The Hammersmith Score Optimises Patient Selection and Predicts for Overall Survival in Early-Phase Cancer Trial Participants Independent of Tumour Burden.

INTRODUCTION: As tumour response rates are increasingly demonstrated in early-phase cancer trials (EPCT), optimal patient selection and accurate prognostication are paramount. Hammersmith Score (HS), a simple prognostic index derived on routine biochemical measures (albumin <35 g/L, lactate dehydrogenase >450 IU/L, sodium <135 mmol/L), is a validated predictor of response and survival in EPCT participants. HS has not been validated in the cancer immunotherapy era. METHODS: We retrospectively analysed characteristics and outcomes of unselected referrals to our early-phase unit (12/2019-12/2022). Independent predictors for overall survival (OS) were identified from univariable and multivariable models. HS was calculated for 66 eligible trial participants and compared with the Royal Marsden Score (RMS) to predict OS. Multivariable logistic regression and C-index was used to compare predictive ability of prognostic models. RESULTS: Of 212 referrals, 147 patients were screened and 82 patients treated in EPCT. Prognostic stratification by HS identifies significant difference in median OS, and HS was confirmed as a multivariable predictor for OS (HR: HS 1 vs. 0 2.51, 95% CI: 1.01-6.24, p = 0.049; HS 2/3 vs. 0: 10.32, 95% CI: 2.15-49.62, p = 0.004; C-index 0.771) with superior multivariable predictive ability than RMS (HR: RMS 2 vs. 0/1 5.46, 95% CI: 1.12-26.57, p = 0.036; RMS 3 vs. 0/1 6.83, 95% CI: 1.15-40.53, p < 0.001; C-index 0.743). CONCLUSIONS: HS is a validated prognostic index for patients with advanced cancer treated in the context of modern EPCTs, independent of tumour burden. HS is a simple, inexpensive prognostic tool to optimise referral for EPCT.

Longitudinal changes in the carotid arteries of head and neck cancer patients following radiation therapy: Results from a prospective serial imaging biomarker characterization study.

INTRODUCTION: We prospectively evaluated morphologic and functional changes in the carotid arteries of patients treated with unilateral neck radiation therapy (RT) for head and neck cancer. METHODS: Bilateral carotid artery duplex studies were performed at 0, 3, 6, 12, 18 months and 2, 3, 4, and 5 years following RT. Intima media thickness (IMT); global and regional circumferential, as well as radial strain, arterial elasticity, stiffness, and distensibility were calculated. RESULTS: Thirty-eight patients were included. A significant difference in the IMT from baseline between irradiated and unirradiated carotid arteries was detected at 18 months (median, 0.073 mm vs -0.003 mm; P = 0.014), which increased at 3 and 4 years (0.128 mm vs 0.013 mm, P = 0.016, and 0.177 mm vs 0.023 mm, P = 0.0002, respectively). A significant transient change was noted in global circumferential strain between the irradiated and unirradiated arteries at 6 months (median difference, -0.89, P = 0.023), which did not persist. No significant differences were detected in the other measures of elasticity, stiffness, and distensibility. CONCLUSIONS: Functional and morphologic changes of the carotid arteries detected by carotid ultrasound, such as changes in global circumferential strain at 6 months and carotid IMT at 18 months, may be useful for the early detection of radiation-induced carotid artery injury, can guide future research aiming to mitigate carotid artery stenosis, and should be considered for clinical surveillance survivorship recommendations after head and neck RT.

Longitudinal Changes in the Carotid Arteries of Head and Neck Cancer Patients Following Radiation Therapy: Results from a Prospective Serial Imaging Biomarker Characterization Study.

INTRODUCTION: We prospectively evaluated morphologic and functional changes in the carotid arteries of patients treated with unilateral neck radiation therapy (RT) for head and neck cancer. METHODS: Bilateral carotid artery duplex studies were performed at 0, 3, 6, 12, 18 months and 2, 3, 4, and 5 years following RT. Intima media thickness (IMT); global and regional circumferential, as well as radial strain, arterial elasticity, stiffness, and distensibility were calculated. RESULTS: Thirty-eight patients were included. A significant difference in the IMT from baseline between irradiated and unirradiated carotid arteries was detected at 18 months (median, 0.073mm vs -0.003mm; P =0.014), which increased at 3 and 4 years (0.128mm vs 0.013mm, P =0.016, and 0.177mm vs 0.023mm, P =0.0002, respectively). A > 0.073mm increase at 18 months was significantly more common in patients who received concurrent chemotherapy (67% vs 25%; P =0.03). A significant transient change was noted in global circumferential strain between the irradiated and unirradiated arteries at 6 months (median difference, -0.89, P =0.023), which did not persist. No significant differences were detected in the other measures of elasticity, stiffness, and distensibility. CONCLUSIONS: Functional and morphologic changes of the carotid arteries detected by carotid ultrasound, such as changes in global circumferential strain at 6 months and carotid IMT at 18 months, may be useful for the early detection of radiation-induced carotid artery injury, can guide future research aiming to mitigate carotid artery stenosis, and should be considered for clinical surveillance survivorship recommendations after head and neck RT.

