Central pathology review with two-stage quality assurance for pathological response after neoadjuvant chemotherapy in the ARTemis Trial

Thomas, Jeremy; Provenzano, Elena; Hiller, Louise; Dunn, Janet A.; Blenkinsop, Clare; Grybowicz, Louise; Vallier, Anne-Laure; Gounaris, Ioannis; Abraham, Jean; Hughes-Davies, Luke; McAdam, Karen; Chan, Sy; Ahmad, Rizvana; Hickish, Tamas; Houston, Stephen; Rea, Daniel; Caldas, Carlos; Bartlett, John M.S.; Cameron, David; Hayward, Richard L; Earl, Helena

doi:10.1038/modpathol.2017.30

Cited by 16 publications

(17 citation statements)

References 17 publications

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“…The primary endpoint was pCR (absence of invasive cancer in both the breast and lymph nodes). Here, whether a pCR had occurred was either determined based on central pathology review or, where central review was not possible, on histopathology reports [ 6 ]. Details of eligibility and follow-up procedures are provided in the main trial report [ 4 ].…”

Section: Methodsmentioning

confidence: 99%

Lymphocyte density determined by computational pathology validated as a predictor of response to neoadjuvant chemotherapy in breast cancer: secondary analysis of the ARTemis trial

et al. 2017

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BackgroundWe have previously shown lymphocyte density, measured using computational pathology, is associated with pathological complete response (pCR) in breast cancer. The clinical validity of this finding in independent studies, among patients receiving different chemotherapy, is unknown.Patients and methodsThe ARTemis trial randomly assigned 800 women with early stage breast cancer between May 2009 and January 2013 to three cycles of docetaxel, followed by three cycles of fluorouracil, epirubicin and cyclophosphamide once every 21 days with or without four cycles of bevacizumab. The primary endpoint was pCR (absence of invasive cancer in the breast and lymph nodes). We quantified lymphocyte density within haematoxylin and eosin (H&E) whole slide images using our previously described computational pathology approach: for every detected lymphocyte the average distance to the nearest 50 lymphocytes was calculated and the density derived from this statistic. We analyzed both pre-treatment biopsies and post-treatment surgical samples of the tumour bed.ResultsOf the 781 patients originally included in the primary endpoint analysis of the trial, 609 (78%) were included for baseline lymphocyte density analyses and a subset of 383 (49% of 781) for analyses of change in lymphocyte density. The main reason for loss of patients was the availability of digitized whole slide images. Pre-treatment lymphocyte density modelled as a continuous variable was associated with pCR on univariate analysis (odds ratio [OR], 2.92; 95% CI, 1.78–4.85; P < 0.001) and after adjustment for clinical covariates (OR, 2.13; 95% CI, 1.24–3.67; P = 0.006). Increased pre- to post-treatment lymphocyte density showed an independent inverse association with pCR (adjusted OR, 0.1; 95% CI, 0.033–0.31; P < 0.001).ConclusionsLymphocyte density in pre-treatment biopsies was validated as an independent predictor of pCR in breast cancer. Computational pathology is emerging as a viable and objective means of identifying predictive biomarkers for cancer patients.ClinicalTrials.govNCT01093235.

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Section: Methodsmentioning

confidence: 99%

Lymphocyte density determined by computational pathology validated as a predictor of response to neoadjuvant chemotherapy in breast cancer: secondary analysis of the ARTemis trial

et al. 2017

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“…There is also a lack of precise definitions on the degree of pathologic response, including major pathologic response (MPR) or complete pathologic response (CPR). In other cancers such as osteosarcoma [1][2][3] and breast, [4][5][6][7][8] colorectal, [9][10][11] and esophageal carcinomas, 12,13 there have been multiple studies investigating pathologic assessment of the effects of neoadjuvant therapy, including some detailed recommendations on how to handle these specimens. [14][15][16][17] A comprehensive mapping approach to gross and histologic processing of osteosarcomas after induction therapy has been used for over 40 years.…”

