Three-dimensional (3D) magnetic resonance volume assessment and loco-regional failure in anal cancer: early evaluation case-control study.

BACKGROUND: The primary aim was to test the hypothesis that deriving pre-treatment 3D magnetic resonance tumour volume (mrTV) quantification improves performance characteristics for the prediction of loco-regional failure compared with standard maximal tumour diameter (1D) assessment in patients with squamous cell carcinoma of the anus undergoing chemoradiotherapy. METHODS: We performed an early evaluation case-control study at two UK centres (2007-2014) in 39 patients with loco-regional failure (cases), and 41 patients disease-free at 3 years (controls). mrTV was determined using the summation of areas method (Volsum). Reproducibility was assessed using intraclass concordance correlation (ICC) and Bland-Altman limits of agreements. We derived receiver operating curves using logistic regression models and expressed accuracy as area under the curve (ROCAUC). RESULTS: The median time per patient for Volsum quantification was 7.00 (inter-quartile range, IQR: 0.57-12.48) minutes. Intra and inter-observer reproducibilities were generally good (ICCs from 0.79 to 0.89) but with wide limits of agreement (intra-observer: - 28 to 31%; inter-observer: - 28 to 46%). Median mrTVs were greater for cases (32.6 IQR: 21.5-53.1 cm3) than controls (9.9 IQR: 5.7-18.1 cm3, p < 0.0001). The ROCAUC for mrT-size predicting loco-regional failure was 0.74 (95% CI: 0.63-0.85) improving to 0.82 (95% CI: 0.72-0.92) when replaced with mrTV (test for ROC differences, p = 0.024). CONCLUSION: Preliminary results suggest that the replacement of mrTV for mrT-size improves prediction of loco-regional failure after chemoradiotherapy for squamous cell carcinoma of the anus. However, mrTV calculation is time consuming and variation in its reproducibility are drawbacks with the current technology.

The prognostic value of dynamic contrast-enhanced MRI contrast agent transfer constant Ktrans in cervical cancer is explained by plasma flow rather than vessel permeability.

BACKGROUND: The microvascular contrast agent transfer constant Ktrans has shown prognostic value in cervical cancer patients treated with chemoradiotherapy. This study aims to determine whether this is explained by the contribution to Ktrans of plasma flow (Fp), vessel permeability surface-area product (PS), or a combination of both. METHODS: Pre-treatment dynamic contrast-enhanced MRI (DCE-MRI) data from 36 patients were analysed using the two-compartment exchange model. Estimates of Fp, PS, Ktrans, and fractional plasma and interstitial volumes (vp and ve) were made and used in univariate and multivariate survival analyses adjusting for clinicopathologic variables tumour stage, nodal status, histological subtype, patient age, tumour volume, and treatment type (chemoradiotherapy vs radiotherapy alone). RESULTS: In univariate analyses, Fp (HR=0.25, P=0.0095) and Ktrans (HR=0.20, P=0.032) were significantly associated with disease-free survival while PS, vp and ve were not. In multivariate analyses adjusting for clinicopathologic variables, Fp and Ktrans significantly increased the accuracy of survival predictions (P=0.0089). CONCLUSIONS: The prognostic value of Ktrans in cervical cancer patients treated with chemoradiotherapy is explained by microvascular plasma flow (Fp) rather than vessel permeability surface-area product (PS).

The assessment of local response using magnetic resonance imaging at 3- and 6-month post chemoradiotherapy in patients with anal cancer.

