Radiotherapy and Oncology最新文献

{"title":"UNDERSTANDING AND OVERCOMING INNATE AND ACQUIRED MAPK-INHIBITION RESISTANCE IN ANAPLASTIC THYROID CANCER","authors":"Peter (Yu Fan) Zeng ,&nbsp;Jalna Meens ,&nbsp;Harrison Pan ,&nbsp;Matthew Cecchini ,&nbsp;Amir Karimi ,&nbsp;David Palma ,&nbsp;Eric Winquist ,&nbsp;John Barrett ,&nbsp;Laurie Ailles ,&nbsp;Anthony Nichols","doi":"10.1016/S0167-8140(25)04690-0","DOIUrl":"10.1016/S0167-8140(25)04690-0","url":null,"abstract":"<div><h3>Purpose:</h3><div>Anaplastic thyroid cancer (ATC) is one of the most lethal human cancers, with some patients succumbing to the disease within weeks of diagnosis. Although a subset of patients with ATC with BRAFV600E mutation respond to the monomeric type I RAF inhibitor (RAFi) dabrafenib in combination with MEK inhibitor (MEKi) trametinib, most rapidly develop adaptive or acquired resistance. These patients, along with those who do not harbor the BRAFV600E alteration, have limited treatment options.</div></div><div><h3>Materials and Methods:</h3><div>To understand the mechanism of resistance to dabrafenib and trametinib, we utilized multi-region whole genome, high-coverage whole exome and single nuclei RNA-sequencing of ATC patient tumours to unravel genomic, transcriptomic, and microenvironmental evolution during type I RAFi and MEKi therapy. Cell-line and patient-derived xenograft ATC models were used to identify and understand the efficacy and mechanisms of treatment response and resistance.</div></div><div><h3>Results:</h3><div>Single-cell nuclei RNA sequencing of matched primary and resistant ATC patient tumours identified reactivation of the MAPK-pathway, along with immunosuppressive macrophage proliferation, underlying the development of acquired resistance. Our translational genomics led us that hypothesize that type II RAFi, which inhibit both RAF monomers and dimers, can be efficacious in overcoming treatment resistance. Screening of a panel of type II RAFi revealed that ATC cell lines are exquisitely sensitive to the type II RAFi, naporafenib, by inhibiting EphA2-mediated MAPK-signaling. We further demonstrated that naporafenib, in combination with the MEKi trametinib, can durably and robustly overcome both innate and acquired treatment resistance to dabrafenib and trametinib using ATC cell lines and patient-derived xenograft models. Finally, we describe a novel mechanism of acquired resistance to type II RAFi and MEKi through compensatory mutations in MAST1.</div></div><div><h3>Conclusions:</h3><div>Taken together, our work using translational and functional genomics has unraveled the differential mechanisms of treatment resistance to type I and type II RAFi in combination with trametinib and rationalizes the clinical investigation of type II RAFi in the setting of thyroid cancer.</div></div>","PeriodicalId":21041,"journal":{"name":"Radiotherapy and Oncology","volume":"210 ","pages":"Page S15"},"PeriodicalIF":5.3,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145100234","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":"SPECIALIZED TEAM MANAGEMENT IMPROVES PERSON-CENTRED CARE FOR PATIENTS UNDERGOING PALLIATIVE RADIOTHERAPY","authors":"Pamela Paterson ,&nbsp;Samir Patel ,&nbsp;Ben Burke ,&nbsp;Melanie Clarkson ,&nbsp;Alysa Fairchild","doi":"10.1016/S0167-8140(25)04697-3","DOIUrl":"10.1016/S0167-8140(25)04697-3","url":null,"abstract":"<div><h3>Purpose:</h3><div>Palliative radiotherapy (PRT) integrated with supportive care provided by a multidisciplinary team (MDT) improves symptoms and quality of life. At our centre, PRT consultations occur in either the general outpatient department (OP) or with a dedicated specialist Palliative Radiation Oncology (PRO) clinic. We explored the differential impact of PRT consult pathway on clinical outcomes.</div></div><div><h3>Materials and Methods:</h3><div>Consecutive adults with four primary cancers prescribed ≤10 fractions of PRT (03-06/2023) with 4-week follow-up were retrospectively reviewed. Data abstracted included patient-reported symptom scores, urgent unplanned cancer centre encounters triggered by symptoms, hospital admissions, analgesic escalation, and MDT referrals. Descriptive and summary statistics were calculated.