Multi-omics staging of locally advanced rectal cancer predicts treatment response: a pilot study.

Treatment response assessment of rectal cancer patients is a critical component of personalized cancer care and it allows to identify suitable candidates for organ-preserving strategies. This pilot study employed a novel multi-omics approach combining MRI-based radiomic features and untargeted metabolomics to infer treatment response at staging. The metabolic signature highlighted how tumor cell viability is predictively down-regulated, while the response to oxidative stress was up-regulated in responder patients, showing significantly reduced oxoproline values at baseline compared to non-responder patients (p-value < 10-4). Tumors with a high degree of texture homogeneity, as assessed by radiomics, were more likely to achieve a major pathological response (p-value < 10-3). A machine learning classifier was implemented to summarize the multi-omics information and discriminate responders and non-responders. Combining all available radiomic and metabolomic features, the classifier delivered an AUC of 0.864 (± 0.083, p-value < 10-3) with a best-point sensitivity of 90.9% and a specificity of 81.8%. Our results suggest that a multi-omics approach, integrating radiomics and metabolomic data, can enhance the predictive value of standard MRI and could help to avoid unnecessary surgical treatments and their associated long-term complications.

Perineural Invasion in Pancreatic Ductal Adenocarcinoma: From Molecules towards Drugs of Clinical Relevance.

Pancreatic ductal adenocarcinoma is one of the most threatening solid malignancies. Molecular and cellular mediators that activate paracrine signalling also regulate the dynamic interaction between pancreatic cancer cells and nerves. This reciprocal interface leads to perineural invasion (PNI), defined as the ability of cancer cells to invade nerves, similar to vascular and lymphatic metastatic cascade. Targeting PNI in pancreatic cancer might help ameliorate prognosis and pain relief. In this review, the modern knowledge of PNI in pancreatic cancer has been analysed and critically presented. We focused on molecular pathways promoting cancer progression, with particular emphasis on neuropathic pain generation, and we reviewed the current knowledge of pharmacological inhibitors of the PNI axis. PNI represents a common hallmark of PDAC and correlates with recurrence, poor prognosis and pain in pancreatic cancer patients. The interaction among pancreatic cancer cells, immune cells and nerves is biologically relevant in each stage of the disease and stimulates great interest, but the real impact of the administration of novel agents in clinical practice is limited. It is still early days for PNI-targeted treatments, and further advanced studies are needed to understand whether they could be effective tools in the clinical setting.

Role of shear-wave and strain elastography to differentiate malignant vs benign subpleural lung lesions.

ABSTRACT: Elastosonography is a non-invasive diagnostic method to evaluate tissue stiffness. The aim of our study was to demonstrate the applicability and efficacy of elastosonography to differentiate benign vs malignant subpleural lung lesions compared to clinical, radiological and histological findings.We performed both strain and shear wave velocity (SWV) elastosonography on subpleural lung lesions. Moreover, we elaborated a composite score called "elasto index".Fourteen patients, 10 males and 4 females were recruited. On strain elastography, 9 lesions showed a hard pattern (type 3), 3 lesions showed an intermediate pattern (type 2), and 2 lesions a soft pattern (type 1). All lesions showed a mean SWV value of 4.46 ±â€Š2.37 m/second. The mean SWV for malignant lesions (n = 6) was 5.92 ±â€Š2.8 m/second. The mean SWV for benign lesions (n = 8) was 3.36 ±â€Š1.20 m/second. SWV shows an area under the curve (AUC) of 0.792, and the Youden index shows a value of 3.6 m/second. The ROC curve elaborated for the diagnosis of malignancy by strain elastography showed an AUC of 0.688. ROC curve for the diagnosis of malignancy by elasto index demonstrated an AUC of 0.802.SWV values obtained by ARFI elastosonographic method are higher in malignant lung lesions (mean SWV: 5.92 m/second) than in benign ones (mean SWV: 3.36); a composite score (elasto index) is characterized by better statistical significance for the differentiation of the lesions.

Clinical outcomes in elderly rectal cancer patients treated with neoadjuvant chemoradiotherapy: impact of tumor regression grade : Tumor regression grade after neoadjuvant chemoradiotherapy in elderly rectal cancer patients.

