctro.2024.100825","DOIUrl":"10.1016/j.ctro.2024.100825","url":null,"abstract":"<div><h3>Purpose</h3><p>To retrospectively identify clinical, pathologic, or imaging factors predictive of local relapse (LR) after preoperative radiotherapy (RT) for soft tissue sarcomas (STS).</p></div><div><h3>Methods and Materials</h3><p>This is a retrospective multicenter study of patients who underwent preoperative RT and surgery for limb or trunk wall STS between 2007 and 2018 in French Sarcoma Group centers and were enrolled in the “Conticabase”. Patterns of LR were investigated taking into account the multimodal response after preoperative RT. Diagnostic and surgical samples were compared after systematic review by expert pathologists and patients were stratified by tumor grade. Log-rank tests and Cox models were used to identify prognostic factors for radiation response and LR.</p></div><div><h3>Results</h3><p>257 patients were included; 17 % had low-grade (LG), 72.5 % had high-grade (HG) sarcomas. In HG group, tumors were larger, mostly undifferentiated, and displayed more necrosis and perilesional edema after RT. Median follow-up was 32 months. Five-year cumulative incidence of LR was 20.3 % in the HG group versus 9.7 % in the LG group (p = 0.026). In multivariate analysis, trunk wall location (HR 6.79, p = 0.012) and proportion of viable tumor cellularity ≥ 20 % (HR 3.15, p = 0.018) were associated with LR. After adjusting for tumor location, combination of histotype and cellularity rate significantly correlated with LR. We described three prognostic subgroups for HG sarcomas, listed from the highest to lowest risk: undifferentiated sarcoma (US) with cellularity rates ≥ 20 %; non-US (NUS) with cellularity rates ≥ 20 % or US with cellularity rates &lt; 20 %; and NUS with cellularity rates &lt; 20 %, which shared similar prognostic risks with LG sarcomas.</p></div><div><h3>Conclusions</h3><p>HG and LG tumors have different morphological and biological behaviors in response to RT. Combination of cellularity rate with histotype could be a major prognostic for LR. Patients with undifferentiated HG sarcomas with cellularity rates ≥ 20 % after preoperative RT had the highest risk of LR and disease-specific death.</p></div>","PeriodicalId":10342,"journal":{"name":"Clinical and Translational Radiation Oncology","volume":"48 ","pages":"Article 100825"},"PeriodicalIF":2.7,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2405630824001022/pdfft?md5=aae88cb84c8a4c85f23d83e0272f7fb8&pid=1-s2.0-S2405630824001022-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141852996","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}