</div></div><div><h3>Results:</h3><div>Of 110 patients (78 assessed in PRO and 32 in OP), 33.6% had breast, 28.2% GU, 20.9% lung, and 17.3% GI cancers. Overall, 93.6% completed PRT as prescribed. At four weeks post-PRT, in PRO patients, pain improved in 32/78 (41.0%), was stable in 45/78 (57.7%), and worse in 1/78 (1.3%). For OP patients (one pain score missing), pain improved in 2/31 (6.5%), was stable in 20/31 (64.5%) and worse in 9/31 (29.0%). Just over half required &gt;1 urgent unplanned outpatient encounter (55.1% of PRO versus 56.3% of OP patients). 13/78 (16.7%) PRO versus 6/32 (18.8%) OP patients required hospital admission. Analgesic adjustment was required by 43.6% (34/78) of PRO and 50% (16/32) of OP patients. Most MDT referrals were made through the PRO Clinic. Median survival was 42.4 wks (95% CI 25.3- 53.1wks) for PRO patients versus 29.6 wks (95%CI 10.1-52.1 wks) for OP patients.</div></div><div><h3>Conclusions:</h3><div>Patients managed through the dedicated PRO program were more likely to report improved pain and be referred for multidisciplinary supportive care, while analgesic escalation and acute care admission occurred more often in OP patients. Integrating PRT delivery with holistic symptom management delivered by a specialized MDT optimizes personalized care.</div></div>","PeriodicalId":21041,"journal":{"name":"Radiotherapy and Oncology","volume":"210 ","pages":"Page S18"},"PeriodicalIF":5.3,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145100253","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":"THE IMPACT OF STEREOTACTIC BODY RADIOTHERAPY ON THE DYNAMICS OF CIRCULATING TUMOUR DNA IN PATIENTS WITH OLIGO-PROGRESSIVE DISEASE","authors":"Joelle Helou ,&nbsp;Eric Zhao ,&nbsp;Philip Ye ,&nbsp;Scott Bratman ,&nbsp;Jinfeng Zou ,&nbsp;Neelabh Rastogi ,&nbsp;Emma Hill ,&nbsp;Ekaterina Kalashnikova ,&nbsp;Rachel Glicksman ,&nbsp;Aisling Barry","doi":"10.1016/S0167-8140(25)04736-X","DOIUrl":"10.1016/S0167-8140(25)04736-X","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Purpose:&lt;/h3&gt;&lt;div&gt;Stereotactic Body Radiotherapy (SBRT) is increasingly used as an ablative treatment in patients with limited progressive metastatic disease (oligo-progression (OP)). Results from recent trials are controversial, suggesting a need for better patient selection. Novel biomarkers such as circulating DNA (ctDNA) offers a unique opportunity to utilize early on-treatment changes in ctDNA for real-time assessment of therapeutic response and outcome, with a potential to ultimately aid clinical decision in this setting. Herein we aim to assess early ctDNA changes in patients with OP treated with SBRT as part of a prospective clinical trial.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Materials and Methods:&lt;/h3&gt;&lt;div&gt;RADIANT is a Phase II prospective single institutional study of patients with OP (≤5 progressing metastatic lesions), treated with SBRT. We prospectively collected frozen plasma samples (3-4mL) and whole blood (Peripheral blood mononuclear cells or germline DNA-MTM/mL) at five timepoints (TP)-baseline (TP1), post fraction 1 of SBRT (TP2), post final fraction (TP3), 6-weeks (TP4) and 3-months post SBRT (TP5). Descriptive statistics were computed using SAS.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results:&lt;/h3&gt;&lt;div&gt;Of 70 patients enrolled, nineteen with 73 plasma samples were included in this analysis, of which 5 (26%), 9 (47%), 4 (21%) and 1 (5%) had a gastrointestinal (GI), hormone receptor positive breast, genito-urinary (GU) and skin cancer diagnosis respectively. Median progression free survival in this cohort was 4.8 months (IQR 3.2-7.7), and median time to change in next line systemic therapy was 5.6 (IQR 4.6-10.3) months. Among all plasma samples (n=73), ctDNA levels were detectable in 49 (67%) samples. Seventeen (89.5%) patients had detectable ctDNA in at least one TP. Median ctDNA level for patients with detectable ctDNA at each TP (1-5) was: 2.4 (n=13) [TP1], 5.1 (n=9) [TP2], 0.6 (n=14) [TP3], 0.6 (n=8) [TP4], and 0.1 (n=5) [TP 5] MTM/mL. At baseline, 13 patients had detectable ctDNA levels; of those, 2 (breast/GU) cleared by TP4, 1 (breast) cleared by TP5. Six patients had undetectable levels at baseline; 2/6 (Breast) were never detectable, 1/6 (GU) experienced a small rise at TP2 (0.06MTM/ Ml), and 3/6 patients at TP3 [0.38 (Breast), 0.45 (Prostate), 0.94 (Breast) MTM/mL], all returned to undetectable levels by week 6 post SBRT. Gastro-intestinal cancers (N=5) had detectable ctDNA at each TP. Compared with other cancer types, GI cancers had significantly higher ctDNA levels at TP1 (14.9 versus 0.17, p=0.04) and TP3 (16.2 versus 0.33 p=0.04).