Section: Introductionmentioning

confidence: 99%

IASLC Multidisciplinary Recommendations for Pathologic Assessment of Lung Cancer Resection Specimens After Neoadjuvant Therapy

Travis

Đačić

Wistuba

et al. 2020

Journal of Thoracic Oncology

255

234

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Currently, there is no established guidance on how to process and evaluate resected lung cancer specimens after neoadjuvant therapy in the setting of clinical trials and clinical practice. There is also a lack of precise definitions on the degree of pathologic response, including major pathologic response or complete pathologic response. For other cancers such as osteosarcoma and colorectal, breast, and

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“…Whilst early clinical trials showed a drop in proportion of cases classified as pCR following central histology review compared with local reports (90), our own experience with the ARTEMIS trial showed excellent agreement between source laboratory reports and central review with respect to pCR (91). However, in an audit of local pathology reports as part of the trial, only 45% of reports included an assessment of tumour response in the breast, dropping to 30% for response in the axillary lymph nodes (92).…”

Section: Assessing Responsementioning

confidence: 85%

“…The RCB is presently the most widely used system and will be described in more detail; it has been well validated, is simple and reproducible (91,102,103), and shows a strong association with survival outcomes across all molecular subtypes. As a result the RCB has been incorporated in the soon to be released International Collaboration on Cancer Reporting (ICCR) minimum dataset for breast pathology reporting post NACT.…”

Section: Residual Cancer Burdenmentioning

confidence: 99%

Neoadjuvant Chemotherapy for Breast Cancer: Moving Beyond Pathological Complete Response in the Molecular Age

Provenzano

2021

ama

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This review focuses on neoadjuvant chemotherapy for breast cancer which introduces practical issues for pathologists, including predicting response, optimising specimen handling, size measurement and assessment of residual disease, and recent advances in management of the axilla. The role of neoadjuvant chemotherapy in breast cancer is increasing, and it has become standard of care for high risk Human Epidermal Growth Factor Receptor 2 positive and triple negative breast cancers. The benefits of the neoadjuvant approach extend beyond pathological complete response to tumour downstaging permitting conservative surgi- cal options in the breast and axilla, and assessment of response provides valuable prognostic information to enable escalation and de-escalation of adjuvant therapy to optimise oncological outcomes. Hence histopathologists play a vital role in patient management in the neoadjuvant setting. Optimal patient selection for neoadjuvant chemotherapy requires consideration of pre- treatment histopathological and molecular tumour characteristics. Post chemotherapy, tumour staging can be challenging, and changes in criteria for measurement of primary tumour and metastases in the 7th and 8th editions of the TNM have led to confu- sion amongst pathologists. This review offers practical guidance on specimen handling and measurement of lesion size. Mov- ing forwards more detailed information on degree of response will be required for adjuvant therapy decision making, and the Residual Cancer Burden is emerging as the preferred method for quantifying residual disease not just within clinical trials but in routine practice. Recent advances in management of the axilla are discussed, including the significance of minimal residual disease in the form of isolated tumour cells and micrometastases which portend a worse prognosis in the neoadjuvant setting.Conclusion. Neoadjuvant chemotherapy now forms part of routine breast cancer management, and detailed histopathological assessment and an understanding of the importance of molecular tumour biology is essential for clinical decision making.

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Central pathology review with two-stage quality assurance for pathological response after neoadjuvant chemotherapy in the ARTemis Trial

Cited by 16 publications

References 17 publications

Lymphocyte density determined by computational pathology validated as a predictor of response to neoadjuvant chemotherapy in breast cancer: secondary analysis of the ARTemis trial

Lymphocyte density determined by computational pathology validated as a predictor of response to neoadjuvant chemotherapy in breast cancer: secondary analysis of the ARTemis trial

IASLC Multidisciplinary Recommendations for Pathologic Assessment of Lung Cancer Resection Specimens After Neoadjuvant Therapy

Neoadjuvant Chemotherapy for Breast Cancer: Moving Beyond Pathological Complete Response in the Molecular Age

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