Radiotherapy and Oncology最新文献

{"title":"Comment on “Analysis of re-recurrent rectal cancer after curative treatment of locally recurrent rectal cancer”","authors":"Chong-jie Zhang","doi":"10.1016/j.radonc.2024.110625","DOIUrl":"10.1016/j.radonc.2024.110625","url":null,"abstract":"","PeriodicalId":21041,"journal":{"name":"Radiotherapy and Oncology","volume":"202 ","pages":"Article 110625"},"PeriodicalIF":4.9,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142639670","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}

{"title":"A systematic review and meta-analysis on the impact of institutional peer review in radiation oncology","authors":"Jane Jomy ,&nbsp;Rachel Lu ,&nbsp;Radha Sharma ,&nbsp;Ke Xin Lin ,&nbsp;David C. Chen ,&nbsp;Jeff Winter ,&nbsp;Srinivas Raman","doi":"10.1016/j.radonc.2024.110622","DOIUrl":"10.1016/j.radonc.2024.110622","url":null,"abstract":"<div><h3>Background</h3><div>Radiotherapy peer review is recognized as a key component of institutional quality assurance, though the impact is ill-defined. We conducted the first systematic review and <em>meta</em>-analysis to date to quantify the impact of institutional peer review on the treatment planning workflow including radiotherapy contours, prescription and dosimetry.</div></div><div><h3>Methods</h3><div>We searched several medical and healthcare databases from January 1, 2000, to May 25, 2024, for papers that report on the impact of institutional radiotherapy peer review on treatment plans. We conducted random-effects <em>meta</em>-analyses of proportions to summarize the rates of any change recommendation and major change recommendation (suggesting re-planning or re-simulation due to safety concerns) following peer review processes. To explore differences in change recommendations dependent on location, radiotherapy intent, technique, and peer review structure characteristics, we conducted analyses of variance.</div></div><div><h3>Results</h3><div>Of 9,487 citations, we identified 55 studies that report on 96,444 case audits in 10 countries across various disease sites. The pooled proportion of any change recommendation was 28 % (95 %CI = 21–35) and major change recommendation was 12 % (95 %CI = 7–18). Proportions of change recommendation were not impacted by any treatment characteristics. The most common reasons for change recommendation include target volume delineation (25/55; 45 %), target dose prescription (18/55; 33 %), organ at risk dose prescription (5/55; 9 %), and organ at risk volume delineation (3/55; 5 %).</div></div><div><h3>Conclusions</h3><div>Our review provides evidence that peer review results in treatment plan change recommendations in over one in four patients. The results suggest that some form of real-time, early peer review may be beneficial for all cases, irrespective of treatment intent or RT technique.</div></div>","PeriodicalId":21041,"journal":{"name":"Radiotherapy and Oncology","volume":"202 ","pages":"Article 110622"},"PeriodicalIF":4.9,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142639669","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}

{"title":"Role of consolidative thoracic and prophylactic cranial radiation in extensive stage small cell lung cancer in chemo-immunotherapy era","authors":"J. Varlotto ,&nbsp;R. Voland ,&nbsp;M. DeCamp ,&nbsp;J. Khatri ,&nbsp;Y. Shweihat ,&nbsp;K. Nwanwene ,&nbsp;M. Tirona ,&nbsp;T. Wright ,&nbsp;T. Pacioles ,&nbsp;M. Jamil ,&nbsp;K. Anwar ,&nbsp;J. Bastidas ,&nbsp;N. Chowdhury ,&nbsp;D. Zander ,&nbsp;D. Silbermins ,&nbsp;M. Abdallah ,&nbsp;J. Flickinger","doi":"10.1016/j.radonc.2024.110619","DOIUrl":"10.1016/j.radonc.2024.110619","url":null,"abstract":"<div><h3>Introduction</h3><div>The role of consolidative thoracic and prophylactic brain radiation for extensive stage small cell lung cancer patients is controversial. We investigated the factors associated with the use of any radiation therapy (RT) and whether RT has a benefit to overall survival (OS) in patients receiving any systemic therapy and whether this benefit is the same if Chemotherapy (CT) or chemo-immunotherapy (CT-IO) is used.