Manil Subesinghe

Functional Imaging for Radiation Treatment Planning, Response Assessment, and Adaptive Therapy in Head and Neck Cancer

Patients with squamous cell carcinomas (SCCs) of the head and neck are increasingly treated nonsurgically. Imaging plays a critical role in helping define the targets for radiation therapy, especially intensity-modulated radiation therapy, in which the dose gradients are steep. Anatomic imaging with conventional modalities, particularly computed tomography (CT), has been used in patients with head and neck SCCs, but this approach has limitations. Functional imaging techniques, including positron emission tomography (PET) combined with CT or magnetic resonance (MR) imaging, offer complementary information and can be used noninvasively to assess a range of biomarkers in patients with head and neck SCCs, including hypoxia, cell proliferation and apoptosis, and epidermal growth factor receptor status. These biologic markers can be monitored before, during, and after treatment to improve patient selection for specific therapeutic strategies, guide adaptation of therapy, and potentially facilitate more accurate assessment of disease response. This article discusses the practical aspects of integrating functional imaging into head-and-neck radiation therapy planning and reviews the potential of molecular imaging biomarkers for response assessment and therapy adaptation. The uses of PET tracers for imaging cellular processes such as metabolism, proliferation, hypoxia, and cell membrane synthesis are explored, and applications for MR techniques such as dynamic contrast material-enhanced imaging, diffusion-weighted imaging, blood oxygenation level-dependent imaging, and MR spectroscopy are reviewed. The potential of integrated PET/CT perfusion imaging and hybrid PET/MR imaging also is highlighted. These developments may allow more individualized treatment planning in patients with head and neck SCCs in the emerging era of personalized medicine.

Delayed response assessment with FDG-PET-CT following (chemo)radiotherapy for locally advanced head and neck squamous cell carcinoma

AIMSnTo analyse the diagnostic accuracy of delayed response assessment 2-[¹⁸F]-fluoro-2-deoxy-d-glucose (FDG) positron-emission tomography-computed tomography (PET-CT) following (chemo)radiation for locally advanced head and neck squamous cell carcinoma (HNSCC).nnnMATERIAL AND METHODSnForty-four consecutive patients who underwent a baseline and response assessment using FDG PET-CT for HNSCC following (chemo)radiation between August 2008 and April 2011 were identified retrospectively. Clinicopathological findings and serial clinical follow-up provided the reference standard.nnnRESULTSnMedian follow-up was 14 months (range 5-43 months). Response assessment FDG PET-CT was performed at 16.8 weeks (inter-quartile range 15.8-18.6 weeks). Thirty-one out of 44 (70%) response assessment examinations showed a complete metabolic response. Seven out of 40 (18%) assessable primary tumours were positive. Eight out of 41 (20%) patients with pre-treatment nodal disease had equivocal or positive FDG uptake at response assessment. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for primary disease and nodal disease were 100, 89, 43, 100, and 100%, and 92, 63, and 100%, respectively. Seven patients had residual FDG-negative soft tissue detectable on the unenhanced CT component of the response assessment images; all remained disease free after clinical observation. Distant metastases were detected on response assessment FDG PET-CT in four out of the 44 patients (10%).nnnCONCLUSIONnThe diagnostic accuracy of response assessment with FDG PET-CT performed at approximately 16 weeks post-(chemo)radiotherapy is good. The very high NPV of a complete metabolic response can be used to guide management decisions. Although the PPV is limited for local residual disease, FDG PET-CT is a powerful screening tool for the detection of interim metastatic disease.

