Rovel Colaco’s research while affiliated with The Christie NHS Foundation Trust and other places

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Publications (39)


P18.43.A THE APPROACH TRIAL (ANALYSIS OF PROTON VS PHOTON RADIOTHERAPY IN OLIGODENDROGLIOMA AND ASSESSMENT OF COGNITIVE HEALTH): OPEN AND RECRUITING IN THE UK
  • Article

October 2024

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18 Reads

Neuro-Oncology

L J Murray

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F Boele

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S Brown

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[...]

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S Short

BACKGROUND Proton beam radiotherapy (PBT), when used in the brain, may spare healthy tissue and preserve neurocognitive function (NCF) compared to photon radiotherapy (RT). Even small deficits in NCF may impact negatively on health-related quality of life (HRQoL) and are especially relevant for patients with oligodendroglioma (ODG), due to their young age and favourable prognosis. Randomised evidence for PBT remains limited. APPROACH is a UK multicentre randomised controlled phase III trial assessing PBT vs photon RT in patients with ODG. MATERIALS AND METHODS Procedures: Adult ODG patients will be randomised 1:1 between PBT (delivered at the NHS PBT centre in London or Manchester) and photon RT (delivered locally). Participants will receive 54Gy(Relative Biological Effectiveness; RBE) in 30 fractions (Grade 2 ODG) or 59.4Gy(RBE) in 33 fractions (Grade 3 ODG). Following RT, participants will receive Procarbazine, Lomustine and Vincristine chemotherapy. Patient and public involvement: To guide trial design, a focus group was held with ODG patients and carers in November 2018. Participants welcomed the opportunity to access PBT in a trial. Randomisation, travel/relocation for treatment, and completion of NCF and HRQoL assessments were deemed acceptable. Endpoints: The primary endpoint is NCF at 5 years, assessed using a standard neurocognitive test battery (EORTC Core Clinical Trial Battery Composite score). Secondary endpoints include additional NCF outcomes, HRQoL, endocrinopathy, work and economic impact, caregiver distress, toxicity, radiological response and, progression-free and overall survival. Trial design: Stage 1: internal pilot: assessing feasibility of recruitment over the first 12 months; Stage 2: first interim analysis: NCF at 2 years, after all participants reach 2-year follow-up, allowing potential early dissemination; Stage 3: second interim analysis: NCF at 5 years, when 50% of participants reach 5 years, assessing futility; Stage 4: final analysis: NCF at 5 years, once all participants reach 5 years. Sample size: For NCF at 5 years, based on a two-sample t-test with 5% two-sided significance and 90% power, 172 patients are required to detect a moderate effect size (Cohen’s d 0.5) between PBT and photon RT. Assuming 30% loss to follow-up, 246 patients are required. We aim to recruit from 18-25 UK centres over 3.5 years. RESULTS Set up began in April 2021. The trial opened to recruitment in January 2024. As of April 2024, 16 centres have completed the Radiotherapy Trials Quality Assurance (RTTQA) contouring and planning exercises, 8 centres are open, and 9 patients have been registered. CONCLUSION The APPROACH trial is one of the first randomised controlled trials of PBT vs photon RT in ODG patients. It aims to evaluate if the dosimetric advantages of PBT translate into clinical or patient benefits regarding NCF, other side effects and HRQoL. Funder: NIHR EME (131082)


Skull Base Chordoma and Chondrosarcoma: Neuroradiologist's Guide to Diagnosis, Surgical Management, and Proton Beam Therapy

October 2024

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28 Reads

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1 Citation

Radiographics

Skull base chordomas and chondrosarcomas are distinct types of rare, locally aggressive mesenchymal tumors that share key principles of imaging investigation and multidisciplinary care. Maximal safe surgical resection is the treatment choice for each, often via an expanded endoscopic endonasal approach, with or without multilayer skull base repair. Postoperative adjuvant radiation therapy is frequently administered, usually with particle therapy such as proton beam therapy (PBT). Compared with photon therapy, PBT enables dose escalation while limiting damage to dose-limiting neurologic structures, particularly the brainstem and optic apparatus, due to energy deposition being delivered at a high maximum with a rapid decrease at the end of the penetration range (Bragg peak phenomenon). Essential requirements for PBT following gross total or maximal safe resection are tissue diagnosis, minimal residual tumor after resection, and adequate clearance from PBT dose-limiting structures. The radiologist should understand surgical approaches and surgical techniques, including multilayer skull base repair, and be aware of evolution of postsurgical imaging appearances over time. Accurate radiologic review of all relevant preoperative imaging examinations and of intraoperative and postoperative MRI examinations plays a key role in management. The radiology report should reflect what the skull base surgeon and radiation oncologist need to know, including distance between the tumor and PBT dose-limiting structures, tumor sites that may be difficult to access via the endoscopic endonasal route, the relationship between intradural tumor and neurovascular structures, and tumor sites with implications for postresection stability. ©RSNA, 2024 Supplemental material is available for this article.