An Intensive 18F-Fludeoxyglucose-Positron Emission Tomography With Computed Tomography-Based Strategy of Follow-Up in Patients Treated for Head and Neck Squamous Cell Carcinoma Who Are Clinically Asymptomatic.

Importance: Patients with head and neck squamous cell carcinoma (HNSCC) have a significant risk of locoregional recurrence within the first 2 years, with approximately two-thirds of patients experiencing such recurrence. While early recurrence detection may be associated with improved patient outcomes, the association of such detection with survival remains uncertain. Objective: To investigate the association of an intensive posttreatment follow-up strategy using 18F-fludeoxyglucose-positron emission tomography with computed tomography (18FDG-PET/CT) with survival among patients with HNSCC. Design, Setting, and Participants: This case-control study was conducted among patients treated at 1 of 3 locations in Brest, France (University Hospital, Military Hospital, or Pasteur Clinic). The statistical analysis was conducted from January to June 2023. All adults with histologically proven HNSCC who were treated with curative intent between January 1, 2006, and December 31, 2019, and achieved a complete response on imaging at 3 to 6 months were included. They had a minimum of 3 years of follow-up. Exposures: Patients undergoing an intensive posttreatment follow-up strategy had 18FDG-PET/CT (PET/CT group) at months 12, 24, and 36, chosen at the discretion of ear, nose, and throat surgeons. Main Outcomes and Measures: Overall survival (OS) at 3 years. Results: Among 782 patients with HNSCC (642 males [82.1%]; median [IQR] age, 61 [56-68] years), 497 patients had 18FDG-PET/CT during follow-up and 285 patients had conventional follow-up (CFU group). Cox regression analysis showed an association between undergoing 18FDG-PET/CT and lower risk of death (odds ratio, 0.71; 95% CI, 0.57-0.88; P = .002) after adjustment for covariates (age, sex, comorbidities, primary location, stage, surgeon, year of treatment, and treatment). The mean (SD) 3-year OS was significantly better in the PET/CT vs CFU group (72.5% [2.0%] vs 64.3% [2.9%]; P = .002). Analysis based on American Joint Committee on Cancer stage showed significantly better mean (SD) 3-year OS for advanced stages III and IV in the PET/CT group (373 patients) vs CFU group (180 patients; 68.5% [2.4%] vs 55.4% [3.8%]; P < .001), while no significant difference was observed between patients with stage I or II HNSCC. Analysis based on primary tumor site revealed significantly longer mean (SD) 3-year OS for oropharyngeal tumor in the PET/CT group (176 patients) than the CFU group (100 patients; 69.9% [3.5%] vs 60.5% [5.0%]; P = .04). Conclusions and relevance: This case-control study found that use of 18FDG-PET/CT in the standard annual CFU of HNSCC was associated with a 3-year survival benefit, with a larger benefit for patients with advanced initial tumor stage (III-IV) and oropharyngeal disease.

Clinical evaluation of atlas-based auto-segmentation in breast and nodal radiotherapy.

OBJECTIVES: Accurate contouring of anatomical structures allows for high-precision radiotherapy planning, targeting the dose at treatment volumes and avoiding organs at risk. Manual contouring is time-consuming with significant user variability, whereas auto-segmentation (AS) has proven efficiency benefits but requires editing before treatment planning. This study investigated whether atlas-based AS (ABAS) accuracy improves with template atlas group size and character-specific atlas and test case selection. METHODS AND MATERIALS: One clinician retrospectively contoured the breast, nodes, lung, heart, and brachial plexus on 100 CT scans, adhering to peer-reviewed guidelines. Atlases were clustered in group sizes, treatment positions, chest wall separations, and ASs created with Mirada software. The similarity of ASs compared to reference contours was described by the Jaccard similarity coefficient (JSC) and centroid distance variance (CDV). RESULTS: Across group sizes, for all structures combined, the mean JSC was 0.6 (SD 0.3, p = .999). Across atlas-specific groups, 0.6 (SD 0.3, p = 1.000). The correlation between JSC and structure volume was weak in both scenarios (adjusted R2-0.007 and 0.185).Mean CDV was similar across groups but varied up to 1.2 cm for specific structures. CONCLUSIONS: Character-specific atlas groups and test case selection did not improve accuracy outcomes. High-quality ASs were obtained from groups containing as few as ten atlases, subsequently simplifying the application of ABAS. CDV measures indicating auto-segmentation variations on the x, y, and z axes can be utilised to decide on the clinical relevance of variations and reduce AS editing. ADVANCES IN KNOWLEDGE: High-quality ABASs can be obtained from as few as ten template atlases.Atlas and test case selection do not improve AS accuracy.Unlike well-known quantitative similarity indices, volume displacement metrics provide information on the location of segmentation variations, helping assessment of the clinical relevance of variations and reducing clinician editing. Volume displacement metrics combined with the qualitative measure of clinician assessment could reduce user variability.

