Immunotherapy is regarded as one of the major breakthroughs in cancer treatment. Despite its success, only a subset of patients responds—urging the quest for predictive biomarkers. We hypothesize ...that artificial intelligence (AI) algorithms can automatically quantify radiographic characteristics that are related to and may therefore act as noninvasive radiomic biomarkers for immunotherapy response.
In this study, we analyzed 1055 primary and metastatic lesions from 203 patients with advanced melanoma and non-small-cell lung cancer (NSCLC) undergoing anti-PD1 therapy. We carried out an AI-based characterization of each lesion on the pretreatment contrast-enhanced CT imaging data to develop and validate a noninvasive machine learning biomarker capable of distinguishing between immunotherapy responding and nonresponding. To define the biological basis of the radiographic biomarker, we carried out gene set enrichment analysis in an independent dataset of 262 NSCLC patients.
The biomarker reached significant performance on NSCLC lesions (up to 0.83 AUC, P<0.001) and borderline significant for melanoma lymph nodes (0.64 AUC, P=0.05). Combining these lesion-wide predictions on a patient level, immunotherapy response could be predicted with an AUC of up to 0.76 for both cancer types (P<0.001), resulting in a 1-year survival difference of 24% (P=0.02). We found highly significant associations with pathways involved in mitosis, indicating a relationship between increased proliferative potential and preferential response to immunotherapy.
These results indicate that radiographic characteristics of lesions on standard-of-care imaging may function as noninvasive biomarkers for response to immunotherapy, and may show utility for improved patient stratification in both neoadjuvant and palliative settings.
Objectives
To identify the main problem areas in the applicability of the current TNM staging system (8
th
ed.) for the radiological staging and reporting of rectal cancer and provide practice ...recommendations on how to handle them.
Methods
A global case-based online survey was conducted including 41 image-based rectal cancer cases focusing on various items included in the TNM system. Cases reaching < 80% agreement among survey respondents were identified as problem areas and discussed among an international expert panel, including 5 radiologists, 6 colorectal surgeons, 4 radiation oncologists, and 3 pathologists.
Results
Three hundred twenty-one respondents (from 32 countries) completed the survey. Sixteen problem areas were identified, related to cT staging in low-rectal cancers, definitions for cT4b and cM1a disease, definitions for mesorectal fascia (MRF) involvement, evaluation of lymph nodes versus tumor deposits, and staging of lateral lymph nodes. The expert panel recommended strategies on how to handle these, including advice on cT-stage categorization in case of involvement of different layers of the anal canal, specifications on which structures to include in the definition of cT4b disease, how to define MRF involvement by the primary tumor and other tumor-bearing structures, how to differentiate and report lymph nodes and tumor deposits on MRI, and how to anatomically localize and stage lateral lymph nodes.
Conclusions
The recommendations derived from this global survey and expert panel discussion may serve as a practice guide and support tool for radiologists (and other clinicians) involved in the staging of rectal cancer and may contribute to improved consistency in radiological staging and reporting.
Key Points
•
Via a case-based online survey (incl. 321 respondents from 32 countries), we identified 16 problem areas related to the applicability of the TNM staging system for the radiological staging and reporting of rectal cancer.
•
A multidisciplinary panel of experts recommended strategies on how to handle these problem areas, including advice on cT-stage categorization in case of involvement of different layers of the anal canal, specifications on which structures to include in the definition of cT4b disease, how to define mesorectal fascia involvement by the primary tumor and other tumor-bearing structures, how to differentiate and report lymph nodes and tumor deposits on MRI, and how to anatomically localize and stage lateral lymph nodes.
•
These recommendations may serve as a practice guide and support tool for radiologists (and other clinicians) involved in the staging of rectal cancer and may contribute to improved consistency in radiological staging and reporting.
Purpose
Detection of peritoneal metastases (PM) is key in the staging and management of gastrointestinal and ovarian cancer patients. The purpose of this meta-analysis was to determine the diagnostic ...performance of CT, PET(CT), and (DW)MRI in detecting PM.
Methods
A literature search in Pubmed, Embase (Ovid), and Scopus was performed (January 1997–May 2018) to identify studies reporting on the accuracy of imaging PM in the diagnostic workup of gastrointestinal or ovarian cancers. Inclusion criteria were region-based or patient-based studies comprising > 15 patients, surgery/histology/radiological follow-up as a reference standard, and sufficient data to construct a 2 × 2 contingency table. Two observers performed data extraction. The sensitivity, specificity, and diagnostic odds ratio (DOR) were calculated using a bivariate random-effects model and hierarchical summary operating curves (HSROC) were generated.
