Opportunistic screening for osteoporosis using routine clinical care computed tomography brain studies.

OBJECTIVE: Osteoporosis and falls are both prevalent in the elderly, and CT brain (CTB) is frequently performed post head-strike. We aim to validate the relationship between frontal bone density (Hounsfield unit) from routine CTB and bone mineral density from dual-energy X-ray absorptiometry (DEXA) scan for opportunistic osteoporosis screening. MATERIALS AND METHODS: Patients who had a non-contrast CTB followed by a DEXA scan in the subsequent year were included in this multi-center retrospective study. The relationship between frontal bone density on CT and femoral neck T-score on DEXA was examined using ANOVA, Pearson's correlation, and receiver operating curve (ROC) analysis. Sensitivity, specificity, negative and positive predictive values, and area under the curve (AUC) were calculated. RESULTS: Three hundred twenty-six patients (205 females and 121 males) were analyzed. ANOVA analysis showed that frontal bone density was lower in patients with DEXA-defined osteoporosis (p < 0.001), while Pearson's correlation analysis demonstrated a fair correlation with femoral neck T-score (r = 0.3, p < 0.001). On subgroup analysis, these were true in females but not in males. On ROC analysis, frontal bone density weakly predicted osteoporosis (AUC 0.6, 95% CI 0.5-0.7) with no optimal threshold identified. HU < 610 was highly specific (87.5%) but poorly sensitive (18.9%). HU > 1200 in females had a strong negative predictive value for osteoporosis (92.6%, 95% CI 87.1-98.1%). CONCLUSION: Frontal bone density from routine CTB is significantly different between females with and without osteoporosis, but not between males. However, frontal bone density was a weak predictor for DEXA-defined osteoporosis. Further research is required to determine the role of CTB in opportunistic osteoporosis screening.

Delineation and agreement of FET PET biological volumes in glioblastoma: results of the nuclear medicine credentialing program from the prospective, multi-centre trial evaluating FET PET In Glioblastoma (FIG) study-TROG 18.06.

PURPOSE: The O-(2-[18F]-fluoroethyl)-L-tyrosine (FET) PET in Glioblastoma (FIG) trial is an Australian prospective, multi-centre study evaluating FET PET for glioblastoma patient management. FET PET imaging timepoints are pre-chemoradiotherapy (FET1), 1-month post-chemoradiotherapy (FET2), and at suspected progression (FET3). Before participant recruitment, site nuclear medicine physicians (NMPs) underwent credentialing of FET PET delineation and image interpretation. METHODS: Sites were required to complete contouring and dynamic analysis by ≥ 2 NMPs on benchmarking cases (n = 6) assessing biological tumour volume (BTV) delineation (3 × FET1) and image interpretation (3 × FET3). Data was reviewed by experts and violations noted. BTV definition includes tumour-to-background ratio (TBR) threshold of 1.6 with crescent-shaped background contour in the contralateral normal brain. Recurrence/pseudoprogression interpretation (FET3) required assessment of maximum TBR (TBRmax), dynamic analysis (time activity curve [TAC] type, time to peak), and qualitative assessment. Intraclass correlation coefficient (ICC) assessed volume agreement, coefficient of variation (CoV) compared maximum/mean TBR (TBRmax/TBRmean) across cases, and pairwise analysis assessed spatial (Dice similarity coefficient [DSC]) and boundary agreement (Hausdorff distance [HD], mean absolute surface distance [MASD]). RESULTS: Data was accrued from 21 NMPs (10 centres, n ≥ 2 each) and 20 underwent review. The initial pass rate was 93/119 (78.2%) and 27/30 requested resubmissions were completed. Violations were found in 25/72 (34.7%; 13/12 minor/major) of FET1 and 22/74 (29.7%; 14/8 minor/major) of FET3 reports. The primary reasons for resubmission were as follows: BTV over-contour (15/30, 50.0%), background placement (8/30, 26.7%), TAC classification (9/30, 30.0%), and image interpretation (7/30, 23.3%). CoV median and range for BTV, TBRmax, and TBRmean were 21.53% (12.00-30.10%), 5.89% (5.01-6.68%), and 5.01% (3.37-6.34%), respectively. BTV agreement was moderate to excellent (ICC = 0.82; 95% CI, 0.63-0.97) with good spatial (DSC = 0.84 ± 0.09) and boundary (HD = 15.78 ± 8.30 mm; MASD = 1.47 ± 1.36 mm) agreement. CONCLUSION: The FIG study credentialing program has increased expertise across study sites. TBRmax and TBRmean were robust, with considerable variability in BTV delineation and image interpretation observed.

