Clinical Studies
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Item Incidental finding of leukaemia in circulating tumour DNA- the importance of a molecular tumour board.(Springer Science and Business Media LLC, 2024-02-13) Mencel, J; Rayarel, N; Proszek, P; Carter, P; Feber, A; Popat, S; McVeigh, TP; George, A; Dunlop, A; Hardy, K; Chau, I; Cunningham, D; Kohoutova, D; Lee, R; Iyengar, S; Starling, N; McVeigh, TerriAs the use of liquid biopsies are increasing across multiple indications in cancer medicine, the detection of incidental findings on circulating tumour DNA is of increasing importance. We report the finding of leukaemia detected in a patient who underwent plasma-based circulating tumour DNA next generation screening as part of a screening liquid biopsy study. A BRAF V600E mutation detected was deemed pathogenic following discussion at a molecular tumour board, and recommendation of further investigations led to the diagnosis of an occult haematological malignancy. We report the importance of molecular tumour board discussion and recommendations in the identification of incidental, pathogenic findings on circulating tumour DNA.Item Treatment of Pediatric, Adolescent, and Young Adult Patients With Fusion-Positive Alveolar Rhabdomyosarcoma Infiltrating Regional Lymph Nodes in the European CWS-2002P and RMS 2005 Studies and the Soft Tissue Sarcoma Registry.(WILEY, 2025-03-01) Heinz, AT; Ciuffolotti, M; Merks, JHM; Schönstein, A; Minard-Colin, V; Fuchs, J; Guillen, G; Timmermann, B; Vokuhl, C; Koscielniak, E; Chisholm, JC; Sparber-Sauer, M; Bisogno, G; Chisholm, JuliaBACKGROUND: Patients with alveolar rhabdomyosarcoma (ARMS) with regional lymph node involvement (N1) are defined as "very-high-risk rhabdomyosarcoma" in Europe. Different chemotherapy regimens were used in European study protocols. METHODS: Patients with FOXO1 fusion-positive N1 ARMS registered in the CWS-2002P study, the EpSSG RMS 2005 study, and SoTiSaR were retrospectively investigated. Patients received systemic treatment with chemotherapy (CHT) and local treatment of primary tumor (PT) and involved lymph nodes (LN) with radiotherapy (RT) and/or surgery. Kaplan-Meier estimators and Cox regression were used to examine event-free survival (EFS) and overall survival (OS) according to prognostic factors and treatment. RESULTS: A total of 156 patients registered in RMS 2005 (n = 99), CWS-2002P (n = 20), and SoTiSaR (n = 37) between 2003 and 2020 were eligible for this analysis. Median age at diagnosis was 10.2 years [0.1-21.9]. Treatment comprised CHT with IVADo (ifosfamide, vincristine, actinomycin-D, doxorubicin, n = 93; 60%), VAIA (vincristine, actinomycin-D, ifosfamide, adriamycin/doxorubicin, n = 53; 34%) or other regimens (n = 10; 6%); resection of the PT (n = 89; 57%), LN sampling or dissection (n = 92; 59%), and/or RT (n = 139; 89%). Maintenance treatment (MT) was added in n = 99/135 (73%) patients who achieved complete remission. Five-year EFS and OS of the cohort were 45% and 47%, respectively. Age and tumor size were independent prognostic factors for EFS. Local treatment applied to the LN with surgery, RT or both significantly improved EFS (p = 0.02) and OS (p = 0.04), with no difference between the modalities (p = 0.7). CONCLUSIONS: Patients with fusion-positive N1 ARMS carry a poor prognosis. Adequate local treatment of LN improved survival.Item Summary from the NCI clinical trials planning meeting on next generation of clinical trials in non-muscle invasive bladder cancer.(SAGE Publications, 2025-01-01) Apolo, A; Baumann, BC; Al-Ahmadie, H; Ballas, L; Bangs, R; Brothers, K; Greenberg, SC; Delacroix, S; Dignam, JJ; Efstathiou, JA; Feldman, AS; Foster, JC; Hahn, NM; Hall, E; Hansel, DE; Hoffman-Censits, J; Kamat, AM; Kamran, SC; Khani, F; Lerner, SP; Lipman, R; Mann, B; McConkey, D; McKiernan, J; Rose, TL; Smith, AB; Tangen, C; Amiri, AT; Weinstock, C; West, PJ; Milowsky, MI; Black, PC; Hall, EmmaThe National Cancer Institute organized a virtual Clinical Trials Planning Meeting (CTPM) on 'Defining the next generation of clinical trials with combination therapies in non-muscle invasive bladder cancer (NMIBC)' led by the Bladder Cancer Task Force of the NCI Genitourinary Cancers Steering Committee. The purpose of this meeting was to accelerate advances in clinical trials for patients with high-risk NMIBC. The meeting delivered a multidisciplinary expert consensus on optimal strategies for next-generation clinical trial designs in NMIBC with prioritization of combination therapies. Two clinical trial concepts were developed for potential implementation within the National Clinical Trials Network.Item Surgical Management of Primary Anorectal Melanoma: Is Less More?