Results
Of 3457 citations retrieved, twenty-four articles met all inclusion criteria. Thirty-seven datasets could be extracted for analysis including 20 for CT, 10 for PET(CT), and 7 for (DW)MRI. The pooled sensitivity, specificity, and DOR for the detection of PM for region-based studies for CT were 68% (CI, 46–84%), 88%(CI, 81–93%), and 15.9 (CI, 4.4–58.0) respectively; 80% (CI, 57–92%), 90% (CI, 80–96%), and 36.5 (CI, 6.7–199.5) for PET(CT), respectively; 92% (CI, 84–96%), 85% (CI, 78–91%), 63.3 (CI, 31.5–127.3) for (DW)MRI. In the patient-based group, not enough studies were included to make a pooled analysis for (DW)MRI and PET(CT).
Conclusion
(DW)MRI and PET(CT) showed comparable diagnostic performance for the detection of peritoneal metastases in ovarian and gastrointestinal cancer patients. Since MRI is more widely available than PET(CT) in clinical practice, this potentially is the imaging method of choice in most centers in the future.
Key Points
• Detection of peritoneal metastases plays an important role in the accurate staging of cancer patients, however, there is no accepted reference standard for the imaging of peritoneal metastases
• This meta-analysis shows that (DW)MRI provided the highest sensitivity for the detection of peritoneal metastases in ovarian and gastrointestinal cancer patients
• Although (DW)MRI and PET(CT) show a comparable overall diagnostic performance, (DW)MRI seems to be the imaging method of choice since it is more available in daily practice than PET(CT).
Purpose
Rectal cancer staging with magnetic resonance imaging (MRI) allows accurate assessment and preoperative staging of rectal cancers. Therefore, complete MRI reports are vital to treatment ...planning. Significant variability may exist in their content and completeness. Template-style reporting can improve reporting standards, but its use is not widespread. Given the implications for treatment, we have evaluated current clinical practice amongst specialist gastrointestinal (GI) radiologists to measure the quality of rectal cancer staging MRI reports.
Materials and methods
Sixteen United Kingdom (UK) colorectal cancer multi-disciplinary teams (CRC-MDTs) serving a population over 5 million were invited to submit up to 10 consecutive rectal cancer primary staging MRI reports from January 2016 for each radiologist participating in the CRC-MDT. Reports were compared to a reference standard based on recognised staging and prognostic factors influencing case management
Results
Four hundred ten primary staging reports were submitted from 41 of 42 (97.6%) eligible radiologists. Three hundred sixty reports met the inclusion criteria, of these, 81 (22.5%) used a template. Template report usage significantly increased recording of key data points versus non-template reports for extra-mural venous invasion (EMVI) status (98.8% v 51.6%,
p
< 0.01) and circumferential resection margin (CRM) status (96.3% v 65.9%,
p
< 0.01). Local tumour stage (97.5% v 93.5%, NS) and nodal status (98.8% v 96.1%, NS) were reported and with similar frequency.
Conclusion
Rectal cancer primary staging reports do not meet published standards. Template-style reports have significant increases in the inclusion of key tumour descriptors. This study provides further support for their use to improve reporting standards and outcomes in rectal cancer.
Key Points
•
MRI primary staging of rectal cancer requires detailed tumour descriptions as these alter the neoadjuvant and surgical treatments.
•
Currently, rectal cancer MRI reports in clinical practice do not provide sufficient detail on these tumour descriptors.
•
The use of template-style reports for primary staging of rectal cancer significantly improves report quality compared to free-text reports.
•Accurate preoperative assessment of the peritoneal tumor load can be done with Diffusion-Weighted MRI.•Diffusion-weighted MRI is able to predict per-operative findings using the Peritoneal Cancer ...Index.•The MRI-PCI showed able to predict whether a complete cytoreduction is feasible for advanced stage ovarian cancer patients.
To determine the diagnostic performance of MRI with diffusion-weighted imaging (DW-MRI) in assessing the peritoneal tumor load and predicting whether a complete cytoreduction can be achieved in patients with epithelial ovarian cancer (EOC).
