Oncology

Checkpoint Inhibitors and Beyond: A Systematic Review of Immunotherapy in Cutaneous Malignancies (2025)

Posted on by

Type of publication:

Systematic Review

Author(s):

Rashid, Yasir; Devi S, Kartika; Gonzalez-Espinosa, Tomas Faustino; Jain, Juhi; Dalain, Mujahed; Baig, Rayyan; D'Amico, Giuseppe Antonio; Mowo-Wale, Adetola G; Khomchenko, Mariia; Baby, Nima; *Yateem, Dana; Duhamel, Axel; Ali, Ramsha.

Citation:

Cureus. 17(12):e98959, 2025 Dec.

Abstract:

Skin cancers represent a major health concern, and there is a need for more effective treatment approaches, among which immune checkpoint inhibitors have become a particularly important recent development. This study aimed to explore the efficacy and tolerability of immune checkpoint inhibitors, intratumoral immunotherapies, targeted agents, and their combinations in advanced cutaneous malignancies. A Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-conform review of PubMed (2012-2024) identified 26 studies, including randomized trials, observational cohorts, network meta-analyses, and systematic reviews, evaluating checkpoint inhibitors, anti-PD-1/PD-L1and anti-CTLA-4. Outcomes included progression-free survival (PFS), objective response rate (ORR), overall survival (OS), biomarkers, and treatment-related adverse events. This meta-analysis of 26 studies (2012-2024) evaluated treatments for cutaneous malignancies, including melanoma, basal cell carcinoma (BCC), cutaneous squamous cell carcinoma (cSCC), and Merkel cell carcinoma (MCC), covering systemic immunotherapies (PD-1, CTLA-4), combination checkpoint inhibitors, and novel approaches like IL-12 electroporation. Melanoma: PD-1 therapies showed durable benefits; ipilimumab retreatment yielded 42% two-year survival. MCC: Avelumab achieved a median OS of 12.9 months. cSCC: Nivolumab PFS 8.2 months; cemiplimab 12-month PFS >53%. Targeted therapy: BRAF/MEK inhibitors reached OS ~33 months. Emerging strategies: TIL-based and neoadjuvant immunotherapy showed high pathological and durable responses. Overall, combination therapies consistently outperformed monotherapies in survival and response. Adverse events were common, especially with combination therapy, with severe immune-related toxicities reported in 30-59% of cases, while monotherapies were generally safer. Overall, immunotherapy offers substantial, often long-lasting benefits, though careful patient selection and monitoring are essential to balance efficacy and toxicity. Combination immunotherapies and targeted regimens are more effective for advanced melanoma, although they have increased toxicity.

DOI: 10.7759/cureus.98959

Link to full-text [open access - no password required]

Tumour immune microenvironment prognostic factors in locally advanced rectal cancer, a systematic review (2025)

Posted on by

Type of publication:

Journal article

Author(s):

Ball, Alasdair; *Lefroy, Rebecca; Price, Malcolm; McArthur, David; Beggs, Andrew.

Citation:

Frontiers in Oncology. 15:1688696, 2025.

Abstract:

Introduction: Understanding factors influencing individual survival outcomes following surgical resection of locally advanced (LARC) rectal cancer remains challenging. Novel biomarkers could show emerging promise in this setting. This study aimed to systematically review the literature on immune prognostic factors in LARC.

Methods: The review protocol was preregistered on the PROSPERO database (CRD42023460541). Included studies were required to report overall survival and at least one immune prognostic factor for at least ten patients with LARC. Final searches of MEDLINE, EMBASE and Central were concluded on 8th September 2023. The risk of bias was assessed using the QUIPS tool.

Results: 22 retrospective cohort studies involving 2,622 LARC patients were included in the review. We did not find any published data on immune prognostic factors in locally recurrent rectal cancer. Due to inconsistency of immune prognostic factor definitions and measurement methods, meta-analysis would not be meaningful. Instead, the results are presented descriptively. Risk of bias was concentrated in the participation, attrition, and confounding domains. Greater cytotoxic cell infiltration was associated with improved overall survival. There was inconsistent evidence of an association of PD-L1 expression and survival. M2 macrophage infiltration and homozygous germline FPR1 loss-of-function were associated with worse survival.

