Central pathology review in multicenter trials and studies

Abstract

BACKGROUND:Central pathology review (CPR) is an important component of multicenter tumor trials. The authors retrospectively analyzed the quality of pathology material submitted to determine the benefits and limitations of rapid CPR.METHODS:Analysis of pathology specimens from previous renal tumors in children trials (1980‐2007) included the number of cases submitted, the number of slides per case, discrepancies in diagnosis and staging between institutional pathologists and CPR, and the impact of rapid CPR on treatment.RESULTS:The percentage of cases submitted for CPR increased from 76% in earlier trials to 100% in the current trial. The number of slides submitted rose from a median of 6 (International Pediatric Oncology Society [SIOP] 9301) to 25 for the SIOP‐UK Renal Tumors 2001 trial. Discrepancies between the institutional pathologists and CPR were as follows: diagnosis: SIOP 9, 17%; SIOP 93‐01, 14%; United Kingdom Wilms Tumour 3 Trial (UKWT3), 3.5%; SIOP‐UK 2001, 3.8%; staging: SIOP 6, 9%; SIOP 93‐01, 14%; UKWT3, 17%; SIOP‐UK 2001, 3.8% of cases. There were clinically significant discrepancies in diagnosis and/or stage in 30 of 152 (20%) cases submitted for delayed CPR in SIOP‐UK 2001.CONCLUSIONS:The number and quality of material submitted for CPR has markedly improved over time, predominantly due to the introduction of a simple standard operating procedure. Discrepancies in diagnosis and staging remain, but rapid review CPR allows clinicians to modify treatment if required. Benefits from the CPR system followed in SIOP‐UK 2001 have been clearly demonstrated, and similar systems should be considered for future trials of other tumors. Cancer 2009. © 2009 American Cancer Society.

Somatic TP53 Mutations Are Detectable in Circulating Tumor DNA from Children with Anaplastic Wilms Tumors

“…Specimens underwent centralized histology review to confirm stage and histology, and those with tumor content of more than 50% were utilized for the study [14]. Tumor DNA and germline DNA from normal tissue were extracted by standard methods using either a standard detergent lysis/phenol-chloroform technique or the DNAeasy Blood and Tissue Kit (Qiagen).…”

The pathology of Wilms' tumour (nephroblastoma): the International Society of Paediatric Oncology approach

“…However, the results from both SIOP and NWTS/COG trials show that staging is a major problem, not only in pretreated but also in primarily operated tumours 2 16. One of the reasons is that these tumours are usually large and distort the normal architecture of the kidney and its anatomical structures, such as the renal sinus and capsule.…”

“…Data from previous trials show that in around 20% of renal tumours there were diagnostic and staging discrepancies between the institutional pathologists and central pathology review 2. The current policy for the UK SIOP WT 2001 trial is that all renal tumours should be submitted for rapid central pathology review, which may allow for changes in management if necessary (box 3).…”

“…Accurate histological diagnosis and staging of these tumours are critical because their treatment and prognosis are very different. Since they are rare, they still represent a diagnostic and therapeutic challenge,2 and it is important to treat and study them through large national and international multicentre collaborative trials which include centralised pathological review in order to verify the diagnosis and stage of cases entered on the trials.…”

Central Pathology Review for Phase III Clinical Trials: The Enabling Effect of Virtual Microscopy

“…The authors argue that the CPR of prostatectomy specimens ''is likely to improve the outcome of the study and should be an integral part of the trial design.' ' Vujanic et al 14 examined the benefits and limitation of CPR in a series of previous renal tumor clinical trials performed between 1980 and 2007 by the International Pediatric Oncology Society (SIOP), German Pediatric Oncology Hematology, and UK Children Study Group. The diagnostic differences between institutional pathologist and CPR ranged from 17% of cases in SIOP9 to 3.5% of cases in the United Kingdom Wilms Tumour (UKWT) trial, while the discrepancies in staging of examined tumors ranged from 3.8% in SIOP UK 2001 to 17% in the UKWT3 trials.…”