The most important part of an Oncology trial is the assessment of tumor lesion and disease responses throughout the study. There are some specific domains in Study Data Tabulation Model Implementation Guide (SDTM IG) which contains all the information regarding the tumor. They are tumor identification domain (TU), tumor results domain (TR) and disease response domain (RS). TU domain contains the information about tumor identification. Each identified lesion is assessed at subsequent visits and these measurements will be captured in the TR domain. From this information, the investigator evaluates the disease response and it is captured in RS domain.
The SDTM domains for Oncology were introduced in SDTMIG v3.1.3. A tumor lesion will be measured only if it is large enough to be measurable. If not, the presence of tumor lesion will be assessed at baseline and in subsequent visits it is measured qualitatively (decreased in size, increased in size, no change). The disease response is assessed using these measurements.
TU Domain
TU domain is used to represent the identification of the tumor. Tumors are usually identified in the baseline visit using some of the methods like MRI Scan, CT Scan or PET Scan. This information is mapped into TUMETHOD variable and anatomic location(TULOC), Laterality(TULAT), Directionality(TUDIR) are also mapped into SDTM database. Each record in the TU domain corresponds to a unique identification of the tumor. TUORRES will be used to capture the result, VISIT variable will be used to represents the corresponding visit and TUDTC is used to capture the date on which the scan in done. The tumor identified in the baseline is measured at each subsequent visit and it is captured in TR domain. In order to link the identified tumors in TU domain to the corresponding measurement results in the TR domain, TULNKID/TRLNKID variable is used.
| USUBJID | TULNKID | TUTESTCD | TUTEST | TUORRES | TULOC | TUMETHOD | VISIT | TUDTC |
| 101 | T01 | TUMIDENT | Tumor Identification | TARGET | CHEST | CT SCAN | Screening | 2018-01-02 |
| 102 | NT02 | TUMIDENT | Tumor Identification | NON-TARGET | LUNG | MRI SCAN | Screening | 2018-01-02 |
| 101 | NEW01 | TUMIDENT | Tumor Identification | NEW | LYMPH NODE | CT SCAN | Visit 2 | 2018-01-08 |
Target lesions are lesions that have been specifically measured. Non-target lesions are lesions whose presences have been noted, but whose measurements have not been taken.
In some cases, post-baseline information might be included in TU domain. In the above table, a new lesion was identified in the lymph node on Visit 2 by using a spiral CT SCAN which was done on 8th of January 2018.
TR Domain
The quantitative/qualitative assessment for each tumor identified in the TU domain is represented in the TR domain at each subsequent visits. For consistency purpose, the same method that is used for the tumor identification is used across all the visits for tumor measurements. So Ideally TUMETHOD/TRMETHOD is similar for a particular lesion throughout the study.
Since Non Target lesions are not measurable, a qualitative representation is used in the result in TR domain. The representation of TU and TR domain for Non Target Lesion, Target Lesion and New Lesion are represented below.
Non Target lesion:
| USUBJID | TULNKID | TUTESTCD | TUTEST | TUORRES | TULOC | TUMETHOD | VISIT | TUDTC |
| 101 | NT01 | TUMIDENT | Tumor Identification | NON-TARGET | CHEST | CT SCAN | Screening | 2018-01-02 |
| USUBJID | TRLNKID | TRTESTCD | TRTEST | TRORRES | TRMETHOD | TREVAL | VISIT | TRDTC |
| 101 | NT01 | LESSTAT | Lesion Status | No Change | CT SCAN | INVESTIGATOR | VISIT 1 | 2018-01-06 |
| 101 | NT01 | LESSTAT | Lesion Status | Decreased in Size | CT SCAN | INVESTIGATOR | VISIT 2 | 2018-01-08 |
| 101 | NT01 | LESSTAT | Lesion Status | Increased in Size | CT SCAN | INVESTIGATOR | VISIT 3 | 2018-01-10 |
Target Lesion:
| USUBJID | TULNKID | TUTESTCD | TUTEST | TUORRES | TULOC | TUMETHOD | VISIT | TUDTC |
| 101 | T01 | TUMIDENT | Tumor Identification | TARGET | CHEST | CT SCAN | Screening | 2018-01-02 |
| USUBJID | TRLNKID | TRTESTCD | TRTEST | TRORRES | TRORRES | TRMETHOD | VISIT | TRDTC |
| 101 | T01 | SAXIS | Short Axis | 7 | mm | CT SCAN | Screening | 2018-01-02 |
| 101 | T01 | LDIAM | Longest Diameter | 9 | mm | CT SCAN | Screening | 2018-01-02 |
| 101 | T01 | SAXIS | Short Axis | 8 | mm | CT SCAN | VISIT 1 | 2018-01-08 |
| 101 | T01 | LDIAM | Longest Diameter | 9 | mm | CT SCAN | VISIT 1 | 2018-01-08 |
| 101 | T01 | SAXIS | Short Axis | 5 | mm | CT SCAN | VISIT 2 | 2018-01-10 |
| 101 | T01 | LDIAM | Longest Diameter | 8 | mm | CT SCAN | VISIT 2 | 2018-01-10 |
New Lesion:
| USUBJID | TULNKID | TUTESTCD | TUTEST | TUORRES | TULOC | TUMETHOD | VISIT | TUDTC |
| 101 | NEW01 | TUMIDENT | Tumor Identification | NEW | CHEST | CT SCAN | Visit 3 | 2018-01-12 |
| USUBJID | TRLNKID | TRTESTCD | TRTEST | TRORRES | TRORRES | TRMETHOD | VISIT | TRDTC |
| 101 | NEW01 | SAXIS | Short Axis | 7 | mm | CT SCAN | Visit 3 | 2018-01-12 |
| 101 | NEW01 | LDIAM | Longest Diameter | 9 | mm | CT SCAN | Visit 3 | 2018-01-12 |
| 101 | NEW01 | SAXIS | Short Axis | 5 | mm | CT SCAN | Visit 4 | 2018-01-14 |
| 101 | NEW01 | LDIAM | Longest Diameter | 8 | mm | CT SCAN | Visit 4 | 2018-01-14 |
RS Domain
RS domain contains the information about response evaluation. This evaluation is based on all the available information for that subject and not restricted to TR domain alone. LB, VS, PE datasets are also can be used as an input to derive RS dataset. Variable like RSLNKID, RSLNKGRP can be used to link the RS domain with the other domains. RSTEST and RSTESTCD can be used to categorize the response assessments like Target Lesion Response, Non Target Lesion Response and New Lesion Response. The response result for each type of lesion in a particular Visit is captured in RSORRES variable. RSLNKGRP variable can be used to identify the type of lesion in a particular visit. RSLNKGRP variable is usually created by concatenating type of lesion with the corresponding visit number since the response is not derived based on Individual lesion. RSCAT usually contains the standardized response criteria used in the study.