Discussion: These findings support a role for both innate and acquired immune systems in mediating outcomes following surgery for LARC and suggest that further work into immunomodulation may show promise in improving LARC treatment.

DOI: 10.3389/fonc.2025.1688696

Link to full-text [open access - no password required]

Artificial Intelligence in Colonoscopy: A Systematic Review of Adenoma Versus Polyp Detection Rates (2025)

Posted on by

Type of publication:

Systematic Review

Author(s):

Rabba, Waseem; *Asif, Fatima; Younis, Muhammad Y; Nasrullah, Haris; Fatima, Laraib; Arif, Muhammad A.

Citation:

Cureus. 17(12):e98528, 2025 Dec.

Abstract:

Colonoscopy is the gold standard in the prevention of colorectal cancer, but the miss rates of adenoma are high, which restricts its efficacy. To improve lesion recognition, artificial intelligence (AI), especially computer-aided detection (CADe) systems, has been introduced. The aim of this systematic review was to compare AI-assisted colonoscopy in terms of its ability to improve adenoma detection rate (ADR) and polyp detection rate (PDR). An extensive search was performed on PubMed, Embase, and Cochrane Library from 2015 to 2025. There were 17 randomized controlled trials (RCTs) comparing the use of AI-assisted colonoscopy with normal colonoscopy. The methodological quality measure of the included RCTs was Cochrane Risk of Bias 2.0 (RoB 2.0), which subdivided the studies based on low risk, some concerns, or high risk of bias based on whether they were biased in this or that domain. The robVis tool was used to produce the visual summaries. AI-aided colonoscopy effectively enhanced both adenoma detection rate (ADR) and polyp detection rate (PDR) in all of the included studies over conventional colonoscopy. In adenoma detection, accuracy was more than 85%, and in polyp detection, more than 90%. The advantage was also found especially in the detection of small and flat adenomas, which are very often missed in routine practice. The use of AI in colonoscopy is strongly associated with an increase in the detection rate of adenoma and polyps, minimizing the risk of underdiagnosis. The results highlight the clinical promise of AI in the form of a decision-support tool across gastroenterologists and suggest that AI can be applied to enhance the outcomes of preventive and screening colorectal cancer. Future research should be cost-efficient and practical, and combined with some clinical activities.

DOI: 10.7759/cureus.98528

Link to full-text [open access - no password required]

RESECT: A Randomised Controlled Trial of Audit and Feedback in Non-muscle-invasive Bladder Cancer Surgery (2025)

Posted on by

Type of publication:

Randomised controlled trial

Author(s):