</div></div><div><h3>Material/Methods</h3><div>The NCDB database was queried from years 2017–2019. Patients receiving systemic therapy- STX (CT or CT-IO) had to have at least 6 months of follow-up and have no brain metastases at diagnosis. All RT patients had to receive upfront systemic therapy, be treated 2–6 months from diagnosis, and if treated to the brain received 25 Gy in 10 fractions only. Multi-variable analyses (MVA) were used to determine factors associated with OS and selection for any radiation. Propensity matching for factors affecting OS were used to generate Kaplan-Meier OS curves. Log-rank tests were used to determine differences in Kaplan Meier survival curves for the effects of RT on OS.</div></div><div><h3>Results</h3><div>The total number of patients receiving RT/STX or STX alone as well as their median follow-up (months) were (890, 17.0 mn) and (6898, 14.0mn). The median time to the start of STX and RT were 22.9 days and 152 days, respectively. MVA noted that RT had a greater effect on OS (Thorax, Brain, Both Brain/Thorax – HRs = 0.80, 0.77, 0.70) than other interventions including IO (HR 0.87) and palliative care without RT (HR 1.06). Selection for radiation depended significantly upon factors affecting OS (HR) including lack of liver metastases, females, age and Charlson co-morbidity index, but did not depend upon insurance status, race, or county income/high school graduation rates. Propensity-score matched OS curves noted the same significant effects of RT on OS in those receiving CT +/- IO, CT-IO, and CT alone with HRs of 0.68/0.68/0.68 for thoracic RT, 0.72/0.72/0.70 for brain RT, and 0.60/0.60/0.60 for brain/thoracic RT, respectively.</div></div><div><h3>Conclusions</h3><div>The patient with extensive stage small cell lung cancer who reach candidacy and receive RT may have a significant improvement in OS compared to the patients treated only with CT or CT-IO. Combined thoracic and prophylactic brain RT seems to be better than either one alone. The impact of radiation whether given to one or two sites may be more beneficial than immunotherapy added to chemotherapy.</div></div>","PeriodicalId":21041,"journal":{"name":"Radiotherapy and Oncology","volume":"202 ","pages":"Article 110619"},"PeriodicalIF":4.9,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142626026","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}

{"title":"Risk factors of level Ib lymph node metastasis and clinical outcome of its selectively prophylactic irradiation in nasopharyngeal carcinoma: A real-world study","authors":"Man-yi Zhu ,&nbsp;Hai-jun Wu ,&nbsp;Ting Fang ,&nbsp;Guang-shun Zhang ,&nbsp;Run-da Huang ,&nbsp;Lu Zhang ,&nbsp;Shun-zhen Lu ,&nbsp;Lin Wang ,&nbsp;Chong Zhao ,&nbsp;Jing-jing Miao","doi":"10.1016/j.radonc.2024.110620","DOIUrl":"10.1016/j.radonc.2024.110620","url":null,"abstract":"<div><h3>Purpose</h3><div>To evaluate the risk factor of level Ib lymph node metastasis (LNM) and the clinical outcome of its selectively prophylactic irradiation (pRT) in nasopharyngeal carcinoma (NPC) patients treated with IMRT.</div></div><div><h3>Methods</h3><div>518 NPC patients receiving radical IMRT were collected. The structures of primary tumor invasions and neck LNM levels were analyzed bilaterally to estimate the risk factors of level Ib LNM. Patients with level Ib LNM and submandibular gland (SMG) invasion received level Ib pRT. The level Ib recurrence-free survival (RFS_Ib), regional recurrence-free survival (RRFS), and the incidence of ≥ grade 2 xerostomia at 1-year post-IMRT were compared in negative level Ib LNM patients who omitted, received unilateral, or bilateral level Ib pRT.</div></div><div><h3>Results</h3><div>Thirteen (2.5 %) patients with 18 sides had level Ib LNM. Ipsilateral SMG invasion was an independent risk factor for level Ib LNM. With a median follow-up time of 98.0 months, the 5-year RFS_Ib, 5-year RRFS and the incidence of xerostomia ≥ grade 2 at 1-year post-IMRT in negative level Ib LNM patients who omitted pRT, received unilateral, bilateral pRT to the level Ib were 99.7 % vs.100 % vs. 97.5 % (<em>P</em> = 0.110), 98.0 % vs. 92.1 % vs. 95.1 % (<em>P</em> = 0.120) and 28.0 % vs. 38.3 % vs. 90.0 % (<em>P</em> &lt; 0.001), respectively.</div></div><div><h3>Conclusions</h3><div>Our study revealed that ipsilateral SMG invasion was the independent risk factor for the level Ib LNM. Omitting pRT in patients without ipsilateral level Ib LNM and SMG invasion did not increase the RFS_IB and RRFS, and reduced the incidence of xerostomia. Further multi-center prospective randomized clinical trial is warranted.</div></div>","PeriodicalId":21041,"journal":{"name":"Radiotherapy and Oncology","volume":"202 ","pages":"Article 110620"},"PeriodicalIF":4.9,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142626025","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}