| USUBJID | RSLNKGRP | RSTESTCD | RSTEST | RSCAT | RSORRES | VISITNUM | VISIT | RSDTC |
| 101 | T-3 | TRGRESP | Target Response | RECIST 1.1 | Partial Response | 3 | Visit 3 | 2018-01-12 |
| 101 | T-3 | NTRGRESP | Non-target Response | RECIST 1.1 | Stable Disease | 3 | Visit 3 | 2018-01-12 |
| 101 | T-4 | TRGRESP | Target Response | RECIST 1.1 | Complete Response | 4 | Visit 4 | 2018-01-14 |
| 101 | T-4 | NTRGRESP | Non-target Response | RECIST 1.1 | Progressive Disease | 4 | Visit 4 | 2018-01-14 |
The below section describes the definitions of criteria used to determine objective tumor response for target and non target lesion as per RECIST v1.1.
Target Lesion:
| Complete Response(CR) | Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm |
| Partial Response (PR) | At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. |
| Progressive Disease (PD) | At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression). |
| Stable Disease (SD) | Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study |
Non Target Lesion:
| Complete Response (CR) | Disappearance of all non-target lesions and normalisation of tumour marker level. All lymph nodes must be non-pathological in size (<10 mm short axis) |
| Non-CR/Non-PD | Persistence of one or more non-target lesion(s) and/or maintenance of tumour marker level above the normal limits. |
| Progressive Disease (PD) | Unequivocal progression (see comments below) of existing non-target lesions. (Note: the appearance of one or more new lesions is also considered progression). Appearance of one or more new lesions is also considered progression). |
The main challenge that we will face while developing oncology specific domains are Splitting/Merging of tumors.
Splitting of Tumors
Merging of Tumors
In the below example, the Target lesion with lesion number 04 has been splitted into 2 lesions and lesion 02 and 03 has been merged to a single lesion during the course of study. The SDTM mapping for TU and TR domain in this scenario is illustrated below.
TU Domain :
| USUBJID | TUGRPID | TULNKID | TUTESTCD | TUTEST | TUORRES | TUMETHOD | VISIT | TUDTC |
| 101 | T04 | T04.1 | TUSPLIT | Tumor Split | TARGET | CT SCAN | Visit 2 | 2018-01-02 |
| 101 | T04 | T04.2 | TUSPLIT | Tumor Split | TARGET | CT SCAN | Visit 2 | 2018-01-02 |
| 101 | T02/T03 | T02/T03 | TUMERGE | Tumor Merged | TARGET | CT SCAN | Visit 2 | 2018-01-02 |
TR Domain:
| USUBJID | TRGRPID | TRLNKID | TRTESTCD | TRTEST | TRORRES | TRORRESU | TRSTAT | TRREASND |
| 101 | T04 | T04 | LDIAM | Longest Diameter | NOT DONE | Tumor Split | ||
| 101 | T04 | T04.1 | LDIAM | Longest Diameter | 9 | mm | ||
| 101 | T04 | T04.2 | LDIAM | Longest Diameter | 8 | mm | ||
| 101 | T02/T03 | T02 | LDIAM | Longest Diameter | NOT DONE | Tumor Merged | ||
| 101 | T02/T03 | T03 | LDIAM | Longest Diameter | NOT DONE | Tumor Merged | ||
| 101 | T02/T03 | T02/T03 | LDIAM | Longest Diameter | 20 | mm |
The Oncology area continues to develop, and more is expected as companies begin to explore combination treatments that will definitely make this therapies more effective. However, the focus of this feature will not be on these types of immunotherapies – much has already been written on them – but on the next wave of treatments coming through, potential treatments of the future and of progress that still needs to be made in certain areas. As tumour definitions become more granular, and treatments more specific and personalised, a new array of challenges are coming into view, central to which is evolving the clinical trial process, while remaining cost-effective.
