The use of pembrolizumab monotherapy for the management of head and neck squamous cell carcinoma (HNSCC) in the UK.

Pembrolizumab has received approval in the UK as first-line monotherapy for recurrent and/or metastatic HNSCC (R/M HNSCC) following the results of the KEYNOTE-048 trial, which demonstrated a longer overall survival (OS) in comparison to the EXTREME chemotherapy regimen in patients with a combined positive score (CPS) ≥1. In this article, we provide retrospective real-world data on the role of pembrolizumab monotherapy as first-line systemic therapy for HNSCC across 18 centers in the UK from March 20, 2020 to May 31, 2021. 211 patients were included, and in the efficacy analysis, the objective response rate (ORR) was 24.7%, the median progression-free survival (PFS) was 4.8 months (95% confidence interval [CI]: 3.6-6.1), and the median OS was 10.8 months (95% CI 9.0-12.5). Pembrolizumab monotherapy was well tolerated, with 18 patients having to stop treatment owing to immune-related adverse events (irAEs). 53 patients proceeded to second-line treatment with a median PFS2 of 10.2 months (95% CI: 8.8-11.5). Moreover, patients with documented irAEs had a statistically significant longer median PFS (11.3 vs. 3.3 months; log-rank p value = <.001) and median OS (18.8 vs. 8.9 months; log-rank p value <.001). The efficacy and safety of pembrolizumab first-line monotherapy for HNSCC has been validated using real-world data.

Single vs. multiple fraction non-inferiority trial of stereotactic ablative radiotherapy for the comprehensive treatment of oligo-metastases/progression: SIMPLIFY-SABR-COMET.

BACKGROUND: Radiotherapy delivery regimens can vary between a single fraction (SF) and multiple fractions (MF) given daily for up to several weeks depending on the location of the cancer or metastases. With limited evidence comparing fractionation regimens for oligometastases, there is support to explore toxicity levels to nearby organs at risk as a primary outcome while using SF and MF stereotactic ablative radiotherapy (SABR) as well as explore differences in patient-reported quality of life and experience. METHODS: This study will randomize 598 patients in a 1:1 ratio between the standard arm (MF SABR) and the experimental arm (SF SABR). This trial is designed as two randomized controlled trials within one patient population for resource efficiency. The primary objective of the first randomization is to determine if SF SABR is non-inferior to MF SABR, with respect to healthcare provider (HCP)-reported grade 3-5 adverse events (AEs) that are related to SABR. Primary endpoint is toxicity while secondary endpoints include lesional control rate (LCR), and progression-free survival (PFS). The second randomization (BC Cancer sites only) will allocate participants to either complete quality of life (QoL) questionnaires only; or QoL questionnaires and a symptom-specific survey with symptom-guided HCP intervention. The primary objective of the second randomization is to determine if radiation-related symptom questionnaire-guided HCP intervention results in improved reported QoL as measured by the EuroQoL-5-dimensions-5levels (EQ-5D-5L) instrument. The primary endpoint is patient-reported QoL and secondary endpoints include: persistence/resolution of symptom reporting, QoL, intervention cost effectiveness, resource utilization, and overall survival. DISCUSSION: This study will compare SF and MF SABR in the treatment of oligometastases and oligoprogression to determine if there is non-inferior toxicity for SF SABR in selected participants with 1-5 oligometastatic lesions. This study will also compare patient-reported QoL between participants who receive radiation-related symptom-guided HCP intervention and those who complete questionnaires alone. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT05784428. Date of Registration: 23 March 2023.

Considerations for the treatment of pancreatic cancer during the COVID-19 pandemic: the UK consensus position.