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions:&lt;/h3&gt;&lt;div&gt;Among patients with OP, ctDNA levels at each TP varied according to primary diagnosis, with lower median levels post SBRT completion. Patients with GI cancer had greater levels compared to other cancers. ctDNA holds promise as a non-invasive tool to potentially guide treatment for patients with OP cancer. Its predictive and prognostic role in the OP setting warrants further","PeriodicalId":21041,"journal":{"name":"Radiotherapy and Oncology","volume":"210 ","pages":"Page S34"},"PeriodicalIF":5.3,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145100108","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":"IMPLEMENTATION OF NON-OPERATIVE MANAGEMENT / ORGAN PRESERVATION FOR LOCALLY ADVANCED RECTAL CANCER IN CANADA: A NATIONAL SURVEY OF CLINICAL PRACTICE","authors":"Kristopher Dennis ,&nbsp;Victoria Ivankovic ,&nbsp;Doris Goubran ,&nbsp;Eliane Paglicaucan ,&nbsp;Mariam Alsobaei ,&nbsp;Nicole Alcasid ,&nbsp;Mary Farnand ,&nbsp;Megan Delisle","doi":"10.1016/S0167-8140(25)04706-1","DOIUrl":"10.1016/S0167-8140(25)04706-1","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Purpose:&lt;/h3&gt;&lt;div&gt;Non-operative management/organ preservation (NOM/ OP) strategies can achieve oncologic outcomes similar to those involving total mesorectal excision (TME), and they are being increasingly offered to patients with locally-advanced rectal cancer. Our study aimed to describe the implementation of these strategies in Canada.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Materials and Methods:&lt;/h3&gt;&lt;div&gt;Through non-probabilistic convenience sampling we recruited a clinical expert representative from each of the 44 Canadian centres that offer radiotherapy, systemic therapy and surgery. Representatives completed an electronic survey to describe NOM/OP strategies for patients with locally-advanced rectal cancer at their centres in terms of availability, patient selection, treatment protocols, response assessments, surveillance, quality assurance resources and perceived challenges. A primary OP strategy was defined as one where neoadjuvant therapy is administered with the explicit initial goal of achieving a complete clinical response (cCR) or a near-complete clinical response (nCR), thereby avoiding an immediate TME. A secondary OP strategy was defined as one where a cCR or nCR allows for previously unplanned avoidance of an immediate TME due to an initial explicit goal of proceeding with surgery.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results:&lt;/h3&gt;&lt;div&gt;From June to August 2023, 40/44(91%) of representatives responded: 24/40(60%) radiation oncologists, 13/40(32.5%) surgeons and 3/40(7.5%) medical oncologists. All provinces were represented: Atlantic (NFL/PEI/NS/NB) 4/40(10%), Quebec 10/40(25%), Ontario 15/40(37.5%), Prairies (MB/SK/AB) 5/40(12.5%), British Columbia 6/40(15%). Of the responding centres, 31/40(77.5%) offered some form of NOM/OP, with 20/40(50%) offering both primary and secondary, 11/40(27.5%) offering only secondary, 8/40(20%) offering neither and 1/40(2.5%) not clarifying. Of the 31 centres offering NOM/OP, 58.6% always/frequently did so after a cCR (17/29 responses) and 14.3% always/frequently did so after a nCR (4/28 responses). Of the 20 centres offering primary OP, 17/20(85%) always/frequently used long course chemoradiation followed by consolidation chemotherapy and 6/20(30%) always/ frequently used long course chemoradiation alone. Standardized criteria for response assessments were used by 18/20(90%) centres for MRI (with 12/20, 60% having synoptic templates) and by 12/20(60%) centres for endoscopy (with only 1/20, 5% having a synoptic template). Among all respondents, the most commonly reported challenges to implementing primary OP were access to MRI (21/40, 52.5%), clinic time/space for the number of required assessments (18/40, 45%), access to timely surgery when required (16/40, 40%), lack of comfort/familiarity with long-term outcomes of supporting evidence (15/40, 37.5%), and staff capacity for the number of required assessments (14/40, 35%).