{"title":"Evaluation of radiation induced brain injury in nasopharyngeal carcinoma patients based on multi-parameter quantitative MRI: A prospective longitudinal study","authors":"Lin-Wen Huang ,&nbsp;Jia-Wei Pan ,&nbsp;Bo Li ,&nbsp;Wen-xiu Wu ,&nbsp;Li Guo ,&nbsp;Xin-han Zhou ,&nbsp;Xianhai Zhang ,&nbsp;Ming-yong Gao ,&nbsp;Zhi-feng Xu","doi":"10.1016/j.radonc.2024.110621","DOIUrl":"10.1016/j.radonc.2024.110621","url":null,"abstract":"<div><h3>Purpose</h3><div>Three dimensional pulsed continuous arterial spin labeling (3D-pCASL) and incoherent movement within voxels (IVIM) imaging was combined to assess dynamic microscopic structure changes of the hippocampus and temporal lobe white matter (TLWM) of nasopharyngeal carcinoma (NPC) patients post intensity-modulated radiation therapy (IMRT).</div></div><div><h3>Methods</h3><div>Forty-six patients who were first diagnosed with NPC and underwent IMRT were prospectively enrolled. 3D-CASL and IVIM were performed pre-RT, within 1 week (1 W) post-RT, 3 months (3 M) post-RT, 6 months (6 M) post-RT, and 18 months (18 M) post-RT. Twenty-seven patients completed follow-ups for all time periods, and their data were analyzed. The cerebral flow (CBF) derived from ASL, and apparent diffusion coefficient (ADC), pure diffusion coefficient (D), pseudo-diffusion coefficient (D*), and perfusion fraction (F) derived from IVIM of hippocampus and TLWM were analyzed. The quantitative parameters were measured before RT as the baseline, and the corresponding parameter values and change rates at each time point post-RT were compared using the non-parametric Wilcoxon rank sum test.</div></div><div><h3>Results</h3><div>At 1 W post-RT, CBF showed a significant increase and peaked in both the hippocampus and TLWM (p &lt; 0.05) with change rate of 30.3 % and 24.1 %. In the hippocampus, both D and D* were significantly increased from pre-RT to 6 M post-RT with change rate of 6.66 % and 34.7 %, while D*-values remained significantly higher than pre-RT at 12 months post-RT with change rate of 41.2 %. In the TLWM, the F firstly increased and then decreased, and was significantly decreased from pre-RT to 6 M post-RT with change rate of 20.2 %.</div></div><div><h3>Conclusion</h3><div>3D-PCASL and IVIM can indirectly reflecting the developmental pattern and molecular mechanism of RT induced brain injury.</div></div>","PeriodicalId":21041,"journal":{"name":"Radiotherapy and Oncology","volume":"202 ","pages":"Article 110621"},"PeriodicalIF":4.9,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142625537","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}

{"title":"Ongoing prospective studies on reirradiation: A systematic review of a clinical trials database","authors":"Jonas Willmann ,&nbsp;Panagiotis Balermpas ,&nbsp;Andreas Rimner ,&nbsp;Ane L Appelt ,&nbsp;Eliana Maria Vasquez Osorio ,&nbsp;Heidi S. Rønde ,&nbsp;Madalyne Day ,&nbsp;Anna Embring ,&nbsp;Dorota Gabryś ,&nbsp;Marianne G. Guren ,&nbsp;Peter Hoskin ,&nbsp;Mariangela Massaccesi ,&nbsp;Charles Mayo ,&nbsp;Louise Murray ,&nbsp;Carsten Nieder ,&nbsp;Matthias Guckenberger ,&nbsp;Nicolaus Andratschke","doi":"10.1016/j.radonc.2024.110624","DOIUrl":"10.1016/j.radonc.2024.110624","url":null,"abstract":"<div><h3>Introduction</h3><div>Reirradiation has gained increasing interest, as advances in systemic therapy increase the survival of patients with cancer, and modern radiation techniques allow more precise treatments. However, high-quality prospective evidence on the safety and efficacy of reirradiation to guide clinical practice remains scarce. This systematic review evaluates ongoing prospective studies on reirradiation to identify research gaps and priorities.