Initial clinical trials of the subrenal capsule assay as a predictor of tumor response to chemotherapy

e12605 Background: Triple-negative breast cancer (TNBC) is a heterogeneous subtype of breast cancer (BC) characterized by the absence of targetable receptors. Traditionally, neoadjuvant chemotherapy (NACT) has been used to downstage the tumors and increase the chance for breast-conserving surgery. The pathological complete response (pCR) has been traditionally considering the best predictive marker for the disease recurrence. Patients with residual disease (RD) have a poor prognosis with a high risk of recurrence, and therefore additional chemotherapy was recommended. Therefore it is an important task for clinical researchers to identify markers to predict the individual tumor response to chemotherapy and avoid in patients potentially resistant tumors. Instead, a surgical approach can be used or combined approach with chemotherapy and immunotherapy. It is not clear yet which approach is optimal for those patients with chemotherapy-resistant tumors since there is no clinical data available and no clinical tool that helps predict the individual tumor response. In this study, we examined breast ultrasound(US) images of patients before and after the completion of NACT and correlated with response to chemotherapy. To better understand the biology of resistance to chemotherapy, we also analyzed the gene expression profile of 15 patients with RD after NACT. Methods: In this study, we retrospective analyzed breast US data from 37 Hispanic patients diagnosed with TNBC and treated with NACT. Patients underwent breast US before and after NACT with documentation of clinical complete response (cCR) or clinical residual disease (cRD). Post-operatively, the pathologic response was defined as the absence of tumor cells (pCR) or presence of residual invasive tumor (RD). A multivariable logistic regression model assessed the influence of patient- and tumor-associated covariates as predictors for pCR. Also, we analyzed formalin-fixed paraffin-embedded tumor samples from 15 patients with RD after NACT. Results: Seventeen patients (45.9%) achieved pCR, and twenty (54.1%) had RD after NACT. The most common US findings connected with RD was the deposition of calcium before NACT six (30%) patients. Gene expression analysis of RD samples identified 446 upregulated and 275 downregulated genes. Among commonly upregulated genes related to cancer, we identified GLI1, IGF1, SERPINE1, ATF3, KLK 5; 7, and TUBB2b, and genes belonging to pathways encoding extracellular matrix–related proteins, DNA-damage response proteins, and pathways related to resistance to chemotherapeutic agents such as Taxol. Conclusions: Our data suggested that gene expression profiling in combination with imaging study can be used to identify patients with TNBC potentially resistant to chemotherapy.

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Prognostic significance of surgery after chemotherapy in patients with type 4 gastric cancer

10.21203/rs.3.rs-39822/v1 ◽

2020 ◽

Author(s):

Takaaki Arigami ◽

Daisuke Matsushita ◽

Keishi Okubo ◽

Takako Tanaka ◽

Ken Sasaki ◽

...

Keyword(s):

Gastric Cancer ◽

Multivariate Analysis ◽

Tumor Response ◽

Prognostic Significance ◽

Distant Metastases ◽

Clinical Indication ◽

R0 Resection ◽

Prognostic Impact ◽

Chemotherapeutic Regimen ◽

Response To Chemotherapy

Abstract Background The majority of patients with type 4 gastric cancer have distant metastases with extremely poor prognosis. Consequently, considering a therapeutic strategy that improves the prognosis of these patients is clinically important. The present study aimed to assess the clinical indication and prognostic impact of surgery in patients with type 4 gastric cancer who underwent chemotherapy. Methods A total of 67 patients with type 4 gastric cancer who underwent chemotherapy were retrospectively enrolled. All patients were grouped into progressive disease (PD) and non-PD groups by tumor response to chemotherapy. Results Distant metastases occurred in 58 patients. With regard to tumor response, 16 and 51 patients had PD and non-PD, respectively. The prognosis was significantly poorer in patients with PD than in those with non-PD (p < 0.0001). Among 23 patients who underwent surgery after chemotherapy, 21 had a R0 resection. The presence or absence of surgery was significantly correlated with age, first-line chemotherapeutic regimen, lymph node metastasis, clinical stage, number of distant metastatic sites, peritoneal dissemination, and tumor response (p = 0.0412, p = 0.0096, p = 0.0024, p = 0.0059, p = 0.0128, and p = 0.0020, and p = 0.0066, respectively). Multivariate analysis selected tumor response and surgery as an independent prognostic factor (p = 0.0001 and p = 0.0009, respectively). Moreover, multivariate analysis for the surgery group demonstrated that metastatic nodal status (N0-1 vs N2-3) and residual tumor status (R0 vs R1-2) were significant independent prognostic factors (p = 0.0258 and p = 0.0458, respectively). Conclusion Our retrospective study suggests that surgery after chemotherapy for type 4 gastric cancer may improve the prognosis of responders with N0-1 status and a curative R0 resection.

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The subrenal capsule assay (SRCA) in nude mice, immunocompetent and pre-irradiated normal mice

Journal of Cancer Research and Clinical Oncology ◽

10.1007/bf02579976 ◽

1986 ◽

Vol 111 (S1) ◽

pp. S52-S52

Author(s):

H. Weigeldt ◽

H. H. Fiebig ◽

C. Schuchhardt ◽

U. Dentler ◽

G. W. Löhr

Keyword(s):

Nude Mice ◽

Subrenal Capsule Assay ◽

Subrenal Capsule

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