Independent and incremental value of ventilation/perfusion PET/CT and CT pulmonary angiography for pulmonary embolism diagnosis: results of the PECAN pilot study.

PURPOSE: This pilot study assessed the independent and incremental value of 68Ga-V/Q PET/CT as compared with CT pulmonary angiography (CTPA) for the management of cancer patients with suspected acute pulmonary embolism (PE). METHODS: All 24 cancer patients with suspected acute PE prospectively recruited underwent both 68Ga-V/Q PET/CT and CTPA within 24 h. PET/CT was acquired after inhalation of Galligas prepared using a Technegas generator and administration of 68Ga-macroaggregated albumin. Initially, PET/CT and CTPA scans were read independently with the reader blinded to the results of the other imaging study. CTPA and PET/CT were then coregistered and reviewed by consensus between a radiologist and nuclear medicine physician. The therapeutic management was established by the managing physician based on all available data. RESULTS: The diagnostic conclusion was concordantly negative in 18 patients (75%). Of the six discordant diagnoses on independent reading, combined interpretation of V/Q PET/CTPA enabled a consensus conclusion in two patients, excluding PE in one and confirming PE in the other, similar to the initial diagnostic conclusion of the V/Q PET/CT. Of the remaining four patients, three had a single subsegmental thrombus on CTPA but a negative V/Q PET/CT scan, and two of these did not receive long-term anticoagulation and did not have a venous thromboembolic event during a 3-year follow-up period. The third patient, along with a patient with a positive V/Q PET/CT scan but a negative CTPA scan, presented with acute complications preventing any conclusions with regard to the appropriateness of the V/Q PET/CT results in the management of PE. Overall, V/Q PET had an impact on management in four patients (17%). CONCLUSION: In this pilot study, we demonstrated the feasibility and potential utility of V/Q PET/CT for the management of patients with suspected PE. V/Q PET/CT may be of particular relevance in patients with equivocal findings or isolated subsegmental findings on CTPA, adding further discriminatory information to allow important decision-making regarding the use or withholding of anticoagulation. Given the other advantages of V/Q PET/CT (reduced acquisition time, low radiation dose), and with the increasing availability of 68Ga generators, PET/CT is a potential replacement for V/Q SPECT/CT imaging.

Prostate-specific membrane antigen-positron emission tomography/computed tomography (PSMA-PET/CT)-guided stereotactic ablative body radiotherapy for oligometastatic prostate cancer: a single-institution experience and review of the published literature.