Surgical management of skull base chordomas and chondrosarcomas: insights from a national cohort study
  • Article
  • Full-text available

July 2024

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66 Reads

BMJ Oncology

Objective Skull base chordoma and chondrosarcoma are distinct sarcomas of the skull base but share significant therapeutic challenges due to their proximity to critical neurovascular structures, making surgical resection difficult. We sought to establish factors associated with outcome predictors in a national cohort of patients. Methods and analysis Data for all patients referred with a diagnosis of skull base chordoma or chondrosarcoma from April 2017 to December 2022 were obtained. We performed analyses of data pertaining to the first cohort of patients treated in the UK with proton beam therapy (PBT) to determine factors associated with obtaining gross total resection (GTR) and adequate clearance of the brainstem and optic apparatus. Results Of 230 patients with skull base chordoma or chondrosarcoma referred for PBT, 71% were accepted for PBT, with a wide regional variation between referring neurosurgical units (29%–93%). Of the first 75 consecutive patients treated with PBT, the only factor predictive of obtaining GTR was surgical resection at a unit with higher volumes of patients accepted for PBT (OR 1.32, 95% CI 1.11 to 1.63, p=0.004). Use of intraoperative MRI (OR 4.84, 95% CI 1.21 to 27.83, p=0.04) and resection at a higher volume unit (OR 1.29, 95% CI 1.07 to 1.64, p=0.013) were associated with increased rates of tumour clearance from the brainstem/optic apparatus. Conclusions Treatment at a higher volume centre was a key determinant of the optimal surgical outcome in this cohort. These data support the management of skull base chordomas and chondrosarcomas in higher volume centres where multidisciplinary experience can be accumulated.

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GCT-12. OUTCOMES OF INTRACRANIAL NON-GERMINOMATOUS GERM CELL TUMOURS (NGGCT) TREATED AT A SINGLE UK PROTON CENTRE ACCORDING TO UK CHILDREN’S CANCER AND LEUKAEMIA GROUP (CCLG) GUIDANCE, INCLUDING EARLY IMPROVED OUTCOMES USING WHOLE VENTRICULAR RADIOTHERAPY (WVRT) FOR LOCALISED DISEASE

June 2024

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21 Reads

Neuro-Oncology

BACKGROUND After SIOP-CNS-GCT-II closed in 2018, the CCLG recommended, with caveats, following standard trial arms: 4 Cisplatin-Etoposide-Ifosfamide (PEI) cycles, then focal radiotherapy (FRT) (54Gy/30fractions) to primary site(s) for localised NGGCT and craniospinal-irradiation (CSI) (30Gy/20fr) + boosts (24Gy/15fr cranial, 20.8Gy/13fr spinal) for metastatic disease. Since 04/2021, the CCLG formally recommended adding WVRT (24Gy/15fr) for localised NGGCT, and considering 2x standard, 2x high-dose PEI for high-risk (HR) cases (diagnostic AFP>1000ng/ml). METHODS Retrospective review of all CNS-NGGCT patients referred 12/2018-06/2023. We collected patient, tumour and treatment factors, acute toxicities (CTCAE grade≥3), and event-free survival (EFS) from radiotherapy until 09/2023. RESULTS Twenty-four patients (21M:3F) included, 14 localised (4xHR), 10 (including 2 incompletely staged) treated as metastatic (3xHR). Median age 11 years, median follow-up 16 months (m). Primary sites: 13 pineal, 5 pituitary/suprasellar, 6 bifocal. Patients were treated according to CCLG guidance. One received FRT without WVRT. One incompletely staged bifocal standard-risk (SR) NGGCT after partial response to PEI had surgery, local+metastatic progression, then second-line chemotherapy before CSI. All seven HR patients received intensified chemotherapy. Nine had post-chemotherapy surgery for residual, two showing necrosis/inflammation, three mature teratoma, two mixed viable GCT. Three relapses (1/17 SR, 2/7 HR) made early EFS 0.875. Of 13 localised patients receiving WVRT, 2 progressed. One bifocal SR patient developed spinal metastases at 5.0m and died despite chemotherapy+spinal irradiation. One unifocal HR patient developed posterior parafalcine metastasis at 3.9m, received GemPOx (Gemcitabine-Paclitaxel-Oxaliplatin), surgery, high dose Carboplatin-Etoposide-Thiotepa with stem-cell rescue, and photon CSI and remains disease-free at 13.2m. One metastatic HR patient progressed at 0.9m and died at 3.0m despite chemotherapy. Acute toxicities were grade 3 lymphopenia in two CSI patients. CONCLUSIONS Despite short follow-up, initial EFS is excellent in SR disease. No localised WRVT-receiving NGGCT patient progressed within the ventricular volume, suggesting benefit of low-dose WVRT.