Primary radiotherapy and deep inferior epigastric perforator flap reconstruction for patients with breast cancer (PRADA): a multicentre, prospective, non-randomised, feasibility study.

BACKGROUND: Radiotherapy before mastectomy and autologous free-flap breast reconstruction can avoid adverse radiation effects on healthy donor tissues and delays to adjuvant radiotherapy. However, evidence for this treatment sequence is sparse. We aimed to explore the feasibility of preoperative radiotherapy followed by skin-sparing mastectomy and deep inferior epigastric perforator (DIEP) flap reconstruction in patients with breast cancer requiring mastectomy. METHODS: We conducted a prospective, non-randomised, feasibility study at two National Health Service trusts in the UK. Eligible patients were women aged older than 18 years with a laboratory diagnosis of primary breast cancer requiring mastectomy and post-mastectomy radiotherapy, who were suitable for DIEP flap reconstruction. Preoperative radiotherapy started 3-4 weeks after neoadjuvant chemotherapy and was delivered to the breast, plus regional nodes as required, at 40 Gy in 15 fractions (over 3 weeks) or 42·72 Gy in 16 fractions (over 3·2 weeks). Adverse skin radiation toxicity was assessed preoperatively using the Radiation Therapy Oncology Group toxicity grading system. Skin-sparing mastectomy and DIEP flap reconstruction were planned for 2-6 weeks after completion of preoperative radiotherapy. The primary endpoint was the proportion of open breast wounds greater than 1 cm width requiring a dressing at 4 weeks after surgery, assessed in all participants. This study is registered with ClinicalTrials.gov, NCT02771938, and is closed to recruitment. FINDINGS: Between Jan 25, 2016, and Dec 11, 2017, 33 patients were enrolled. At 4 weeks after surgery, four (12·1%, 95% CI 3·4-28·2) of 33 patients had an open breast wound greater than 1 cm. One (3%) patient had confluent moist desquamation (grade 3). There were no serious treatment-related adverse events and no treatment-related deaths. INTERPRETATION: Preoperative radiotherapy followed by skin-sparing mastectomy and immediate DIEP flap reconstruction is feasible and technically safe, with rates of breast open wounds similar to those reported with post-mastectomy radiotherapy. A randomised trial comparing preoperative radiotherapy with post-mastectomy radiotherapy is required to precisely determine and compare surgical, oncological, and breast reconstruction outcomes, including quality of life. FUNDING: Cancer Research UK, National Institute for Health Research.

Comparison of Volumetric Quantitative PET Parameters Before and After a CT-Based Elastic Deformation on Dual-Time 18FDG-PET/CT Images: A Feasibility Study in a Perspective of Radiotherapy Planning in Head and Neck Cancer.