OBJECTIVES: To report the outcomes of stereotactic ablative body radiotherapy (SABR) in men with oligometastatic prostate cancer (PCa) diagnosed on prostate-specific membrane antigen (PSMA)-positron emission tomography/computed tomography (PET/CT), based on a single-institution experience and the published literature. PATIENTS AND METHODS: This was a retrospective cohort study of the first 20 consecutive men with oligometastatic PCa, treated with SABR in a single institution, who had biochemical recurrence after previous curative treatment (surgery/radiotherapy), had no evidence of local recurrence, were not on palliative androgen deprivation therapy (ADT), and had PSMA-PET/CT-confirmed oligometastatic disease (≤3 lesions). These men were treated with SABR to a dose of 30 Gy in three fractions for bone metastases, and 35-40 Gy in five fractions for nodal metastases. The outcomes of interest were: PSA response; local progression-free survival (LPFS); distant progression-free survival (DPFS); and ADT-free survival (ADTFS). A literature review was performed to identify published studies reporting on outcomes of PSMA-PET/CT-guided SABR. RESULTS: In our institutional cohort, 12 men (60%) had a decline in PSA post-SABR. One man had local progression 9.6 months post-SABR, with 12-month LPFS of 93%. Ten men had distant progression outside of their SABR treatment field, confirmed on PSMA-PET/CT, with 12-month DPFS of 62%, of whom four were treated with palliative ADT, two received prostate bed radiotherapy for prostate bed progression (confirmed on magnetic resonance imaging), and four received a further course of SABR (of whom one had further progression and was treated with palliative ADT). At last follow-up, six men (one with local progression and five with distant progression) had received palliative ADT. The 12-month ADTFS was 70%. Men with longer intervals between local curative treatment and SABR had better DPFS (P = 0.03) and ADTFS (P = 0.005). Four additional studies reporting on PSMA-PET/CT-guided SABR for oligometastatic PCa were identified and included in the review, giving a total of 346 patients. PSA decline was reported in 60-70% of men post-SABR. The 2-year LPFS, DPFS and ADTFS rates were 76-100%, 27-52%, and 58-62%, respectively. CONCLUSION: Our results showed that PSMA-PET/CT could have an important role in identifying men with true oligometastatic PCa who would benefit the most from metastases-directed therapy with SABR.

TROG 15.03 phase II clinical trial of Focal Ablative STereotactic Radiosurgery for Cancers of the Kidney - FASTRACK II.

BACKGROUND: Stereotactic ablative body radiotherapy (SABR) is a non-invasive alternative to surgery to control primary renal cell cancer (RCC) in patients that are medically inoperable or at high-risk of post-surgical dialysis. The objective of the FASTRACK II clinical trial is to investigate the efficacy of SABR for primary RCC. METHODS: FASTRACK II is a single arm, multi-institutional phase II study. Seventy patients will be recruited over 3 years and followed for a total of 5 years. Eligible patients must have a biopsy confirmed diagnosis of primary RCC with a single lesion within a kidney, have ECOG performance ≤2 and be medically inoperable, high risk or decline surgery. Radiotherapy treatment planning is undertaken using four dimensional CT scanning to incorporate the impact of respiratory motion. Treatment must be delivered using a conformal or intensity modulated technique including IMRT, VMAT, Cyberknife or Tomotherapy. The trial includes two alternate fractionation schedules based on tumour size: for tumours ≤4 cm in maximum diameter a single fraction of 26Gy is delivered; and for tumours > 4 cm in maximum diameter 42Gy in three fractions is delivered. The primary outcome of the study is to estimate the efficacy of SABR for primary RCC. Secondary objectives include estimating tolerability, characterising overall survival and cancer specific survival, estimating the distant failure rate, describing toxicity and renal function changes after SABR, and assessment of cost-effectiveness of SABR compared with current therapies. DISCUSSION: The present study design allows for multicentre prospective validation of the efficacy of SABR for primary RCC that has been observed from prior single institutional and retrospective series. The study also allows assessment of treatment related toxicity, overall survival, cancer specific survival, freedom from distant failure and renal function post therapy. TRIAL REGISTRATION: Clinicaltrials.gov NCT02613819 , registered Nov 25th 2015.

The clinical utility of fluorodeoxyglucose-positron emission tomography for investigation of fever in immunocompromised children.