</div></div><div><h3>Methods</h3><div>A systematic review of <span><span>ClinicalTrials.gov</span><svg><path></path></svg></span> was conducted on July 11, 2024, using search terms related to reirradiation. Inclusion criteria were prospective studies that were “recruiting,” “not yet recruiting,” or “active, not recruiting.” Studies with published results, retrospective, and in-silico studies were excluded. The review followed PRISMA 2020 guidelines and recommendations for systematic searches of clinical trial registries.</div></div><div><h3>Results</h3><div>Among 1026 identified studies, 307 were screened, 99 were included. Fourty (40%) focused on central nervous system (CNS), 23 (23%) head and neck, and 17 (17%) on pelvic reirradiation. Most studies (90%) were interventional, with 32 (32%) phase II and 4 (4%) phase III trials. Sixteen trials were randomized (RCTs), including the 4 phase III trials for recurrent glioblastoma, rectal and nasopharyngeal cancer. Ten dose escalation trials focus on recurrent prostate, rectal, and non-small cell lung cancer as well as glioma. Modern high-precision radiotherapy techniques were frequently used, with 21 (21%) studies using stereotactic radiotherapy and 17 (17%) using particle therapy. Combinations with systemic therapies were investigated in 41 (41%) studies.</div></div><div><h3>Conclusion</h3><div>Ongoing studies most frequently focus on CNS, head and neck, and pelvic reirradiation. There remains a critical need for RCTs, in particular for lung, breast, and gynecological cancers. Dose escalation trials, application of precision radiation techniques and combinations with modern systemic therapy may help define the optimal multimodality treatment schedules.</div></div>","PeriodicalId":21041,"journal":{"name":"Radiotherapy and Oncology","volume":"202 ","pages":"Article 110624"},"PeriodicalIF":4.9,"publicationDate":"2024-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142625927","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}

{"title":"Proton FLASH-arc therapy (PFAT): A feasibility study for meeting FLASH dose-rate requirements in the clinic","authors":"Bethany Rothwell,&nbsp;Alejandro Bertolet,&nbsp;Jan Schuemann","doi":"10.1016/j.radonc.2024.110623","DOIUrl":"10.1016/j.radonc.2024.110623","url":null,"abstract":"<div><h3>Background and purpose</h3><div>Proton arc therapy and FLASH radiotherapy (FLASH-RT) each offer unique advantages in proton therapy. However, clinical translation of FLASH-RT faces challenges in defining and delivering high dose rates. We propose the use of proton FLASH-arc therapy (PFAT) to leverage the benefits of arc while addressing FLASH delivery concerns by spatially fractionating dose delivery to healthy tissue.</div></div><div><h3>Materials and methods</h3><div>Treatment plans for an abdominal phantom and a clinical brain case were designed in OpenTPS, using monoenergetic beams within a 360-degree gantry rotation. Beams were optimized to achieve target coverage while maximizing spatial fractionation in non-target regions. The temporal dose delivery to healthy-tissue voxels, or in specified organs-at-risk (OARs), was constrained via selective spot removal in the beamlets matrix. The dose, LET, number of spots per voxel, and voxel-wise average dose rate were calculated for each PFAT plan and compared to a corresponding IMPT scenario.</div></div><div><h3>Results</h3><div>PFAT plans demonstrated comparable dose conformity to IMPT, with LET hotspots shifted towards the target center. The number of spots influencing healthy-tissue voxels was reduced, leading to regions of substantially higher dose rates in many points outside the target. OAR dose-rate optimization in the brain plan resulted in dose rates exceeding 40 Gy/s in the majority of points in the brainstem.</div></div><div><h3>Conclusion</h3><div>The PFAT technique combines the advantages of FLASH and arc therapy, providing improved LET distributions and enhanced biological effect in the target, while achieving high dose rates in healthy tissue, thus reducing healthy tissue damage. This feasibility study demonstrates the capability of PFAT, setting the foundation for further optimization and application in diverse patient cases and complex geometries.</div></div>","PeriodicalId":21041,"journal":{"name":"Radiotherapy and Oncology","volume":"202 ","pages":"Article 110623"},"PeriodicalIF":4.9,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142626117","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}

