Junting Zheng

Diffusion-weighted Endorectal MR Imaging at 3 T for Prostate Cancer: Tumor Detection and Assessment of Aggressiveness

PURPOSEnTo assess the incremental value of diffusion-weighted (DW) magnetic resonance (MR) imaging over T2-weighted MR imaging at 3 T for prostate cancer detection and to investigate the use of the apparent diffusion coefficient (ADC) to characterize tumor aggressiveness, with whole-mount step-section pathologic analysis as the reference standard.nnnMATERIALS AND METHODSnThe Internal Review Board approved this HIPAA-compliant retrospective study and waived informed consent. Fifty-one patients with prostate cancer (median age, 58 years; range, 46-74 years) underwent T2-weighted MR imaging and DW MR imaging (b values: 0 and 700 sec/mm(2) [n = 20] or 0 and 1000 sec/mm(2) [n = 31]) followed by prostatectomy. The prostate was divided into 12 regions; two readers provided a score for each region according to their level of suspicion for the presence of cancer on a five-point scale, first using T2-weighted MR imaging alone and then using T2-weighted MR imaging and the ADC map in conjunction. Areas under the receiver operating characteristic curve (AUCs) were estimated to evaluate performance. Generalized estimating equations were used to test the ADC difference between benign and malignant prostate regions and the association between ADCs and tumor Gleason scores.nnnRESULTSnFor tumor detection, the AUCs for readers 1 and 2 were 0.79 and 0.76, respectively, for T2-weighted MR imaging and 0.79 and 0.78, respectively, for T2-weighted MR imaging plus the ADC map. Mean ADCs for both cancerous and healthy prostatic regions were lower when DW MR imaging was performed with a b value of 1000 sec/mm(2) rather than 700 sec/mm(2). Regardless of the b value used, there was a significant difference in the mean ADC between malignant and benign prostate regions. A lower mean ADC was significantly associated with a higher tumor Gleason score (mean ADCs of [1.21, 1.10, 0.87, and 0.69] × 10(-3) mm(2)/sec were associated with Gleason score of 3 + 3, 3 + 4, 4 + 3, and 8 or higher, respectively; P = .017).nnnCONCLUSIONnCombined DW and T2-weighted MR imaging had similar performance to T2-weighted MR imaging alone for tumor detection; however, DW MR imaging provided additional quantitative information that significantly correlated with prostate cancer aggressiveness.

Magnetic Resonance Imaging for Predicting Prostate Biopsy Findings in Patients Considered for Active Surveillance of Clinically Low Risk Prostate Cancer

PURPOSEnA barrier to the acceptance of active surveillance for men with prostate cancer is the risk of underestimating the cancer burden on initial biopsy. We assessed the value of endorectal magnetic resonance imaging in predicting upgrading on confirmatory biopsy in men with low risk prostate cancer.nnnMATERIALS AND METHODSnA total of 388 consecutive men (mean age 60.6 years, range 33 to 89) with clinically low risk prostate cancer (initial biopsy Gleason score 6 or less, prostate specific antigen less than 10 ng/ml, clinical stage T2a or less) underwent endorectal magnetic resonance imaging before confirmatory biopsy. Three radiologists independently and retrospectively scored tumor visibility on endorectal magnetic resonance imaging using a 5-point scale (1-definitely no tumor to 5-definitely tumor). Inter-reader agreement was assessed with weighted kappa statistics. Associations between magnetic resonance imaging scores and confirmatory biopsy findings were evaluated using measures of diagnostic performance and multivariate logistic regression.nnnRESULTSnOn confirmatory biopsy, Gleason score was upgraded in 79 of 388 (20%) patients. Magnetic resonance imaging scores of 2 or less had a high negative predictive value (0.96-1.0) and specificity (0.95-1.0) for upgrading on confirmatory biopsy. A magnetic resonance imaging score of 5 was highly sensitive for upgrading on confirmatory biopsy (0.87-0.98). At multivariate analysis patients with higher magnetic resonance imaging scores were more likely to have disease upgraded on confirmatory biopsy (odds ratio 2.16-3.97). Inter-reader agreement and diagnostic performance were higher for the more experienced readers (kappa 0.41-0.61, AUC 0.76-0.79) than for the least experienced reader (kappa 0.15-0.39, AUC 0.61-0.69). Magnetic resonance imaging performed similarly in predicting low risk and very low risk (Gleason score 6, less than 3 positive cores, less than 50% involvement in all cores) prostate cancer.nnnCONCLUSIONSnAdding endorectal magnetic resonance imaging to the initial clinical evaluation of men with clinically low risk prostate cancer helps predict findings on confirmatory biopsy and assess eligibility for active surveillance.