AIM: Fever in immunocompromised children presents significant challenges. We aimed to determine the clinical impact of fluorodeoxyglucose-positron emission tomography (FDG-PET) in combination with computed tomography (CT) in children with malignancy or following haematopoietic stem cell transplantation with prolonged or recurrent fever. METHODS: Immunocompromised children who underwent FDG-PET/CT for investigation of prolonged or recurrent fever were identified from hospital databases. The clinical impact of the FDG-PET/CT was considered 'high' if it contributed to any of the following: diagnosis of a new site infection/inflammation, change to antimicrobials or chemotherapy, or additional investigations or specialist consult contributing to final diagnosis. RESULTS: Fourteen patients underwent an FDG-PET/CT for prolonged or recurrent fever. Median age was 11 years and 46% had diagnosis of acute lymphoblastic leukaemia. The median absolute neutrophil count on the day of FDG-PET/CT was 0.47 cells/µL. The clinical impact of FDG-PET/CT was 'high' in 11 (79%) patients, contributing to rationalisation of antimicrobials in three, and cessation of antimicrobials in five. Compared to conventional imaging, FDG PET/CT identified seven additional sites of clinically significant infection/inflammation in seven patients. Of the 10 patients who had a cause of fever identified, FDG-PET/CT contributed to the final diagnosis in six (60%). CONCLUSION: This study has identified potential utility for FDG-PET/CT in immunocompromised children with prolonged or recurrent fever. Further prospective studies are needed to compare FDG-PET/CT versus conventional imaging, to identify the optimal timing of FDG-PET/CT and to study the role of subsequent scans to monitor response to therapy.

What, where and why: exploring fluorodeoxyglucose-PET's ability to localise and differentiate infection from cancer.

PURPOSE OF REVIEW: To review the utility of FDG-PET imaging in detecting the cause of fever and infection in patients with cancer. RECENT FINDINGS: FDG-PET has been shown to have high sensitivity and accuracy for causes of neutropenic fever, leading to higher diagnostic certainty in this group. Recent advances in pathogen-specific labelling in PET to identify Aspergillus spp. and Yersinia spp. infections in mice, as well as differentiating between Gram-positive, Gram-negative and mycobacterial infections are promising. SUMMARY: Patients with cancer are vulnerable to infection and fever, and the causes of these are frequently unclear using conventional diagnostic methods leading to high morbidity and mortality, length of stay and costs of care. FDG-PET/CT, with its unique complementary functional and anatomical information as well as its whole-body imaging capability, has demonstrated use in detecting occult infection in immunocompromised patients, including invasive fungal and occult bacterial infections, as well as defining extent of infection. By demonstrating disease resolution following treatment and allowing earlier cessation of therapy, FDG-PET acts as a key tool for antimicrobial and antifungal stewardship. Limitations include at times poor differentiation between infection, malignancy and sterile inflammation, however, exciting new technologies specific to infectious pathogens may help alleviate that issue. Further prospective randomised research is needed to explore these benefits in a nonbiased fashion.

Utility of positron emission tomography/computed tomography for nodal staging of cutaneous squamous cell carcinoma in patients with chronic lymphocytic leukemia.

PURPOSE: Cutaneous squamous cell carcinoma (cSCC) behaves aggressively in patients with chronic lymphocytic leukemia (CLL). Lymphadenopathy due to CLL can obscure the clinical and radiological assessment of nodal involvement by cSCC. This study aimed to evaluate whether functional imaging with positron emission tomography (PET)/computed tomography (CT) may clarify the clinical picture. METHODS: Five consecutive patients with cSCC and CLL who had a PET/CT scan for the purposes of cSCC staging between July 2000 and July 2010 were analyzed. PET/CT findings were compared to histopathology from subsequent neck dissection. RESULTS: PET/CT can distinguish nodal cSCC from leukemic infiltration with high specificity, allowing prompt appropriate management of nodal disease. CONCLUSIONS: PET/CT is a promising modality for nodal staging in patients with cSCC and CLL, with the potential to improve outcomes in this poor prognosis group. Larger confirmatory studies are needed.

Narrative review of the utility of magnetic resonance imaging in radiotherapy for cervical cancer.

