A Novel Histopathological Evaluation Method Predicting the Outcome of Non-small Cell Lung Cancer Treated by Neoadjuvant Therapy: The Prognostic Importance of the Area of Residual Tumor

Yamane, Yuki; Ishii, Genichiro; Goto, Kōichi; Kojima, Masaru; Nakao, Masayuki; Shimada, Yoshihisa; Nishiwaki, Yutaka; Nagai, Kanji; Kohrogi, Hirotsugu; Ochiai, Atsushi

doi:10.1097/jto.0b013e3181c0a1f8

Cited by 52 publications

(44 citation statements)

References 24 publications

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“…According to the previous studies [19,22], the percentage of viable tumor cells predicted better OS and DFS in NSCLC patients treated with neoadjuvant CTx even when pathologic stage was controlled. In another study, smaller area of residual tumor had correlation with better OS, also consistent with our study result [16].…”

Section: Commentsupporting

confidence: 93%

“…For patients receiving neoadjuvant chemotherapy (CTx) or CCRT for locally advanced NSCLC, there is abundant information on histopathologic factors establishing their role in the prediction of tumor response and patient survival [6,7,[10][11][12][13][14][15][16][17][18][19]. In contrast, the predictive value of imaging factors after neoadjuvant therapy for patients' OS and recurrence is still controversial and has been discussed in only a few studies [20][21][22].…”

Section: Introductionmentioning

confidence: 95%

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Predictive factors for survival in stage IIIA N2 NSCLC patients treated with neoadjuvant CCRT followed by surgery

Lim

Lee

et al. 2014

Cancer Chemother Pharmacol

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Section: Commentsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 95%

Predictive factors for survival in stage IIIA N2 NSCLC patients treated with neoadjuvant CCRT followed by surgery

Lim

Lee

et al. 2014

Cancer Chemother Pharmacol

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“…When absolute OPN and GTV values were evaluated in multivariate an analysis, we found baseline OPN (t0) and GTV1 before RT as well as OPN at the end of RT (t1) and GTV2 (after 40 Gy) to be independent predictors of OS in different prognostic models. These results amend current literature such as the work of Yamane et al (25) who reported residual tumor volume after neoadjuvant chemotherapy of NSCLC to be prognostic, contrasting the results of Koo et al (14) who did not find a prognostic significance of post-RT GTV in the CCRT of NSCLC.…”

Section: Opn T0 To T1 ----------------------------------------------contrasting

confidence: 57%

The relationship between tumor volume changes and serial plasma osteopontin detection during radical radiotherapy of non-small-cell lung cancer

et al. 2016

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Abstract. The prognostic quality of increased osteopontin (OPN) plasma levels has been demonstrated for the chemotherapy and surgery of lung cancer. There is also evidence in the literature that tumor volume impacts prognosis in definitive radiotherapy (RT) of (lung) cancer. We previously demonstrated that elevated plasma levels of OPN before, and increasing OPN plasma levels after RT significantly correlate with survival and outcome after curative-intent RT of non-small-cell lung cancer (NSCLC). Tumor volume was also associated with prognosis. The present prospective clinical study investigated the prognostic interrelation of OPN plasma levels and tumor volume and their changes in the radical RT of NSCLC. We evaluated a subset of patients (n=27) with inoperable, non-metastasized NSCLC of the previously published patient collective. Patients were treated with radical radiochemotherapy (2 Gy ad 66 Gy). OPN plasma concentrations were determined by ELISA before (t0), at the end (t1), and 4 weeks after RT (t2). GTV was delineated PET-and CT-correlated before RT (GTV1) and after 40 Gy (GTV2). The course of OPN during and after RT and the change of GTV during RT was monitored over time and correlated with prognosis. Median GTV2 after 40 Gy (63 ml) was significantly lower than pre-RT GTV1 (90 ml, P<0.0001). Median OPN before (t0), at the end of (t1) and four weeks after RT (t2) was 846, 777 and 624 ng/ml and not significantly different. GTV significantly declined by 39 ml during RT (P<0.0001) and OPN non-significantly decreased by 56 ng/ml during (t0 to t1) and by 54 ng/ml after RT (t1 to t2). No correlations were determined between absolute OPN and GTV values or their relative changes during RT. In univariate analysis, only GTV2 significantly predicted overall survival (OS, P=0.03). In multivariate analysis, both OPN t1 (P<0.001) and GTV2 (P= 0.001) remained significant predictors of OS. Relative OPN plasma level changes after (t1 to t2) and GTV changes during RT (GTV 1 to GTV 2) significantly predicted OS (P=0.02). The combination of absolute GTV values before RT (GTV1) and GTV changes during RT (GTV1 to 2) were significantly associated with OS in both uni-and multivariate analysis (P=0.03). The combination of absolute OPN plasma levels and their changes with GTV and its changes did not reach statistical significance. The lack of a significant correlation between OPN and GTV together with the finding that OPN and GTV remained independent predictors of survival outcome but were not associated with OS in combination supports the hypothesis that tumor volume (GTV) and OPN plasma levels (both their changes and absolute values) are not interrelated in terms of prognosis but do possess each parameter separately, a prognostic quality in the radical RT of NSCLC which justifies further prospective studies to validate these results.