BACKGROUND: The use of 18FDG-PET/CT for delineating a gross tumor volume (GTV, also called MTV metabolic tumor volume) in radiotherapy (RT) planning of head neck squamous cell carcinomas (HNSCC) is not included in current recommendations, although its interest for the radiotherapist is of evidence. Because pre-RT PET scans are rarely done simultaneously with dosimetry CT, the validation of a robust image registration tool and of a reproducible MTV delineation method is still required. OBJECTIVE: Our objective was to study a CT-based elastic registration method on dual-time pre-RT 18FDG-PET/CT images to assess the feasibility of PET-based RT planning in patients with HNSCC. METHODS: Dual-time 18FDG-PET/CT [whole-body examination (wbPET) + 1 dedicated step (headPET)] were selected to simulate a 2-times scenario of pre-RT PET images deformation on dosimetry CT. ER-headPET and RR-headPET images were, respectively, reconstructed after CT-to-CT rigid (RR) and elastic (ER) registrations of the headPET on the wbPET. The MTVs delineation was performed using two methods (40%SUVmax, PET-Edge). The percentage variations of several PET parameters (SUVmax, SUVmean, SUVpeak, MTV, TLG) were calculated between wbPET, ER-headPET, and RR-headPET. Correlation between MTV values was calculated (Deming linear regression). MTVs intersections were assessed by two indices (OF, DICE) and compared together (Wilcoxon test). Additional per-volume analysis was evaluated (Mann-Whitney test). Inter- and intra-observer reproducibilities were evaluated (ICC = intra-class coefficient). RESULTS: 36 patients (30M/6F; median age = 65 y) were retrospectively included. The changes in SUVmax, SUVmean and SUVpeak values between ER-headPET and RR-headPET images were <5%. The variations in MTV values between ER-headPET and wbPET images were -6 and -3% with 40%SUVmax and PET Edge, respectively. Their correlations were excellent whatever the delineation method (R2 > 0.99). The ER-headPET MTVs had significant higher mean OF and DICE with the wbPET MTVs, for both delineation methods (p ≤ 0.002); and also when lesions had a volume > 5cc (excellent OF = 0.80 with 40%SUVmax). The inter- and intra-observer reproducibilities for MTV delineation were excellent (ICC ≥ 0.8, close to 1 with PET-Edge). CONCLUSION: Our study demonstrated no significant changes in MTV after an elastic deformation of pre-RT 18FDG-PET/CT images acquired in dual-time mode. This opens possibilities for HNSCC radiotherapy planning improvement by transferring GTV-PET on dosimetry CT.

Incidental uptake of fluorodeoxyglucose in the Waldeyer's ring and risk of oropharyngeal malignancy.

PURPOSE: Fluorodeoxyglucose (FDG) positron emission tomography (PET) is increasingly used to diagnose and stage malignancy. The aim of this article is to investigate the significance of incidental FDG uptake in the Waldeyer's ring and to assess its value in predicting clinically occult oropharyngeal malignancy. METHODS: All FDG-PET/CT scans performed in Imperial College NHS Foundation Trust, UK between January 2012 and November 2018 were included. Patients with known or suspected oropharyngeal malignancy or lymphoma were excluded. Minimum follow-up was 12 months. RESULTS: A total of 724 scans revealed oropharyngeal uptake of FDG. Of these, 102 were included in the study. Most patients (62.1%) were scanned as part of staging for other malignancies. Oropharyngeal FDG uptake was asymmetrical in 57.3% of the cases. Uptake was more common in the tonsils (56.3%), followed by the tongue base (31.1%) and both sites (12.6%). In 41.7% of reports, appearance was described as likely physiological; however, 52.4% of reports advised direct visualisation, clinical correlation or ENT opinion. Only 24.3% (25/102) of patients were referred and seen by ENT, 14.6% (15/102) of which had an interval PET scan and 8.7% (9/102) proceeded to tissue diagnosis. There was one oropharyngeal cancer identified and one unexpected metastasis from esophageal cancer. CONCLUSION: Incidental uptake on PET/CT in the oropharynx is common. However, malignancy is rare (1.9%) and, when present, is associated with high SUVmax and asymmetrical uptake. Imaging results must be correlated clinically. These patients should be seen by an ENT specialist yet most may not require further investigations.

A dosimetric study to improve the quality of nodal radiotherapy in breast cancer.

OBJECTIVES: Field-based planning for regional nodal breast radiotherapy (RT) used to be standard practice. This study evaluated a field-based posterior axillary boost (PAB) and two forward-planned intensity-modulated RT (IMRT) techniques, aiming to replace the first. METHODS: Supraclavicular and axillary nodes, humeral head, brachial plexus, thyroid, and oesophagus were retrospectively delineated on 12 CT scans. Three plans, prescribed to 40.05 Gy, were produced for each patient. Breast plans consisted of field-in-field IMRT tangential fields in all three techniques. Nodal plans consisted of a field-based PAB (anterior and posterior boost beam), and 2 forward-planned techniques: simple IMRT 1 (anterior and posterior beam with limited segments), and a more advanced IMRT 2 technique (anterior and fully modulated posterior beam). RESULTS: The nodal V90% was similar between IMRT 1: mean 99.5% (SD 1.0) and IMRT 2: 99.4% (SD 0.5). Both demonstrated significantly improved results (p = 0.0001 and 0.005, respectively) compared to the field-based PAB technique. IMRT 2 lung V12Gy and humeral head V10Gy were significantly lower (p = 0.002, 0.0001, respectively) than the field-based PAB technique. IMRT 1 exhibited significantly lower brachial plexus Dmax and humeral head V5, 10, and 15Gy doses (p = 0.007, 0.013, 0.007 and 0.007, respectively) compared to the field-based PAB technique. The oesophagus and thyroid dose difference between methods was insignificant. CONCLUSIONS: Both IMRT techniques achieved the dose coverage requirements and reduced normal tissue exposure, decreasing the risk of radiation side effects. Despite the increased cost of IMRT, compared to non-IMRT techniques 1, both IMRT techniques are suitable for supraclavicular and axillary nodal RT. ADVANCES IN KNOWLEDGE: Forward-planned IMRT already resulted in significant dose reduction to organs at risk and improved planning target volume coverage.1 This new, simplified forward-planned IMRT one technique has not been published in this context and is easy to implement in routine clinical practice.