Gallagher K.; MacLennan S.; Bhatt N.; Clement K.; Zimmermann E.; Khadhouri S.; Kulkarni M.; Gaba MPhil F.; Anbarasan T.; Asif A.; Light A.; Ng A.; Chan V.W.-S.; Nathan A.; Cooper D.; Aucott L.; Sakthivel D.; Akand M.; Piazza P.; Marcq G.; O'Brien T.; Nielsen M.; Giudice F.D.; Simpson K.; Orecchia L.; Teixeira B.; Geisenhoff A.; Hill G.; Fukuokaya W.; Hidalgo B.G.; El-Hajj A.; Elgamal M.; Fanshawe J.; Wang B.; Lee T.; Manecksha R.; Rivas J.G.; Arda E.; Elhadi M.; Rossi S.; Teoh J.Y.-C.; Kasivisvanathan V.; Hussein I.; Longshaw A.; Kostakopoulos N.; Khadhouri S.A.S.; Kruczynska A.E.; Dimitropoulos K.K.D.; McPhee A.; Gilanliogullari K.P.; Natalie S.; Rutigliani L.; Shallcross O.R.; Dokubo I.I.; Lamb B.W.; Jimie J.H.; Hussein B.; O'Neill C.; Nelson A.R.; MacLeod A.; Arumainayagam N.; Maqboul F.; Agrawal S.; Burns H.; Bekarma H.J.; Mohammad S.; Misurati M.O.; Raslan M.Y.; Anwar A.; Gkikas C.; Alexander C.; Warren H.; Byrnes K.; Edison M.; Croghan S.; Oo E.; Beder D.; Thurtle D.R.; Janebdar H.; Reeves F.; Chua C.U.; Mcalindon J.; Hasan H.; Ng P.Y.; Mayor N.; Attar H.A.; Delacave H.S.T.; Atiyah A.; Atiyah Z.; Jelski J.E.R.; Peacock J.; Davenport K.; Shipstone D.; Malla R.A.; Krishna K.K.I.; Nizov A.; Somov P.; Ahmed Z.; McCann C.; Glackin A.J.; Asaad W.; Bain A.J.; Bordenave M.G.; Ray E.R.; Ghonaimy A.S.; Madaan S.; Fontaine C.L.L.; Daggamseh A.M.K.; Pascoe J.J.; Horn C.; Fuge O.; Laoye A.; Deytrikh A.; Thomas A.G.; Ravishankar K.; Clark M.C.; Panayi Z.; Shillito S.H.; Srirangam S.J.; Bradley C.; Lee X.W.J.W.J.; Mcilhenny C.; Leask J.; sarkar S.; chetwood A.S.A.; Paramore L.; Ali A.S.A.; Odey J.; Sheweita M.S.S.; Ekwueme K.C.; Yogeswaran C.; Mohamed Y.; Trimboli M.; Shafii M.; Duffy S.A.; Morton S.; Bandeira de Mello K.L.; Harris A.; Bruce A.; Fanshawe J.R.; Tan N.J.; Mensah E.; Walters U.; Lami M.; Omar M.A.; Kadhim H.; Gami M.N.; Hawizy A.A.M.H.; Devadoss B.J.; Breish M.; Pina I.; Cresswell J.; Simoes A.; Papadopolous G.G.; Thomas M.M.T.; Ahmed I.I.A.; Sekhon N.C.; Alleemudder A.; Okwuchi D.D.; Willmott S.V.; Majumdar P.; Coyle M.; Simson N.; Egbe A.; Nair A.; Nair M.A.N.; Kailavasan M.; Douglas-Moore J.L.; Elajnaf M.R.; Jackson B.L.; Hamami H.; Hemmant J.; Siraj M.; Craciun M.E.; Lyttle M.; Shendy M.S.; Abdalla A.; Mukherjee R.; Mihuna A.; Kantartzi A.; Atkins C.R.M.; Uddin J.; Motiwala F.; Fanshawe J.B.; Mxxxensah E.; Chan K.H.Y.; Vasdev N.N.V.; Hassan M.M.; Pushkaran A.K.; Salik M.; Barrass B.J.R.; Jones A.; Shakir J.; Waterhouse R.H.; Tan S.; Shah S.; Simpson R.G.; Mohee A.R.; Smith P.M.; Middela S.G.; Gunendran T.; Bhat T.; Mehmood S.M.; Masood S.; Karna S.; Ibiok I.A.; Ollandini G.; Yarwood A.; Hill G.T.; Kanda Swamy G.V.; Healy R.; Faek Halaseh S.A.; Lee S.