BACKGROUND AND OBJECTIVE: In radiotherapy (RT) for locally advanced cervical cancer, high soft tissue contrast on magnetic resonance imaging (MRI) can ensure accurate delineation of target volumes (TVs) and optimal dose distribution to the RT target and organs at risk (OAR). MRI-guided adaptive RT (MRIgART) is a novel technology that revises RT plans according to anatomical changes occurring throughout the treatment to improve target coverage and minimise OAR toxicity. This review aims to assess the evidence and gaps of MRI use in RT planning and MRIgART in the treatment of cervical cancer, as well as challenges in its clinical implementation. METHODS: Ovid Medline and PubMed were searched using keywords for MRI in RT for cervical cancer. After applying the inclusion and exclusion criteria, the initial search was deduced to 32 studies. A total of 37 final studies were reviewed, including eight additional articles from references. KEY CONTENT AND FINDINGS: In the primary studies, TVs and organ motion were assessed before, during, and after treatment. MRI was used to investigate dose distribution and therapeutic response to the treatment in association with its outcome. Lastly, rationales for MRIgART were evaluated. CONCLUSIONS: It was concluded that MRI enables accurate target delineation, assessment of organ motion and interfraction changes, and monitoring of treatment response through dynamic parameters. Enhanced target coverage and reduced OAR irradiation through MRIgART can improve local control and the overall outcome, although its rationales against the logistical challenges need to be evaluated on further research.

High FDG activity in focal fat necrosis: a pitfall in interpretation of posttreatment PET/CT in patients with non-Hodgkin lymphoma.

PURPOSE: PET/CT has a major role in lymphoma imaging, but glycolytic activity in inflammatory processes can reduce specificity. In this study we evaluated restaging PET/CT findings in patients with non-Hodgkin lymphoma (NHL) and fat necrosis. METHODS: We identified 16 patients from 8,819 restaging FDG PET/CT scans with suspicion of or biopsy-proven fat necrosis on PET/CT. RESULTS: All patients had NHL and demonstrated focal FDG-avid nodular change on CT with density higher than that of fat but lower than that of soft tissue. Histological confirmation was obtained in eight patients, with high GLUT-1 staining between necrotic tissue and organizing fat necrosis evident. Uptake resolved in four patients, and surveillance was continuing in four without relapse. CONCLUSION: Although rare, identification of fat necrosis in patients with a solitary FDG-avid nodule after therapy is important and may lead to the avoidance of unnecessary interventions or treatment. Specific features on CT aid identification, whilst follow-up imaging can be helpful as the metabolic abnormality regresses with time.

A review of diffusion-weighted magnetic resonance imaging in head and neck cancer patients for treatment evaluation and prediction of radiation-induced xerostomia.

The incidence of head and neck cancers (HNC) is rising worldwide especially with HPV-related oropharynx squamous cell carcinoma. The standard of care for the majority of patients with locally advanced pharyngeal disease is curative-intent radiotherapy (RT) with or without concurrent chemotherapy. RT-related toxicities remain a concern due to the close proximity of critical structures to the tumour, with xerostomia inflicting the most quality-of-life burden. Thus, there is a paradigm shift towards research exploring the use of imaging biomarkers in predicting treatment outcomes. Diffusion-weighted imaging (DWI) is a functional MRI feature of interest, as it quantifies cellular changes through computation of apparent diffusion coefficient (ADC) values. DWI has been used in differentiating HNC lesions from benign tissues, and ADC analyses can be done to evaluate tumour responses to RT. It is also useful in healthy tissues to identify the heterogeneity and physiological changes of salivary glands to better understand the inter-individual differences in xerostomia severity. Additionally, DWI is utilised in irradiated salivary glands to produce ADC changes that correlate to clinical xerostomia. The implementation of DWI into multi-modal imaging can help form prognostic models that identify patients at risk of severe xerostomia, and thus guide timely interventions to mitigate these toxicities.

Radiation exposure from radiological procedures in liver transplant candidates with hepatocellular carcinoma.

