INTRODUCTION
Currently, 11.4% of new cancer cases and 18% of all cancer deaths are attributed to lung cancer, as per the Global Cancer Observatory ( GLOBOCAN) 2020 data.[ 1 ] The importance of a comprehensive lung cancer imaging report for the efficient management of these patients by the treating physician cannot be overemphasized. For this purpose, the Lung Cancer Reporting and Data System (LC-RADS) was proposed and published by Mahajan in 2021 in Cancer Research Statistics and Treatment.[ 2 ] In this article, we would like to build on the concept of LC-RADS by proposing two separate lung cancer imaging reporting templates based on contrast-enhanced computed tomography (CECT) or fluorodeoxyglucose positron emission tomography CT (FDG-PET/CT): Synoptic reporting template 1 on “Pre-treatment Lung Cancer Imaging - Reporting and Data System (LCI-RADS),” and Synoptic reporting template 2 on “Post-therapy Lung Cancer Imaging - Reporting and Data System (pLCI-RADS)” [Figures 1 and 2 ]. We believe that implementation of these two synoptic reporting templates will positively influence patient management.
Figure 1: Synoptic reporting format 1 on Pre-treatment Lung Cancer Imaging - Reporting and Data System (LCI-RADS) based on CECT or FDG-PET/CT. CECT: Contrast Enhanced Computed Tomography, FDG-PET/CT: Fluorodeoxyglucose Positron Emission Tomography Computed Tomography, RIS: Radiology Information System, DICOM: Digital Imaging and Communications in Medicine, COPD: Chronic Obstructive Pulmonary Disease, EGFR: Epidermal growth factor receptor, ALK: Anaplastic lymphoma kinase, BRAF: v-Raf murine sarcoma viral oncogene homolog B, NTRK: Neurotrophic tyrosine receptor kinase, ROS1: ROS proto-oncogene 1, KRAS: Kirsten rat sarcoma virus, MET: mesenchymal-epithelial transition, RET: rearranged during transfection, PD-L1: programmed death ligand-1, SUV max: Maximum Standardized Uptake Value, TNM: Tumor Node Metastasis, MRI: Magnetic Resonance Imaging, SCLC: Small cell lung cancer
Figure 2: Synoptic reporting format 2 on Post-therapy Lung Cancer Imaging - Reporting and Data System (pLCI-RADS) based on CECT or FDG-PET/CT. CECT: Contrast Enhanced Computed Tomography, FDG-PET/CT: Fluorodeoxyglucose Positron Emission Tomography Computed Tomography, RIS: Radiology Information System, DICOM: Digital Imaging and Communications in Medicine, NACT: Neoadjuvant Chemotherapy, SUV peak: Standardized uptake value corrected for lean body mass, FNA: Fine Needle Aspiration, RECIST: Response Evaluation Criteria in Solid Tumors, PERCIST: Positron Emission Tomography Response Criteria In Solid Tumors, iRECIST: Immune Response Evaluation Criteria In Solid Tumors
METHODS
The contents for this review article were obtained by performing an internet search using Google. The search terms used were “lung cancer imaging,” “AJCC staging,” “NCCN guidelines,” “CT in lung cancer,” and “post-therapy imaging”. All articles that had been published in the preceding 25 years were assessed for inclusion. All the articles that contained information relevant to our review topic were included. We excluded articles for which the full text was not available. We manually searched all the references of the selected articles. Our search strategy is depicted in a flow diagram in Figure 3 .