-M.; Hughes C.M.; Ali O.H.; Boaz R.J.; Gabriel M.M.; Finch W.; Hammad O.O.; Heba S.T.; Yun J.W.; Pandian S.K.; Oliver R.L.; Almpanis S.S.A.; Boxall N.E.; Adamu-Biu F.I.; Pushpa-Rajah J.A.; Miakhil I.; Mera Z.; Sultana A.; Potter J.J.; Coombs L.; Laghari S.; Khan I.A.; Warner R.M.; Olaitan O.; Akman J.; Green W.J.F.; Dooldeniya M.D.; Turo R.K.; Kabia A.A.; Onowa V.E.; Anand C.V.; Tanasescu G.G.T.; Sells L.A.; Acyatan M.G.; Smith T.G.; Lokman U.U.L.; Ramachandra M.; Hodgson D.J.; *Sid Ahmed M.A.M.B.; *Moghe D.; *Ong K.K.; *Tasleem A.M.; Blick C.; Toia B.B.T.; Maduwe Gedara S.R.K.R.K.; Mohsin H.; Bleakley C.; McGrath M.J.; Ng M.G.; Parsons B.; Lindsay J.S.; Volanis D.; Wijayasuriya D.S.C.R.; Wilkinson J.; White A.; Cox A.; Calmuc A.; Fung C.; Taktak S.; Lazarowicz H.P.; Starmer B.; Chippagiri A.S.; Gallegos C.; Kerr E.; Penny N.M.; Green E.A.; Jones C.M.; Colvin H.V.; David R.; Davies M.; Qamar B.Q.; Humayun-Zakaria N.K.; Hussain A.; Dhanasekaran A.K.; Mangera A.F.; Pereca J.L.P.; Akinjise-Ferdinand O.; Rosario D.J.; *Dhother J.; *Mohamed G.; *Jenny Bo Y.N.; *Chin Chin Y.F.Y.F.; *Varma R.K.; *Elves A.; Elmansouri A.J.N.V.; Edris F.F.E.; Voss J.; Parfitt C.M.; Buckland G.R.E.; Antoniou V.; Sinha M.M.; Douglas J.; Campbell J.M.; Bondad J.; Khuoge S.; Gipson C.; Dawam D.; Lecoyte A.; Waley L.G.; Hawthorne R.; Ridgway A.; Warren K.S.; Maniarasu S.; Mistry R.; Stroman L.; Hassan M.; Ayres B.; Pinkney R.T.M.; El-Taji O.; McCabe J.; Oliyide A.E.; Chibuzo I.N.C.; Vaggers S.N.; Dyer J.E.; MacKenzie K.R.; Miller A.; Tait C.D.; Thorman H.E.; Ippoliti S.; Ilie P.C.; Babawale O.D.; Mitchell V.; O'Rourke S.; Ross A.; O'Halloran R.; Hayes J.; Gray S.B.; Day E.K.; Shirwac H.; jaibaji R.; Tang S.C.; Kennedy C.; Szabados B.; Baldini C.; Nowers J.; Sarmah P.P.B.; Williams K.G.; Tan L.J.; Boden A.K.; Simpkins S.J.; Clement K.D.; Khan R.S.S.; Ravindraanandan M.; Lango A.; Kitchen M.; Gommersall L.M.; Thomas M.; Al-Mitwalli A.; Featherstone J.M.; Catto J.; Chari N.; Nikolinakos P.; Ellis D.S.J.; Papadopoulos D.I.; Charitopoulos K.; Carey M.M.; Gordon E.M.; Lau D.H.W.H.; El-Koubani O.; Ayers J.R.S.; Hina S.; Gartner T.; James J.E.G.; Simpson K.R.S.; Mariappan P.; Ibrahim M.E.; Dallash M.H.; Jallad S.; Bencatova Z.; Karanjia R.N.; Whiting D.; Frymann R.J.; Farag S.S.F.; Whitburn J.A.S.; Miah S.; Khattab H.; Kondylis F.; Amin Alsayed Alkhawalka M.A.