Alterations in anatomic and functional imaging parameters with repeated FDG PET-CT and MRI during radiotherapy for head and neck cancer: a pilot study

BackgroundThe use of imaging to implement on-treatment adaptation of radiotherapy is a promising paradigm but current data on imaging changes during radiotherapy is limited. This is a hypothesis-generating pilot study to examine the changes on multi-modality anatomic and functional imaging during (chemo)radiotherapy treatment for head and neck squamous cell carcinoma (HNSCC).MethodsEight patients with locally advanced HNSCC underwent imaging including computed tomography (CT), Fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography (PET)-CT and magnetic resonance imaging (MRI) (including diffusion weighted (DW) and dynamic contrast enhanced (DCE)) at baseline and during (chemo)radiotherapy treatment (after fractions 11 and 21). Regions of interest (ROI) were drawn around the primary tumour at baseline and during treatment. Imaging parameters included gross tumour volume (GTV) assessment, SUVmax, mean ADC value and DCE-MRI parameters including Plasma Flow (PF). On treatment changes and correlations between these parameters were analysed using a Wilcoxon rank sum test and Pearson’s linear correlation coefficient respectively. A p-value <0.05 was considered statistically significant.ResultsStatistically significant reductions in GTV-CT, GTV-MRI and GTV-DW were observed between all imaging timepoints during radiotherapy. Changes in GTV-PET during radiotherapy were heterogeneous and non-significant. Significant changes in SUVmax, mean ADC value, Plasma Flow and Plasma Volume were observed between the baseline and the fraction 11 timepoint, whilst only changes in SUVmax between baseline and the fraction 21 timepoint were statistically significant. Significant correlations were observed between multiple imaging parameters, both anatomical and functional; 20 correlations between baseline to the fraction 11 timepoint; 12 correlations between baseline and the fraction 21 timepoints; and 4 correlations between the fraction 11 and fraction 21 timepoints.ConclusionsMulti-modality imaging during radiotherapy treatment demonstrates early changes (by fraction 11) in both anatomic and functional imaging parameters. All functional imaging modalities are potentially complementary and should be considered in combination to provide multi-parametric tumour assessment, to guide potential treatment adaptation strategies.Trial RegistrationISRCTN Registry: ISRCTN34165059. Registered 2nd February 2015.

Multimodality imaging with CT, MR and FDG-PET for radiotherapy target volume delineation in oropharyngeal squamous cell carcinoma

BackgroundThis study aimed to quantify the variation in oropharyngeal squamous cell carcinoma gross tumour volume (GTV) delineation between CT, MR and FDG PET-CT imaging.MethodsA prospective, single centre, pilot study was undertaken where 11 patients with locally advanced oropharyngeal cancers (2 tonsil, 9 base of tongue primaries) underwent pre-treatment, contrast enhanced, FDG PET-CT and MR imaging, all performed in a radiotherapy treatment mask. CT, MR and CT-MR GTVs were contoured by 5 clinicians (2 radiologists and 3 radiation oncologists). A semi-automated segmentation algorithm was used to contour PET GTVs. Volume and positional analyses were undertaken, accounting for inter-observer variation, using linear mixed effects models and contour comparison metrics respectively.ResultsSignificant differences in mean GTV volume were found between CT (11.9xa0cm3) and CT-MR (14.1xa0cm3), pu2009<u20090.006, CT-MR and PET (9.5xa0cm3), pu2009<u20090.0009, and MR (12.7xa0cm3) and PET, pu2009<u20090.016. Substantial differences in GTV position were found between all modalities with the exception of CT-MR and MR GTVs. A mean of 64xa0%, 74xa0% and 77xa0% of the PET GTVs were included within the CT, MR and CT-MR GTVs respectively. A mean of 57xa0% of the MR GTVs were included within the CT GTV; conversely a mean of 63xa0% of the CT GTVs were included within the MR GTV. CT inter-observer variability was found to be significantly higher in terms of position and/or volume than both MR and CT-MR (pu2009<u20090.05). Significant differences in GTV volume were found between GTV volumes delineated by radiologists (9.7xa0cm3) and oncologists (14.6xa0cm3) for all modalities (pu2009=u20090.001).ConclusionsThe use of different imaging modalities produced significantly different GTVs, with no single imaging technique encompassing all potential GTV regions. The use of MR reduced inter-observer variability. These data suggest delineation based on multimodality imaging has the potential to improve accuracy of GTV definition.Trial registrationISRCTN Registry: ISRCTN34165059. Registered 2nd February 2015.