Prostate Cancer Aggressiveness: Assessment with Whole-Lesion Histogram Analysis of the Apparent Diffusion Coefficient

PURPOSEnTo evaluate the relationship between prostate cancer aggressiveness and histogram-derived apparent diffusion coefficient (ADC) parameters obtained from whole-lesion assessment of diffusion-weighted magnetic resonance (MR) imaging of the prostate and to determine which ADC metric may help best differentiate low-grade from intermediate- or high-grade prostate cancer lesions.nnnMATERIALS AND METHODSnThe institutional review board approved this retrospective HIPAA-compliant study of 131 men (median age, 60 years) who underwent diffusion-weighted MR imaging before prostatectomy for prostate cancer. Clinically significant tumors (tumor volume > 0.5 mL) were identified at whole-mount step-section histopathologic examination, and Gleason scores of the tumors were recorded. A volume of interest was drawn around each significant tumor on ADC maps. The mean, median, and 10th and 25th percentile ADCs were determined from the whole-lesion histogram and correlated with the Gleason score by using the Spearman correlation coefficient (ρ). The ability of each parameter to help differentiate tumors with a Gleason score of 6 from those with a Gleason score of at least 7 was assessed by using the area under the receiver operating characteristic curve (Az).nnnRESULTSnIn total, 116 clinically significant lesions (89 in the peripheral zone, 27 in the transition zone) were identified in 85 of the 131 patients (65%). Forty-six patients did not have a clinically significant lesion. For mean ADC, median ADC, 10th percentile ADC, and 25th percentile ADC, the Spearman ρ values for correlation with Gleason score were -0.31, -0.30, -0.36, and -0.35, respectively, whereas the Az values for differentiating lesions with a Gleason score of 6 from those with a Gleason score of at least 7 were 0.704, 0.692, 0.758, and 0.723, respectively. The Az of 10th percentile ADC was significantly higher than that of the mean ADC for all lesions and peripheral zone lesions (P = .0001).nnnCONCLUSIONnWhen whole-lesion histograms were used to derive ADC parameters, 10th percentile ADC correlated with Gleason score better than did other ADC parameters, suggesting that 10th percentile ADC may prove to be optimal for differentiating low-grade from intermediate- or high-grade prostate cancer with diffusion-weighted MR imaging.

Distinct Clinical Course of EGFR-Mutant Resected Lung Cancers: Results of Testing of 1118 Surgical Specimens and Effects of Adjuvant Gefitinib and Erlotinib

Background: EGFR and KRAS mutations are mutually exclusive and predict outcomes with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) treatment in patients with stage IV lung cancers. The clinical significance of these mutations in patients with resected stage I–III lung cancers is unclear. Methods: At our institution, resection specimens from patients with stage I–III lung adenocarcinomas are tested for the presence of EGFR or KRAS mutations during routine pathology analysis such that the results are available before consideration of adjuvant therapy. In a cohort of 1118 patients tested over 8 years, overall survival was analyzed using multivariate analysis to control for potential confounders, including age, sex, stage, and smoking history. The impact of adjuvant erlotinib or gefitinib was examined in an independent data set of patients exclusively with EGFR mutation, in which date of recurrence was recorded. Results: In the overall population, we identified 227 KRAS (25%) and 222 EGFR (20%) mutations. Patients with EGFR-mutant lung cancers had a lower risk of death compared with those without EGFR mutations, overall survival (OS) HR 0.51 (95% confidence interval [CI]: 0.34–0.76, p < 0.001). Patients with KRAS-mutant lung cancers had similar outcomes compared with individuals with KRAS wild-type tumors, OS HR 1.17 (95% CI: 0.87–1.57, p = 0.30). A separate data set includes only patients with EGFR-mutant lung cancers identified over 10 years (n = 286). In patients with resected lung cancers and EGFR mutation, treatment with adjuvant erlotinib or gefitinib was associated with a lower risk of recurrence or death, disease-free survival HR 0.43 (95% CI: 0.26–0.72, p = 0.001), and a trend toward improved OS. Conclusions: Patients with resected stage I–III lung cancers and EGFR mutation have a lower risk of death compared with patients without EGFR mutation. This may be because of treatment with EGFR TKIs. Patients with, and without KRAS mutation have similar OS. These data support reflex testing of resected lung adenocarcinomas for EGFR mutation to provide prognostic information and identify patients for enrollment on prospective clinical trials of adjuvant EGFR TKIs.