Citation:

European Urology. (no pagination), 2025. Date of Publication: 2025.

Abstract:

Background and objective We aimed to determine whether audit, feedback, and education improves surgical performance after transurethral resection of bladder tumour surgery for non-muscle-invasive bladder cancer and as a secondary aim if it reduced recurrence rates. Methods This cluster randomised controlled trial compared audit and feedback plus peer comparison and education, with audit alone for four coprimary outcomes: (1) Single-instillation chemotherapy, (2) detrusor muscle sampling, (3) documentation of tumour features, and (4) resection completeness. Early recurrence was a secondary outcome. Key findings and limitations A total of 100 sites were randomised to intervention and 101 to control. In total, 14 915 patients were included. Intervention sites significantly improved documentation of tumour features (adjusted mean difference [95% confidence interval {CI}]: 6.0 [1.8, 10], p = 0.005) and of resection completeness (adjusted mean difference [95% CI]: 5.5 [1.5, 9.5], p = 0.007). There was no statistically significant difference in chemotherapy use (adjusted mean difference [95% CI]: 0.3 [-4.7, 5.3], p = 0.9) or detrusor muscle sampling (adjusted mean difference [95% CI]: 2.6 [-1.3, 6.4], p = 0.2). There was no statistically significant difference in early recurrence rate between arms (adjusted odds ratio [95% CI]: 1.02 [0.8, 1.4], p = 0.9); however, in the control arm, the early recurrence rate reduced compared with baseline (adjusted odds ratio [95% CI]: 0.7 [0.6, 0.9]). Conclusions and clinical implications Audit and feedback with education improved the documentation of important surgical findings that influence clinical management, but not the performance of detrusor muscle sampling, adjuvant chemotherapy use, or early recurrence rates. Improvements observed in the control arm may explain a lack of effect of the intervention in some outcomes.

DOI: 10.1016/j.eururo.2025.09.4174

Link to full-text [open access - no password required]

Learning from Interventions Within Cancer Services (2024)

Posted on by

Type of publication:

Conference abstract

Author(s):

*Flynn K.; *Poulsom R.; *Wilfred D.;* Lindsey K.; *Tibitendwa A.

Citation:

Journal of Oncology Pharmacy Practice. Conference: 26th Annual BOPA Symposium. Wales United Kingdom. 30(1 Supplement) (pp 74), 2024. Date of Publication: 01 Mar 2024.

Abstract:

Introduction / objectives: This Service Evaluation was carried out to assess interventions for oncology SACT prescriptions, identify trends and potential areas for improvement. The primary objective was to quantify and categorise the interventions of the Cancer Pharmacist team, encompassing IV and oral oncology SACT prescriptions in the inpatient and outpatient setting, over a 12-week period. The secondary objective was to look in more detail at the interventions logged under the high-risk categories of 'Regimen query/error', 'Dose query' and 'Dose error'. This would enable greater understanding of the issues contributing to prescription errors and will form the basis for future work to improve patient safety. Method(s): Cancer pharmacists completed a data collection form for each oncology SACT prescription query over a 12-week period. A support document defining each category ensured standardisation among pharmacists when classifying queries. The data was collated and analysed using Microsoft Excel. Each patient case in the specified high-risk categories was examined retrospectively to provide more detailed insight into the intervention and identify common themes. Result(s): In total, 124 interventions were logged (Fig.1), the highest number related to 'funding queries', 36%, with 'missing prescription' and 'dose query' both at 15%. The high-risk categories accounted for 31%, (n = 39). Of the 39 high-risk interventions, 9 related to intended dose changes that had not been actioned; 14 related to patient factors (bloods, DPYD, co-morbidities), of which 6 involved carboplatin; 5 prescriptions were missing a critical element. Discussion / conclusions: Funding queries were identified as the largest category of interventions; consultants were reminded to complete Blueteq forms when planning treatment to ensure the patient is eligible for the chosen regime. Prescriptions not available in advance mean that treatment cannot be ordered in time from third-party compounders. Pharmacy and oncology are working to find an efficient way of identifying patients scheduled for treatment that has not yet been prescribed to reduce delays to patients due to treatment not being available. From the in-depth analysis of high-risk categories, key areas for service development were identified. 1) Establishing a clear process for communicating changes to planned treatment. 2) Creating a policy and educating staff on carboplatin dosing to reduce unnecessary changes. 3) Improving blood test scheduling with the administration team. 4) Reviewing regimens requiring two prescriptions and considering combined prescriptions. This would reduce the number of prescriptions missing a critical element. Our Service Evaluation had limitations, mainly due to manual documentation. There was a noticeable drop in number of queries logged during extremely busy periods; it is likely that some interventions have been missed. Some duplication was identified when collating the data, particularly where more than one pharmacist was involved in following up a query. Of the 39 high-risk interventions, 4 were excluded from the data, 3 were duplicate entries and 1 had the incorrect patient number documented so further follow up was not possible. Future work will involve liaising with the oncology team to address the areas identified above with reference to improvement projects that have been successful in other hospitals.