OBJECTIVES: To assess the use of MRI-determined tumour regression grading (TRG) in local response assessment and detection of salvageable early local relapse after chemoradiotherapy (CRT) in patients with anal squamous cell carcinoma (ASCC). METHODS: From a prospective database of patients with ASCC managed through a centralised multidisciplinary team, 74 patients who completed routine post-CRT 3- and 6-month MRIs (2009-2012) were reviewed. Two radiologists blinded to the outcomes consensus read and retrospectively assigned TRG scores [1 (complete response) to 5 (no response)] and related these to early local relapse (within 12 months) and disease-free survival (DFS). RESULTS: Seven patients had early local relapse. TRG 1/2 scores at 3 and 6 months had a 100 % negative predictive value; TRG 4/5 scores at 6 months had a 100 % positive predictive value. All seven patients underwent salvage R0 resections. We identified a novel 'tram-track' sign on MRI in over half of patients, with an NPV for early local relapse of 83 % at 6 months. No imaging characteristic or TRG score independently prognosticated for late relapse or 3-year DFS. CONCLUSIONS: Post-CRT 3- and 6-month MRI-determined TRG scores predicted salvageable R0 early local relapses in patients with ASCC, challenging current clinical guidelines. KEY POINTS: • Post-chemoradiotherapy MRI (3 and 6 months) helps local response assessment in ASCC. • The MRI-TRG system can be used reproducibly in patients with ASCC. • The TRG system facilitates patient selection for examination under anaesthesia and biopsy. • The use of MRI-TRG predicts for detection of salvageable early local relapses. • The TRG system allows for a standardised follow-up pathway.

Dynamic sentinel lymph node biopsy for penile cancer: a comparison between 1- and 2-day protocols.

OBJECTIVE: To determine the outcome of clinically negative node (cN0) patients with penile cancer undergoing dynamic sentinel node biopsy (DSNB), comparing the results of a 1- and 2-day protocol that can be used as a minimal invasive procedure for staging of penile cancer. PATIENTS AND METHODS: This is a retrospective analysis of 151 cN0 patients who underwent DSNB from 2008 to 2013 for newly diagnosed penile cancer. Data were analysed per groin and separated into groups according to the protocol followed. The comparison of the two protocols involved the number of nodes excised, γ-counts, false-negative rates (FNR), and complication rates (Clavien-Dindo grading system). RESULTS: In all, 280 groins from 151 patients underwent DSNB after a negative ultrasound ± fine-needle aspiration cytology. The 1-day protocol was performed in 65 groins and the 2-day protocol in 215. Statistically significantly more nodes were harvested with the 1-day protocol (1.92/groin) compared with the 2-day protocol (1.60/groin). The FNRs were 0%, 6.8% and 5.1%, for the 1-day protocol, 2-day protocol, and overall, respectively. Morbidity of the DSNB was 21.4% for all groins, and 26.2% and 20.1% for the 1-day and 2-day protocols, respectively. Most of the complications were of Clavien-Dindo Grade 1-2. CONCLUSIONS: DSNB is safe for staging patients with penile cancer. There is a trend towards a 1-day protocol having a lower FNR than a 2-day protocol, albeit at the expense of a slightly higher complication rate.

Imaging of anal carcinoma.

OBJECTIVE: The purpose of this article is to review the role of imaging in the management of patients with anal cancer. The relevant anatomy, imaging techniques, and interpretation of images of patients before and after therapy will be discussed. CONCLUSION: Anal carcinomas are uncommon but increasing in frequency. Radiologists must recognize typical patterns of disease at initial evaluation, posttherapy appearances, and when to suspect residual or recurrent disease to guide clinicians and achieve optimal patient outcome.

A comparison of tracer kinetic models for T1-weighted dynamic contrast-enhanced MRI: application in carcinoma of the cervix.

The Tofts tracer kinetic models are often used to analyze dynamic contrast-enhanced MRI data. They are derived from a general two-compartment exchange model (2CXM) but assume negligible plasma mean transit time. The 2CXM estimates tissue plasma perfusion and capillary permeability-surface area; the Tofts models estimate the transfer constant K(trans), which reflects a combination of these two parameters. The aims of this study were to compare the 2CXM and Tofts models and report microvascular parameters in patients with cervical cancer. Thirty patients were scanned pretreatment using a dynamic contrast-enhanced MRI protocol with a 3 sec temporal resolution and a total scan duration of 4 min. Whole-tumor parameters were estimated with both models. The 2CXM provided superior fits to the data for all patients (all 30 P values < 0.005), and significantly different parameter estimates were obtained (P < 0.01). K(trans) (mean = 0.35 +/- 0.26 min(-1)) did not equal absolute values of tissue plasma perfusion (mean = 0.65 +/- 0.56 mL/mL/min) or permeability-surface area (mean = 0.14 +/- 0.09 mL/mL/min) but correlated strongly with tissue plasma perfusion (r = 0.944; P = 0.01). Average plasma mean transit time, calculated with the 2CXM, was 22 +/- 16 sec, suggesting the assumption of negligible plasma mean transit time is not appropriate in this dataset and the 2CXM is better suited for its analysis than the Tofts models. The results demonstrate the importance of selecting an appropriate tracer kinetic model in dynamic contrast-enhanced MRI.