{"title":"Protocol compliance in a multicentric phase III trial investigating scheduled adaptive radiotherapy and dose painting in head and neck cancer","authors":"Anna Liza M.P. de Leeuw ,&nbsp;Jordi Giralt ,&nbsp;Yungan Tao ,&nbsp;Sergi Benavente ,&nbsp;Thanh-Vân F Nguyen ,&nbsp;Frank J.P. Hoebers ,&nbsp;Ann Hoeben ,&nbsp;Chris H.J. Terhaard ,&nbsp;Lip Wai Lee ,&nbsp;Signe Friesland ,&nbsp;Roel J.H.M. Steenbakkers ,&nbsp;Lisa Tans ,&nbsp;Simon R. van Kranen ,&nbsp;Jeroen B. van de Kamer ,&nbsp;Harry Bartelink ,&nbsp;Coen R.N. Rasch ,&nbsp;Jan-Jakob Sonke ,&nbsp;Olga Hamming-Vrieze","doi":"10.1016/j.radonc.2024.110612","DOIUrl":"10.1016/j.radonc.2024.110612","url":null,"abstract":"<div><h3>Purpose</h3><div>To report on quality assurance (QA) and protocol adherence (PA) in a multicentre phase III trial for head and neck cancer, evaluate patterns of protocol deviations and investigate the effect of PA on study outcomes.</div></div><div><h3>Methods</h3><div>All 221 patients from the ARTFORCE trial (NCT01504815) were included in this study. Pre- and per-treatment QA measures included protocol guidelines, a dummy run, early case reviews and trial meetings. FDG-PET-guided dose painting and scheduled adaptive radiotherapy were reviewed in patients in the experimental arm (eRT). Patient and disease characteristics, as well as institutes’ accrual rate and timing were examined for correlation with PA. Cox regression was used to determine the impact of PA on outcome.</div></div><div><h3>Results</h3><div>The dummy run was completed in all nine institutes and early case reviews were completed in five out of nine institutes that contributed 190 out of 221 patients. Among all patients randomized to eRT, 64 % had at least one deviation of the experimental trial components. Protocol deviations were significantly correlated with the institute patients were treated at (Cramer’sV 0.34–0.48). Despite early identification of institute-specific deviations in QA, these continued during the trial. No significant associations were seen between deviations and accrual timing or rate (P ≥ 0.26). Within eRT, no significant relation was observed between experimental PA and locoregional control (LRC), the primary endpoint of the trial (P≥.15).</div></div><div><h3>Conclusions</h3><div>Despite QA, protocol deviations persisted during the trial, which were mostly institute-specific. However, deviations of the experimental treatment strategy did not significantly impact LRC and therefore the trial conclusion.</div></div>","PeriodicalId":21041,"journal":{"name":"Radiotherapy and Oncology","volume":"202 ","pages":"Article 110612"},"PeriodicalIF":4.9,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142625957","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}

{"title":"Optimum radiation dose for palliation in head and neck squamous cell carcinoma (OpRAH) – A phase 3 randomized controlled trial","authors":"Supriya Mallick ,&nbsp;Abhilash Dagar ,&nbsp;Adrija Ghosh ,&nbsp;Aashita ,&nbsp;Jaswin Raj ,&nbsp;Sangeeta Hazarika ,&nbsp;Jitendra K. Meena ,&nbsp;Akash Kumar ,&nbsp;Jyoti Sharma ,&nbsp;Smriti Panda ,&nbsp;Aman Sharma ,&nbsp;Mayank Singh ,&nbsp;Dayanand Sharma ,&nbsp;Alok Thakar","doi":"10.1016/j.radonc.2024.110611","DOIUrl":"10.1016/j.radonc.2024.110611","url":null,"abstract":"<div><h3>Purpose</h3><div>Radiotherapy is frequently employed for palliative treatment in locally advanced head and neck squamous cell carcinoma (HNSCC) but radiation dose fractionation regimens are not well-defined. We designed this phase 3 randomized controlled trial to compare two weekly hypo fractionated regimes and study the effect on progression-free survival (PFS) in this subset of patients.