DOI: 10.1177/10781552241228011

Link to full-text [NHS OpenAthens account required]

Quality improvement programme for 2 week wait Gynaecology suspected cancer referrals (2025)

Posted on by

Type of publication:

Service improvement case study

Author(s):

*Claire Carr

Citation:

SaTH Improvement Hub, November 2025

SMART Aim:

To improve the triage system for patients on the faster diagnosis pathway for suspected gynaecological cancers by 1st October 2025 as evidenced by more people being seen within the 28 days target.

Link to PDF poster

Cure vs. toxicity: quantifying preferences for non-surgical management of rectal cancer using a prospective discrete choice experiment study (2025)

Posted on by

Type of publication:

Conference abstract

Author(s):

Webb E.J.; Twiddy M.; Noutch S.; Adapala R.; Bach S.P.; Brown S.; Burnett C.; Burrage A.; Gilbert A.; Hawkins M.; Howard D.; Hudson E.; Jefford M.; Kochhar R.; Saunders M.; Seligmann J.; Smith A.; Teo M.; West N.; Sebag-Montefiore D.; *Gollins S.; Appelt A.L.

Citation:

Radiotherapy and Oncology. Conference: ESTRO 2025. Vienna Austria. 206(Supplement 1) (pp S1253-S1255), 2025. Date of Publication: 01 May 2025.

Abstract:

Purpose/Objective: Dose-escalation may increase the chance of successful non-surgical rectal cancer management, but requires an understanding of acceptable trade-offs between chance of cure and toxicity risks. This study is the first to measure patient preferences for non-surgical management (NOM) of rectal cancer using a discrete choice experiment (DCE). Material/Methods: A prospective, multicentre study conducted in seven UK radiotherapy centres. Patients consented to participation prior to initiation of radiotherapy-based NOM for rectal cancer (any stage), and completed the survey pre-treatment and 6 months post-treatment. The DCE was developed with qualitative patient input and had a Bayesian D-efficient design. Patients made repeated choices between hypothetical NOM treatments, described using six attributes: treatment length; chance of being cancer-free two years post-treatment; side effect risks during and two years posttreatment; support available. Participants indicated preferences for non-surgical vs. surgical treatment on a Likert scale. Baseline responses were analysed using mixed logit, quantifying trade-offs between attributes, using preference for chance of cure as the unit of measurement. Post-estimation, individual preferences conditional on choices were estimated. Changes in mean preferences pre/post-treatment were analysed using multinomial logit, with the delta method used to test for pre/post-treatment differences. Differences in preferences for surgical/nonsurgical management were assessed using Mann-Whitney U tests. Result(s): There were 96 participants recruited, and 51 completed follow-up. Participants had a mean baseline age of 68.4 and were 38.9% female. There were no significant differences between characteristics of people who did/did not complete follow-up. Figure 1 shows distributions of patients' baseline preferences. Patients on average required a 0.34 percentage point (pp) higher chance of cure to accept a 1pp higher chance of short-term side effects, compared to 0.78pp for a 1pp higher chance of long-term side effects, and 3.3pp higher chance of cure to accept support from usual GP rather than a dedicated nurse. The mean chance of cure patients would trade for shorter treatment lengths was not significantly different from 0 (p=.900). Preferences for treatment attributes did not change significantly pre/post-treatment (p-values between.374 and.759, Figure 2a). There was a significant shift in preferences towards non-surgical vs. surgical management post-treatment (p=.017, Figure 2b). Conclusion(s): Participants would accept extra toxicity in exchange for better chances of cure, suggesting most would accept treatment intensification, including dose-escalation. Participants were more concerned about long-term than shortterm side effects, highlighting the need for long-term follow-up of toxicity, and for clinical decision-making to take account of individual patients' preferences.