Assessment of outcomes with delayed (18)F-FDG PET-CT response assessment in head and neck squamous cell carcinoma.

OBJECTIVEnTo assess the accuracy of a 4-month post-(chemo)radiotherapy 18-fludeoxyglucose ((18)F-FDG) positron emission tomography (PET)-CT for head and neck squamous cell carcinoma (HNSCC).nnnMETHODSn105 patients who underwent a baseline and response assessment (18)F-FDG PET-CT scan between 2008 and April 2013 were identified. (18)F-FDG PET-CT outcomes were analysed with reference to clinicopathological outcomes.nnnRESULTSn79 of 105 (75%) (18)F-FDG PET-CT scans demonstrated a complete metabolic response; 19 of 101 (19%) for assessable primary tumours were positive; and 19 of 93 (20%) for patients with nodal disease were equivocal (nu2009=u200910) or positive (nu2009=u20099). The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for primary and nodal disease were 90%, 89%, 47%, 99% and 91%, 89%, 53% and 99%, respectively. Eight of nine patients with a positive nodal response scan had clinicopathological evidence of residual nodal disease (PPV, 89%). 2 of 10 patients with equivocal nodal responses had clinicopathological evidence of residual nodal disease (PPV, 20%).nnnCONCLUSIONn(18)F-FDG PET-CT 4 months post treatment has a very high NPV. A positive (18)F-FDG PET-CT has a high PPV for residual nodal disease. By contrast, patients who have an equivocal nodal response have a low PPV.nnnADVANCES IN KNOWLEDGEnResponse assessment (18)F-FDG PET-CT is a valuable tool in guiding the selective use of neck dissection following (chemo)radiotherapy for HNSCC. An equivocal lymph node response has a limited predictive value for persistent disease, and optimal management remains a clinical challenge.

F-18 FDG PET/CT imaging of follicular dendritic cell sarcoma of the mediastinum.

A 52-year-old female smoker presenting with unexplained weight loss underwent CT and FDG PET/CT imaging, which demonstrated an extremely hypermetabolic mediastinal mass with calcification, necrosis, and features of local invasiveness. Mediastinoscopy and biopsy were followed by successful surgical resection of an encapsulated mass showing the typical histologic features of follicular dendritic cell sarcoma (FDCS). FDCS of the mediastinum is a rare neoplasm arising from accessory cells of the immune system. Integrated FDG PET/CT of mediastinal FDCS highlights the importance of histologic assessment of mediastinal tumors that may seem unresectable on initial imaging.

Diagnostic yield of FDG-PET/CT in fever of unknown origin: a systematic review, meta-analysis, and Delphi exercise

AIMnTo perform a systematic review, meta-analysis and Delphi exercise to evaluate diagnostic yield of combined 2-[18F]-fluoro-2-deoxy-d-glucose (FDG) positron-emission tomography and computed tomography (FDG-PET/CT) in fever of unknown origin (FUO).nnnMATERIALS AND METHODSnFour databases were searched for studies of FDG-PET/CT in FUO 1/1/2000-1/12/2015. Exclusions were non-English language, case reports, non-standard FDG radiotracer, and significant missing data. Quality was assessed by two authors independently using a standardised tool. Pooled diagnostic yield was calculated using a random-effects model. An iterative electronic and face-to-face Delphi exercise generated interspeciality consensus.nnnRESULTSnPooled diagnostic yield was 56% (95% confidence interval [CI]: 50-61%, I2=61%) from 18 studies and 905 patients. Only five studies reported results of previous imaging, and subgroup analysis estimated diagnostic yield beyond conventional CT at 32% (95% CI: 22-44%; I2=66%). Consensus was established that FDG-PET/CT is increasingly available with an emerging role, but there is prevailing variability in practice.nnnCONCLUSIONnThere is insufficient evidence to support the value of FDG-PET/CT in investigative algorithms of FUO. A paradigm shift in research is needed, involving prospective studies recruiting at diagnosis of FUO, with updated case definitions and hard outcome measures. Although these studies will be a significant undertaking with multicentre collaboration, their completion is vital for balancing both radiation exposure and costs against the possible benefits of utilising FDG-PET/CT.