For this observational prospective study, 25 patients with epithelial ovarian cancer scheduled for cytoreductive surgery were included. Patients underwent a 3 T DW-MRI scan prior to surgery. The MR protocol consisted of a T1 and T2 weighted, a contrast-enhanced T1 weighted, and a diffusion-weighted (b0, b1000) sequence. The Peritoneal Cancer Index (PCI) was determined on DW-MR images (MRI-PCI) by two readers, independently, and was compared to the PCI determined during surgery (S-PCI). The inter-observer agreement between the two radiologists was evaluated. In addition, receiver operating characteristics curves were calculated for predicting complete cytoreduction with the S-PCI and MRI-PCI.
Staging with DW-MRI showed a correlation to surgical staging with an intraclass correlation coefficient (ICC) 0.86 and 0.85 for reader 1 and 2, respectively. Inter-observer agreement was excellent with an ICC of 0.90 (95% CI: 0.64-0.96). The MRI-PCI scores of reader 1 (AUC = 0.96), reader 2 (AUC = 0.98), and the S-PCI (AUC = 0.92) showed similar predictive values for complete cytoreduction.
DW-MRI is accurate in predicting the S-PCI and can be helpful to predict whether a complete resection in ovarian cancer patients is feasible.
•Assessing ratios between texture of liver metastases and surrounding-liver can be valuable.•Ratios between texture features are capable of assessing extent of disease.•Emetastases/Eliver ratio is ...associated with survival, albeit not significant.
To study the ratio between the CT texture of colorectal liver metastases (CRLM) and the surrounding liver parenchyma and assess the potential of various texture measures and ratios as predictive/prognostic imaging markers.
Seventy patients with colorectal cancer and synchronous CRLM were included. All visible metastases, as well as the whole-volume of the surrounding liver, were separately delineated on the portal venous phase primary staging CT. Texture features entropy (E) and uniformity (U) were extracted and ratios between the texture features (T) of the metastases and background liver (Tmetastases/Tliver) calculated. Texture features were compared with clinical outcome parameters: 1 extent of disease (i.e. number of metastases), 2 response to chemotherapy (in 56/70 patients who underwent chemotherapy and CT for response evaluation), and 3 overall survival.
The Emetastases/Eliver ratio was lower in patients with limited disease (P = 0.02) and associated with overall survival, albeit not statistically significant when tested in multivariable analyses (HR 1.90; P = 0.07); Umetastases/Uliver was higher in patients with limited disease (P = 0.02). Emetastases showed a trend towards a higher value in patients that responded well to chemotherapy (P = 0.08).
The ratio between the texture of liver metastases and the surrounding liver appears to reflect relevant changes in tissue microarchitecture and may be of value to assess the extent of disease and help predict overall survival.
To assess whether CT-based radiomics of the ablation zone (AZ) can predict local tumour progression (LTP) after thermal ablation for colorectal liver metastases (CRLM).
Eighty-two patients with 127 ...CRLM were included. Radiomics features (with different filters) were extracted from the AZ and a 10 mm periablational rim (PAR)on portal-venous-phase CT up to 8 weeks after ablation. Multivariable stepwise Cox regression analyses were used to predict LTP based on clinical and radiomics features. Performance (concordance c-statistics) of the different models was compared and performance in an ‘independent’ dataset was approximated with bootstrapped leave-one-out-cross-validation (LOOCV).
Thirty-three lesions (26 %) developed LTP. Median follow-up was 21 months (range 6−115).
The combined model, a combination of clinical and radiomics features, included chemotherapy (HR 0.50, p = 0.024), cT-stage (HR 10.13, p = 0.016), lesion size (HR 1.11, p = <0.001), AZ_Skewness (HR 1.58, p = 0.016), AZ_Uniformity (HR 0.45, p = 0.002), PAR_Mean (HR 0.52, p = 0.008), PAR_Skewness (HR 1.67, p = 0.019) and PAR_Uniformity (HR 3.35, p < 0.001) as relevant predictors for LTP. The predictive performance of the combined model (after LOOCV) yielded a c-statistic of 0.78 (95 %CI 0.65−0.87), compared to the clinical or radiomics models only (c-statistic 0.74 (95 %CI 0.58−0.84) and 0.65 (95 %CI 0.52−0.83), respectively).
Combining radiomics features with clinical features yielded a better performing prediction of LTP than radiomics only. CT-based radiomics of the AZ and PAR may have potential to aid in the prediction of LTP during follow-up in patients with CRLM.
Background
Patients with limited peritoneal metastases from colorectal cancer may be candidates for an aggressive surgical approach including cytoreductive surgery and hyperthermic intraperitoneal ...chemotherapy (CRS–HIPEC). Selection is based on surgical inspection during laparoscopy or laparotomy. The aim of this study was to investigate whether diffusion‐weighted MRI (DW‐MRI) can be used to select patients for CRS–HIPEC.