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“…11 Several small studies have suggested that the degree of tumor regression after neoadjuvant therapy as determined by histopathologic findings in the resected tumor may be a more objective criterion of chemotherapy response (Table 4). 12–15 Our data on 192 patients with NSCLC treated with neoadjuvant chemotherapy suggest that the percentage of viable tumor cells does indeed predict OS even when controlled for pathologic stage. Importantly, in patients who are not treated with neoadjuvant chemotherapy (Table 2), the percentage of viable tumor cells is not predictive of OS.…”

Section: Discussionmentioning

confidence: 92%

Histopathologic Response Criteria Predict Survival of Patients with Resected Lung Cancer After Neoadjuvant Chemotherapy

Pataer

Kalhor

Correa

et al. 2012

Journal of Thoracic Oncology

305

303

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Introduction We evaluated the ability of histopathologic response criteria to predict overall survival (OS) and disease-free survival (DFS) in patients with surgically resected non-small cell lung cancer (NSCLC) treated with or without neoadjuvant chemotherapy. Methods Tissue specimens from 358 patients with NSCLC were evaluated by pathologists blinded to the patient treatment and outcome. The surgical specimens were reviewed for various histopathologic features in the tumor including percentage of residual viable tumor cells, necrosis, and fibrosis. The relationship between the histopathologic findings and OS was assessed. Results The percentage of residual viable tumor cells and surgical pathologic stage were associated with OS and DFS in 192 patients with NSCLC receiving neoadjuvant chemotherapy in multivariate analysis (p = 0.005 and p = 0.01, respectively). There was no association of OS or DFS with percentage of viable tumor cells in 166 patients with NSCLC who did not receive neoadjuvant chemotherapy (p = 0.31 and p = 0.45, respectively). Long-term OS and DFS were significantly prolonged in patients who had ≤10% viable tumor compared with patients with >10% viable tumor cells (5 years OS, 85% versus 40%, p < 0.0001 and 5 years DFS, 78% versus 35%, p < 0.001). Conclusion The percentages of residual viable tumor cells predict OS and DFS in patients with resected NSCLC after neoadjuvant chemotherapy even when controlled for pathologic stage. Histopathologic assessment of resected specimens after neoadjuvant chemotherapy could potentially have a role in addition to pathologic stage in assessing prognosis, chemotherapy response, and the need for additional adjuvant therapies.

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A Novel Histopathological Evaluation Method Predicting the Outcome of Non-small Cell Lung Cancer Treated by Neoadjuvant Therapy: The Prognostic Importance of the Area of Residual Tumor

Abstract: Smaller ART and p (-) predict a better outcome of NSCLC treated by neoadjuvant therapy. We concluded that ART is a novel histopathological evaluation method for predicting the outcome of NSCLC treated by neoadjuvant therapy.

Cited by 52 publications

References 24 publications

Predictive factors for survival in stage IIIA N2 NSCLC patients treated with neoadjuvant CCRT followed by surgery

Predictive factors for survival in stage IIIA N2 NSCLC patients treated with neoadjuvant CCRT followed by surgery

The relationship between tumor volume changes and serial plasma osteopontin detection during radical radiotherapy of non-small-cell lung cancer

Histopathologic Response Criteria Predict Survival of Patients with Resected Lung Cancer After Neoadjuvant Chemotherapy

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