PURPOSE: The effect of neoadjuvant chemoradiotherapy (CRT) and the relationship between pathological complete response (pCR) with clinical outcomes has been evaluated in elderly locally advanced rectal cancer (LARC) patients. METHODS: We retrospectively analyzed 117 LARC patients treated with conformal RT and concomitant fluoropirimidine-based chemotherapy. A dose of 4500 cGy, on the pelvis, up to 5500 cGy on the tumor was delivered. Multidisciplinary evaluation, including geriatric assessment, was previously performed to identify frail patients unsuitable for combined treatment. RESULTS: The median age was 75 (range 70-88 years), and 103 (88%) patients had ECOG Performance Status (PS) = 0. All patients except one completed CRT. Ten (8.5%) patients temporarily suspended CRT for acute severe hematologic complication, diarrhea and/or proctitis and hypokalemia. Of the 103 operated patients (88%), a pCR, according to Mandard tumor regression grade (TRG) score, was obtained in 28 patients (27.2%), with TRG1-2 rate of 43.7%. The 3- and 5-year overall survival (OS) rates were 80.2% ± 4.2% and 68.0% ± 5.2%, 72.4% ± 4.5% and 57.8% ± 5.2% for disease-free survival (DFS), and 92.2% ± 2.8% and 89.5% ± 3.9% for loco-regional control. Patients with TRG1-2 had 3- and 5-year OS rates of 84.1% ± 6.6% and 84.1% ± 6.6% compared with 82.8% ± 5.5% and 67.7% ± 7.2% for patients with TRG3-5 (p = 0.012). The 3- and 5-year DFS rates for patients with TRG1-2 were 77.6% ± 7.0% and 74.2% ± 7.5% compared with 70.9% ± 6.3% and 54.7% ± 7.3% for patients with TRG3-5 (p = 0.009). CONCLUSION: Our results reported good tolerability and clinical outcomes of neoadjuvant CRT, with a benefit in patients ≥ 70 years, confirming the prognostic role of pCR on clinical outcomes.

MRI-based clinical-radiomics model predicts tumor response before treatment in locally advanced rectal cancer.

Neoadjuvant chemo-radiotherapy (CRT) followed by total mesorectal excision (TME) represents the standard treatment for patients with locally advanced (≥ T3 or N+) rectal cancer (LARC). Approximately 15% of patients with LARC shows a complete response after CRT. The use of pre-treatment MRI as predictive biomarker could help to increase the chance of organ preservation by tailoring the neoadjuvant treatment. We present a novel machine learning model combining pre-treatment MRI-based clinical and radiomic features for the early prediction of treatment response in LARC patients. MRI scans (3.0 T, T2-weighted) of 72 patients with LARC were included. Two readers independently segmented each tumor. Radiomic features were extracted from both the "tumor core" (TC) and the "tumor border" (TB). Partial least square (PLS) regression was used as the multivariate, machine learning, algorithm of choice and leave-one-out nested cross-validation was used to optimize hyperparameters of the PLS. The MRI-Based "clinical-radiomic" machine learning model properly predicted the treatment response (AUC = 0.793, p = 5.6 × 10-5). Importantly, the prediction improved when combining MRI-based clinical features and radiomic features, the latter extracted from both TC and TB. Prospective validation studies in randomized clinical trials are warranted to better define the role of radiomics in the development of rectal cancer precision medicine.

Volume Delineation in Cervical Cancer With T2 and Diffusion-weighted MRI: Agreement on Volumes Between Observers.

AIM: To delineate cervical cancer gross tumor volume (GTV) on T2-magnetic resonance imaging (MRI) and apparent diffusion coefficient (ADC) maps, assessing volumes and inter-observer agreement between two observers. PATIENTS AND METHODS: A radiologist and a radiation oncologist delineated GTV on T2 (T2GTV) and ADC (ADCGTV) sequences. Dice similarity index (DICE) and Bland-Altman analysis were used to estimated concordance. RESULTS: Mean T2GTV and ADCGTV volumes were 43.84±71.47 cc and 37.28±68.92 cc according to the radiologist, and 43.4±70.44 cc and 36.65±69.21 cc according to the radiation oncologist. ADC led to statistically significantly smaller volumes compared to T2. The mean DICE index was 0.86 for T2GTV and 0.84 for ADCGTV The Bland-Altman plots globally showed concordance. CONCLUSION: GTV delineation was smaller in the ADC maps compared to T2-MRI, reaching an almost perfect agreement between observers. Thanks to this acceptable variability, adding functional imaging might provide more information for tumor delineation, improving reproducibility for image-guided adaptive radiotherapy.

Peritoneal sarcoidosis mimicking peritoneal carcinomatosis.

AIM: Describtion of a rare case of intestinal obstruction due to peritoneal sarcoidosis mimicking peritoneal carcinomatosis, and of the literature review about its surgical management. MATERIAL OF STUDY: A 69 year-old woman was referred to our emergency department with diffuse abdominal pain, enteric vomiting and constipation. Abdominal CT showed a dilatated small bowel loops extended to the jejunum with a mechanical obstruction. Given the failure of a non operative management, an explorative laparotomy was performed. RESULTS: Intraoperative evaluation showed an omental cake with extensive adhesions between small bowel and abdominal wall. The adhesion band determining occlusion was identified and cut. Furthermore, several peritoneal and omental biopsies were performed. Postoperative period was uneventful. Unfortunately, one month later, the patient died following an episode of spontaneous pneumothorax and respiratory complications. DISCUSSION: Sarcoidosis is a chronic multisystemic disorder of unknown aetiology with granulomatous inflammation. Peritoneal involvement is a rare presentation of sarcoidosis. Clinical presentation depends on the extent of organ involvement. In some cases,symptoms are no specific and uncommon findings have been reported so far. CONCLUSION: Despite a peritoneal carcinomatosis was suspeted, this case shows that abdominal sarcoidosis might be considered as a differential diagnosis when a lesion suspected of being peritoneal carcinomatosis shows non-typical clinical presentations. KEY WORDS: Peritoneal sarcoidosis, Small bowel obstruction.