Enhancing fraction predicts clinical outcome following first-line chemotherapy in patients with epithelial ovarian carcinoma.

PURPOSE: To define a simple radiologic biomarker of prognosis in patients with advanced epithelial ovarian carcinoma on first-line chemotherapy. EXPERIMENTAL DESIGN: Twenty-seven patients receiving platinum-based chemotherapy with >2 cm residual disease [International Federation of Gynecology and Obstetrics (FIGO) stages IIIC or IV] after surgery were identified. The proportion of enhancing tumor tissue--the enhancing fraction--was calculated on pre-chemotherapy computed tomography scans at four Hounsfield unit (HU) thresholds and assessed for correlation with CA125 response, Response Evaluation Criteria in Solid Tumors (RECIST) radiologic response, and time to progression. Discriminative power was assessed by leave-one-out discriminant analysis. RESULTS: Pre-chemotherapy residual tumor volume did not correlate with clinical outcome. Pre-chemotherapy enhancing fraction at all thresholds significantly correlated with CA125 response (P < 0.001, rho = 0.553 for 50 HU; P < 0.001, rho = 0.565 for 60 HU; P < 0.001, rho = 0.553 for 70 HU; P = 0.001, rho = 0.516 for 80 HU). Significant correlations were also shown for radiologic response at all thresholds. Enhancing fraction predicted CA125 response with 81.9% to 86.4% specificity and Response Evaluation Criteria in Solid Tumors response with 74.9% to 76.8% specificity at 95% sensitivity (dependent on threshold). Enhancing fraction correlated with time to progression at the 60 HU (P = 0.045, rho = 0.336) and 70 HU (P = 0.042; rho = 0.340) thresholds. CONCLUSION: Pre-chemotherapy enhancing fraction is a simple quantitative radiologic measure. Further evaluation in larger trials is required to confirm the potential of enhancing fraction as a predictive factor, particularly for patients who may benefit from the addition of antiangiogenic therapy.

Pre-treatment tumour perfusion parameters and initial RECIST response do not predict long-term survival outcomes for patients with head and neck squamous cell carcinoma treated with induction chemotherapy.

OBJECTIVES: Previously, we showed that pre-treatment tumour plasma perfusion (Fp) predicts RECIST response to induction chemotherapy (ICT) in locoregionally advanced head and neck squamous cell carcinoma (HNSCC). The aim here was to determine whether the pre-treatment tumour Fp estimate, changes in tumour Fp or RECIST response post 2 cycles of ICT were prognostic for long-term survival outcomes. METHODS: A prospective study enrolled patients with high stage HNSCC treated with docetaxel (T), cisplatin (P) and 5-fluorouracil (F) (ICT) followed by synchronous cisplatin and intensity modulated radiotherapy. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) before and after two cycles of ICT was used to measure Fp and RECIST response. RESULTS: Forty-two patients were recruited and 37 underwent two scans. The median follow-up was 36 (range 23-49) months. Pre-treatment tumour Fp (stratified by median) was not prognostic for overall survival (p = 0.42), disease specific survival (p = 0.20) and locoregional control (p = 0.64). Neither change in tumour Fp nor RECIST response post two cycles of ICT was prognostic for any outcome (p>0.21). CONCLUSION: DCE-MRI parameters do not predict long-term survival outcomes following ICT and RECIST response to ICT may not be an appropriate endpoint to determine early efficacy of a treatment in HNSCC patients.

Tumor plasma flow determined by dynamic contrast-enhanced MRI predicts response to induction chemotherapy in head and neck cancer.

