Andrea Knezevic

Prevalence of Germline Mutations in Cancer Susceptibility Genes in Patients With Advanced Renal Cell Carcinoma

Importance Identification of patients with hereditary renal cell carcinoma (RCC) is important for cancer screening and, in patients with advanced disease, for guiding treatment. The prevalence of cancer-related germline mutations in patients with advanced RCC and the phenotypes associated with some rare mutations are unknown. Objectives To examine the prevalence of germline mutations in both known RCC predisposition genes and other cancer-associated genes and to identify clinical and pathologic factors associated with germline mutations. Design, Setting, and Participants In this cohort study conducted from October 1, 2015, to July 31, 2017, 254 of 267 patients with advanced (American Joint Committee on Cancer stage III or IV) RCC who were seen in medical oncology or urology clinics agreed to germline sequencing and disclosure of results under an institutional protocol of matched tumor-germline DNA sequencing. Main Outcomes and Measures Mutation prevalence and spectrum in patients with advanced RCC were determined. Clinical characteristics were assessed by mutation status. Results Of the 254 patients (median age [range], 56 [13-79] years; 179 [70.5%] male; 211 [83.1%] non-Hispanic white), germline mutations were identified in 41 (16.1%); 14 (5.5%) had mutations in syndromic RCC-associated genes (7 in FH, 3 in BAP1, and 1 each in VHL, MET, SDHA, and SDHB). The most frequent mutations were CHEK2 (nu2009=u20099) and FH (nu2009=u20097). Of genes not previously associated with RCC risk, CHEK2 was overrepresented in patients compared with the general population, with an odds ratio of RCC of 3.0 (95% CI, 1.3-5.8; Pu2009=u2009.003). Patients with non–clear cell RCC were significantly more likely to have an RCC-associated gene mutation (9 [11.7%] of 74 vs 3 [1.7%] of 177; Pu2009=u2009.001), and 8 (10.0%) had a mutation in a gene that could guide therapy. Of patients with mutations in RCC-associated genes, 5 (35.7%) failed to meet current clinical guidelines for genetic testing. Conclusions and Relevance Of patients with non–clear cell RCC, more than 20% had a germline mutation, of which half had the potential to direct systemic therapy. Current referral criteria for genetic testing did not identify a substantial portion of patients with mutations, supporting the role of a more inclusive sequencing approach.

Value of adding dynamic contrast-enhanced MRI visual assessment to conventional MRI and clinical assessment in the diagnosis of complete tumour response to chemoradiotherapy for rectal cancer

PurposeTo determine if DCE-MRI adds diagnostic value to the combined use of T2WI and DWI-MRI in the determination of clinical complete response (cCR) after neoadjuvant treatment (NAT) in patients with locally advanced rectal cancer.Methods and materialsIn this IRB-approved, HIPAA-compliant retrospective study, response was assessed using a 5-point confidence score by T2WI and DWI-MRI only (‘standard MRI’), then with addition of DCE-MRI. Review of digital rectal exams and endoscopy notes produced a clinical overall response score. The reference standard was CR by histopathology or cCR determined after a minimum of 18 months’ follow-up. Diagnostic accuracy and ROC curves were calculated for standard MRI and added DCE-MRI (to detect complete or good response), for clinical evaluation (to detect CR) and for MRI and clinical methods combined.ResultsOf 65 patients undergoing NAT, 20 had cCR (31%). Sensitivity, specificity and area under the ROC (AUC) were 0.55, 0.87 and 0.69 for clinical evaluation; 0.42, 0.77 and 0.66 for standard MRI, and 0.53, 0.76 and 0.68 for added DCE-MRI, respectively. Combined clinical evaluation and standard MRI with DCE-MRI resulted in the highest specificity of 0.96 and highest AUC of 0.72.ConclusionFor the assessment of cCR after neoadjuvant therapy using clinical and multi-sequence MRI reading strategies, the addition of DCE-MRI increased specificity and PPV, but not significantly.Key Points• The addition of dynamic contrast-enhanced MRI to standard MRI, including DWI-MRI, may not significantly improve accuracy of response assessment in rectal cancer treatment.• Clinical assessment consisting of digital rectal examination and endoscopy is the most accurate standalone test to assess response to chemoradiotherapy in rectal cancer.• Combining MRI using DWI and DCE with the clinical assessment may potentially improve the accuracy for response assessment in rectal cancer.

Pelvic MRI after induction chemotherapy and before long-course chemoradiation therapy for rectal cancer: What are the imaging findings?

ObjectivesTo determine the appearance of rectal cancer on MRI after oxaliplatin-based chemotherapy (ICT) and make a preliminary assessment of MRI’s value in predicting response to total neoadjuvant treatment (TNT).MethodsIn this IRB-approved, HIPAA-compliant, retrospective study between 1 January 2010–20 October 2014, pre- and post-ICT tumour T2 volume, relative T2 signal intensity (rT2SI), node size, signal intensity and border characteristics were assessed in 63 patients (65 tumours) by three readers. The strength of association between the reference standard of histopathological percent tumour response and tumour volume change, rT2SI and lymph node characteristics was assessed with Spearman’s correlation coefficient and Wilcoxon’s rank sum test. Cox regression was used to assess association between DFS and radiological measures.ResultsChange in T2 volume was not associated with TNT response. Change in rT2SI showed correlation with TNT response for one reader only using selective regions of interest (ROIs) and borderline correlation with response using total volume ROI. There was a significant negative correlation between baseline and post-ICT node size and TNT response (r = -0.25, p = 0.05; r = -0.35, p = 0.005, readers 1 and 2, respectively). Both baseline and post-induction median node sizes were significantly smaller in complete responders (p = 0.03, 0.001; readers 1 and 2, respectively). Change in largest baseline node size and decrease in post-ICT node signal heterogeneity were associated with 100% tumour response (p = 0.04). Nodal sizes at baseline and post-ICT MRI correlated with DFS.ConclusionIn patients undergoing post-ICT MRI, tumour volume did not correlate with TNT response, but decreased lymph node sizes were significantly associated with complete response to TNT as well as DFS. Relative T2SI showed borderline correlation with TNT response.Key Points• MRI-based tumour volume after induction chemotherapy and before chemoradiotherapy did not correlate with overall tumour response at the end of all treatment.• Lymph node size after induction chemotherapy and before chemoradiotherapy was strongly associated with complete pathological response after all treatment.• Lymph node sizes at baseline and post-induction chemotherapy MRI correlated with disease-free survival.

Use of magnetic resonance imaging in rectal cancer patients: Society of Abdominal Radiology (SAR) rectal cancer disease-focused panel (DFP) recommendations 2017

PurposeTo propose guidelines based on an expert-panel-derived unified approach to the technical performance, interpretation, and reporting of MRI for baseline and post-treatment staging of rectal carcinoma.MethodsA consensus-based questionnaire adopted with permission and modified from the European Society of Gastrointestinal and Abdominal Radiologists was sent to a 17-member expert panel from the Rectal Cancer Disease-Focused Panel of the Society of Abdominal Radiology containing 268 question parts. Consensus on an answer was defined asu2009≥u200970% agreement. Answers not reaching consensus (<u200970%) were noted.ResultsConsensus was reached for 87% of items from which recommendations regarding patient preparation, technical performance, pulse sequence acquisition, and criteria for MRI assessment at initial staging and restaging exams and for MRI reporting were constructed.ConclusionThese expert consensus recommendations can be used as guidelines for primary and post-treatment staging of rectal cancer using MRI.