TY - JOUR
T1 - Controversies and challenges in the pathologic examination of lung resection specimens after neoadjuvant treatment
AU - Weissferdt, Annikka
AU - Pataer, Apar
AU - Swisher, Stephen G.
AU - Heymach, John V.
AU - Gibbons, Don L.
AU - Cascone, Tina
AU - Sepesi, Boris
N1 - Funding Information:
Support for the study was partially provided by Bristol-Myers Squibb , the Lung SPORE grant 5 P50 CA070907 , the P30 CA016672 MD Anderson Cancer Center Support Grant, and the Conquer Cancer Foundation of the American Society of Clinical Oncology Career Development Award 2018 . The study was also partially supported by the generous philanthropic contributions to the University of Texas MD Anderson Cancer Center Lung Cancer Moon Shot Program, the University of Texas MD Anderson Cancer Center Khalifa Scholars Program (from Khalifa Bin Zayed Al Nahyan Foundation), the University of Texas MD Anderson Cancer Center Physician Scientist Program, the TJ Martell Foundation, the Bob Mayberry Foundation, the Gil and Dody Weaver Foundation and Bill and Katie Weaver Charitable Trust.
Funding Information:
Support for the study was partially provided by Bristol-Myers Squibb, the Lung SPORE grant 5 P50 CA070907, the P30 CA016672MD Anderson Cancer Center Support Grant, and the Conquer Cancer Foundation of the American Society of Clinical Oncology Career Development Award 2018. The study was also partially supported by the generous philanthropic contributions to the University of Texas MD Anderson Cancer Center Lung Cancer Moon Shot Program, the University of Texas MD Anderson Cancer Center Khalifa Scholars Program (from Khalifa Bin Zayed Al Nahyan Foundation), the University of Texas MD Anderson Cancer Center Physician Scientist Program, the TJ Martell Foundation, the Bob Mayberry Foundation, the Gil and Dody Weaver Foundation and Bill and Katie Weaver Charitable Trust.
Publisher Copyright:
© 2021 Elsevier B.V.
PY - 2021/4
Y1 - 2021/4
N2 - New therapy approaches in the treatment of surgically resectable non-small cell lung cancer (NSCLC) challenge the traditional handling and examination of pathology specimens. The increasingly common use of neoadjuvant therapies before surgical resection, due to advantages in novel drug administration, tolerance, and measurement of radiographic and pathologic response compared to adjuvant treatment, has the potential to alter the microscopic tumor appearance and its biology. Currently, many clinical trials use pathologic response as a surrogate endpoint of clinical efficacy, since the extent of residual viable tumor appears to correlate with outcome in patients treated with neoadjuvant chemotherapy. Consequently, pathologic assessment of the extent of residual viable tumor is of paramount importance. However, high level evidence-based guidelines on how to process and evaluate such specimens are lacking. Moreover, while pathologic response has been shown to be associated with survival after chemotherapy, its significance after immunotherapy remains to be determined. Additionally, many clinical trials do not routinely include pathologists in trial design, which may lead to non-standardized evaluation of pathologic response. Although recently, several algorithms have been proposed to address these issues, none of them represents evidence-based recommendations or is universally applied. Therefore, controversies and challenges continue to exist, raising concerns about the validity, reproducibility, and comparability of the results of many neoadjuvant clinical trials. Herein, we discuss the current difficulties in pathologic specimen evaluation following neoadjuvant therapy in NSCLC and propose potential approaches to overcome these challenges.
AB - New therapy approaches in the treatment of surgically resectable non-small cell lung cancer (NSCLC) challenge the traditional handling and examination of pathology specimens. The increasingly common use of neoadjuvant therapies before surgical resection, due to advantages in novel drug administration, tolerance, and measurement of radiographic and pathologic response compared to adjuvant treatment, has the potential to alter the microscopic tumor appearance and its biology. Currently, many clinical trials use pathologic response as a surrogate endpoint of clinical efficacy, since the extent of residual viable tumor appears to correlate with outcome in patients treated with neoadjuvant chemotherapy. Consequently, pathologic assessment of the extent of residual viable tumor is of paramount importance. However, high level evidence-based guidelines on how to process and evaluate such specimens are lacking. Moreover, while pathologic response has been shown to be associated with survival after chemotherapy, its significance after immunotherapy remains to be determined. Additionally, many clinical trials do not routinely include pathologists in trial design, which may lead to non-standardized evaluation of pathologic response. Although recently, several algorithms have been proposed to address these issues, none of them represents evidence-based recommendations or is universally applied. Therefore, controversies and challenges continue to exist, raising concerns about the validity, reproducibility, and comparability of the results of many neoadjuvant clinical trials. Herein, we discuss the current difficulties in pathologic specimen evaluation following neoadjuvant therapy in NSCLC and propose potential approaches to overcome these challenges.
KW - Chemotherapy
KW - Immunotherapy
KW - Neoadjuvant treatment
KW - NSCLC
KW - Pathologic response
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U2 - 10.1016/j.lungcan.2021.02.014
DO - 10.1016/j.lungcan.2021.02.014
M3 - Review article
C2 - 33631448
AN - SCOPUS:85101413866
SN - 0169-5002
VL - 154
SP - 76
EP - 83
JO - Lung Cancer
JF - Lung Cancer
ER -