GCT-13. OUTCOMES OF INTRACRANIAL GERMINOMA TREATED AT A SINGLE UK PROTON CENTRE ACCORDING TO UK CHILDREN’S CANCER AND LEUKAEMIA GROUP (CCLG) GUIDELINES

June 2024

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11 Reads

Neuro-Oncology

BACKGROUND After SIOP-CNS-GCT II closed in 2018, the CCLG recommended, with caveats, following the standard trial arms: 4 cycles of chemotherapy (Etoposide-Carboplatin alternating with Etoposide-Ifosfamide) followed by whole ventricular radiotherapy (WVRT) (24Gy/15fractions) and boost (16Gy/10fr) to the primary site(s) for localised germinoma and craniospinal irradiation (CSI) (24Gy/15fr) followed by boost (16Gy/10fr) to primary and metastatic sites for metastatic disease. Since 04/2021, the CCLG formally recommended omitting the boost for localised unifocal germinoma in complete radiological response after chemotherapy. From autumn 2022, we also omitted boosts to completely responded primary sites for localised bifocal germinoma. METHODS Retrospective reviewed of all patients referred to our proton centre 12/2018–06/2023. We collected patient, tumour and treatment factors, acute toxicities (CTCAE grade≥3), and event-free survival(EFS) from radiotherapy until 09/2023. RESULTS Forty-two patients (36M:6F) were included, 23 localised and 19 (including 3 incompletely staged) treated as metastatic. Primary sites: 21 pineal, 8 pituitary/suprasellar, 10 bifocal and 3 atypical (optic nerve, periventricular, thalamic). Diagnosis was by histopathology in 40 and bifocal disease with negative CSF and serum markers in 2. Median age was 15 years (IQR 13-16), median follow-up 13 months (IQR 6-15). Patients were treated according to CCLG guidance, apart from three patients with metastatic pure germinoma, of whom one received 2 cycles Cisplatin-Etoposide, and two received 5 and 3 cycles of Vinblastine before CSI, and one patient with metastatic germinoma plus teratoma who received 2 cycles of Cisplatin-Etoposide and non-germinoma radiotherapy doses (30Gy/20fr CSI, 24Gy/15fr cranial boosts). No patient had subsequent surgery. All remained progression free at last follow-up. Eight patients developed acute grade 3 toxicities: 3 vomiting (2 CSI, 1 WVRT), and 5 lymphopenia (all CSI). CONCLUSIONS Disease control was excellent, with no relapses to date. Proton therapy was well tolerated with low rates of acute high grade toxicities.






Citations (12)


... The prospective EORTC 22042-26042 trial reported superior local control with doseescalation to 60Gy in WHO Grade 2 meningiomas, but did not come to definitive conclusions surrounding the outcomes for WHO Grade 3 meningiomas [40]. Separate studies have reported superior local control in grade 2 and 3 meningiomas in cohorts of patients dose-escalated to ≥60Gy [41,42]. ...

Reference:

Management approaches in WHO Grade III Meningioma: a National Oncology Trainees' Collaborative for Healthcare Research (NOTCH) UK multi-centre retrospective study
Radiotherapy intensification for atypical and malignant meningiomas: A systematic review
  • Citing Article
  • December 2023

Neuro-Oncology Practice

... Finally, the choice of particles including proton and ion therapies could improve the treatment of relapsed tumor by reducing the delivered dose in the healthy tissues and/or by increasing the dose into the tumor [90][91][92][93][94]. ...

Proton Beam Therapy in the Reirradiation Setting of Brain and Base of Skull Tumour Recurrences
  • Citing Article
  • August 2023

Clinical Oncology

... 10 Despite the different treatment options available, the decision to pursue specific therapies is dependent on several patient and tumor characteristics. 11,12 In this report, we present the case of a facial nerve schwannoma that experienced significant hearing improvement after radiation therapy. This is a rare clinical finding given the high rates of hearing decline that is most often documented after radiation to tumors within this region of the brain. ...

