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Article ; Online: Circulating Human Papillomavirus DNA as a Marker of Minimally Residual Disease After Surgery for Oropharyngeal Cancer.

Bhide, Shreerang

International journal of radiation oncology, biology, physics

2022 Volume 113, Issue 3, Page(s) 539–541

MeSH term(s)	Alphapapillomavirus ; DNA ; Humans ; Neoplasm, Residual ; Oropharyngeal Neoplasms/surgery ; Papillomavirus Infections/complications
Chemical Substances	DNA (9007-49-2)
Language	English
Publishing date	2022-07-01
Publishing country	United States
Document type	Editorial ; Comment
ZDB-ID	197614-x
ISSN	1879-355X ; 0360-3016
ISSN (online)	1879-355X
ISSN	0360-3016
DOI	10.1016/j.ijrobp.2022.03.022
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Article ; Online: Quantitative analysis of diffusion weighted imaging in rectal cancer during radiotherapy using a magnetic resonance imaging integrated linear accelerator.

Ingle, Manasi / Blackledge, Matthew / White, Ingrid / Wetscherek, Andreas / Lalondrelle, Susan / Hafeez, Shaista / Bhide, Shreerang

Physics and imaging in radiation oncology

2022 Volume 23, Page(s) 32–37

Abstract: Background and purpose: Magnetic resonance imaging integrated linear accelerator (MR-Linac) platforms enable acquisition of diffusion weighted imaging (DWI) during treatment providing potential information about treatment response. Obtaining DWI on ... ...

Abstract	Background and purpose: Magnetic resonance imaging integrated linear accelerator (MR-Linac) platforms enable acquisition of diffusion weighted imaging (DWI) during treatment providing potential information about treatment response. Obtaining DWI on these platforms is technically different from diagnostic magnetic resonance imaging (MRI) scanners. The aim of this project was to determine feasibility of obtaining DWI and calculating apparent diffusion coefficient (ADC) parameters longitudinally in rectal cancer patients on the MR-Linac. Materials and methods: Nine patients undergoing treatment on MR-Linac had DWI acquired using b-values 0, 30, 150, 500 s/mm Results: Seven out of nine patients were included in the analysis; all demonstrated downstaging at follow-up. A total of 63 out of 70 DWI were analysed (7 excluded due to poor image quality). An increasing trend of ADC median for GTV (1.15 × 10 Conclusions: DWI assessment in rectal cancer patients on MR-Linac is feasible. Initial results provide foundations for further studies to determine DWI use for treatment adaptation in rectal cancer.
Language	English
Publishing date	2022-06-10
Publishing country	Netherlands
Document type	Journal Article
ISSN	2405-6316
ISSN (online)	2405-6316
DOI	10.1016/j.phro.2022.06.003
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Article: T-cell receptor determinants of response to chemoradiation in locally-advanced HPV16-driven malignancies.

Nenclares, Pablo / Larkeryd, Adrian / Manodoro, Floriana / Lee, Jen Y / Lalondrelle, Susan / Gilbert, Duncan C / Punta, Marco / O'Leary, Ben / Rullan, Antonio / Sadanandam, Anguraj / Chain, Benny / Melcher, Alan / Harrington, Kevin J / Bhide, Shreerang A

Frontiers in oncology

2024 Volume 13, Page(s) 1296948

Abstract: Background: The effect of chemoradiation on the anti-cancer immune response is being increasingly acknowledged; however, its clinical implications in treatment responses are yet to be fully understood. Human papillomavirus (HPV)-driven malignancies ... ...

Abstract	Background: The effect of chemoradiation on the anti-cancer immune response is being increasingly acknowledged; however, its clinical implications in treatment responses are yet to be fully understood. Human papillomavirus (HPV)-driven malignancies express viral oncogenic proteins which may serve as tumor-specific antigens and represent ideal candidates for monitoring the peripheral T-cell receptor (TCR) changes secondary to chemoradiotherapy (CRT). Methods: We performed intra-tumoral and pre- and post-treatment peripheral TCR sequencing in a cohort of patients with locally-advanced HPV16-positive cancers treated with CRT. An in silico computational pipeline was used to cluster TCR repertoire based on epitope-specificity and to predict affinity between these clusters and HPV16-derived epitopes. Results: Intra-tumoral repertoire diversity, intra-tumoral and post-treatment peripheral CDR3β similarity clustering were predictive of response. In responders, CRT triggered an increase peripheral TCR clonality and clonal relatedness. Post-treatment expansion of baseline peripheral dominant TCRs was associated with response. Responders showed more baseline clustered structures of TCRs maintained post-treatment and displayed significantly more maintained clustered structures. When applying clustering by TCR-specificity methods, responders displayed a higher proportion of intra-tumoral TCRs predicted to recognise HPV16 peptides. Conclusions: Baseline TCR characteristics and changes in the peripheral T-cell clones triggered by CRT are associated with treatment outcome. Maintenance and boosting of pre-existing clonotypes are key elements of an effective anti-cancer immune response driven by CRT, supporting a paradigm in which the immune system plays a central role in the success of CRT in current standard-of-care protocols.
Language	English
Publishing date	2024-01-03
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2649216-7
ISSN	2234-943X
ISSN	2234-943X
DOI	10.3389/fonc.2023.1296948
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Article ; Online: FUME-TCRseq Enables Sensitive and Accurate Sequencing of the T-cell Receptor from Limited Input of Degraded RNA.