Haralick texture analysis of prostate MRI: utility for differentiating non-cancerous prostate from prostate cancer and differentiating prostate cancers with different Gleason scores

AbstractObjectivesTo investigate Haralick texture analysis of prostate MRI for cancer detection and differentiating Gleason scores (GS).MethodsOne hundred and forty-seven patients underwent T2- weighted (T2WI) and diffusion-weighted prostate MRI. Cancers ≥0.5xa0ml and non-cancerous peripheral (PZ) and transition (TZ) zone tissue were identified on T2WI and apparent diffusion coefficient (ADC) maps, using whole-mount pathology as reference. Texture features (Energy, Entropy, Correlation, Homogeneity, Inertia) were extracted and analysed using generalized estimating equations.ResultsPZ cancers (nu2009=u2009143) showed higher Entropy and Inertia and lower Energy, Correlation and Homogeneity compared to non-cancerous tissue on T2WI and ADC maps (p-values: <.0001–0.008). In TZ cancers (nu2009=u200943) we observed significant differences for all five texture features on the ADC map (all p-values: <.0001) and for Correlation (pu2009=u20090.041) and Inertia (pu2009=u20090.001) on T2WI. On ADC maps, GS was associated with higher Entropy (GS 6 vs. 7: pu2009=u20090.0225; 6 vs. >7: pu2009=u20090.0069) and lower Energy (GS 6 vs. 7: pu2009=u20090.0116, 6 vs. >7: pu2009=u20090.0039). ADC map Energy (pu2009=u20090.0102) and Entropy (pu2009=u20090.0019) were significantly different in GS ≤3u2009+u20094 versus ≥4u2009+u20093 cancers; ADC map Entropy remained significant after controlling for the median ADC (pu2009=u20090.0291).ConclusionSeveral Haralick-based texture features appear useful for prostate cancer detection and GS assessment.Key Points• Several Haralick texture features may differentiate non-cancerous and cancerous prostate tissue.n • Tumour Energy and Entropy on ADC maps correlate with Gleason score.n • T2w-image-derived texture features are not associated with the Gleason score.

Impact on disease-free survival of adjuvant erlotinib or gefitinib in patients with resected lung adenocarcinomas that harbor EGFR mutations.

Background: Patients with stage IV lung adenocarcinoma and epidermal growth factor receptor (EGFR) mutation derive clinical benefit from treatment with EGFR tyrosine kinase inhibitors (TKIs). Whether treatment with TKI improves outcomes in patients with resected lung adenocarcinoma and EGFR mutation is unknown. Methods: Data were analyzed from a surgical database of patients with resected lung adenocarcinoma harboring EGFR exon 19 or 21 mutations. In a multivariate analysis, we evaluated the impact of treatment with adjuvant TKI. Results: The cohort consists of 167 patients with completely resected stages I to III lung adenocarcinoma. Ninety-three patients (56%) had exon 19 del, 74 patients (44%) had exon 21 mutations, and 56 patients (33%) received perioperative TKI. In a multivariate analysis controlling for sex, stage, type of surgery, and adjuvant platinum chemotherapy, the 2-year disease-free survival (DFS) was 89% for patients treated with adjuvant TKI compared with 72% in control group (hazard ratio = 0.53; 95% confidence interval: 0.28–1.03; p = 0.06). The 2-year overall survival was 96% with adjuvant EGFR TKI and 90% in the group that did not receive TKI (hazard ratio: 0.62; 95% confidence interval: 0.26–1.51; p = 0.296). Conclusions: Compared with patients who did not receive adjuvant TKI, we observed a trend toward improvement in DFS among individuals with resected stages I to III lung adenocarcinomas harboring mutations in EGFR exon 19 or 21 who received these agents as adjuvant therapy. Based on these data, 320 patients are needed for a randomized trial to prospectively validate this DFS benefit.