A multi-centre survey reveals variations in the standard treatments and treatment modifications for head and neck cancer patients during Covid-19 pandemic.

BACKGROUND: The onset of the COVID-19 pandemic necessitated rapid changes to the practice of head and neck oncology in UK. There was a delay between the onset of the pandemic and the release of guidelines from cancer societies and networks, leading to a variable response of individual centres. This survey was conducted to assess the pre-Covid-19 pandemic standard of practice for head and neck oncology patients and the treatment modifications introduced during the first wave of the pandemic in UK. METHODOLOGY: The UK National Cancer Research Institute (NCRI) Head and Neck Clinical Studies Group initiated a multi-centre survey using questionnaire to investigate the effect on feeding tube practice, radiotherapy (RT) fractionation and volumes, use of chemotherapy in the neo-adjuvant, concurrent and palliative setting, the use of immunotherapy in the palliative setting, access to radiology and histopathology services, and availability of surgical procedures. RESULTS: 30 centres were approached across UK; 23 (76.7%) centres responded and were included in the survey. There were differences in the standard practices in feeding tube policy, RT dose and fractionation as well as concurrent chemotherapy use. 21 (91%) participating centres had at least one treatment modification. 15 (65%) centres initiated a change in radical RT; changing to either a hypofractionation or acceleration schedule. For post-operative RT 10 centres (43.5%) changed to a hypofractionation schedule. 12 (52.2%) centres stopped neo-adjuvant chemotherapy for all patients; 13 (56.5%) centres followed selective omission of chemotherapy in concurrent chemo-radiotherapy patients, 17 (73.9%) centres changed first-line chemotherapy treatment to pembrolizumab (following NHS England's interim guidance) and 8 (34.8%) centres stopped the treatment early or offered delays for patients that have been already on systemic treatment. The majority of centres did not have significant changes associated with surgery, radiology, histopathology and dental screening. CONCLUSION: There are variations in the standard of practice and treatment modifications for head and neck cancer patients during Covid-19 pandemic. A timely initiative is required to form a consensus on head and neck cancer management in the UK and other countries.

Dose-escalated intensity-modulated radiotherapy in patients with locally advanced laryngeal and hypopharyngeal cancers: ART DECO, a phase III randomised controlled trial.

BACKGROUND: Radical (chemo)radiotherapy offers potentially curative treatment for patients with locally advanced laryngeal or hypopharyngeal cancer. We aimed to show that dose-escalated intensity-modulated radiotherapy (DE-IMRT) improved locoregional control. METHODS: We performed a phase III open-label randomised controlled trial in patients with laryngeal or hypopharyngeal cancer (AJCC III-IVa/b, TNM 7). Patients were randomised (1:1) to DE-IMRT or standard dose IMRT (ST-IMRT) using a minimisation algorithm, balancing for centre, tumour site, nodal status and chemotherapy use. DE-IMRT was 67.2 gray (Gy) in 28 fractions (f) to the primary tumour and 56Gy/28f to at-risk nodes; ST-IMRT was 65Gy/30f to primary tumour and 54Gy/30f to at-risk nodes. Suitable patients received 2 cycles of concomitant cisplatin and up to 3 cycles of platinum-based induction chemotherapy. The primary end-point was time to locoregional failure analysed by intention-to-treat analysis using competing risk methodology. FINDINGS: Between February 2011 and October 2015, 276 patients (138 ST-IMRT; 138 DE-IMRT) were randomised. A preplanned interim futility analysis met the criterion for early closure. After a median follow-up of 47.9 months (interquartile range 37.5-60.5), there were locoregional failures in 38 of 138 (27.5%) ST-IMRT patients and 42 of 138 (30.4%) DE-IMRT patients; an adjusted subhazard ratio of 1.16 (95% confidence interval: 0.74-1.83, p = 0.519) indicated no evidence of benefit with DE-IMRT. Acute grade 2 pharyngeal mucositis was reported more frequently with DE-IMRT than with ST-IMRT (42% vs. 32%). No differences in grade ≥3 acute or late toxicity rates were seen. CONCLUSION: DE-IMRT did not improve locoregional control in patients with laryngeal or hypopharyngeal cancer. The trial is registered: ISRCTN01483375.