DOI: 10.1016/S0167-8140%2825%2901971-1

ARISTOTLE: Mature results of a phase 3 trial evaluating the addition of irinotecan to capecitabine chemoradiation in locally advanced rectal cancer (2025)

Posted on by

Type of publication:

Conference abstract

Author(s):

Sebag-Montefiore D.; Samuel L.; *Gollins S.; Glynne-Jones R.; Harte R.; West N.; Quirke P.; Myint A.S.; Bach S.; Falk S.; Parsons P.; Dhadda A.; Misra V.; Brown G.; Harrison M.; White L.; Duggan M.; Begum R.; Chang E.; Musleh R.; Lopes A.; Adams R.

Citation:

Radiotherapy and Oncology. Conference: ESTRO 2025. Vienna Austria. 206(Supplement 1) (pp S1192-S1194), 2025. Date of Publication: 01 May 2025

Abstract:

Purpose/Objective: To determine if the addition of irinotecan to capecitabine chemoradiation (CRT) improves disease-free survival in MRI-defined locally advanced rectal cancer (LARC). Material/Methods: ARISTOTLE (ISRCTN:09351447) is a phase III, multi-centre, open-label trial that randomly assigned (1:1) patients with MRI-defined LARC threatening or involving resection margins without metastases to pre-operative radiotherapy:45Gy/25 fractions combined with either capecitabine 900mg/m2 (CRT) or 650 mg/m2 bd weekdays with Irinotecan iv once-weekly 60mg/m2 (IrCRT) weeks 1-4. The primary endpoint is disease-free survival (DFS). Result(s): 75 UK sites randomised 564 eligible patients from 10/2011 to 07/2018; 284 to CRT and 280 to IrCRT. 66% male; median age 61 years (range:24-83). Radiological staging in both arms was similar:mrT3(77%), mrT4(16%); mrCRM involved(49%);resection margin threatened <=1mm(38%). Median follow-up is 62.1 months.Compared with CRT, IrCRT patients were less likely to receive 45Gy RT: 208(75%) vs 251(89%), p < 0.001; or receive >=90% capecitabine dose:187(68%) in IrCRT vs 253(89%) CRT, p < 0.001. 205(74%) IrCRT patients received >=90% irinotecan dose. >=Gd 3 non-haematological adverse events included fatigue 17(6%) vs 8(3%) p=0.06; diarrhoea:14% vs 4% p<0.001; abdominal pain 5% vs <1% p=0.001 for IrCRT and CRT respectively. >=Gd 3 haematological adverse events included leucopaenia: 9% vs 2%, p<0.001; neutropaenia: 10% vs 1%,p<0.001; and febrile neutropaenia: 1% vs <1% for IrCRT and CRT respectively. 5 patients had a grade 5 adverse event (3 lrCRT,2 CRT). The median time from the end of RT to surgery was 10.6 weeks. 238(85%) and 243(86%) patients underwent surgery in the IrCRT and CRT arms. The R0 resection rate was 90% vs 89% p=0.75 for IrCRT and CRT respectively. The pCR rate was 20% for IrCRT vs 18% for CRT p = 0.52. The rate of any post-surgical complications was similar in both arms:94(39%) for IrCRT and 91(37%) for CRT p=0.65). There is no evidence of a difference in loco-regional failure free (HR 0.94 [0.46-1.90]p=0.86, distant metastasis free (HR 0.89 [0.63-1.25] p=0.51), disease free HR 0.87 [0.64-1.18] p=0.37) or overall survival (HR 0.91[0.63-1.30],p=0.59) when IrCRT is compared with CRT. Conclusion(s): For patients with MRI-defined high risk LARC, low rates of CRM involvement and 36 month loco-regional failure were observed.The addition of irinotecan to CRT was associated with decreased radiotherapy and chemotherapy compliance and a higher rate of adverse events.There is no evidence of a difference in the pCR rate,36 month locoregional recurrence free or disease-free survival.