The coronavirus disease 2019 (COVID-19) pandemic epicentre has moved to the USA and Europe, where it is placing unprecedented demands on healthcare resources and staff availability. These service constraints, coupled with concerns relating to an increased incidence and severity of COVID-19 among patients with cancer, should lead to re-consideration of the risk-benefit balance for standard treatment pathways. This is of particular importance to pancreatic cancer, given that standard diagnostic modalities such as endoscopy may be restricted, and that disease biology precludes significant delays in treatment. In light of this, we sought consensus from UK clinicians with an interest in pancreatic cancer for management approaches that would minimise patient risk and accommodate for healthcare service restrictions. The outcomes are described here and include recommendations for treatment prioritisation, strategies to bridge to later surgical resection in resectable disease and factors that modify the risk-benefit balance for treatment in the resectable through to the metastatic settings. Priority is given to strategies that limit hospital visits, including through the use of hypofractionated precision radiotherapy and chemoradiotherapy treatment approaches.

Comparative cohort study of volumetric modulated arc therapy for squamous cell cancer of unknown primary in the head and neck-Involved neck only versus mucosal irradiation.

OBJECTIVES: Target volumes for irradiation remain ill-defined for squamous cell cancer of unknown primary in the head and neck (SCCUP). The aim of this study was to compare involved neck only (INO) radiotherapy (RT) with irradiating involved neck plus potential mucosal primary sites and contralateral neck (MUC) in patients diagnosed and treated with modern diagnostics and techniques. DESIGN: This is a retrospective cohort study. Patients with a diagnosis of SCCUP with unilateral neck disease were included. RESULTS: Thirty patients were identified. All underwent FDG PET-CT. 47% of patients had HPV-positive SCC. 20 patients received RT to INO, 10 patients to MUC, all with volumetric modulated arc therapy (VMAT). A significantly lower dose for each organ at risk was delivered in INO-treated patients, with mean dose to contralateral parotid gland 57% less. The proportion of patients with late grade 2 or worse xerostomia was higher in MUC patients. The incidence of grade 2-3 mucositis (89% vs 45%) and grade 3 or worse dysphagia (50% vs 10%) was higher in MUC patients. Median follow-up was 31 months. No mucosal primaries emerged. Progression-free survival at 2 years was 74.7% for INO patients, 70% in the MUC group. Overall survival at 2 years was 79.7% in the INO group and 70% in the MUC patients. CONCLUSION: INO radiotherapy for patients with SCCUP of the head and neck is a safe treatment strategy resulting in clinically significant lower RT doses to OARS. Acute and late toxicities are reduced without detriment to patient survival.

A phase-I trial of pre-operative, margin intensive, stereotactic body radiation therapy for pancreatic cancer: the 'SPARC' trial protocol.

BACKGROUND: Standard therapy for borderline-resectable pancreatic cancer in the UK is surgery with adjuvant chemotherapy, but rates of resection with clear margins are unsatisfactory and overall survival remains poor. Meta-analysis of single-arm studies shows the potential of neo-adjuvant chemo-radiotherapy but the relative radio-resistance of pancreatic cancer means the efficacy of conventional dose schedules is limited. Stereotactic radiotherapy achieves sufficient accuracy and precision to enable pre-operative margin-intensive dose escalation with the goal of increasing rates of clear resection margins and local disease control. METHODS/DESIGN: SPARC is a "rolling-six" design single-arm study to establish the maximum tolerated dose for margin-intensive stereotactic radiotherapy before resection of pancreatic cancer at high risk of positive resection margins. Eligible patients will have histologically or cytologically proven pancreatic cancer defined as borderline-resectable per National Comprehensive Cancer Network criteria or operable tumour in contact with vessels increasing the risk of positive margin. Up to 24 patients will be recruited from up to 5 treating centres and a 'rolling-six' design is utilised to minimise delays and facilitate ongoing recruitment during dose-escalation. Radiotherapy will be delivered in 5 daily fractions and surgery, if appropriate, will take place 5-6 weeks after radiotherapy. The margin-intense radiotherapy concept includes a systematic method to define the target volume for a simultaneous integrated boost in the region of tumour-vessel infiltration, and up to 4 radiotherapy dose levels will be investigated. Maximum tolerated dose is defined as the highest dose at which no more than 1 of 6 patients or 0 of 3 patients experience a dose limiting toxicity. Secondary endpoints include resection rate, resection margin status, response rate, overall survival and progression free survival at 12 and 24 months. Translational work will involve exploratory analyses of the cytological and humoral immunological responses to stereotactic radiotherapy in pancreatic cancer. Radiotherapy quality assurance of target definition and radiotherapy planning is enforced with pre-trial test cases and on-trial review. Recruitment began in April 2015. DISCUSSION: This prospective multi-centre study aims to establish the maximum tolerated dose of pre-operative margin-intensified stereotactic radiotherapy in pancreatic cancer at high risk of positive resection margins with a view to subsequent definitive comparison with other neoadjuvant treatment options. TRIAL REGISTRATION: ISRCTN14138956 . Funded by CRUK.