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions:&lt;/h3&gt;&lt;div&gt;Canadian centres are increasingly using non-operative manage","PeriodicalId":21041,"journal":{"name":"Radiotherapy and Oncology","volume":"210 ","pages":"Page S21"},"PeriodicalIF":5.3,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145100199","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":"FEASIBILITY OF INTEGRATING RECTAL HYDROGEL SPACER FOR SALVAGE TREATMENT USING STEREOTACTIC ABLATIVE BODY RADIOTHERAPY FOR LOCALLY RECURRENT PROSTATE CANCER","authors":"Amandeep Taggar ,&nbsp;Andrea Deabreu ,&nbsp;John Hudson ,&nbsp;Hans Chung ,&nbsp;Gerard Morton ,&nbsp;Andrew Loblaw","doi":"10.1016/S0167-8140(25)04741-3","DOIUrl":"10.1016/S0167-8140(25)04741-3","url":null,"abstract":"<div><h3>Purpose:</h3><div>Salvage stereotactic ablative body radiotherapy (SBRT) is an emerging option for radio-recurrent prostate cancer (PCa). To mitigate the increased risk of rectal toxicity, the use of a rectal spacer is an attractive option. However, increased fibrosis in previously irradiated tissue can make spacer placement a challenge. We aimed to assess the feasibility of successful rectal spacer placement in patients receiving SBRT for radio-recurrent PCa.</div></div><div><h3>Materials and Methods:</h3><div>This is a single institution Phase-I/II feasibility study. All patients had histologically confirmed locally recurrent PCa without any evidence of distant metastasis. All patients received 25 Gy to the whole gland and 35 Gy to the recurrent lesion in 5 weekly fractions following placement of a rectal spacer. The primary endpoint was the feasibility of spacer placement, defined as the ability to successfully deploy the spacer without complications. Secondary endpoints included acute and late toxicity (graded per CTCAE v5.0), quality of life using EPIC and IPSS as well as biochemical disease-free survival-based on PSA kinetics.</div></div><div><h3>Results:</h3><div>Between 2022-2024, 10 patients were enrolled. Median age and PSA at recurrence were 68.1 years (IQR: 66.1-72.7) and 3.45 (IQR: 3.2-4.8), respectively. Six and 4 patients had ISUP Grade group 2 and 3 disease. Rectal spacer placement was successfully performed in 9 of the 10 patients (90%). Spacer placement was unsuccessful in 1 patient due to inability to hydrodissect. No acute or late complications were reported with spacer placement. Radiation related acute Grade 2 or higher gastrointestinal (GI) and genitourinary (GU) toxicities were observed in 10% and 30% of patients, respectively. No acute Grade ≥3 toxicities were reported (Table 1). At a median follow-up of 19.6 months, PSA kinetics was available for 8 patients, and all were alive without evidence of local or distant failure. The PSA nadir achieved a median value of 0.07 ng/mL at a median time of 12.6 months.</div></div><div><h3>Conclusions:</h3><div>Rectal spacer placement in conjunction with SBRT for radio-recurrent prostate cancer was feasible in most patients, with no acute or late complications. This treatment option provides acceptable toxicity and encouraging early oncologic outcomes. Longer follow-up is necessary to assess long-term efficacy and safety.