Methods
This was a prospective study at a tertiary referral centre. Patients with confirmed or suspected colorectal peritoneal metastases scheduled for exploratory laparotomy or laparoscopy were eligible. Two radiologists assessed the peritoneal cancer index (PCI) on CT (CT‐PCI) and DW‐MRI (MRI‐PCI). The reference standard was PCI at surgery. Radiologists were blinded to the surgical PCI and to each other's findings. The main outcome was the accuracy of DW‐MRI in predicting whether patients had resectable disease (PCI less than 21) or not.
Results
Fifty‐six patients were included in the study, of whom 49 could be evaluated. The mean(s.d.) PCI at surgery was 11·27(7·53). The mean MRI‐PCI was 10·18(7·07) for reader 1 and 8·59(7·08) for reader 2. Readers 1 and 2 correctly staged 47 of 49 and 44 of 49 patients respectively (accuracy 96 and 90 per cent). Both readers detected all patients with resectable disease with a PCI below 21 at surgery (sensitivity 100 per cent). No patient was overstaged. The intraclass correlation (ICC) between readers was excellent (ICC 0·91, 95 per cent c.i. 0·77 to 0·96). MRI‐PCI had a stronger correlation with surgical PCI (ICC 0·83–0·88) than did CT‐PCI (ICC 0·39–0·44).
Conclusion
DW‐MRI is a promising non‐invasive tool to guide treatment selection in patients with peritoneal metastases from colorectal cancer.
Promising staging tool
Patients with colorectal peritoneal metastases (PM) treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are at high risk of recurrent disease. Understanding ...where and why recurrences occur is the first step in finding solutions to reduce recurrence rates. Although diffusion-weighted (DW) MRI is not routinely used in the follow-up of CRC patients, it has a clear advantage over CT in detecting the location and spread of (recurrent) PM. This study aimed to identify common locations of recurrence in CRC patients after CRS-HIPEC with MRI.
This was a single-centre retrospective study of patients with recurrent PM after CRS-HIPEC performed between January 2016 and August 2020. Patients were eligible for inclusion if they had both an MRI preoperatively (MRI1) and at the time of recurrent disease (MRI2). Two abdominal radiologists reviewed in consensus and categorized recurrences according to their location on MRI2 and in correlation with previous disease location on prior imaging (MRI1) and the surgical report of the CRS-HIPEC.
Thirty patients were included, with a median surgical PCI of 7 (range 3–21) at the time of primary CRS-HIPEC. In total, 68 recurrent metastases were detected on MRI2, of which 14 were extra-peritoneal. Of the remaining 54 PM, 42 (78%) occurred where the peritoneum was damaged due to earlier resections or other surgical procedures (e.g. inserted surgical abdominal drains). Most recurrent metastases were found in the mesentery, lower abdomen/pelvis and abdominal wall (87%).
Most recurrent PMs appeared in the mesentery, lower abdomen/pelvis and abdominal wall, especially where the peritoneum was previously damaged.
Selecting patients with peritoneal metastases from colorectal cancer (CRCPM) who might benefit from cytoreductive surgery followed by hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) is ...challenging. Computed tomography generally underestimates the peritoneal tumor load. Diagnostic laparoscopy is often used to determine whether patients are amenable for surgery. Magnetic resonance imaging (MRI) has shown to be accurate in predicting completeness of CRS. The aim of this study is to determine whether MRI can effectively reduce the need for surgical staging.
The study is designed as a multicenter randomized controlled trial (RCT) of colorectal cancer patients who are deemed eligible for CRS-HIPEC after conventional CT staging. Patients are randomly assigned to either MRI based staging (arm A) or to standard surgical staging with or without laparoscopy (arm B). In arm A, MRI assessment will determine whether patients are eligible for CRS-HIPEC. In borderline cases, an additional diagnostic laparoscopy is advised. The primary outcome is the number of unnecessary surgical procedures in both arms defined as: all surgeries in patients with definitely inoperable disease (PCI > 24) or explorative surgeries in patients with limited disease (PCI < 15). Secondary outcomes include correlations between surgical findings and MRI findings, cost-effectiveness, and quality of life (QOL) analysis.
This randomized trial determines whether MRI can effectively replace surgical staging in patients with CRCPM considered for CRS-HIPEC.
Registered in the clinical trials registry of U.S. National Library of Medicine under NCT04231175 .
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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