Comorbidities in lung cancer: prevalence, severity and links with socioeconomic status and treatment.

BACKGROUND: Survival from lung cancer remains poor in Scotland, UK. Although the presence of comorbidities is known to influence outcomes, detailed quantification of comorbidities is not available in routinely collected audit or cancer registry data. The aim of the present study was to assess the prevalence and severity of comorbidities in patients with newly diagnosed lung cancer across four centres throughout Scotland using validated criteria. METHODS: Between 2005 and 2008, all patients with newly diagnosed lung cancer coming through the multidisciplinary teams in four Scottish centres were included in the study. Patient demographics, WHO/Eastern Cooperative Oncology Group performance status, clinicopathological features and primary treatment modality were recorded. RESULTS: Details of 882 patients were collected prospectively. The majority of patients (87.3%) had at least one comorbidity, the most common being weight loss (53%), chronic obstructive pulmonary disease (43%), renal impairment (28%) and ischaemic heart disease (27%). A composite score was produced that included both number and severity of comorbidities. One in seven patients (15.3%) had severe comorbidity scores. There were statistically significant variations in comorbidity scores between treatment centres and between non-small cell lung carcinoma treatment groups. Disease stage was not associated with comorbidity score. CONCLUSIONS: There is a high prevalence of multiple, severe comorbidities in Scottish patients with lung cancer, and these vary by site and treatment group. Further research is needed to determine the relationship between comorbidity scores and survival in these patients.

Long term survival in patients with human papillomavirus-positive oropharyngeal cancer and equivocal response on 12-week PET-CT is not compromised by the omission of neck dissection.

BACKGROUND AND AIM: The aim of this study was to evaluate the long-term safety of the omission of immediate neck dissections (IND) in patients with human papillomavirus (HPV)-positive head and neck squamous cell carcinoma (HNSCC) achieving a less than complete nodal response on 12-week FDG PET-CT. MATERIAL AND METHODS: Patients with HPV-positive, node-positive HNSCC that were treated with radical (chemo) radiotherapy (RT) between January 2013 and September 2019 were identified. PET-CT responses were classified as complete (CR), incomplete (ICR) or equivocal (EQR) nodal responses. Clinical outcomes were obtained. RESULTS: 347 patients were identified. Median follow-up was 43.9 (IQR, 30.8-61.2) months. 62.8% (218/347) achieved a CR, 23.4% (81/347) EQR and 13.8% (48/347) ICR nodal response. 70 of 81 (86.4%) patients with an EQR and 25 of 48 (52.1%) with an ICR had no residual disease during follow up (a pathologically negative ND if surgery undertaken or no subsequent neck or distant relapse clinically/radiologically). Median survival of the EQR and CR groups were not reached, and despite the omission of IND in 95% of the EQR group there was no statistically significant differences in overall survival (OS) between the groups, p = 1.0. Median survival of ICR was not reached. However, OS for ICR group was significantly worse than that of CR, and EQR, both p < 0.001. CONCLUSION: The omission of IND in those achieving an EQR nodal response does not compromise long-term survival. This supports the safety of extended surveillance in patients with HPV-positive disease and an EQR on 12-week FDG PET-CT.