Who should have pelvic vessel imaging prior to renal transplantation

Subesinghe M, Cherukuri A, Ecuyer C, Baker RJ. Who should have pelvic vessel imaging prior to renal transplantation?u2028Clin Transplant 2011: 25: 97–103.

Clinical impact of 18 F-FDG PET-CT in recurrent stage III/IV melanoma: a tertiary centre Specialist Skin Cancer Multidisciplinary Team (SSMDT) experience

ObjectivesTo assess the clinical impact of 18F-fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET-CT) compared with contrast-enhanced computed tomography (CECT) in patients referred via the Specialist Skin Cancer Multidisciplinary Team (SSMDT) with recurrent stage III/IV malignant melanoma (MM).MethodsForty-five patients were referred for further evaluation with FDG PET-CT. Findings on FDG PET-CT were compared with prior CECT and the clinical impact on subsequent management decisions was determined retrospectively. A major clinical impact was defined as a change in treatment plan resulting from identification of additional sites of disease or by characterisation of indeterminate findings on prior imaging. A minor impact was defined as confirmation of known sites of disease as identified on prior CECT.ResultsFifty-one PET-CT examinations were performed. FDG PET-CT had a major clinical impact in 21 cases (41.2xa0%), of which 18 examinations were performed in patients with proven or suspected stage IV MM. FDG PET-CT had a minor impact in 23 cases (45.1xa0%), and there were five false-positive cases (9.8xa0%) and two false-negative cases (3.9xa0%).ConclusionFDG PET-CT is an effective tool in recurrent stage III/IV MM with a significant clinical impact on management decisions in patients who are appropriately referred via the highly specialised forum of the SSMDT.Key Points• FDG PET-CT is an effective tool in recurrent stage III/IV malignant melanoma.• FDG PET-CT has a significant clinical impact on management decisions.• Effective use of FDG PET-CT is via referral from the Specialist Skin Cancer Multidisciplinary Team.

The proliferation of multidisciplinary team meetings (MDTMs): how can radiology departments continue to support them all?

AbstractObjectivesTo quantify the changes in multidisciplinary team meeting (MDTM) workload for consultant radiologists working in a single UK tertiary referral cancer institution, assess its impact and suggest solutions to these challenges.MethodsThe annual number of MDTM cases was collated over a 5-year period (2009u2009−u20092013). Qualitative information was obtained through questionnaire-based interviews of 47 consultant radiologists. Data analysed included number of MDTMs involved with, type of MDTM (oncological or non-oncological), time allocation for preparation and perceived deficiencies in the current MDTM.ResultsThirteen thousand and forty-nine cases were discussed in MDTMs in 2009 with a continued yearly increase over the 5-year period. Fifty-five percent of MDTM attendances were at oncological MDTMs. Consultant radiologists attended a median of two MDTMs per week, each requiring 4xa0hours time commitment; 60 % used out-of-hours time for MDTM preparation. The most frequently cited MDTM deficiency was lack of sufficient clinical input.ConclusionsThe MDTM is a challenging but worthwhile demand on the modern radiologist’s time. Solutions to the increasing MDTM workload include demonstration of the benefits of MDTMs to hospital administrators to justify additional resources required, improving MDTM efficiency and ensuring this increased workload is accurately represented and remunerated in individual job plans.Key Points• MDTMs improve cancer outcomes and are being recommended for non-oncological conditions.n • MDTM cases have more than doubled over 5xa0years at our institution.n • Incorporating MDTM workload into current consultant radiologist job plans is difficult.n • Solutions include demonstrating MDTM related benefits, improved efficiency, and accurate job planning.