Figure 3: Flow diagram depicting the screening and selection process for the articles selected for inclusion in the article on the pre- and post-treatment synoptic reporting formats for lung cancer imaging
Foundation for LCI-RADS and pLCI-RADS
The 8th edition of the American Joint Committee on Cancer (AJCC) lung cancer staging, which has also been approved by the International Association for the Study of Lung Cancer (IASLC), is used for the tumor, node, metastasis (TNM) staging of lung cancer [Table 1 ].[ 3 , 4 ] LCI-RADS has been designed for reporting as per the 8th edition of the TNM staging system, incorporating the pertinent clinical/laboratory findings, and information on the molecular testing for the various genomic alterations and expressions like epidermal growth factor receptor (EGFR ) mutations, anaplastic lymphoma kinase (ALK ) gene rearrangements, v-Raf murine sarcoma viral oncogene homolog B (BRAF ) mutations, neurotrophic tyrosine receptor kinase (NTRK ) gene fusion, ROS proto-oncogene 1 (ROS1 ) rearrangements, Kirsten rat sarcoma virus (KRAS ) mutations, mesenchymal-epithelial transition (MET ) genomic alterations, rearranged during transfection (RET ) rearrangements, and programmed death ligand-1 (PD-L1) expression, as they have a bearing on the treatment options.[ 5 ] Various thoracic nodal stations, which form an integral component of the TNM stage-based reporting, have been provided in Table 2 along with their descriptors.[ 6 ] In pLCI-RADS, the disease status after surgery is recorded based on the presence or absence of residual disease/recurrence, and post-therapy changes are mentioned as per the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and the Positron Emission Tomography Response Criteria In Solid Tumors (PERCIST 1.0) on the contrast-enhanced computed tomography (CECT) and fluorodeoxyglucose positron emission tomography (FDG-PET/CT), respectively. Findings are labeled as complete response (CR), partial response (PR), progressive disease (PD), or stable disease (SD) as per RECIST 1.1; and complete metabolic response, partial metabolic response, progressive metabolic disease, or stable metabolic disease as per PERCIST 1.0.[ 7 , 8 ] In patients on immunotherapy, findings are recorded as per the Immune Response Evaluation Criteria In Solid Tumor (iRECIST)- which includes immune-related unconfirmed progressive disease (iUPD) and immune-related confirmed progressive disease (iCPD) in addition to the other RECIST 1.1 categories, to account for post-immunotherapy pseudoprogression, which requires follow-up imaging after at least 4 weeks for confirmation.[ 9 , 10 ]
Table 1: Adapted from the 8th edition American Joint Committee on Cancer (AJCC) lung cancer Tumor Node Metastasis (TNM) staging
Table 2: Thoracic nodal stations and their descriptors
Both LCI-RADS and pLCI-RADS require acute (urgent) findings to be mentioned at the beginning of the report. In the reporting template of LCI-RADS, the imaging TNM stage needs to be provided at the end of the report, whereas in pLCI-RADS, the categories of lung injury, presence or absence of residual disease, post-therapy response (as per RECIST 1.1, PERCIST 1.0, iRECIST), and follow-up recommendations need to be mentioned, for facilitating management decisions. As imaging plays a pivotal role in staging as well as assessment of post-therapy response and complications (as described subsequently), we have formulated these two synoptic reporting templates, which, we hope, will positively impact patient management.
Role of imaging in the staging of lung cancer
Non-small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC) have separate management recommendations as per the National Comprehensive Cancer Network (NCCN) and other guidelines.[ 5 , 11 , 12 ]
The CECT thorax with upper abdomen plays an important role in ascertaining the T and N categories and also in ruling out metastases to the liver and adrenal glands. The CECT provides information on the tumor location, size, and relation of the tumor to the adjacent structures. The CT also helps to plan and guide the site of the biopsy from the suspected primary tumor. Besides providing information on the frankly metastatic nodes, the CT scan helps in visualizing the indeterminate nodes that may require a biopsy. Along with staging, the CECT scan provides information on acute findings like pneumothorax or pulmonary thromboembolism. Additionally, the status of the underlying lung, for example, the presence of interstitial lung disease (ILD) or chronic obstructive pulmonary disease (COPD), which can have implications on the management decisions, is well depicted on the CT scan.