</div></div>","PeriodicalId":21041,"journal":{"name":"Radiotherapy and Oncology","volume":"210 ","pages":"Pages S35-S36"},"PeriodicalIF":5.3,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145100103","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 SEVERE RADIATION INDUCED SKIN TOXICITY (RIST) IN BLACK WOMEN RECEIVING ADJUVANT RADIOTHERAPY FOR BREAST CANCER IN ZIMBABWE. A PROSPECTIVE COHORT STUDY","authors":"Melinda Mushonga ,&nbsp;Shirley Chibonda ,&nbsp;Anna Mary Nyakabau ,&nbsp;Danielle Rodin ,&nbsp;Philip Ye ,&nbsp;Zhihui Amy Liu ,&nbsp;Mercia Mutimuri ,&nbsp;Ntokozo Ndlovu ,&nbsp;Webster Kadzatsa ,&nbsp;Albert Nyamhunga ,&nbsp;Nomsa Tsikai ,&nbsp;Nothando Mutizira ,&nbsp;Edith Matsikidze ,&nbsp;Tinashe Mazhindu ,&nbsp;Patience Musiwa ,&nbsp;Silas Mafuhure","doi":"10.1016/S0167-8140(25)04705-X","DOIUrl":"10.1016/S0167-8140(25)04705-X","url":null,"abstract":"<div><h3>Purpose:</h3><div>Radiotherapy is an essential component of breast cancer treatment, but fear of radiation induced skin toxicity (RIST) in Zimbabwe has been suggested to be associated with hesitancy to undergo treatment. This study sought to determine the incidence of severe RIST in Black women and identify modifiable predictive factors to allow development of patient-oriented strategies to mitigate negative perceptions of radiotherapy which potentially reduce compliance to treatment.</div></div><div><h3>Materials and Methods:</h3><div>A prospective cohort study of Zimbabwean women undergoing adjuvant radiotherapy for breast cancer was conducted. Patient reported and Physician reported skin toxicity assessments were completed using validated skin toxicity scoring tools during radiotherapy. The level of agreement between patient and physician reported incidence of RIST was tested using kappa statistics. Predictive factors for severe RIST were analyzed using a univariate logistics regression.</div></div><div><h3>Results:</h3><div>Fifty-six patients met eligibility criteria. The most common physician and patient reported skin type was type V at 65% and 85% respectively. A total of 54 (96%) patients had at least 2 patient reported assessments and 46 (82%) had at least 2 physician reported assessments. The incidence of physician reported severe RIST was 12.8%, lower than patient reported one (26.8%), p=0.09. There was a low level of agreement between the patient and physician reported severe RIST, kappa= -0.08 (-0.31, 0.14). No patient characteristics were predictive of severe patient reported RIST. More patients with severe RIST had higher median fraction number, 25 (16.0-30.) (p=.05), total dose, 5500 cGy (4250-60000) (p=.016) and maximum dose 6023.5 cGy (5101-6580) (p=.045). Total dose was predictive of severe patient reported RIST, OR 1.12 (1.01-1.25) p=0.038. More patients using a cream had severe patient reported toxicity when compared to patients who did not report severe RIST, 93% compared to 34% (p=&lt;0.001).</div></div><div><h3>Conclusions:</h3><div>The patient’s reported incidence of severe RIST was higher than the physician reported. Radiotherapy prescription, maximum dose and use of a cream were associated with worse patient reported toxicity. Findings support consideration of hypo fractionated treatment regiments in patients receiving adjuvant radiotherapy and exploration of ideal skin care creams/ interventions for use during treatment are needed to improve treatment experience mitigating negative perceptions associated with radiotherapy.</div></div>","PeriodicalId":21041,"journal":{"name":"Radiotherapy and Oncology","volume":"210 ","pages":"Pages S20-S21"},"PeriodicalIF":5.3,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145100198","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 PHASE I DUAL DOSE ESCALATION STUDY OF RADIATION AND NAB-PACLITAXEL IN PATIENTS WITH UNRESECTABLE AND BORDERLINE RESECTABLE PANCREATIC CANCER","authors":"Uri Amit ,&nbsp;John Plastaras ,&nbsp;Rohi Gheewala ,&nbsp;James Metz ,&nbsp;Ursina Teitelbaum ,&nbsp;Nevena Damjanov ,&nbsp;Charles Schneider ,&nbsp;Major Kenneth Lee ,&nbsp;Mark O’Hara ,&nbsp;Kim Reiss-Binder ,&nbsp;Erica Carpenter ,&nbsp;Thomas Karasic ,&nbsp;Andre Konski ,&nbsp;Paul Wileyto ,&nbsp;Edgar Ben-Josef","doi":"10.1016/S0167-8140(25)04683-3","DOIUrl":"10.1016/S0167-8140(25)04683-3","url":null,"abstract":"<div><h3>Purpose:</h3><div>This Phase I dual dose-escalation study aimed to evaluate the safety, feasibility, and toxicity profile of combining dose-escalated radiation therapy with high-dose nab-paclitaxel in patients with unresectable or borderline resectable pancreatic cancer. The primary objective was to determine the maximum tolerated radiation dose for the combination.