</div></div><div><h3>Materials and Methods</h3><div>Non-metastatic locally advanced HNSCC patients (n = 305) who were not suitable for curative treatment were randomized to Arm A (20 Gy/5#/5 days) and Arm B (30 Gy/5#/5 days). PFS and OS were recorded along with acute toxicity using patient-reported quality of life HN QLQ 43.</div></div><div><h3>Results</h3><div>From April 2020 to August 2023, 390 patients were randomized, of which 305 were eligible for final analysis. At a median follow-up of 13.9 months, PFS and median overall survival (OS) for the entire cohort was 7.4 and 10.03 months, respectively. PFS (p-0.553) and OS (p-0.203) did not differ significantly between the two groups. Toxicity rates were similar between the two arms and dose escalation was well tolerated. Patients with a better PS were found to have significantly better OS. No significant benefit in OS or PFS was observed in patients who received neoadjuvant chemotherapy (NACT), underwent definitive conversion, or received palliative chemotherapy at progression.</div></div><div><h3>Conclusion</h3><div>This is the largest phase 3 RCT to analyze the safety and efficacy of weekly palliative radiotherapy regimens and has not demonstrated further improvement with dose escalation.</div></div>","PeriodicalId":21041,"journal":{"name":"Radiotherapy and Oncology","volume":"202 ","pages":"Article 110611"},"PeriodicalIF":4.9,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142625865","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}

{"title":"A metabolic switch to the pentose-phosphate pathway induces radiation resistance in pancreatic cancer","authors":"Ariel Shimoni-Sebag ,&nbsp;Ifat Abramovich ,&nbsp;Bella Agranovich ,&nbsp;Rami Massri ,&nbsp;Chani Stossel ,&nbsp;Dikla Atias ,&nbsp;Maria Raites-Gurevich ,&nbsp;Keren Yizhak ,&nbsp;Talia Golan ,&nbsp;Eyal Gottlieb ,&nbsp;Yaacov Richard Lawrence","doi":"10.1016/j.radonc.2024.110606","DOIUrl":"10.1016/j.radonc.2024.110606","url":null,"abstract":"<div><h3>Purpose</h3><div>Pancreatic ductal adenocarcinoma (PDAC) is remarkably resistant to standard modalities, including radiotherapy. We hypothesized that metabolic reprogramming may underlie PDAC radioresistance, and moreover, that it would be possible to exploit these metabolic changes for therapeutic intent.</div></div><div><h3>Methods and materials</h3><div>We established two matched models of radioresistant PDAC cells by exposing the AsPC-1 and MIAPaCa-2 human pancreatic cancer cells to incremental doses of radiation. The metabolic profile of parental and radioresistant cells was investigated using Nanostring technology, labeled-glucose tracing by liquid chromatography-mass spectrometry, Seahorse analysis and exposure to metabolic inhibitors. The synergistic effect of radiation combined with a pentose-phosphate pathway inhibitor, 6-aminonicotinamide (6-AN) was evaluated in a xenograft model established by subcutaneous injection of radioresistant-AsPC-1 cells into nude mice.</div></div><div><h3>Results</h3><div>The radioresistant cells overexpressed pyruvate dehydrogenase kinase (PDK) and consistently, displayed increased glycolysis and downregulated the tricarboxylic acid (TCA) cycle and oxidative phosphorylation. Metabolic flux through the pentose-phosphate pathway (PPP) was increased, as were levels of reduced glutathione; pharmacological inhibition of the PPP dramatically potentiated radiation-induced cell death. Furthermore, the combined treatment of radiation with the PPP inhibitor 6-AN synergistically inhibited tumor growth in-vivo.</div></div><div><h3>Conclusions</h3><div>We provide a mechanistic understanding of the metabolic changes that underlie radioresistance in PDAC. Furthermore, we demonstrate that pancreatic cancer cells can be re-sensitized to radiation via metabolic manipulation, in particular, inhibition of the PPP. Exploitation of the metabolic vulnerabilities of radioresistant pancreatic cancer cells constitutes a new approach to pancreatic cancer, with a potential to improve clinical outcomes.</div></div>","PeriodicalId":21041,"journal":{"name":"Radiotherapy and Oncology","volume":"202 ","pages":"Article 110606"},"PeriodicalIF":4.9,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142625433","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}