The primary role of the FDG PET/CT is to rule out distant metastasis. The PET/CT can also help plan the best site for biopsy. If the PET/CT scan reveals the presence of disease in the mediastinum, pathologic confirmation is warranted for the lymph node status.[ 5 ] The standardized uptake value (SUV) of the primary or metastatic tumor and the suspicious lymph nodes should be mentioned in the PET/CT report. In case of SCLC/combined SCLC and NSCLC, a CECT thorax with abdomen and pelvis is recommended, and a PET/CT should be performed if limited-stage disease is suspected.[ 11 ]
Contrast-enhanced magnetic resonance imaging (CEMRI) of the brain is required for patients with stages II, IIIA, and IB (optional) NSCLC as per the NCCN guidelines.[ 5 ] A CECT brain should be performed if MRI is not possible.[ 5 ] Contrast-enhanced MRI of the spine along with the brachial plexus should be performed for superior sulcus lesions abutting the spine, subclavian vessels, or brachial plexus.[ 5 ] Primary tumor/metastasis involving the vertebra may need MRI to rule out intraspinal extension, and cord and nerve root compression. The MRI thorax serves as a problem-solving tool in case of indeterminate involvement of the pericardium, great vessels, or heart on CECT. In patients with SCLC/combined SCLC and NSCLC, CEMRI brain or CECT brain, if MRI is not possible, should be performed.[ 11 ] In SCLC, MRI may be required for bone marrow imaging if the PET/CT is indeterminate.[ 11 ]
Post-therapy imaging (post-surgery/post-neoadjuvant chemotherapy [NACT]/post-chemotherapy/post-radiotherapy/post-immunotherapy/post-systemic therapy)
Response evaluation/surveillance
In NSCLC, following definitive therapy (surgery with or without chemotherapy) for stages I-II disease, CT with or without contrast may be required every 6 months for 2-3 years, followed by low-dose non-contrast-enhanced CT thorax annually.[ 5 ] For stages I-II NSCLC following definitive therapy with RT, stage III or stage IV oligometastatic disease, where treatment to all the sites has been with radical intent, CT thorax with or without contrast should be done every 3-6 months for 3 years, then every 6 months for 2 years, then a low-dose non-CECT thorax should be done annually.[ 5 ] If there is recurrence, then PET/CT and CEMRI brain are recommended.[ 5 ] For patients with SCLC receiving systemic therapy alone or sequential systemic therapy followed by radiotherapy, response assessment should be done after every two cycles of systemic therapy and at the completion of therapy by CECT thorax/abdomen/pelvis. In extensive stage SCLC with asymptomatic brain metastases on systemic therapy, CEMRI/CECT brain should be repeated after every two cycles until brain radiotherapy is commenced or systemic therapy is completed.[ 11 ] For surveillance of SCLC, CECT thorax with abdomen/pelvis should be performed every 2-6 months (more frequently in years 1-2 and less frequently thereafter).[ 11 ] Additionally, as a part of surveillance, CEMRI/CECT brain is recommended every 3-4 months during the first year, then every 6 months during the second year.
For patients on immunotherapy, if progression is noted on CECT thorax, then a repeat CECT is warranted after at least 4 weeks for confirmation of the progression and to rule out pseudoprogression.[ 9 , 10 , 13 ]
Post-treatment lung changes/injury
Post-NACT, chemoradiotherapy, and immunotherapy lung changes/injury can be categorized as hyperprogression after immunotherapy, and post-therapy acute and late changes. All of these can be visualized on a CT scan, although a definitive diagnosis may not always be possible. Hyperprogression after starting immunotherapy is seen on imaging as an increase in the tumor burden by 50% from the baseline and is associated with worse clinical outcomes.[ 13 ] In hyperprogression, there is aberrant systemic proliferation of senescent CD4-positive T cells after the first cycle of immunotherapy which mostly occurs in patients having a rapid tumor growth rate.[ 13 ] Lung injury due to chemotherapeutic agents could be either due to direct toxic effects on the lung, immunologic response, or increased capillary permeability.