OBJECTIVES: Non-response to induction chemotherapy (IC) occurs in 30% of head and neck squamous cell carcinoma (HNSCC) and has been predicted by tumor plasma flow (Fp) derived by perfusion computed tomography. The present study was designed to test whether baseline tumor Fp determined by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) would predict IC response. MATERIALS AND METHODS: A prospective open study powered to test the relationship between tumor Fp and response to IC (docetaxel, cisplatin, 5-fluorouracil) enrolled 50 patients with stage IV HNSCC. Response after two IC cycles was measured by MRI using Response Evaluation Criteria in Solid Tumors in 37 patients. Tumor Fp (primary end point) and multiple parameters in tumors and lymph nodes (secondary end points) were generated at baseline. Differences in baseline DCE-MRI parameters according to IC response were assessed by the Mann-Whitney U test, and predictive value by receiver operating characteristic (ROC) analysis. RESULTS: Median baseline tumor Fp was 53.2ml/100ml/min in 25 responders and 23.9 in 12 non-responders (U 82; P=0.027; area under ROC curve (AUC) 0.73). Median baseline Fp in lymph nodes was 25.8ml/100ml/min for 37 nodes in 25 responders and 17.1 for 15 nodes in 12 non-responders (U 186, P=0.066; AUC 0.67). Frequency of IC response in 37 patients was 68% overall, 83% for tumor Fp above the median (40.6ml/100ml/min) and 45% below the median. Other DCE-MRI parameters were not associated with IC response. CONCLUSION: Pre-treatment tumor Fp determined by DCE-MRI predicts IC response in HNSCC.

Prediction of radiotherapy outcome using dynamic contrast enhanced MRI of carcinoma of the cervix.

PURPOSE: To investigate whether analysis of MRI enhancement data using a pharmacokinetic model improved a previously found correlation between contrast enhancement and tumor oxygenation measured using PO2 histograph. To evaluate the prognostic value of gadolinium enhancement data for radiotherapy outcome, and to study the efficacy of combined enhancement and MRI volume data. METHODS AND MATERIALS: Fifty patients underwent dynamic gadolinium-enhanced MRI as part of their initial staging investigations before treatment. Gadolinium enhancement was analyzed using the Brix pharmacokinetic model to obtain the parameters amplitude and rate of contrast enhancement. Pretreatment tumor oxygen measurements (Eppendorf PO2 histograph) were available for 35 patients. RESULTS: Both standard and pharmacokinetic-derived enhancement data correlated with tumor oxygenation measurements, and poorly enhancing tumors had low tumor oxygen levels. However, only the pharmacokinetic-analyzed data correlated with patient outcome and patients with poorly (amplitude less than median) vs. well-enhancing tumors had significantly worse disease-specific survival (p = 0.024). For the 50 patients studied, no relationship was found between enhancement and volume data. Combining MRI volume and enhancement information highlighted large differences in outcome (p = 0.0054). At the time of analysis, only 55% of patients with large, poorly enhanced tumors were alive compared with 92% of patients with small, well-enhanced tumors. CONCLUSION: These preliminary results suggest that pharmacokinetic modeling of dynamic contrast-enhanced MRI provides data that reflect tumor oxygenation and yields useful prognostic information in patients with locally advanced carcinoma of the cervix. Combining MRI-derived enhancement and volume data delineates large differences in radiotherapy outcome.

Utility of FDG-PETCT and magnetic resonance spectroscopy in differentiating between cerebral lymphoma and non-malignant CNS lesions in HIV-infected patients.