PURPOSE: Candidates for liver transplantation (LT) with hepatocellular carcinoma (HCC) undergo a large number of diagnostic and interventional radiology procedures. A significant proportion of such procedures involve ionizing radiation with increased lifetime risk of cancer. The objective of our study was to review LT candidates with HCC to quantify ionizing radiation doses from different radiology procedures performed at a single transplant center. METHOD: We retrospectively reviewed 179 adult patients with HCC (median age 58.6 years [IQR, 55-62]; 155 [86.6%] males) who were accepted for LT between April 2010 and Dec 2018. Radiology procedures and radiation doses were retrieved and the total and median radiation effective dose in millisieverts (mSv) were calculated for different procedures. Exposure to ionizing radiation was categorized based on previously reported thresholds. RESULTS: We assessed 9,986 radiology procedures for our cohort. Patients had a median effective dose prior to transplantation of 254 mSv (IQR, 130-421) with an annualized rate of 152 mSv (IQR, 92-266). Patient median dose increased to 316 mSv (IQR, 159-478) when including exposures post-LT within the study period. 85% of overall exposure was in the extremely high exposure category (>100 mSv). Interventional procedures represented 13% of procedures with substantial radiation and contributed to 45% of radiation exposure while abdominal CTs represented 39% of total procedures and contributed to 45% of radiation exposure. CONCLUSIONS: Patients with HCC considered for LT undergo radiology procedures with significant cumulative radiation exposure. Attempts to reduce radiation exposure are suggested by minimizing unnecessary procedures and utilizing ones without ionizing radiation. Improving interventional techniques to reduce radiation doses is needed without compromising treatment delivery.

PSMA-PET Detection of Unusual Metastases in Castrate-Sensitive Prostate Carcinoma.

ABSTRACT: Prostate cancer (PCa) is a multifaceted, heterogeneous disease (with 7 molecular subtypes), which can metastasize to common sites, such as bone, lymph nodes, liver, and lungs. However, with PSMA PET imaging, rare sites of metastasis are increasingly discovered. We report 5 cases of unusual metastases in patients with castrate-sensitive PCa: solitary right inguinal nodal metastasis, solitary abdominal wall metastasis, penile shaft metastases, solitary perineum metastasis, and pleural metastases. These cases further support the use of PSMA-PET imaging in PCa monitoring, with the ability to detect solitary, small volume, and rare sites of metastases, which may not be apparent on conventional imaging.

[18F]-fluoroethyl-L-tyrosine (FET) in glioblastoma (FIG) TROG 18.06 study: protocol for a prospective, multicentre PET/CT trial.

INTRODUCTION: Glioblastoma is the most common aggressive primary central nervous system cancer in adults characterised by uniformly poor survival. Despite maximal safe resection and postoperative radiotherapy with concurrent and adjuvant temozolomide-based chemotherapy, tumours inevitably recur. Imaging with O-(2-[18F]-fluoroethyl)-L-tyrosine (FET) positron emission tomography (PET) has the potential to impact adjuvant radiotherapy (RT) planning, distinguish between treatment-induced pseudoprogression versus tumour progression as well as prognostication. METHODS AND ANALYSIS: The FET-PET in Glioblastoma (FIG) study is a prospective, multicentre, non-randomised, phase II study across 10 Australian sites and will enrol up to 210 adults aged ≥18 years with newly diagnosed glioblastoma. FET-PET will be performed at up to three time points: (1) following initial surgery and prior to commencement of chemoradiation (FET-PET1); (2) 4 weeks following concurrent chemoradiation (FET-PET2); and (3) within 14 days of suspected clinical and/or radiological progression on MRI (performed at the time of clinical suspicion of tumour recurrence) (FET-PET3). The co-primary outcomes are: (1) to investigate how FET-PET versus standard MRI impacts RT volume delineation and (2) to determine the accuracy and management impact of FET-PET in distinguishing pseudoprogression from true tumour progression. The secondary outcomes are: (1) to investigate the relationships between FET-PET parameters (including dynamic uptake, tumour to background ratio, metabolic tumour volume) and progression-free survival and overall survival; (2) to assess the change in blood and tissue biomarkers determined by serum assay when comparing FET-PET data acquired prior to chemoradiation with other prognostic markers, looking at the relationships of FET-PET versus MRI-determined site/s of progressive disease post chemotherapy treatment with MRI and FET-PET imaging; and (3) to estimate the health economic impact of incorporating FET-PET into glioblastoma management and in the assessment of post-treatment pseudoprogression or recurrence/true progression. Exploratory outcomes include the correlation of multimodal imaging, blood and tumour biomarker analyses with patterns of failure and survival. ETHICS AND DISSEMINATION: The study protocol V.2.0 dated 20 November 2020 has been approved by a lead Human Research Ethics Committee (Austin Health, Victoria). Other clinical sites will provide oversight through local governance processes, including obtaining informed consent from suitable participants. The study will be conducted in accordance with the principles of the Declaration of Helsinki and Good Clinical Practice. Results of the FIG study (TROG 18.06) will be disseminated via relevant scientific and consumer forums and peer-reviewed publications. TRIAL REGISTRATION NUMBER: ANZCTR ACTRN12619001735145.