Single modality radical radiotherapy is an acceptable alternative for the older patient with squamous cell carcinoma of the oesophagus.

BACKGROUND: Oesophageal cancer remains a common cause of cancer mortality worldwide. Increasingly, oncology centres are treating an older population and comorbidities may preclude multimodality treatment with chemoradiotherapy (CRT). We review outcomes of radical radiotherapy (RT) in an older population treating squamous cell carcinoma (SCC) oesophagus. METHODS: Patients over 65 years receiving RT for SCC oesophagus between 2013 and 2016 in the West of Scotland were identified. Kaplan-Meier and Cox-regression analysis were used to compare overall survival (OS) between patients treated with radical RT and radical CRT. RESULTS: There were 83 patients over 65 years treated with either RT (n=21) or CRT (n=62). There was no significant difference in median OS between CRT versus RT (26.8 months vs 28.5 months, p=0.92). All patients receiving RT completed their treatment whereas 11% of CRT patients did not complete treatment. CONCLUSION: Survival in this non-trial older patient group managed with CRT is comparable to that reported in previous trials. RT shows better than expected outcomes which may reflect developments in RT technique. This review supports RT as an alternative in older patients, unfit for concurrent treatment.

SPARC, a phase-I trial of pre-operative, margin intensified, stereotactic body radiation therapy for pancreatic cancer.

BACKGROUND AND PURPOSE: Following resection of pancreatic cancer, risk of positive margins and local recurrence remain high, especially for borderline-resectable pancreatic cancer (BRPC). We aimed to establish the maximum tolerated dose of a margin-intensified five-fraction stereotactic body radiotherapy (SBRT) regimen designed to treat the region at risk. MATERIALS AND METHODS: We conducted a prospective multicentre phase-1 rolling-six dose-escalation study. BRPC patients received pre-operative SBRT, with one dose to the primary tumour and an integrated boost to the region where tumour was in contact with vasculature. Four dose-levels were proposed, with starting dose 30 Gy to primary PTV and 45 Gy to boost volume (PTV_R), in five daily fractions. Primary endpoint was maximum tolerated dose (MTD), defined as highest dose where zero of three or one of six patients experienced dose-limiting toxicity (DLT). RESULTS: Twelve patients were registered, eleven received SBRT. Radiotherapy was well tolerated with all treatment completed as scheduled. Dose was escalated one level up from starting dose without encountering any DLT (prescribed 32.5 Gy PTV, 47.5 Gy PTV_R). Nine serious adverse reactions or events occurred (seven CTCAE Grade 3, two Grade 4). Two patients went on to have surgical resection. Median overall survival for SBRT patients was 8.1 months. The study closed early when it was unable to recruit to schedule. CONCLUSION: Toxicity of SBRT was low for the two dose-levels that were tested, but MTD was not established. Few patients subsequently underwent resection of pancreatic tumour after SBRT, and it is difficult to draw conclusions regarding the safety or toxicity of these therapies in combination.

Analysis of dose using CBCT and synthetic CT during head and neck radiotherapy: A single centre feasibility study.

OBJECTIVES: The study aimed to assess the suitability of deformable image registration (DIR) software to generate synthetic CT (sCT) scans for dose verification during radiotherapy to the head and neck. Planning and synthetic CT dose volume histograms were compared to evaluate dosimetric changes during the treatment course. METHODS: Eligible patients had locally advanced (stage III, IVa and IVb) oropharyngeal cancer treated with primary radiotherapy. Weekly CBCT images were acquired post treatment at fractions 1, 6, 11, 16, 21 and 26 over a 30 fraction treatment course. Each CBCT was deformed with the planning CT to generate a sCT which was used to calculate the dose at that point in the treatment. A repeat planning CT2 was acquired at fraction 16 and deformed with the fraction 16 CBCT to compare differences between the calculations mid-treatment. RESULTS: 20 patients were evaluated generating 138 synthetic CT sets. The single fraction mean dose to PTV_HR between the synthetic and planning CT did not vary, although dose to 95% of PTV_HR was smaller at week 6 compared to planning (difference 2.0%, 95% CI (0.8 to 3.1), p = 0.0). There was no statistically significant difference in PRV_brainstem or PRV_spinal cord maximum dose, although greater variation using the sCT calculations was reported. The mean dose to structures based on the fraction 16 sCT and CT2 scans were similar. CONCLUSIONS: Synthetic CT provides comparable dose calculations to those of a repeat planning CT; however the limitations of DIR must be understood before it is applied within the clinical setting.