DOI: 10.1016/S0167-8140%2825%2900901-6

Link to full-text

Simultaneous integrated boost and organ at risk constraints in the APHRODITE trial (2024)

Posted on by

Type of publication:

Conference abstract

Author(s):

Iddenden J.; Howard D.; Hudson E.; Teo M.; Diez P.; Miles E.; Turtle L.; Patel R.; Appelt A.; *Gollins S.

Citation:

Radiotherapy and Oncology. Conference: ESTRO 2024. Glasgow United Kingdom. 194(Supplement 1) (pp S5977-S5980), 2024. Date of Publication: 01 May 2024.

Abstract:

Purpose/Objective: APHRODITE (ISRCTN16158514), funded by Yorkshire Cancer Research, is a phase II randomised controlled trial comparing radical (chemo)radiotherapy (CRT) alone versus dose-escalated CRT with a simultaneous integrated boost (SIB). Patients with early stage rectal cancer, who are considered by their multidisciplinary team as unsuitable for radical total mesorectum excision or have a strong preference for organ preservation, will all receive 50.4Gy in 28 fractions to a small mesorectal-only planning target volume (PTV). Those in the experimental dose-escalation arm also receive up to 62Gy SIB to the primary tumour volume (PTVp). The trial is currently in active recruitment with a target sample size of 104 patients. Few studies exist detailing dose-volume constraints applied in this setting and none which examine the frequency to which they are achieved1. Anonymised trial plans were retrospectively reviewed to determine if the optimal organ at risk (OAR) dose-volume constraints as set out in the trial protocol are achievable. The conformity of the target volumes coverage was also assessed. Material/Methods: All centres completed the pre-trial radiotherapy quality assurance programme prior to recruiting. Radiotherapy planning data was requested for all patients. To date, 8 centres have recruited patients, with plan data for 46 out of 73 trial patients available at the time of analysis. Radiotherapy was planned according to their randomisation following APHRODITE dose-volume constraints. All plans were retrospectively reviewed on Velocity version 4.1 (Varian Medical Systems, Inc.) and dose-volume constraints extracted from DVH data. Conformity indices, as defined by RTOG (95% isodose volume/volume of PTV), were calculated for all PTVs. The standard deviation was calculated for optimal OAR dose-volume constraints and target volume conformity. Mann-Whitney U tests (two-tailed) were performed to test differences between the standard and dose-escalated arms. Result(s): Dose-volume constraints for the APHRODITE trial were developed from a retrospective mesorectum only planning study for a cohort of early-stage rectal cancer patients2. All constraints were considered optimal, rather than mandatory, due to the paucity of data on normal tissue dose limits in the setting of rectal cancer organ preservation. In all cases, the V95% >= 99% for both PTV and PTVp (dose-escalated arm only) were achieved. Table 1 demonstrates that centres were able to meet the optimal OAR dose-volume constraints in both trial arms in the majority of cases. Randomisation to receive a 62Gy boost did not have a statistically significant impact on achieving optimal OAR dosevolume constraints when compared to the standard arm dose. Evaluation of conformity indices in Table 2 suggested that there was a negligible difference in the conformity of PTV coverage between standard and dose-escalated patients. Mean conformity index for the mesorectal PTV was 1.15 for standard arm patients and 1.16 for patients in the escalated arm (p=0.67). For comparison, mean conformity index for the boost PTVp in the escalated arm was 1.18. The analysis of the target volume conformity test showed that 95% dose conformity is widely achievable across both trial arms in this multi-centre study. Table 2: Conformity indices of target volume and standard deviation Target Volume Mean Conformity Index Standard Deviation Standard (PTV) 1.15 0.06 Escalated (PTV) 1.16 0.05 Escalated (PTVp) 1.18 0.11 Conclusion(s): Delivering a SIB dose of up to 62.0Gy to the primary tumour volume does not have a statistically significant impact on the achievability of optimal OAR dose-volume constraints set out in the APHRODITE trial. Retrospective analysis of available plan data has shown that highly conformal SIB plans can be produced in a multi-centre setting, with resulting dose distributions being comparable to those in the standard arm.

DOI: 10.1016/S0167-8140%2824%2902083-8