Radiomics Analysis of 3D Dose Distributions to Predict Toxicity of Radiotherapy for Cervical Cancer.

Standard treatment for locally advanced cervical cancer (LACC) is chemoradiotherapy followed by brachytherapy. Despite radiation therapy advances, the toxicity rate remains significant. In this study, we compared the prediction of toxicity events after radiotherapy for locally advanced cervical cancer (LACC), based on either dose-volume histogram (DVH) parameters or the use of a radiomics approach applied to dose maps at the voxel level. Toxicity scores using the Common Terminology Criteria for Adverse Events (CTCAE v4), spatial dose distributions, and usual clinical predictors for the toxicity of 102 patients treated with chemoradiotherapy followed by brachytherapy for LACC were used in this study. In addition to usual DVH parameters, 91 radiomic features were extracted from rectum, bladder and vaginal 3D dose distributions, after discretization into a fixed bin width of 1 Gy. They were evaluated for predictive modelling of rectal, genitourinary (GU) and vaginal toxicities (grade ≥ 2). Logistic Normal Tissue Complication Probability (NTCP) models were derived using clinical parameters only or combinations of clinical, DVH and radiomics. For rectal acute/late toxicities, the area under the curve (AUC) using clinical parameters was 0.53/0.65, which increased to 0.66/0.63, and 0.76/0.87, with the addition of DVH or radiomics parameters, respectively. For GU acute/late toxicities, the AUC increased from 0.55/0.56 (clinical only) to 0.84/0.90 (+DVH) and 0.83/0.96 (clinical + DVH + radiomics). For vaginal acute/late toxicities, the AUC increased from 0.51/0.57 (clinical only) to 0.58/0.72 (+DVH) and 0.82/0.89 (clinical + DVH + radiomics). The predictive performance of NTCP models based on radiomics features was higher than the commonly used clinical and DVH parameters. Dosimetric radiomics analysis is a promising tool for NTCP modelling in radiotherapy.

Integration of 18-FDG PET/CT in the Initial Work-Up to Stage Head and Neck Cancer: Prognostic Significance and Impact on Therapeutic Decision Making.

Background: The objective of this study was to assess the therapeutic and prognostic impact of integrating18F-fluorodeoxyglucose (18-FDG) positron emission tomography (PET)/computed tomography (CT) into work-up (WU) at initial staging of patients with head and neck squamous cell carcinoma (HNSCC). Method: 477 consecutive patients (414M/63F, mean age 62.3 ± 9.7 years) with newly diagnosed HNSCC who underwent pre-treatment 18-FDG PET/CT were retrospectively included. The 18-FDG PET/CT stage (sPET) was compared to the conventional work-up stage (sCWU). A group of cancer specialists determined whether integrating PET/CT into WU at initial staging had an impact on the therapeutic decision, classifying the clinical impact as high (change in therapeutic modality), medium (change in the radiotherapy or surgical procedure), or low (modification of TNM staging and/or detection of synchronous cancer without high or medium impact). Three-year overall survival (OS) was considered as primary endpoint of the prognostic analysis. Results: 18-FDG PET/CT had a clinical impact in 221 patients (46.3%) with a medium or high impact on management in 94 (19.5%) patients. Medium and high impact of 18-FDG PET/CT was statistically equivalent between sCWU-stage I/II and III/IV subgroups (p = 0.02). 42 patients were PET/CT-upstaged from early stage I/II to advanced stage III/IV and had a significantly lower 3-year OS than those with concordant CWU and 18-FDG PET/CT early stage (54.8 vs. 82.6%, p = 0.001). Conclusion: This study demonstrated that implementing 18-FDG PET/CT in the initial WU of HNSCC provides valuable staging information with a better prognostic stratification. Patient management was modified for any disease stage, even for early stage I-II, with consequences on survival.

Correlation Between FDG Hotspots on Pre-radiotherapy PET/CT and Areas of HNSCC Local Relapse: Impact of Treatment Position and Images Registration Method.