12 week PET-CT has low positive predictive value for nodal residual disease in human papillomavirus-positive oropharyngeal cancers.

OBJECTIVES: Surveillance PET-CT scans at 12 weeks post-radiotherapy for head and neck cancer can be used to omit neck dissections with no detriment in overall survival. Human Papillomavirus (HPV) driven tumours behave differently on conventional imaging after radiotherapy but it is unknown if this effect is seen on PET-CT and if HPV status affects the accuracy of PET-CT. We aimed to determine the negative and positive predictive values (NPV and PPV) of 12 week surveillance PET-CT in HPV positive and negative tumours, and investigate predictors of relapse in equivocal responders. MATERIALS AND METHODS: A retrospective cohort study in a UK tertiary level oncology hospital, between 2013 and 2016 included adults with oropharyngeal squamous cell carcinoma, or HPV positive head and neck squamous cell cancers of unknown primary, treated with radiotherapy. RESULTS: The PPVs of 12 week PET-CT in HPV positive and negative disease are 30% and 81.8% respectively (p < 0.01). The NPVs of 12 week PET-CT in HPV positive and negative disease are 92.9% and 55.6% respectively (p < 0.01). 67% of HPV positive patients with equivocal responses on 12 week PET-CT achieved complete response by 24 weeks. Equivocal responses in HPV positive disease had statistically similar survival to patients with complete responses. Comparing disease and imaging characteristics, there were no predictors of residual tumour. CONCLUSIONS: HPV positive tumours have a poor PPV of 30% on 12 week surveillance PET-CTs and take longer to achieve complete response. A period of further surveillance can be considered instead of an immediate neck dissection in this group of patients.

The downstaging approach to irresectable oesophageal and gastric cancer: a single centre experience.

BACKGROUND: There is uncertainty over optimal management of locally advanced non-metastatic oesophageal and gastric (OG) adenocarcinomas which are deemed irresectable at time of diagnosis due to local tumour or nodal burden. Current practice in our regional centre is to administer chemotherapy in a "downstaging" strategy in the hope of achieving tumour shrinkage to allow radical treatment. Patients without sufficient response to downstaging are treated palliatively. The aim of this study was to review our single unit outcomes of this treatment strategy. METHODS: Data was collected retrospectively from electronic patient records on all cases discussed at regional MDT over a 32-month period (January 2015-August 2017). RESULTS: A total of 44 patients [70.5% male, median age 70 years, 13 (29.5%) oesophageal, 12 (27.3%) junctional and 19 (43.2%) gastric] were included in the study. Thirty-six (81.8%) of patients received the full number of planned cycles of chemotherapy; toxicity and disease progression (both 6.8% of cases) were the most common reasons for early cessation of treatment. Seventeen (38.6%) patients underwent resection and an R0 resection was achieved in 13 (76.5%) of these patients. After median follow up of 16.8 months, the median overall survival (OS) in the resection vs. palliative cohorts was 42.6 vs. 16.4 months (P<0.05). CONCLUSIONS: Our data show that a downstaging approach can be successfully implemented (R0 resection achieved) in up to a third of patients with good survival results. Further prospective data identifying patient and pathological characteristics predicting response to treatment are needed to optimise selection into a downstaging programme.

Neoadjuvant FOLFIRINOX in Patients With Borderline Resectable Pancreatic Cancer: A Systematic Review and Patient-Level Meta-Analysis.