Baker, Ann-Marie / Nageswaran, Gayathri / Nenclares, Pablo / Ronel, Tahel / Smith, Kane / Kimberley, Christopher / Laclé, Miangela M / Bhide, Shreerang / Harrington, Kevin J / Melcher, Alan / Rodriguez-Justo, Manuel / Chain, Benny / Graham, Trevor A

Cancer research

2024 Volume 84, Issue 10, Page(s) 1560–1569

Abstract: Genomic analysis of the T-cell receptor (TCR) reveals the strength, breadth, and clonal dynamics of the adaptive immune response to pathogens or cancer. The diversity of the TCR repertoire, however, means that sequencing is technically challenging, ... ...

Abstract	Genomic analysis of the T-cell receptor (TCR) reveals the strength, breadth, and clonal dynamics of the adaptive immune response to pathogens or cancer. The diversity of the TCR repertoire, however, means that sequencing is technically challenging, particularly for samples with low-quality, degraded nucleic acids. Here, we developed and validated FUME-TCRseq, a robust and sensitive RNA-based TCR sequencing methodology that is suitable for formalin-fixed paraffin-embedded samples and low amounts of input material. FUME-TCRseq incorporates unique molecular identifiers into each molecule of cDNA, allowing correction for sequencing errors and PCR bias. Using RNA extracted from colorectal and head and neck cancers to benchmark the accuracy and sensitivity of FUME-TCRseq against existing methods demonstrated excellent concordance between the datasets. Furthermore, FUME-TCRseq detected more clonotypes than a commercial RNA-based alternative, with shorter library preparation time and significantly lower cost. The high sensitivity and the ability to sequence RNA of poor quality and limited amount enabled quantitative analysis of small numbers of cells from archival tissue sections, which is not possible with other methods. Spatially resolved FUME-TCRseq analysis of colorectal cancers using macrodissected archival samples revealed the shifting T-cell landscapes at the transition to an invasive phenotype and between tumor subclones containing distinct driver alterations. In summary, FUME-TCRseq represents an accurate, sensitive, and low-cost tool for the characterization of T-cell repertoires, particularly in samples with low-quality RNA that have not been accessible using existing methodology. Significance: FUME-TCRseq is a TCR sequencing methodology that supports sensitive and spatially resolved detection of TCR clones in archival clinical specimens, which can facilitate longitudinal tracking of immune responses through disease course and treatment.
MeSH term(s)	Humans ; Receptors, Antigen, T-Cell/genetics ; Receptors, Antigen, T-Cell/immunology ; Colorectal Neoplasms/genetics ; Colorectal Neoplasms/immunology ; High-Throughput Nucleotide Sequencing/methods ; Sequence Analysis, RNA/methods ; Head and Neck Neoplasms/genetics ; Head and Neck Neoplasms/immunology ; RNA/genetics ; RNA Stability
Language	English
Publishing date	2024-03-13
Publishing country	United States
Document type	Journal Article
ZDB-ID	1432-1
ISSN	1538-7445 ; 0008-5472
ISSN (online)	1538-7445
ISSN	0008-5472
DOI	10.1158/0008-5472.CAN-23-3340
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Article: Early-Stage Glottic Squamous Cell Carcinoma in the Era of Image-Guided Radiotherapy.

Gupta, Amit / Wong, Kee Howe / Newbold, Kate / Bhide, Shreerang / Nutting, Chris / Harrington, Kevin Joseph

Frontiers in oncology

2021 Volume 11, Page(s) 753908

Abstract: Early-stage squamous cell cancer (SCC) of the glottis has a good prognosis. Therefore, patients have long survival outcomes and may potentially suffer from late toxicities of radiotherapy. Radiotherapy with a conventional parallel-opposed-pair or ... ...