Aim: Several series have already demonstrated that intratumoral subvolumes with high tracer avidity (hotspots) in 18F-flurodesoxyglucose positron-emission tomography (FDG-PET/CT) are preferential sites of local recurrence (LR) in various solid cancers after radiotherapy (RT), becoming potential targets for dose escalation. However, studies conducted on head and neck squamous cell carcinoma (HNSCC) found only a moderate overlap between pre- and post-treatment subvolumes. A limitation of these studies was that scans were not performed in RT treatment position (TP) and were coregistred using a rigid registration (RR) method. We sought to study (i) the influence of FDG-PET/CT acquisition in TP and (ii) the impact of using an elastic registration (ER) method to improve the localization of hotpots in HNSCC. Methods: Consecutive patients with HNSCC treated by RT between March 2015 and September 2017 who underwent FDG-PET/CT in TP at initial staging (PETA) and during follow-up (PETR) were prospectively included. We utilized a control group scanned in non treatment position (NTP) from our previous retrospective study. Scans were registered with both RR and ER methods. Various sub-volumes (AX; x = 30, 40, 50, 60, 70, 80, and 90%SUVmax) within the initial tumor and in the subsequent LR (RX; x = 40 and 70%SUVmax) were overlaid on the initial PET/CT for comparison [Dice, Jaccard, overlap fraction = OF, common volume/baseline volume = AXnRX/AX, common volume/recurrent volume = AXnRX/RX]. Results: Of 199 patients included, 43 (21.6%) had LR (TP = 15; NTP = 28). The overlap between A30, A40, and A50 sub-volumes on PETA and the whole metabolic volume of recurrence R40 and R70 on PETR showed moderate to good agreements (0.41-0.64) with OF and AXnRX/RX index, regardless of registration method or patient position. Comparison of registration method demonstrated OF and AXnRX/RX indices (x = 30% to 50%SUVmax) were significantly higher with ER vs. RR in NTP (p < 0.03), but not in TP. For patient position, the OF and AXnRX/RX indices were higher in TP than in NTP when RR was used with a trend toward significance, particularly for x=40%SUVmax (0.50±0.22 vs. 0.31 ± 0.13, p = 0.094). Conclusion: Our study suggested that PET/CT acquired in TP improves results in the localization of FDG hotspots in HNSCC. If TP is not possible, using an ER method is significantly more accurate than RR for overlap estimation.

Radiotherapy target volume definition in newly diagnosed high grade glioma using 18F-FET PET imaging and multiparametric perfusion MRI: A prospective study (IMAGG).

PURPOSE: The aim of this study was to prospectively investigate tumor volume delineation by amino acid PET and multiparametric perfusion magnetic resonance imaging (MRI) in patients with newly diagnosed, untreated high grade glioma (HGG). MATERIALS AND METHODS: Thirty patients with histologically confirmed HGG underwent O-(2-[18F]-fluoroethyl)-l-tyrosine (18F-FET) positron emission tomography (PET), conventional Magnetic Resonance Imaging (MRI) as contrast-enhanced (CE) and fluid-attenuated inversion recovery (FLAIR) and multiparametric MRI as relative cerebral blood volume (rCBV) and permeability estimation map (K2). Areas of MRI volumes were semi-automatically segmented. The percentage overlap volumes, Dice and Jaccard spatial similarity coefficients (OV, DSC, JSC) were calculated. RESULTS: The 18F-FET tumor volume was significantly larger than the CE volume (median 43.5 mL (2.5-124.9) vs. 23.8 mL (1.4-80.3), p = 0.005). The OV between 18F-FET uptake and CE volume was low (median OV 0.59 (0.10-1)), as well as spatial similarity (median DSC 0.52 (0.07-0.78); median JSC 0.35 (0.03-0.64)). Twenty-five patients demonstrated both rCBV and CE on MRI: The median rCBV tumor volume was significantly smaller than the median CE volume (p < 0.001). The OV was high (median 0.83 (0.54-1)), but the spatial similarity was low (median DSC 0.45 (0.04-0.83); median JSC 0.29 (0.07-0.71)). Twenty-eight patients demonstrated both K2 and CE on MRI. The median K2 tumor volume was not significantly larger than the median CE volume. The OV was high (median OV 0.90 (0.61-1)), and the spatial similarity was moderate (median DSC 0.75 (0.01-0.83); median JSC 0.60 (0.11-0.89)). CONCLUSION: We demonstrated that multiparametric perfusion MRI volumes (rCBV, K2) were highly correlated with CE T1 gadolinium volumes whereas 18F-FET PET provided complementary information, suggesting that the metabolically active tumor volume in patients with newly diagnosed untreated HGG is critically underestimated by contrast enhanced MRI. 18F-FET PET imaging may help to improve target volume delineation accuracy for radiotherapy planning.

Impact of suboptimal dosimetric coverage of pretherapeutic 18F-FDG PET/CT hotspots on outcome in patients with locally advanced cervical cancer treated with chemoradiotherapy followed by brachytherapy.