BACKGROUND: FOLFIRINOX is a standard treatment for metastatic pancreatic cancer patients. The effectiveness of neoadjuvant FOLFIRINOX in patients with borderline resectable pancreatic cancer (BRPC) remains debated. METHODS: We performed a systematic review and patient-level meta-analysis on neoadjuvant FOLFIRINOX in patients with BRPC. Studies with BRPC patients who received FOLFIRINOX as first-line neoadjuvant treatment were included. The primary endpoint was overall survival (OS), and secondary endpoints were progression-free survival, resection rate, R0 resection rate, and grade III-IV adverse events. Patient-level survival outcomes were obtained from authors of the included studies and analyzed using the Kaplan-Meier method. RESULTS: We included 24 studies (8 prospective, 16 retrospective), comprising 313 (38.1%) BRPC patients treated with FOLFIRINOX. Most studies (n = 20) presented intention-to-treat results. The median number of administered neoadjuvant FOLFIRINOX cycles ranged from 4 to 9. The resection rate was 67.8% (95% confidence interval [CI] = 60.1% to 74.6%), and the R0-resection rate was 83.9% (95% CI = 76.8% to 89.1%). The median OS varied from 11.0 to 34.2 months across studies. Patient-level survival data were obtained for 20 studies representing 283 BRPC patients. The patient-level median OS was 22.2 months (95% CI = 18.8 to 25.6 months), and patient-level median progression-free survival was 18.0 months (95% CI = 14.5 to 21.5 months). Pooled event rates for grade III-IV adverse events were highest for neutropenia (17.5 per 100 patients, 95% CI = 10.3% to 28.3%), diarrhea (11.1 per 100 patients, 95% CI = 8.6 to 14.3), and fatigue (10.8 per 100 patients, 95% CI = 8.1 to 14.2). No deaths were attributed to FOLFIRINOX. CONCLUSIONS: This patient-level meta-analysis of BRPC patients treated with neoadjuvant FOLFIRINOX showed a favorable median OS, resection rate, and R0-resection rate. These results need to be assessed in a randomized trial.

The role of induction chemotherapy + chemoradiotherapy in localised pancreatic cancer: initial experience in Scotland.

BACKGROUND: Despite being relatively rare pancreatic cancer is one of the highest causes of death. Even within the potentially resectable group outcomes are poor. We present our initial experiences utilising a neoadjuvant approach to localised pancreatic cancer, evaluating survival, response rates and tolerability. METHODS: This was a retrospective analysis of a prospectively maintained database. Patients from 2012 to 2015 referred to a busy regional Hepato-Pancreatic Biliary (HPB) MDT were included. Patients were classified according to respectability criteria (utilising NCCN guidelines) and a treatment plan agreed. Systemic therapy with either FOLFIRINOX or Gem/Cap was delivered followed by chemoradiotherapy if disease remained localised. Toxicity, response, pathological outcomes and survival were all recorded. RESULTS: A total of 85 patients were included in the study: 45 had initially resectable disease; 19 required a response for resection and 21 had locally advanced inoperable disease; 34 patients underwent resection. The median survival for the potentially resectable group was 22.2 months while for those undergoing resection it was 37 months. CONCLUSIONS: We have demonstrated that a neoadjuvant approach is deliverable and tolerable. In addition we have demonstrated impressive survival results in patients undergoing resection with no detriment in outcome for those not proceeding to surgery.

Single centre outcomes from definitive chemo-radiotherapy and single modality radiotherapy for locally advanced oesophageal cancer.