BACKGROUND AND PURPOSE: In HIV infected patients, MRI cannot reliably differentiate between central nervous system (CNS) lymphoma and non-malignant CNS lesions, particularly cerebral toxoplasmosis (CTOX). This study prospectively investigates the utility of FDG PET-CT and magnetic resonance spectroscopy (MRS) in discriminating CNS lymphoma from non-malignant CNS lesions in HIV infected patients, and assesses the ability of FDG PET-CT to guide the use of early brain biopsy. METHODS: 10 HIV patients with neurological symptoms and contrast enhancing lesions on MRI were commenced on anti-toxoplasmosis therapy before undergoing FDG PET-CT and MRS. Brain biopsies were sought in those with FDG PET-CT suggestive of CNS lymphoma, and in those with a negative FDG PET-CT scan who failed to respond to therapy. Final diagnosis was based on histology or treatment response. RESULTS: Two patients were confirmed to have CNS lymphoma and FDG PET-CT was consistent with this diagnosis in both. Six patients had cerebral toxoplasmosis in all of whom FDG PET-CT was consistent with non-malignant disease. One patient had progressive multifocal leukoencephalopathy (PML), FDG PET-CT was equivocal. One patient had a haemorrhagic brain metastasis and FDG PET-CT wrongly suggested non-malignant disease. MRS was performed successfully in eight subjects: three results were suggestive of CNS lymphoma (one true positive, two false positive), four suggested CTOX (two false negative, two true negative), one scan was equivocal. CONCLUSION: FDG PET-CT correctly identified all cases of CNS lymphoma and CTOX, supporting its use in this situation. MRS was unhelpful in our cohort.

Dynamic contrast-enhanced MRI in patients with muscle-invasive transitional cell carcinoma of the bladder can distinguish between residual tumour and post-chemotherapy effect.

INTRODUCTION: Treatment of muscle-invasive bladder cancer with chemotherapy results in haemorrhagic inflammation, mimicking residual tumour on conventional MR images and making interpretation difficult. The aim of this study was to use dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to estimate descriptive and tracer kinetic parameters post-neoadjuvant chemotherapy and to investigate whether parameters differed in areas of residual tumour and chemotherapy-induced haemorrhagic inflammation (treatment effect, Tr-Eff). METHODS AND MATERIALS: Twenty-one patients underwent DCE-MRI scans with 2.5s temporal resolution before and following neoadjuvant chemotherapy. Regions-of-interest (ROIs) were defined in areas suspicious of residual tumour on T2-weighted MRI scans. Data were analysed semi-quantitatively and with a two-compartment exchange model to obtain parameters including relative signal intensity (rSI80s) and plasma perfusion (Fp) respectively. The bladder was subsequently examined histologically after cystectomy for evidence of residual tumour and/or Tr-Eff. Differences in parameters measured in areas of residual tumour and Tr-Eff were examined using Student's t-test. RESULTS: Twenty-four abnormal sites were defined after neoadjuvant chemotherapy. On pathology, 10 and 14 areas were identified as residual tumour and Tr-Eff respectively. Median rSI80s and Fp were significantly higher in areas of residual tumour than Tr-Eff (rSI80s = 2.9 vs 1.7, p < 0.001; Fp = 20.7 vs 9.1 ml/100ml/min, p = 0.03). The sensitivity and specificity for differentiating residual tumour from Tr-Eff were 70% and 100% (rSI80s), 60% and 86% (Fp), and 75% and 100% when combined. CONCLUSION: DCE-MRI parameters obtained post-treatment are capable of distinguishing between residual tumour and treatment effect in patients treated for bladder cancer with neoadjuvant chemotherapy.

The accuracy of the sentinel node procedure after excision biopsy in squamous cell carcinoma of the vulva.

INTRODUCTION: Restricting inguinofemoral lymphadenectomy to patients with malignant nodes would reduce treatment-related morbidity in vulval cancer patients. A prospective study was conducted to determine the diagnostic accuracy of the Sentinel Lymph Node (SLN) procedure in vulval cancer patients referred following either diagnostic or excision biopsy. METHODS: Patients with clinical stage I and II squamous cell carcinoma of the vulva underwent SLN identification with peri-scar/lesional injection of (99m)Technetium-labelled nanocolloid (pre-operative lymphoscintigraphy and intra-operative use of a hand-held probe) and intra-operative blue dye. Radical excision of the vulval tumour or scar and formal inguinofemoral lymphadenectomy was then performed as necessary. SLN were processed separately and further examined at multiple levels to exclude micrometastases (H&E/cytokeratin staining) if negative on routine analysis. Clinical follow-up was carried out to identify and treat recurrences or treatment-related morbidity. RESULTS: Thirty-two women took part. Fifteen were referred following excision biopsy and seventeen following diagnostic biopsy of their primary vulval tumour. One or more SLN was successfully detected intra-operatively in 31 patients (97%) and 45 groins. An SLN could not be identified intra-operatively in one case (re-excision of scar). On average, more SLN were identified in patients with their primary vulval lesion in situ compared with those whose tumour had previously been excised (2.6 vs. 1.8, p = 0.03). Midline tumours were more likely (15/17) than lateral tumours (1/15) to have bilateral SLN identified pre-operatively. Two patients with midline tumours previously excised had unilateral SLN. Seven patients (23%) and ten groins had inguinofemoral lymph node metastases. The SLN procedure correctly identified inguinofemoral metastases in six patients (nine groins). In one case (midline tumour, re-excision of scar) the sentinel node was positive on one side but false negative on the other. CONCLUSIONS: The SLN procedure may be used to identify malignant groins in selected patients with vulval cancer. The extent to which previous vulval surgery might influence the accuracy of the SLN procedure deserves further investigation.