(SPRINGER, 2024-06-01) Fadel, MG; Mohamed, HS; Weir, J; Hayes, AJ; Larkin, J; Smith, MJ; Mohamed, Hesham Mohamed Sayed; Larkin, James; Smith, MylesPURPOSE: Ano-uro-genital (AUG) Mucosal Melanoma UK guidelines recommended a less radical surgical strategy for anorectal melanoma (ARM) where possible. We report our experience of ARM consistent with that approach including clinical presentation, intervention undertaken and prognosis. METHODS: We present a retrospective study of 15 consecutive patients with ARM surgically treated between November 2014 and April 2023. Patients were divided into the two surgery types: wide local excision (WLE, n = 9) and abdominoperineal resection (APR, n = 6). Data on demographics, diagnosis, treatment and oncological outcomes were assessed between the groups. RESULTS: The mean age was 65.3 ± 17.4 years and 6 (40.0%) were female patients. Nine patients (60.0%) were diagnosed with stage I and six patients (40.0%) with stage II disease. R0 margins were achieved in all cases. The overall mean length of stay was lower following WLE compared to APR (2.6 ± 2.4 days versus 14.0 ± 9.8 days, p = 0.032). Two complications were observed in the WLE group compared to four complications after APR (p = 0.605). Five patients (55.5%) developed local/distant recurrence in the WLE group compared to three patients (50.0%) in the APR group (p = 0.707), with a median overall survival of 38.5 (12-83) months versus 26.5 (14-48) months, respectively. CONCLUSIONS: Achieving clear margins by the least radical fashion may have equivalent oncological outcomes to radical surgery, potentially reducing patient morbidity and preserving function. In our experience, the surgical management of ARM consistent with the 'less is more' approach adhering to AUG guidelines has acceptable outcomes.Item The interplay between acute and late toxicity among patients receiving prostate radiotherapy: an individual patient data meta-analysis of six randomised trials.(ELSEVIER SCIENCE INC, 2025-01-30) Nikitas, J; Jamshidian, P; Tree, AC; Hall, E; Dearnaley, D; Michalski, JM; Lee, WR; Nguyen, PL; Sandler, HM; Catton, CN; Lukka, HR; Incrocci, L; Heemsbergen, W; Pos, FJ; Roy, S; Malone, S; Horwitz, E; Wong, JK; Arcangeli, S; Sanguineti, G; Romero, T; Sun, Y; Steinberg, ML; Valle, LF; Weidhaas, JB; Spratt, D; Telesca, D; Kishan, AU; Tree, Alison; Hall, Emma; Dearnaley, DavidBACKGROUND: The association between acute and late toxicity following prostate radiotherapy has not been well studied using data from multiple randomised clinical trials and fractionation schedules. We aimed to characterise the relationship between acute and late genitourinary and gastrointestinal toxicity among patients receiving conventionally fractionated or moderately hypofractionated prostate radiotherapy. METHODS: This was an individual patient data meta-analysis that identified randomised phase 3 trials of conventionally fractionated or moderately hypofractionated prostate radiotherapy in the Meta-Analysis of Randomized trials in Cancer of the Prostate (MARCAP) Consortium that had individual-level acute and late toxicity data available and were available before Dec 1, 2023. Trials without individual patient data were excluded. Data were provided to MARCAP by study investigators. The associations between acute (≤3 months after radiotherapy) and late (>3 months after radiotherapy) grade 2 or greater genitourinary and gastrointestinal toxicities were assessed using adjusted generalised linear mixed models (adjusted for age, androgen deprivation therapy status, type of radiotherapy, radiation dose, and radiation schedule). In the subset of trials that collected Expanded Prostate Cancer Index Composite quality of life (QOL) evaluations, the association between acute genitourinary and gastrointestinal toxicity and decrements at least twice the minimal clinically important difference (MCID) for urinary and bowel QOL were also evaluated. FINDINGS: Six of 26 available trials met all the eligibility criteria. 6593 patients were included (conventionally fractionated: n=4248; moderately hypofractionated: n=2345). Median follow-up was 72 months (IQR 61-94). Acute grade 2 or greater genitourinary toxicity was associated with both late grade 2 or greater genitourinary toxicity (odds ratio 2·20 [95% CI 1·88-2·57], p<0·0001) and decrement at least twice the MCID in urinary QOL (1·41 [1·17-1·68], p=0·0002). Acute grade 2 or greater gastrointestinal toxicity was associated with both late grade 2 or greater gastrointestinal toxicity (2·53 [2·07-3·08], p<0·0001) and decrement at least twice the MCID in bowel QOL (1·52 [1·26-1·83], p<0·0001). INTERPRETATION: Acute toxicity following prostate radiotherapy was statistically significantly associated with late toxicity and with decrement in patient-reported QOL metrics. These data support efforts to evaluate whether interventions that reduce acute toxicity ultimately reduce the risk of late toxicity. FUNDING: National Institutes of Health and US Department of Defense.