Abstract	Early-stage squamous cell cancer (SCC) of the glottis has a good prognosis. Therefore, patients have long survival outcomes and may potentially suffer from late toxicities of radiotherapy. Radiotherapy with a conventional parallel-opposed-pair or anterior-oblique beam arrangements for stage 1 and 2 glottic SCC have field borders that traditionally cover the entire larynx, exposing organs-at-risk (e.g. carotid arteries, contralateral vocal cord, contralateral arytenoid and inferior pharyngeal constrictor muscles) to high radiation doses. The potential long-term risk of cerebrovascular events has attracted much attention to the dose that carotid arteries receive. Swallow and respiratory motion of laryngeal structures has been an important factor that previously limited reduction of the radiation treatment volume. Motion has been evaluated using multiple imaging modalities and this information has been used to calculate PTV margins for generation of more limited target volumes. This review discusses the current literature surrounding dose-effect relationships for various organs-at-risk and the late toxicities that are associated with them. This article also reviews the currently available data and effects of laryngeal motions on dosimetry to the primary target. We also review the current limitations and benefits of a more targeted approach of radiotherapy for early-stage glottic SCCs and the evolution of CT-based IGRT and MR-guided radiotherapy techniques that may facilitate a shift away from a conventional 3D-conformal radiotherapy approach.
Language	English
Publishing date	2021-09-20
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2649216-7
ISSN	2234-943X
ISSN	2234-943X
DOI	10.3389/fonc.2021.753908
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Article ; Online: Systematic review and meta-analysis of occult contralateral nodal metastases in patients with oropharyngeal squamous carcinoma undergoing elective neck dissection.

Malik, Akshat / Hardman, John C / Devabalan, Yadsan / Nutting, Christopher / Bhide, Shreerang / Harrington, Kevin / Schilling, Clare / Paleri, Vinidh

European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology

2022 Volume 49, Issue 2, Page(s) 316–322

Abstract: A systematic review and meta-analysis was conducted to evaluate the occult contralateral nodal metastases (OCM) in patients undergoing bilateral neck dissection for surgically treated oropharyngeal squamous cell carcinoma (OPSCC). Following PRISMA ... ...

Abstract	A systematic review and meta-analysis was conducted to evaluate the occult contralateral nodal metastases (OCM) in patients undergoing bilateral neck dissection for surgically treated oropharyngeal squamous cell carcinoma (OPSCC). Following PRISMA guidelines, MEDLINE, Embase and Cochrane Controlled Register of Trials databases were searched for observational and experimental studies until March 2021. Search yielded 175 articles, of which 13 were included. Overall, OCM were seen in 9.8% of patients (95% CI: [5.7, 16.4], 839 patients, 12 studies, I
MeSH term(s)	Humans ; Neck Dissection ; Squamous Cell Carcinoma of Head and Neck/pathology ; Neoplasm Staging ; Carcinoma, Squamous Cell/pathology ; Retrospective Studies ; Lymphatic Metastasis ; Head and Neck Neoplasms/pathology
Language	English
Publishing date	2022-10-13
Publishing country	England
Document type	Meta-Analysis ; Systematic Review ; Journal Article ; Review
ZDB-ID	632519-1
ISSN	1532-2157 ; 0748-7983
ISSN (online)	1532-2157
ISSN	0748-7983
DOI	10.1016/j.ejso.2022.10.004
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Zs.A 1149: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article: Measurement and Incorporation of Laryngeal Motion Using cine-MRI on an MR-Linear Accelerator to Generate Radiation Therapy Plans for Early-stage Squamous Cell Cancers of the Glottis.

Gupta, Amit / McQuaid, Dualta / Dunlop, Alex / Barnes, Helen / Mohajer, Jonathan / Smith, Gillian / Nartey, Jayde / Morrison, Kian / Herbert, Trina / Alexander, Sophie / McNair, Helen / Newbold, Kate / Nutting, Chris / Bhide, Shreerang / Harrington, Kevin Joseph / Wong, Kee Howe

Advances in radiation oncology

2024 Volume 9, Issue 6, Page(s) 101490

Abstract: Purpose: Swallow-related motion of the larynx is most significant in the cranio-caudal directions and of` short duration. Conventional target definition for radical radiation therapy includes coverage of the whole larynx. This study longitudinally ... ...