Performance Characteristics of MR Imaging in the Evaluation of Clinically Low-Risk Prostate Cancer: A Prospective Study

PURPOSEnTo prospectively evaluate diagnostic performance of T2-weighted magnetic resonance (MR) imaging and MR spectroscopic imaging in detecting lesions stratified by pathologic volume and Gleason score in men with clinically determined low-risk prostate cancer.nnnMATERIALS AND METHODSnThe institutional review board approved this prospective, HIPAA-compliant study. Written informed consent was obtained from 183 men with clinically low-risk prostate cancer (cT1-cT2a, Gleason score≤6 at biopsy, prostate-specific antigen [PSA] level<10 ng/mL [10 μg/L]) undergoing MR imaging before prostatectomy. By using a scale of 1-5 (score 1, definitely no tumor; score 5, definitely tumor), two radiologists independently scored likelihood of tumor per sextant on T2-weighted images. Two spectroscopists jointly recorded locations of lesions with metabolic features consistent with tumor on MR spectroscopic images. Whole-mount step-section histopathologic analysis constituted the reference standard. Diagnostic performance at sextant level (T2-weighted imaging) and detection sensitivities (T2-weighted imaging and MR spectroscopic imaging) for lesions of 0.5 cm3 or larger were calculated.nnnRESULTSnFor T2-weighted imaging, areas under the receiver operating characteristic curves for sextant-level detection were 0.77 (reader 1) and 0.82 (reader 2). For lesions of ≥0.5 cm3 and, 1<cm3, sensitivities were significantly lower when the lesion Gleason score was ≤6 (0.44 [reader 1] and 0.61 [reader 2]) rather than when the Gleason score was ≥7 (0.73, P=.02 [reader 1]; and 0.84, P=.05 [reader 2]). For lesions of ≥1 cm3, lesion Gleason score did not significantly affect sensitivity (0.83 [reader 1] and 1.00 [reader 2] for Gleason score≤6 vs 0.82 and 0.92 for Gleason score≥7; P≥.07). MR spectroscopic imaging sensitivity was low and was not significantly affected by pathologic lesion volume or Gleason score.nnnCONCLUSIONnIn men with clinically low-risk prostate cancer, detection of lesions of <1 cm3 with T2-weighted imaging is significantly dependent on lesion Gleason score; detection of lesions of ≥1 cm3 is significantly better than detection of smaller lesions and is not affected by lesion Gleason score. The role of MR spectroscopic imaging alone in this population is limited.

Multiparametric Prostate MR Imaging with T2-weighted, Diffusion-weighted, and Dynamic Contrast-enhanced Sequences: Are All Pulse Sequences Necessary to Detect Locally Recurrent Prostate Cancer after Radiation Therapy?

PURPOSEnTo compare diagnostic accuracy of T2-weighted magnetic resonance (MR) imaging with that of multiparametric (MP) MR imaging combining T2-weighted imaging with diffusion-weighted (DW) MR imaging, dynamic contrast material-enhanced (DCE) MR imaging, or both in the detection of locally recurrent prostate cancer (PCa) after radiation therapy (RT).nnnMATERIALS AND METHODSnThis retrospective HIPAA-compliant study was approved by the institutional review board; informed consent was waived. Fifty-three men (median age, 70 years) suspected of having post-RT recurrence of PCa underwent MP MR imaging, including DW and DCE sequences, within 6 months after biopsy. Two readers independently evaluated the likelihood of PCa with a five-point scale for T2-weighted imaging alone, T2-weighted imaging with DW imaging, T2-weighted imaging with DCE imaging, and T2-weighted imaging with DW and DCE imaging, with at least a 4-week interval between evaluations. Areas under the receiver operating characteristic curve (AUC) were calculated. Interreader agreement was assessed, and quantitative parameters (apparent diffusion coefficient [ADC], volume transfer constant [K(trans)], and rate constant [k(ep)]) were assessed at sextant- and patient-based levels with generalized estimating equations and the Wilcoxon rank sum test, respectively.nnnRESULTSnAt biopsy, recurrence was present in 35 (66%) of 53 patients. In detection of recurrent PCa, T2-weighted imaging with DW imaging yielded higher AUCs (reader 1, 0.79-0.86; reader 2, 0.75-0.81) than T2-weighted imaging alone (reader 1, 0.63-0.67; reader 2, 0.46-0.49 [P ≤ .014 for all]). DCE sequences did not contribute significant incremental value to T2-weighted imaging with DW imaging (reader 1, P > .99; reader 2, P = .35). Interreader agreement was higher for combinations of MP MR imaging than for T2-weighted imaging alone (κ = 0.34-0.63 vs κ = 0.17-0.20). Medians of quantitative parameters differed significantly (P < .0001 to P = .0233) between benign tissue and PCa (ADC, 1.64 × 10(-3) mm(2)/sec vs 1.13 × 10(-3) mm(2)/sec; K(trans), 0.16 min(-1) vs 0.33 min(-1); k(ep), 0.36 min(-1) vs 0.62 min(-1)).nnnCONCLUSIONnMP MR imaging has greater accuracy in the detection of recurrent PCa after RT than T2-weighted imaging alone, with no additional benefit if DCE is added to T2-weighted imaging and DW imaging.