INTRODUCTION: Areas of high uptake on pre-treatment 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT), denoted as "hotspots", have been identified as preferential sites of local relapse in locally advanced cervical cancer (LACC). The purpose of this study was to analyze the dosimetric coverage of these hotspots with high dose-rate brachytherapy (BT). METHODS: For each patient, a rigid registration of the CT from the pre-treatment PET/CT with the radiotherapy planning CT was performed using 3D SlicerTM, followed by a manual volume correction by translation and deformation if necessary. The fuzzy locally adaptive Bayesian (FLAB) algorithm was applied to PET images to simultaneously define an overall tumour volume and the high-uptake sub-volume V1. The inclusion of V1 in the high-risk clinical target volume (CTV HR) and its dosimetric coverage were evaluated using 3D SlicerTM. The average of the 3-4 BT sessions was reported. RESULTS: Forty-two patients with recurrence after chemoradiotherapy (CRT) for LACC were matched to 42 patients without recurrence. Mean ± standard deviation follow-up was 26 ± 11 months. In the recurrence group, V1 was not included in the CTV HR and not covered by the 85 Gy isodose in 17/42 patients (41%) (1/20 with pelvic recurrence and 16/22 with distant recurrence) and not by the 80 Gy isodose in 7/42 patients (17%) (all with distant recurrence). In the non-recurrence group, V1 was not included in CTV HR and not covered by the 85 Gy isodose in 3 patients only (7%). The hotspots coverage by the 85 Gy isodose was significantly better in patients who did not recur, but only when compared to patients with distant relapse (p < 0.0001). CONCLUSION: Suboptimal dosimetric coverage of high FDG uptakes on pretherapeutic PET could be associated with an increased risk of recurrence.

Transoral Robotic Surgery for Oropharyngeal Squamous Cell Carcinoma: Improving Function While Maintaining Oncologic Outcome.

The improved survival in patients with HPV-positive (human papilloma virus) oropharyngeal squamous cell carcinoma as compared with HPV-negative disease calls for treatment that preserves quality of life, particularly a functional swallow. There are several trials currently assessing treatment de-escalation in terms of less invasive transoral robotic surgery, reduced-dose radiotherapy, and omission of chemotherapy in this disease cohort. It is important for head and neck oncology surgeons to stay abreast of developments in this area to offer their patients the most up-to-date treatment and consider recruiting patients to trials at their institutions. For this purpose, we provide a summary of current trials and associated challenges in managing a disease with fast-evolving treatment algorithms.

Survival outcomes for head and neck cancer patients with N3 cervical nodal metastases.

BACKGROUND: Management of metastatic N3 nodal disease from primary head and neck squamous cell carcinoma (HNSCC) is controversial. Recently, there has been a move to observation of the neck for those who achieve complete response (CR) after chemoradiotherapy (CRT). We sought to determine survival outcomes for N3 nodal disease, particularly for patients with human papilloma virus (HPV)-positive HNSCC. METHODS: We carried out a systematic search of MEDLINE and Embase for articles between 01/2008 and 12/2017. Articles on N3 nodal disease in HNSCC patients treated with CRT or surgery + adjuvant RT/CRT were included if they reported on oropharyngeal or HPV+ subgroups. Local control (LC), nodal control (NC), distant metastasis-free survival (DMFS), disease-free survival (DFS) or overall survival (OS) was assessed. RESULTS: Nine studies met the inclusion criteria. Eight of these studies (N = 5304) allowed further comparison: 4 were on CRT, 2 on surgery + RT/CRT and 2 on both. Four of these eight studies and the remaining included study reported on residual nodal disease on histology after neck dissection (ND) following CRT. Patients treated with CRT achieved LC rates of 77%-94% at 2-3 years; those who had a CR had LC of >90%. Better NC was noted in patients who achieved a CR. Three-year OS was better for HPV+ HNSCC (range, 55.2%-81%). Patients with CR had better survival outcomes (DMFS 77% at 3 years vs 69.8% for HPV+; OS 68.9% at 3 years vs 55.2% for HPV+). Primary surgery demonstrated similar survival for HPV+ vs HPV- and better survival in oropharyngeal cancers. Five-year DFS rates varied from 30% to 87%, and OS from 26.6% to 84%. For patients with non-CR, positive histology rates varied from 27.3% to 100%, with average positive histology rates of 27.3% in HPV+ patients with non-CR vs 60% for HPV- patients with non-CR. CONCLUSION: The current literature does not support the de-escalation of treatment with HPV- N3 disease. Observation of HPV+ patients who achieve a CR post-CRT is reasonable but further prospective studies are required given the heterogeneity and risk of bias within these current studies. Planned ND should remain standard of care for non-CR cohort.