Surgery vs radiosurgery for vestibular schwannoma: shared decision making in a multi-disciplinary clinic

Neuro-Oncology Advances

... Photon-based stereotactic radiosurgery (SRS) and stereotactic body radiotherapy have recently emerged as promising treatment options for patients with cranial and extra-cranial oligometastatic diseases (Videtic 2014, Ahmed and Torres-Roca 2016, Chen et al 2020, Onderdonk et al 2020, and their role in combination with systemic therapies is well established (Dengina et al 2019, Tonse et al 2021. Per contra, there are only very few clinical studies considering proton therapy for the treatment of oligo-and poly-metastatic cancer patients (Gaito et al 2023), even though selected patients with multiple metastases may benefit from reduced integral dose through proton beams. For example, in patients with large tumor burden in the liver, protons may allow for dose escalation, whereas in patients repeatedly treated for multiple brain metastases, protons may reduce integral dose to the brain. ...

Proton Beam Therapy in the Oligometastatic/Oligorecurrent Setting: Is There a Role? A Literature Review

... 46 A phase I POBIG trial with awaited results tests the preoperative stereotactic radiosurgery followed by maximal safe resection and standard adjuvant CRT and TMZ. 47 When it comes to preoperative systemic therapy, we only found 2 studies that looked into the impact of neoadjuvant chemotherapy on surgical results for those with GBM. This is shown in Table 1. ...

Study protocol: PreOperative Brain Irradiation in Glioblastoma (POBIG) - A phase I trial

Clinical and Translational Radiation Oncology

... Much attention is given to the reduction of machine physical footprints and power consumption, while delivering high intensity beams (1×10 10 particles per extraction cycle) to enable efficient treatment delivery [6,7]. These critical changes will improve access to particle therapy, which could benefit around 10% of radiotherapy patients [8], but is far less available than conventional radiotherapy [9]. ...

Estimating the percentage of patients who might benefit from proton beam therapy instead of X-ray radiotherapy

The British journal of radiology

... Primary SGLTS are considered to be derived from neoplastic transformation of SGRs in the sella. SGLTS cover a morphologic spectrum more typical of salivary gland neoplasia, including pleomorphic adenoma [31,35], adenocarcinoma [31,36], acinic cell carcinoma [37], adenoid cystic carcinoma [36], and epithelial-myoepithelial carcinoma [38]. In 2007, van Furth et al. reviewed 12 previously reported cases of SGLTS [37], and subsequently new cases of pleomorphic adenoma and symptomatic salivary gland rest cysts in the sella have been reported, as part of the benign spectrum of SGLTS [39,40]. ...

Primary epithelial‐myoepithelial carcinoma of the pituitary gland
  • Citing Article
  • January 2020

Neuropathology

... Those patients for whom late follow-up data were missing were reported as unknown, as the definition threshold was not met. As literature evidence suggests that surgery may impact on late RISTs [31,32], specific radiotherapy toxicities, such as telangiectasia and hyperpigmentation, were reported separately. ...

Acute and late skin toxicity assessment in paediatric/young adult patients with Ewing’s sarcomas treated with chemo-radiotherapy

... 1,2 Radiation-induced brain injury, particularly following stereotactic radiosurgery, [3][4][5][6][7] accounts for 68% of such complications, including radiation necrosis, with a frequency of 3%-24%. 4,[8][9][10] Risk factors for radiation necrosis include the radiation dose, fractionation, the use of chemotherapy (especially concurrent chemotherapy), reirradiation, and additional boost irradiation. 4,11 The pathogenesis of radiation-induced brain injury is still poorly understood but is known to involve vascular endothelial cell injury, glial cell damage, and autoimmune reaction. ...

Radiation Necrosis following SRS for Brain Metastases: is there an Increased Incidence with Immunotherapy and Targeted Therapy?
  • Citing Article
  • June 2018

Clinical Oncology

... This shift signifies that ODG diagnosis integrates both histopathological and molecular criteria, rather than relying solely on histopathology. The 1p/19q co-deletion is recognized as an early event in oligodendroglioma tumorigenesis, resulting from an unbalanced whole-arm translocation between chromosomes 1 and 19 [3,4]. This diagnostic criterion has been retained in the latest (5th) edition of the WHO classification [5]. ...

FISHing Tips: What Every Clinician Should Know About 1p19q Analysis in Gliomas Using Fluorescence in situ Hybridisation
  • Citing Article
  • May 2015

Clinical Oncology