Original ArticlesImpact on Disease-Free Survival of Adjuvant Erlotinib or Gefitinib in Patients with Resected Lung Adenocarcinomas that Harbor EGFR Mutations

Background: Patients with stage IV lung adenocarcinoma and epidermal growth factor receptor (EGFR) mutation derive clinical benefit from treatment with EGFR tyrosine kinase inhibitors (TKIs). Whether treatment with TKI improves outcomes in patients with resected lung adenocarcinoma and EGFR mutation is unknown. Methods: Data were analyzed from a surgical database of patients with resected lung adenocarcinoma harboring EGFR exon 19 or 21 mutations. In a multivariate analysis, we evaluated the impact of treatment with adjuvant TKI. Results: The cohort consists of 167 patients with completely resected stages I to III lung adenocarcinoma. Ninety-three patients (56%) had exon 19 del, 74 patients (44%) had exon 21 mutations, and 56 patients (33%) received perioperative TKI. In a multivariate analysis controlling for sex, stage, type of surgery, and adjuvant platinum chemotherapy, the 2-year disease-free survival (DFS) was 89% for patients treated with adjuvant TKI compared with 72% in control group (hazard ratio = 0.53; 95% confidence interval: 0.28–1.03; p = 0.06). The 2-year overall survival was 96% with adjuvant EGFR TKI and 90% in the group that did not receive TKI (hazard ratio: 0.62; 95% confidence interval: 0.26–1.51; p = 0.296). Conclusions: Compared with patients who did not receive adjuvant TKI, we observed a trend toward improvement in DFS among individuals with resected stages I to III lung adenocarcinomas harboring mutations in EGFR exon 19 or 21 who received these agents as adjuvant therapy. Based on these data, 320 patients are needed for a randomized trial to prospectively validate this DFS benefit.

Incremental value of diffusion weighted and dynamic contrast enhanced MRI in the detection of locally recurrent prostate cancer after radiation treatment: preliminary results

ObjectivesTo assess the incremental value of diffusion-weighted (DW-MRI) and dynamic contrast-enhanced MRI (DCE-MRI) to T2-weighted MRI (T2WI) in detecting locally recurrent prostate cancer after radiotherapy.MethodsTwenty-four patients (median age, 70xa0years) with a history of radiotherapy-treated prostate cancer underwent multi-parametric MRI (MP-MRI) and transrectal prostate biopsy. Two readers independently scored the likelihood of cancer on a 1–5 scale, using T2WI alone and then adding DW-MRI and DCE-MRI. Areas under receiver operating characteristic curves (AUCs) were estimated at the patient and prostate-side levels. The apparent diffusion coefficient (ADC) from DW-MRI and the Ktrans, kep, ve, AUGC90 and AUGC180 from DCE-MRI were recorded.ResultsBiopsy was positive in 16/24 (67%) and negative in 8/24 (33%) patients. AUCs for readers 1 and 2 increased from 0.64 and 0.53 to 0.95 and 0.86 with MP-MRI, at the patient level, and from 0.73 and 0.66 to 0.90 and 0.79 with MP-MRI, at the prostate-side level (p valuesu2009<u20090.05). Biopsy-positive and biopsy-negative prostate sides differed significantly in median ADC [1.44 vs. 1.68 (×10−3xa0mm2/s)], median Ktrans [1.07 vs. 0.34 (1/min)], and kep [2.06 vs 1.0 (1/min)] (p valuesu2009<u20090.05).ConclusionsMP-MRI was significantly more accurate than T2WI alone in detecting locally recurrent prostate cancer after radiotherapy.