Tumor detectability and conspicuity comparison of standard b1000 and ultrahigh b2000 diffusion-weighted imaging in rectal cancer.

PURPOSE: To compare tumor detectability and conspicuity of standard b = 1000 s/mm2 (b1000) versus ultrahigh b = 2000 s/mm2 (b2000) diffusion-weighted imaging (DWI) in rectal cancer. METHODS: Fifty-five patients for a total of 81 3T DWI-MR scans were retrospectively evaluated by two differently experienced readers. A comparison between b1000 and b2000 for tumor detectability and conspicuity was performed. The conspicuity was qualitatively and quantitatively assessed by using three-point scale and whole tumor volume manual delineation, respectively. Receiver-operating characteristic curve (ROC) with area under the curve (AUC) analysis provided diagnostic accuracy in tumor detectability of restaging MR scans. Qualitative scores and quantitative features including mean signal intensity, variance, 10th percentile and 90th percentile, were compared using the Wilcoxon test. Interobserver agreement (IOA) for qualitative and quantitative data was calculated using Cohen's Kappa and intraclass correlation coefficient (ICC) respectively. RESULTS: Diagnostic accuracy was comparable between b1000 and b2000 for both readers (p > 0.05). Overall quality scores were significantly better for b2000 than b1000 (2.29 vs 1.65 Reader 1, p = 0.01; 2.18 vs 1.69 Reader 2, p = 0.04). IOA was equally good for both b values (k = 0.86 b1000, k = 0.86 b2000). Quantitative analysis revealed more uniform signal (measured in variance) of b2000 in both healthy surrounding tissue (p < 0.05) and tumor (p < 0.05), with less outliers (measured using 10th and 90th percentile). Additionally, b2000 offered lower mean signal intensity in tissue sorrounding the tumor (p < 0.05). Finally, ICC improved from 0.92 (b1000) to 0.97 (b2000). CONCLUSION: Ultrahigh b value (b2000) may improve rectal cancer conspicuity and introbserver agreement maintaining comparable diagnostic accuracy to standard b1000.

Diagnostic accuracy of biparametric vs multiparametric MRI in clinically significant prostate cancer: Comparison between readers with different experience.

BACKGROUND: MRI plays a crucial role to identify men with a high likelihood of clinically significant prostate cancer who require immediate biopsy. The added value of DCE MRI in combination with T2-weighted imaging and DWI is controversial (risks related to gadolinium administration, duration of MR exam, financial burden, effects on diagnostic performance). A comparison of a biparametric and a standard multiparametric MR imaging protocol, taking into account the different experience of the readers, may help to choose the best MR approach regarding diagnostic performance. PURPOSE: To determine the added value of dynamic contrasted-enhanced imaging (DCE) over T2-weighted imaging (T2-WI) and diffusion weighted imaging (DWI) for the detection of clinically significant prostate cancer, and to evaluate how it affects the diagnostic performance of three readers with different grade of experience in prostate imaging. MATERIALS AND METHODS: Eighty-five patients underwent prostate MR examination at 1.5 T MR scanner performed because of elevated prostate-specific antigen level and/or suspicion of prostate cancer at digital rectal examination. Two MR images sets (Set 1 = biparametric, Set 2 = multiparametric) were retrospectively and independently scored by three radiologists with 7, 3 and 1 years of experience in prostate MR imaging respectively, according to PI-RADS v2. Sensitivity, specificity, positive predictive value, and negative predictive value were calculated by dichotomizing reader scores. Receiver operating characteristic (ROC) analysis was performed and areas under the curve (AUCs) were calculated for each reader and image set. A comparison of ROC curves was performed to test the difference between the areas under the ROC curves among the three readers. RESULTS: There was no significant difference regarding the detection of clinically significant tumor among the three readers between the two image sets. The AUC for the bi-parametric and multi-parametric MR imaging protocol was respectively 0.68-0.72 (Reader 1), 0.72-0.70 (Reader 2) and 0.60-0.54 (Reader 3). ROC curve comparison revealed no statistically significant differences for each protocol among the most experienced (Reader 1) and the other readers (Readers 2-3). CONCLUSION: The diagnostic accuracy of a bi-parametric MR imaging protocol consisting of T2-weighted imaging and DWI is comparable with that of a standard multi-parametric imaging protocol for the detection of clinically significant prostate cancer. The experience of the reader does not significantly modify the diagnostic performance of both MR protocols.