BACKGROUND: Definitive chemo-radiotherapy (dCRT) has been advocated as an alternative to surgical resection for the treatment of locally advanced oesophageal cancer (OC). We have retrospectively reviewed 4 years' experience of patients (pts) who underwent contemporary staging and were treated with concurrent chemo-radiotherapy (dCRT) or single modality radical radiotherapy (RT) with curative intent. METHODS: Retrospective analysis permitted identification of consecutive patients who underwent contemporary staging prior to non-surgical treatment for locally advanced oesophageal carcinoma. The primary outcomes were overall survival (OS) and disease-free survival (DFS), adjusted for baseline differences in age, tumour staging and histological cell type. All patients were treated with either dCRT or single modality RT within a single centre between 2009 and 2012. RESULTS: We identified 235 patients in total [median age 69.8 years, male =130 pts, female =105 pts, adenocarcinoma (ACA) =85 pts, squamous =150 pts]. A total of 190 pts received dCRT and 45 patients were treated with RT. All patients were staged with CT of chest, abdomen and pelvis, 226 patients underwent endoscopic ultrasound (EUS), and 183 patients had PET-CT. Patients treated with dCRT demonstrated longer OS (27 vs. 25 months respectively, P=0.02) and DFS (31 vs. 16 months respectively, P=0.01) compared to those treated with RT. More advanced tumour stage (stage 3 vs. stage 1/2) at presentation conferred poorer OS (32 vs. 38.2 months, P=0.02) and DFS (11 vs. 28 months, P=0.013). We demonstrated an acceptable toxicity profile with only 77 patients (32.8%) suffering grade 3 toxicity and 9 patients (4.2%) experiencing grade 4 toxicity by CTC criteria. The NG/PEG feeding rates were 4% across all treated patients. CONCLUSIONS: This retrospective analysis is in keeping with current treatment paradigms emphasising the importance and safety of concurrent CRT in maximising curative potential for patients undergoing non-surgical treatment of OC. Although retrospective, in comparison to similar retrospective series from both our centre and historical literature, this data suggest improvements in OS and DFS, possibly due to improved patient selection through the use of more effective tumour staging.

Conformity analysis to demonstrate reproducibility of target volumes for Margin-Intense Stereotactic Radiotherapy for borderline-resectable pancreatic cancer.

BACKGROUND AND PURPOSE: Margin-directed neoadjuvant radiotherapy for borderline-resectable pancreatic cancer (BRPC) aims to facilitate clear surgical margins. A systematic method was developed for definition of a boost target volume prior to a formal phase-I study. MATERIAL AND METHODS: Reference structures were defined by two oncologists and one radiologist, target structures were submitted by eight oncologist investigators and compared using conformity indices. Resultant risk of duodenal bleed (NTCP) was modelled. RESULTS: For GTV, reference volume was 2.1cm3 and investigator mean was 6.03cm3 (95% CI 3.92-8.13cm3), for boost volume 1.1cm3 and 1.25cm3 (1.02-1.48cm3). Mean Dice conformity coefficient for GTV was 0.47 (0.38-0.56), and for boost volume was significantly higher at 0.61 (0.52-0.70, p=0.01). Discordance index (DI) for GTV was 0.65 (0.56-0.75) and for boost volume was significantly lower at 0.39 (0.28-0.49, p=0.001). NTCP using reference contours was 2.95%, with mean for investigator contour plans 3.93% (3.63-4.22%). Correlations were seen between NTCP and GTV volume (p=0.02) and NTCP and DI (correlation coefficient 0.83 (0.29-0.97), p=0.01). CONCLUSIONS: Better conformity with reference was shown for boost volume compared with GTV. Investigator GTV volumes were larger than reference, had higher DI scores and modelled toxicity risk. A consistent method of target structure definition for margin-directed pancreatic radiotherapy is demonstrated.

3-dimensional throat region segmentation from MRI data based on Fourier interpolation and 3-dimensional level set methods.

A new algorithm for 3D throat region segmentation from magnetic resonance imaging (MRI) is presented. The proposed algorithm initially pre-processes the MRI data to increase the contrast between the throat region and its surrounding tissues and to reduce artifacts. Isotropic 3D volume is reconstructed using the Fourier interpolation. Furthermore, a cube encompassing the throat region is evolved using level set method to form a smooth 3D boundary of the throat region. The results of the proposed algorithm on real and synthetic MRI data are used to validate the robustness and accuracy of the algorithm.