Abstract	Purpose: Swallow-related motion of the larynx is most significant in the cranio-caudal directions and of` short duration. Conventional target definition for radical radiation therapy includes coverage of the whole larynx. This study longitudinally examined respiration- and swallow-related laryngeal motions using cine-magnetic resonance imaging. We further analyzed the dosimetry to organs at risk by comparing 3D-conformal radiation therapy (3D-CRT), volumetric modulated arc therapy (VMAT), and intensity modulated radiation therapy (IMRT) techniques. Methods: Fifteen patients with T1-2 N0 glottic squamous cell carcinomas were prospectively recruited for up to 3 cine-MRI scans on the Elekta Unity MR-Linear accelerator, at the beginning, middle, and end of a course of radical radiation therapy. Swallow frequency and motion of the hyoid bone, cricoid and thyroid cartilages, and vocal cords were recorded during swallow and rest. Adapted treatment volumes consisted of gross tumor volume + 0.5-1 cm to a clinical target volume with an additional internal target volume (ITV) for personalized resting-motion. Swallow-related motion was deemed infrequent and was not accounted for in the ITV. We compared radiation therapy plans for 3D-CRT (whole larynx), VMAT (whole larynx), and VMAT and IMRT (ITV for resting motion). Results: Resting- and swallow-related motions were most prominent in the cranio-caudal plane. There were no significant changes in the magnitude of motion over the course of radiation therapy. There was a trend of a progressive reduction in the frequency of swallow. Treatment of partial larynx volumes with intensity modulated methods significantly reduced the dose to carotid arteries, compared with treatment of whole larynx volumes. Robustness analysis demonstrated that when accounting for intrafraction swallow, the total dose delivered to the ITV/planning target volume was maintained at above 95%. Conclusions: Swallow-related motions are infrequent and accounting for resting motion in an ITV is sufficient. VMAT/IMRT techniques that treat more conformal targets can significantly spare critical organs at risk such as the carotid arteries and thyroid gland, potentially reducing the risk of carotid artery stenosis-related complications and other long-term complications.
Language	English
Publishing date	2024-03-12
Publishing country	United States
Document type	Journal Article
ISSN	2452-1094
ISSN	2452-1094
DOI	10.1016/j.adro.2024.101490
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Article: Predicting Response to Radical Chemoradiotherapy with Circulating HPV DNA (cHPV-DNA) in Locally Advanced Uterine Cervix Cancer.

Lalondrelle, Susan / Lee, Jen / Cutts, Rosalind J / Garcia Murillas, Isaac / Matthews, Nik / Turner, Nicholas / Harrington, Kevin / Vroobel, Katherine / Moretti, Emily / Bhide, Shreerang A

Cancers

2023 Volume 15, Issue 5

Abstract: Background: The majority of locally advanced cervical cancers (LaCC) are causally related to HPV. We sought to investigate the utility of an ultra-sensitive HPV-DNA next generation sequencing (NGS) assay-panHPV-detect-in LaCC treated with ... ...

Abstract	Background: The majority of locally advanced cervical cancers (LaCC) are causally related to HPV. We sought to investigate the utility of an ultra-sensitive HPV-DNA next generation sequencing (NGS) assay-panHPV-detect-in LaCC treated with chemoradiotherapy, as a marker of treatment response and persistent disease. Method: Serial blood samples were collected from 22 patients with LaCC before, during and after chemoradiation. The presence of circulating HPV-DNA was correlated with clinical and radiological outcomes. Results: The panHPV-detect test demonstrated a sensitivity and specificity of 88% (95% CI-70-99%) and 100% (95% CI-30-100%), respectively, and correctly identified the HPV-subtype (16, 18, 45, 58). After a median follow up of 16 months, and three relapses all had detectable cHPV-DNA at 3 months post-CRT despite complete response on imaging. Another four patients with radiological partial or equivocal response and undetectable cHPV-DNA at the 3-month time point did not go on to develop relapse. All patients with radiological CR and undetectable cHPV-DNA at 3-months remained disease free. Conclusions: These results demonstrate that the panHPV-detect test shows high sensitivity and specificity for detecting cHPV-DNA in plasma. The test has potential applications in assessment of the response to CRT and in monitoring for relapse, and these initial findings warrant validation in a larger cohort.
Language	English
Publishing date	2023-02-22
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers15051387
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Article: Circulating HPV DNA as a Biomarker for Pre-Invasive and Early Invasive Cervical Cancer: A Feasibility Study.