The relationship between oncologists and peripheral hospital radiologists in the North-West of England.

AIM: To audit the relationship between Cancer Centre oncologists visiting peripheral hospitals and peripheral hospital radiologists by assessing (i) oncologists' knowledge of local radiological services; (ii) oncologists' perceptions of peripheral radiological services; (iii) peripheral radiologist's perceptions of oncologists; (iv) barriers to communication. MATERIALS AND METHODS: A postal questionnaire was sent to all radiology departments visited by an oncologist, and to all medical and clinical oncologists from two regional oncology centres. RESULTS: The response rate was 100% (21 peripheral hospital radiology departments and all 35 oncologists). (i) Oncologists' knowledge of peripheral hospital imaging modalities was limited (especially MRI and intervention). (ii) 72% of oncologists rated the peripheral hospital radiology service as excellent or good, 46% rated the radiology report quality excellent to good. Deficiencies in oncological reports were identified. (iii) 44% of radiologists thought the oncologist did not relate well with the local radiology department. 50% of radiologists did not know the visiting oncologist's specialist interest. (iv) 69% of oncologists did not regularly attend peripheral hospital clinico-radiological meetings. Lack of written and oral information was hampering both specialties. CONCLUSION: Communication between oncologists and the local radiology department should include: (1) information about local radiology services for visiting oncologists (including trainees) and on the oncology team for radiologists; (2) standardized report content; (3) improved clinical information for radiologists; (4) regular clinico-radiological meetings.

Recurrent or residual pelvic bowel cancer: accuracy of MRI local extent before salvage surgery.

PURPOSE: To determine pre-operative MRI accuracy in assessing local disease extent in recurrent/residual pelvic bowel cancer by comparing MRI assessment and staging examination under anaesthesia (EUA), with laparotomy/histopathological findings. MATERIALS AND METHODS: Twenty-seven consecutive patients with recurrent (n = 21) or residual (n = 6) pelvic bowel cancer (13 of the rectum, eleven of the anus and three of the colon) underwent EUA and pelvic MRI (1T) using a phased array pelvic coil. Retrospective analysis of eight specific anatomical regions for tumour involvement on MRI was performed. Findings at EUA and biopsy were recorded. The MRI and EUA findings were correlated with findings at surgery and histopathology. Statistical comparison between MRI and EUA results was performed using the chi-squared test. RESULTS: Overall MRI accuracy in determining tumour invasion for all sites assessed was 452/499 (91%), sensitivity was 95/109 (87%), specificity was 357/390 (92%), positive predictive value (PPV) was 95/128 (74%) and negative predictive value (NPV) was 357/371 (96%). PPV and NPV for specific areas were 21/38 (55%) and 134/136 (99%) for genitourinary tract, 4/6 (67%) and 61/65 (94%) for pelvic side wall, 21/26 (81%) and 40/41 (98%) for pelvic floor, 1/6 (17%) and 40/43 (93%) for the posterior pelvis pre-sacrum/sacrum. For those anatomical sites evaluated by both EUA and MRI, MRI was superior to EUA, with an accuracy of 89% vs 73% (P < 0.05). CONCLUSION: MRI is an accurate technique for assessing disease extent in recurrent/residual pelvic bowel cancer.