</div></div><div><h3>Materials and Methods:</h3><div>Twenty-one evaluable patients were enrolled and allocated three radiation dose levels, 55 Gy, 57.5 Gy, and 60 Gy, administered over five weeks in 25 fractions. Concurrent nab-paclitaxel was given weekly at a dose of 125 mg/m². Radiation dose escalation was guided by a time-to-event continual reassessment method. Toxicities were monitored and classified according to CTCAE v4.0, with dose-limiting toxicities (DLT) defined as Grade 3 or higher gastrointestinal events or substantial decline in performance status. Surgical resection was pursued in patients achieving sufficient tumour downstaging.</div></div><div><h3>Results:</h3><div>Hematologic toxicities were the most common Grade ≥3 adverse events occurring in 76.2% of patients. Non-hematologic toxicities were less frequent (57.1%). Two Grade 3 gastrointestinal DLT cases occurred at dose levels 57.5 Gy and 60 Gy. The maximum tolerated dose was determined to be 60 Gy with a probability of DLT of 0.155 at this dose. Surgical resection with negative margins (R0) was achieved in 33.3% of patients, including all borderline resectable cases and 22.2% of initially unresectable cases. The median overall survival and time to local progression from the start of radiation therapy were 22.3 months and 20.3 months, respectively.</div></div><div><h3>Conclusions:</h3><div>This study demonstrates the feasibility and safety of combining dose-escalated radiation with high-dose nab-paclitaxel in locally advanced pancreatic cancer. The regimen is associated with manageable toxicity and promising local control and survival. These findings support further evaluation in larger trials to assess its impact on clinical outcomes.</div></div>","PeriodicalId":21041,"journal":{"name":"Radiotherapy and Oncology","volume":"210 ","pages":"Page S12"},"PeriodicalIF":5.3,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145100224","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":"INVESTIGATING PATTERNS OF PROSTATE CANCER RECURRENCE FOLLOWING BRACHYTHERAPY USING PSMA-PET ANALYSIS","authors":"Alex Dhaliwal ,&nbsp;Michael Peacock","doi":"10.1016/S0167-8140(25)04713-9","DOIUrl":"10.1016/S0167-8140(25)04713-9","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Purpose:&lt;/h3&gt;&lt;div&gt;Radiation therapies such as external beam radiation therapy (EBRT) and brachytherapy (BT) are mainstays of localized prostate cancer (PCa) management. The ASCENDE-RT trial demonstrated an extension in the biochemical progression-free survival of patients with intermediate- to high-risk prostate cancer that received a BT boost alongside androgen deprivation therapy (ADT)+EBRT compared to those that received ADT+EBRT alone (83% versus 62%), highlighting the synergistic impact of these multiparametric treatments. However, the patterns of recurrence after brachytherapy remain largely unknown. Additionally, the growing role of functional radioimaging using prostate specific membrane antigen (PSMA) positron emission tomography (PET) is radically improving our sensitivity for detection of small volumes of disease at local, regional, and metastatic sites.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Materials and Methods:&lt;/h3&gt;&lt;div&gt;This prospective cohort study characterizes the locations, times-to-progression, and disease burden of local, regional, and distant recurrent disease using PSMA-PET imaging. A total of 153 patients who received either BT monotherapy (n=116) or EBRT+BT boost (n=36) and underwent PSMA-PET imaging after experiencing biochemical failure were analyzed. The differences between groups subanalyzed by Gleason score and time-to-progression were tested using Mann-Whitney U and chi-square tests.