Use of FDG PET/CT for investigation of febrile neutropenia: evaluation in high-risk cancer patients.

PURPOSE: Febrile neutropenia (FNP) is a frequent complication of cancer care and evaluation often fails to identify a cause. [(18) F]FDG PET/CT has the potential to identify inflammatory and infectious foci, but its potential role as an investigation for persistent FNP has not previously been explored. The aim of this study was to prospectively evaluate the clinical utility of FDG PET/CT in patients with cancer and severe neutropenia and five or more days of persistent fever despite antibiotic therapy. METHODS: Adult patients with a diagnosis of an underlying malignancy and persistent FNP (temperature ≥38°C and neutrophil count <500 cells/µl for 5 days) underwent FDG PET/CT as an adjunct to conventional evaluation and management. RESULTS: The study group comprised 20 patients with FNP who fulfilled the eligibility criteria and underwent FDG PET/CT in addition to conventional evaluation. The median neutrophil count on the day of the FDG PET/CT scan was 30 cells/µl (range 0-730 cells/µl). Conventional evaluation identified 14 distinct sites of infection, 13 (93 %) of which were also identified by FDG PET/CT, including all deep tissue infections. FDG PET/CT identified 9 additional likely infection sites, 8 of which were subsequently confirmed as "true positives" by further investigations. FDG PET/CT was deemed to be of 'high' clinical impact in 15 of the 20 patients (75 %). CONCLUSION: This study supports the utility of FDG PET/CT scanning in severely neutropenic patients with five or more days of fever. Further evaluation of the contribution of FDG PET/CT in the management of FNP across a range of underlying malignancies is required.

A pilot study investigating the role of 18 F-FDG-PET in the early identification of chemoradiotherapy response in anal cancer.

INTRODUCTION: Anal cancer (AC) is 18 F-FDG-PET avid and has been used to evaluate treatment response several months after chemoradiotherapy. This pilot study aimed to assess the utility of semi-automated contouring methods and quantitative measures of treatment response using 18 F-FDG-PET imaging at the early time point of 1-month post-chemoradiotherapy. METHODS: Eleven patients with AC referred for chemoradiotherapy were prospectively enrolled into this study, with 10 meeting eligibility requirements. 18 F-FDG-PET imaging was obtained pre-chemoradiotherapy (TP1), and then 1-month (TP2), 3-6 months (TP3) and 9-12 months (TP4) post-chemoradiotherapy. Manual and semi-automated (Threshold) contouring methods were used to define the primary tumour on all 18 F-FDG-PET images. Resultant contours from each method were interrogated using quantitative measures, including volume, response index (RI), total lesion glycolysis (TLG), SUVmax , SUVmedian and SUVmean . Response was assessed quantitatively as reductions in these measures and also qualitatively against established criteria. RESULTS: Nine patients were qualitatively classified as complete metabolic responders at TP2 and all 10 at TP3. All quantitative measures demonstrated significant (P < 0.05) reductions at TP2 for both Manual and Threshold methods. All reduced further at TP3 and again at TP4 for Threshold methods. TLG showed the highest reduction at all post-chemoradiotherapy time points and classified the most responders for each method at each time point. All patients are recurrence-free at minimum 4-year follow-up. CONCLUSION: Based on our small sample size, semi-automated methods of disease definition using 18 F-FDG-PET imaging are feasible and appear to facilitate quantitative response classification of AC as early as 1-month post-chemoradiotherapy. Early identification of treatment response may potentially improve disease management.

Tumor volumes as a predictor of response to the anti-EGFR antibody drug conjugate depatuxizumab mafadotin.