[ 14 ] The pathophysiologic basis for radiation-induced lung injury (RILI) could be post-radiotherapy infiltration by inflammatory cells and synthesis of reactive nitrogen and oxygen species responsible for oxidative damage of DNA and epithelial cell death.[ 14 ] Post-therapy acute changes could manifest as diffuse alveolar damage (diffuse ground glass opacity on CT), hypersensitivity pneumonitis (centrilobular ground glass density nodules on CT), organizing pneumonia pattern (peripheral ground glass opacity [GGO], consolidation, or nodules with central GGO and peripheral rim of consolidation known as reverse halo or atoll sign), or sarcoidosis-like pattern (perilymphatic nodules and mediastinal lymphadenopathy).[ 15 ] Post-radiotherapy pneumonitis (diffuse or patchy consolidation, diffuse or patchy GGO within the radiation field on CT) can also manifest in the acute stage.[ 14 , 15 ]
Fibrotic non-specific interstitial pneumonia (subpleural reticulation, architectural distortion on CT along with GGO) and findings of radiation recall pneumonitis (sharply demarcated margins of focal GGO and consolidation seen within the prior radiation field on CT, precipitated by chemotherapeutic agents) present in the late stages.[ 15 ]
CONCLUSION
Pre- and post-treatment synoptic reporting templates, LCI-RADS and pLCI-RADS, respectively, for lung cancer imaging will positively impact patient management by providing systematic, comprehensive, and relevant information to the treating physician for timely intervention. We recommend universal application of these reporting formats for effective communication between the radiologist and the treating physician.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
REFERENCES
2. Mahajan A Synoptic reporting in lung cancers using Lung Cancer Reporting and Data System (LC-RADS):The road ahead for standardization of imaging in lung cancer staging. Cancer Res Stat Treat 2021;4:61–6.
3. Lababede O, Meziane MA The Eighth Edition of TNM staging of lung cancer:Reference chart and diagrams. Oncologist 2018;23:844–8.
4. Feng SH, Yang ST The new 8
th TNM staging system of lung cancer and its potential imaging interpretation pitfalls and limitations with CT image demonstrations. Diagn Interv Radiol 2019;25:270–9.
6. El-Sherief AH, Lau CT, Wu CC, Drake RL, Abbott G F, Rice TW International Association for the study of lung cancer (IASLC) lymph node map:Radiologic review with CT illustration. RadioGraphics 2014;34:1680–91.
7. O JH, Lodge MA, Wahl RL Practical PERCIST:A simplified guide to PET response criteria in solid tumors 1.0. Radiology 2016;280:576–84.
8. Chalian H, Töre HG, Horowitz JM, Salem R, Miller FH, Yaghmai V Radiologic assessment of response to therapy:Comparison of RECIST Versions 1.1 and 1.0. Radiographics 2011;31:2093–105.
9. Chakrabarty N, Mahajan A, Baheti AD, Choudhari A, Patil V, Popat P, et al. A Radiologist's perspective on treatment-related pseudoprogression:Clues and hues. Indian J Med Paediatr Oncol 2022;43:1–8.
10. Persigehl T, Lennartz S, Schwartz LH iRECIST:How to do it. Cancer Imaging 2020;20:2.
12. Prabhash K, Vora A, Limaye S, Sahoo TP, Batra U, Patil S, et al. Treatment of advanced non-small-cell lung cancer:First line, maintenance, and second line–Indian consensus statement update (Under the aegis of Lung Cancer Consortium Asia, Indian Cooperative Oncology Network, Indian Society of Medical and Pediatric Oncology, Molecular Oncology Society, and Association of Physicians of India). Cancer Res Stat Treat 2021;4:279–314.
13. Onesti CE, Frères P, Jerusalem G Atypical patterns of response to immune checkpoint inhibitors:Interpreting pseudoprogression and hyperprogression in decision making for patients'treatment. J Thorac Dis 2019;11:35–8.
14. Albano D, Benenati M, Bruno A, Bruno F, Calandri M, Caruso D, et al. Imaging side effects and complications of chemotherapy and radiation therapy:A pictorial review from head to toe. Insights Imaging 2021;12:76.
15. Sridhar S, Kanne JP, Henry TS, Revels JW, Gotway MB, Ketai LH Medication-induced pulmonary injury:A scenario- and pattern-based approach to a perplexing problem. RadioGraphics 2021;42:38–55.