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results:&lt;/h3&gt;&lt;div&gt;The rates of cancer recurrence in the prostate were lower following boosted therapy than monotherapy (22.2% versus 48.3%, p&lt;0.05), with reduced recurrence in the prostate base and proportionally greater recurrence in the middle and apex. Boosted therapies were less likely to develop in-field recurrence at the seminal vesicles compared to monotherapies for all groups except low-grade cancers, where the rate of recurrence was comparable. Cancers treated with monotherapy were more likely to develop single node recurrence (44.8% versus 6.67%, p&lt;0.05), whereas boosted therapies were more likely to recur in multiple nodes by the time of PET imaging (60.0% versus 34.5%, p&lt;0.05). Furthermore, whereas the distribution and likelihood of nodal recurrence following monotherapy was similar for early and late recurrences of low- and high-grade cancers, boosted therapies had markedly different distribution patterns depending on the times-to-progression and initial disease stage. Finally, analysis of bony metastases shows that earlier recurrences are more likely to be outside of the pelvis and vertebrae than later recurrences (84.6% versus 37.5%, p&lt;0.05), with boosted therapies leading to greater out-of-field metastases than monotherapies (64.6% versus 41.2%, p&lt;0.05).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions:&lt;/h3&gt;&lt;div&gt;In total, this improves our understanding of treatment response to prostate brachytherapies. It highlights how patterns of recurrence can vary dramatically depending on initial treatment, cancer staging, ","PeriodicalId":21041,"journal":{"name":"Radiotherapy and Oncology","volume":"210 ","pages":"Page S24"},"PeriodicalIF":5.3,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145100097","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":"SHORT-TERM AND LONG-TERM IMPACT OF DIDACTIC INSTRUCTION UPON MEDICOLEGAL QUALITY OF RADIATION ONCOLOGY RESIDENT PHYSICIAN DOCUMENTATION","authors":"Vaishvi Patel ,&nbsp;Adele Duimering ,&nbsp;Shaun Loewen ,&nbsp;Conley Kriegler","doi":"10.1016/S0167-8140(25)04745-0","DOIUrl":"10.1016/S0167-8140(25)04745-0","url":null,"abstract":"<div><h3>Purpose:</h3><div>Effective documentation is essential in medical practice, particularly in Radiation Oncology (RO), where interdisciplinary collaboration is key. While documentation guidelines exist, it is uncertain if RO residents are aware of or adhere to them. This study assessed RO residents’ medicolegal knowledge of clinical documentation and evaluated the short- and long-term impact of an educational intervention on documentation practices.</div></div><div><h3>Materials and Methods:</h3><div>Grading rubrics for consultation and progress notes were created using existing guidelines. Residents from two academic institutions attended a virtual didactic seminar on medicolegal documentation. An electronic anonymous survey assessed resident knowledge and perspectives, both pre- and post-seminar. Randomly selected consultation and progress notes completed before the seminar and during short-term (&lt;3 months) and long-term (&lt;18 months) intervals were evaluated using the rubrics. Descriptive statistics and T-tests were utilized to analyze the data.</div></div><div><h3>Results:</h3><div>14 residents participated and completed surveys, while 11 submitted documentation. None had prior education specific to RO documentation, nor were they aware of available resources. Post-seminar, participants’ understanding of documentation (2.79 versus 3.43, <em>p</em>=0.045), informed consent (2.71 versus 3.79, <em>p</em>=0.002), and knowledge testing quiz scores (86.6% versus 95.5%, <em>p</em>=0.001) increased. Clinically, sustained improvements were observed in consultation notes (69.8% versus 79.9% &amp; 87.4%, <em>p</em>=0.001 &amp; <em>p</em>&lt;0.001; short-term and long-term respectively) and progress notes (55% versus 75.2% &amp; 79.4%, <em>p</em>&lt;0.001 &amp; <em>p</em>&lt;0.001; short-term and long-term respectively).</div></div><div><h3>Conclusions:</h3><div>Our seminar significantly enhanced residents’ medicolegal knowledge and documentation quality, with immediate and sustained effects. Additionally, surveys revealed a lack of specialty-specific documentation education. Given the observed improvements in knowledge and clinical documentation, integrating structured medicolegal training into residency curricula could help standardize documentation practices. Future studies could explore the sustained retention of these skills and assess the impact of continued reinforcement through periodic educational seminars.