BACKGROUND: The adverse impact of increasing brain tumor size on the efficacy of antibody-drug conjugates (ADCs) was investigated preclinically then validated with clinical data. METHODS­PRECLINICAL STUDY: The impact of tumor size on ADC tumor delivery and treatment response was evaluated in an EGFR-amplified patient-derived glioblastoma (GBM) model following treatment with Depatuxizumab mafadotin (Depatux-M). Biodistribution and imaging studies correlated drug distribution with starting treatment volume and anti-tumor activity. METHODS­CLINICAL STUDY: M12-356 was a Phase I study of Depatux-M in patients with GBM. Blinded volumetric analysis of baseline tumor volumes of M12-356 patients was undertaken by two reviewers and results correlated with response and survival. RESULTS: Preclinically, imaging and biodistribution studies showed specific and significantly higher tumor uptake of zirconium-89 labeled Depatux-M (89Zr-Depatux-M) in mice with smaller tumor volume (~98 mm3) versus those with larger volumes (~365 mm3); concordantly, mice with tumor volumes ≤100 mm3 at treatment commencement had significantly better growth inhibition by Depatux-M (93% vs 27%, P < .001) and significantly longer overall survival (P < .0001) compared to tumors ≥400 mm3. Clinically, patients with tumor volumes <25 cm3 had significantly higher response rates (17% vs. 0%, P = .009) and longer overall survival (0.5 vs 0.89 years, P = .001) than tumors above 25 cm3. CONCLUSION: Both preclinical and clinical data showed intra-tumoral concentration and efficacy of Depatux-m inversely correlated with tumor size. This finding merit further investigation with pretreatment tumor volume as a predictor for response to ADCs, in both gliomas and other solid tumors.

Unusual location of recurrent mantle cell lymphoma on fluorodeoxyglucose-positron emission tomography despite complete metabolic resolution of previous sites of disease.

This case report presents a patient with recurrent pleomorphic mantle cell lymphoma (MCL), which is a relatively rare but aggressive type of lymphoma. A positron emission tomography/computed tomography scan performed to assess treatment response demonstrated a complete metabolic response in the sites of primary disease while also revealing new subcutaneous lesions, which were biopsy-proven recurrent disease. This case illustrates the importance of the different biological behavior of MCL, whereby new sites of metabolically active lesions can represent recurrent disease, even though there is a complete metabolic response at sites of primary disease.

Breast ultrasound in breast cancer surveillance; incremental cancers found at what cost?

PURPOSE: To determine the diagnostic parameters of breast ultrasound (US) in the setting of routine radiological surveillance after a diagnosis of breast cancer and evaluate costs of the inclusion of breast US as well as any survival benefit of US detected cases of recurrence in surveillance. METHODS: 622 patients underwent breast cancer surgery and follow up at Austin Health from July 2009 to December 2015. Retrospective data analysis was performed to determine; diagnostic parameters, financial costs of US and survival outcomes of US detected cases of recurrence. RESULTS: Patients underwent 1-9 years of breast cancer surveillance, with a median of 4.24 years. 390 (62.7%) patients underwent additional breast US surveillance to mammography. 232 (38.3%) fit criteria for use of additional breast US. 199 abnormal imaging episodes occurred, leading to 16 screen detected-cases of locoregional recurrence. US alone generated 107 abnormal images and found 9 cancers. US had a sensitivity of 44.1%, specificity of 95.2% and positive predictive value of 11.7% in comparison to mammography; 20.6%, 97.4% and 9.9% respectively. US had a biopsy rate of 4.0% and lead to an incremental cancer detection rate of 0.38%. The cost of incremental cancer found was $31,463.72 AUD. Survival outcomes based on method of detection of recurrence were insignificant (p value = 0.71). CONCLUSIONS: Breast US has a sensitivity of 44.1% and detected seven recurrences that were mammographically occult. Breast US has a similar PPV to mammography in surveillance. Breast US generated considerable biopsy rates and costs. Survival analysis was not able to detect any benefit of US detected cases of recurrence.