Bryan, Stacey J / Lee, Jen / Gunu, Richard / Jones, Allison / Olaitan, Adeola / Rosenthal, Adam N / Cutts, Ros J / Garcia-Murillas, Isaac / Turner, Nick / Lalondrelle, Susan / Bhide, Shreerang A

Cancers

2023 Volume 15, Issue 9

Abstract: Background: High-risk HPV infection is responsible for >99% of cervix cancers (CC). In persistent infections that lead to cancer, the tumour breaches the basement membrane, releasing HPV-DNA into the bloodstream (cHPV-DNA). A next-generation sequencing ... ...

Abstract	Background: High-risk HPV infection is responsible for >99% of cervix cancers (CC). In persistent infections that lead to cancer, the tumour breaches the basement membrane, releasing HPV-DNA into the bloodstream (cHPV-DNA). A next-generation sequencing assay (NGS) for detection of plasma HPV circulating DNA (cHPV-DNA) has demonstrated high sensitivity and specificity in patients with locally advanced cervix cancers. We hypothesised that cHPV-DNA is detectable in early invasive cervical cancers but not in pre-invasive lesions (CIN). Methods: Blood samples were collected from patients with CIN ( Results: None of the patients with pre-invasive lesions were positive for CHPV-DNA. In invasive tumours, plasma from one patient (10%) reached the threshold of positivity for cHPV-DNA in plasma. Conclusion: Low detection of cHPV-DNA in early CC may be explained by small tumour size, poorer access to lymphatics and circulation, and therefore little shedding of cHPV-DNA in plasma at detectable levels. The detection rate of cHPV-DNA in patients with early invasive cervix cancer using even the most sensitive of currently available technologies lacks adequate sensitivity for clinical utility.
Language	English
Publishing date	2023-05-02
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers15092590
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Article ; Online: Practice patterns for the radical treatment of nasopharyngeal cancer by head and neck oncologists in the United Kingdom.

Petkar, Imran / Bhide, Shreerang / Newbold, Kate / Harrington, Kevin / Nutting, Chris

The British journal of radiology

2018 Volume 91, Issue 1085, Page(s) 20170590

Abstract: Objective: Advances in radiation delivery, imaging techniques, and chemotherapy have significantly improved treatment options for non-metastatic nasopharyngeal cancers (NPC). However, their impact on the practice in the United Kingdom (UK), where this ... ...

Abstract	Objective: Advances in radiation delivery, imaging techniques, and chemotherapy have significantly improved treatment options for non-metastatic nasopharyngeal cancers (NPC). However, their impact on the practice in the United Kingdom (UK), where this tumour is rare, is unknown. This study examined the current attitudes of UK head and neck oncologists to the treatment of NPC. Methods: UK head and neck oncologists representing 19/23 cancer networks were sent an invitation email with a personalised link to a web-based survey designed to identify the influence of tumour and nodal staging on current NPC management practices. Results: 26/42 (61%) of clinicians responded. Induction chemotherapy followed by concomitant chemoradiation was the treatment of choice for Stage III (69%) and IVa/b (96%), with cisplatin and 5-fluorouracil combination being the most commonly used induction chemotherapy regimen (88%). 16 centres (61%) used a geometric approach, adding variable margins of 0-10 mm to the gross tumour volume to define their therapeutic dose clinical target volume. 54% of respondents used 3 radiotherapy (RT) prescription doses to treat NPC. Retropharyngeal nodal region irradiation policy was inconsistent, with nearly one-quarter treating the entire group to a radical dose. Conclusion: Significant heterogeneity currently exists in the RT practice of NPC in the UK. A consensus regarding the optimal curative, function-sparing treatment paradigm for NPC is necessary to ensure cancer survivors have satisfactory long-term health-related quality of life. Advances in knowledge: This is the first study to highlight the significant variation in RT practice of NPC in the UK.
MeSH term(s)	Head/pathology ; Humans ; Nasopharyngeal Neoplasms/drug therapy ; Nasopharyngeal Neoplasms/pathology ; Nasopharyngeal Neoplasms/radiotherapy ; Neck/pathology ; Neoplasm Staging ; Oncologists ; Practice Patterns, Physicians' ; United Kingdom
Language	English
Publishing date	2018-02-13
Publishing country	England
Document type	Journal Article ; Observational Study
ZDB-ID	2982-8
ISSN	1748-880X ; 0007-1285
ISSN (online)	1748-880X
ISSN	0007-1285
DOI	10.1259/bjr.20170590
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