</div></div>","PeriodicalId":21041,"journal":{"name":"Radiotherapy and Oncology","volume":"210 ","pages":"Page S37"},"PeriodicalIF":5.3,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145100206","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":"LONG-TERM OUTCOMES FOLLOWING SUBSTANTIAL DE-ESCALATION OF ELECTIVE RADIOTHERAPY DOSE AND VOLUME IN PATIENTS TREATED WITH DEFINITIVE CHEMORADIOTHERAPY FOR HUMAN PAPILLOMAVIRUS-ASSOCIATED OROPHARYNGEAL CANCER","authors":"Amir H. Safavi ,&nbsp;E. Christopher Dee ,&nbsp;C. Jillian Tsai ,&nbsp;Yingzhi Wu ,&nbsp;Sean M. McBride ,&nbsp;Daphna Y. Gelblum ,&nbsp;Yao Yu ,&nbsp;Linda C. Chen ,&nbsp;Kaveh Zakeri ,&nbsp;Achraf Shamseddine ,&nbsp;Jung J. Kang ,&nbsp;Jennifer R. Cracchiolo ,&nbsp;Richard J. Wong ,&nbsp;Marc A. Cohen ,&nbsp;Ian Ganly ,&nbsp;Lara A. Dunn ,&nbsp;Alan L. Ho ,&nbsp;Eric J. Sherman ,&nbsp;Nadeem Riaz ,&nbsp;Nancy Y. Lee","doi":"10.1016/S0167-8140(25)04682-1","DOIUrl":"10.1016/S0167-8140(25)04682-1","url":null,"abstract":"<div><h3>Purpose:</h3><div>Major de-escalation of elective radiotherapy dose and volume for human papillomavirus (HPV)-associated oropharyngeal cancer (OPC) can maintain two-year locoregional control (LRC) and survival while achieving excellent quality-of-life (QOL) profiles. We analyzed five-year follow-up to determine if these outcomes are sustained following definitive concurrent chemoradiotherapy (CCRT).</div></div><div><h3>Materials and Methods:</h3><div>This single-institution retrospective cohort study included consecutive patients with HPV-associated OPC starting CCRT at least five years prior to study inception. Patients underwent PET-CT and MRI staging. HPV diagnosis was confirmed by p16 immunohistochemistry and/or HPV-RNA in-situ hybridization. Elective volumes consisting of nodal levels and at-risk regions surrounding gross disease were treated to 30 Gy in 15 fractions. Cone-down volumes (gross disease without expansion) were sequentially boosted to 70 Gy in 35 fractions. Omitted nodal levels included level VII in the node-negative neck and uninvolved levels IB and V bilaterally. LRC was the primary outcome estimated using cumulative incidence functions with death as a competing risk. Overall (OS), progression-free (PFS), and distant metastasis-free survival (DMFS) were secondary outcomes estimated using Kaplan-Meier method. MD Anderson Dysphagia Index (MDADI) scores were obtained at each visit where available and compared to baseline using sign test; a clinically meaningful change (CMC) was 10 points.</div></div><div><h3>Results:</h3><div>From 2017-2019, 276 patients underwent CCRT; 172 (62.3%) received 300 mg/m2 high-dose cisplatin. Stage distribution included 87 (31.5%) patients with cT3-4 and 65 (23.5%) with cN2-3 disease (AJCC 8th Edition). With median follow-up of 64 months (IQR 50-74), 60-month LRC was 97.0%; OS 90.8%; PFS 85.9%, and DMFS 91.2%. No LR failure occurred after 18 months. One solitary elective nodal failure (1/267 patients [0.4%]) occurred at 6 months; this gross node, present but unidentified at diagnosis, received 30 Gy instead of the required 70 Gy. The remaining LR failures occurred in 70 Gy volumes. No failures occurred in omitted nodal levels. Two patients (0.7%) were gastrostomy-tube dependent for 12+ months. Mean (SE) MDADI composite score at baseline was 90.1 (0.86); 6 months 79.1 (1.1); 12 months 85.7 (1.3); 24 months 88.2 (1.3); 36 months 90.9 (1.7); 48 months 91.0 (1.8); and 60 months 92.2 (1.5). MDADI composite scores worsened at 6 months (p&lt;0.001 and CMC) then stabilized (p&gt;0.05) or numerically improved compared to baseline through 60 months.</div></div><div><h3>Conclusions:</h3><div>Long-term outcomes affirm the durable oncologic efficacy and QOL following substantially de-escalated elective radiotherapy. Confirmatory phase III data will help establish this systematic approach as the new standard-of-care for HPV-associated OPC treated with definitive CCRT.</div></div>","PeriodicalId":21041,"journal":{"name":"Radiotherapy and Oncology","volume":"210 ","pages":"Pages S11-S12"},"PeriodicalIF":5.3,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145100223","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}