DETECTION OF RESIDUAL LUNG CANCER CELLS BY PCR-BASED GENETIC TESTING FOR ROS1-TRANSLOCATION: CASE REPORT

2018 ◽  
Vol 64 (3) ◽  
pp. 331-334
Author(s):  
Fedor Moiseenko ◽  
Vladislav Tyurin ◽  
Nikita Levchenko ◽  
Yevgeniy Levchenko ◽  
Aglaya Ievleva ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Morphological Analysis ◽  
Pathologic Complete Response ◽  
Residual Tumor ◽  
Complete Response ◽  
Convincing Evidence ◽  
Pcr Analysis ◽  
Specific Gene ◽  
Highly Sensitive ◽  
Reliable Monitoring

A patient with lung cancer carrying ROS1 translocation was treated by crizotinib and then subjected to surgery. Morphological analysis revealed pathologic complete response in surgically removed tissues, while PCR test provided convincing evidence for the presence of residual tumor cells. PCR analysis of lung cancer specific gene translocations allows carrying out highly sensitive and reliable monitoring of tumor disease during the course of treatment.

scholarly journals Different pathologic responses to neoadjuvant anti-PD-1 in primary squamous lung cancer and regional lymph nodes

2020 ◽  
Vol 4 (1) ◽  
Author(s):  
Yun Ling ◽  
Ning Li ◽  
Lin Li ◽  
Changyuan Guo ◽  
Jiacong Wei ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Lymph Nodes ◽  
Pathologic Complete Response ◽  
Complete Response ◽  
Regional Lymph Nodes ◽  
Primary Tumors ◽  
Neoadjuvant Immunotherapy ◽  
Squamous Lung Cancer ◽  
Nsclc Patients ◽  
Residual Viable Tumor

AbstractNeoadjuvant immunotherapy provides a unique opportunity for understanding therapeutic responses. We analyzed pathologic responses in surgical specimens obtained from 31 squamous non-small cell lung cancer (NSCLC) patients receiving neoadjuvant anti-PD-1 treatment. Fifteen (48.4%) patients achieved pathologic complete response (pCR) or major pathologic response (MPR). Among them, seven (46.7%) were assessed as radiological partial response and eight (53.3%) as stable disease. Among 20 patients with pathologically identified tumor beds in lymph nodes (LNs), 10 and six patients achieved pCR/MPR in primary tumors and paired LNs, respectively. pCR was achieved in 6/19 N1 nodes and 1/7 N2 nodes. Residual viable tumor (RVT) cells in 8/9 MPR specimens had 100% immune-activated phenotype, while a median of 80% of RVT cells in pathologic nonresponse specimens presented immune-excluded/desert phenotype. These findings demonstrated that assessment of pathologic responses in both primary tumor and LNs may be important as a surrogate for assessing neoadjuvant immunotherapeutic efficacy.

Prognostic value of pathologic complete response to preoperative chemotherapy in early-stage non small cell lung cancer: Combined analysis of two IFCT randomized trials.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 7057-7057
Author(s):  
Guillaume Mouillet ◽  
Elisabeth Monnet ◽  
Bernard Milleron ◽  
Marc Puyraveau ◽  
Elisabeth Quoix ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Preoperative Chemotherapy ◽  
Early Stage ◽  
Pathologic Complete Response ◽  
Complete Response ◽  
Small Cell ◽  
Small Cell Lung ◽  
Stage Ib ◽  
Favorable Prognostic Factor

7057 Background: Our study aimed to evaluate whether pathologic complete response (pCR) in early-stage non-small cell lung cancer (NSCLC) following neoadjuvant chemotherapy resulted in improved outcome and to determine predictive factors for pCR. Methods: Eligible patients with stage IB or II NSCLC were included in two consecutive Intergroupe Francophone de Cancérologie Thoracique (IFCT) phase III trials evaluating platinum-based neoadjuvant chemotherapy, with pCR defined by the absence of viable cancer cells in the resected surgical specimen. Results: Among the 492 patients analyzed, 41 (8.3%) achieved pCR. In the pCR group, 5-year overall survival (OS) was 80.0% compared to 55.8% in the non-pCR group (p=0.0007). In multivariate analyses, pCR was a favorable prognostic factor of OS (RR=0.34; 95% CI=0.18-0.64) in addition to squamous cell carcinoma (SCC), weight loss ≤5%, and stage IB disease. Five-year disease-free survival (DFS) was 80.1% in the pCR group compared to 44.8% in the non-pCR group (p<0.0001). Two patients (4.9%) in the pCR group experienced disease recurrence compared to 193 patients (42.8%) in the non-pCR group. SCC subtype was the only independent predictor of pCR (OR=4.30; 95% CI=1.90-9.72). Conclusions: Our results showed that pCR after preoperative chemotherapy was a favorable prognostic factor in Stage IB-II NSCLC. Our study is the largest published series evaluating pCRs following preoperative chemotherapy. The only factor predictive of pCR was SCC. Identifying molecular predictive markers for pCR may help in distinguishing patients likely to benefit from neoadjuvant chemotherapy and in choosing the most adequate preoperative chemotherapy regimen.

Residual rectal cancer after preoperative radiochemotherapy (ypT1-2): An indication for local excision instead of radical surgery?

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 546-546
Author(s):  
Thilo Sprenger ◽  
Hilka Rothe ◽  
Lena-Christin Conradi ◽  
Kia Homayounfar ◽  
Tim Beissbarth ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Local Excision ◽  
Bowel Wall ◽  
Radical Surgery ◽  
Pathologic Complete Response ◽  
Residual Tumor ◽  
Complete Response ◽  
Phase Iii ◽  
Preoperative Radiochemotherapy ◽  
Cancer Trial

546 Background: Preoperative radiochemotherapy (RCT) followed by total mesorectal excision (TME) has improved local tumor control and led to a significant tumor downstaging. For patients with pathologic complete response (ypT0) as well as residual tumor restricted only to the bowel wall (ypT1-2) local excision has increasingly been discussed to avoid significant morbidity and functional deficits associated with TME. Therefore we investigated the incidence, distribution and tumor-related localization of mesorectal lymph node (LN) metastases in TME specimens with ypT0, ypT1-2 and ypT3-4 rectal cancers, respectively. Methods: TME specimens from 81 patients with locally advanced rectal cancer treated with neoadjuvant RCT within the phase III German Rectal Cancer Trial CAO/ARO/AIO-04 were evaluated. The entire mesorectal compartment was screened microscopically after complete paraffin embedding. The number and localization of all detectable LN metastases was specified in relation to the primary tumor. Results: Whereas 50 patients (62%) had ypT3-4 carcinomas after neoadjuvant RCT 20 patients (25%) presented with residual tumor within the bowel wall (ypT1-2). 11 patients (14%) had pathologic complete response (ypT0). 28 ± 13.7 LN were detected per specimen. 25 patients (31%) had residual LN metastases after RCT. Although the incidence was higher in the ypT3-4 group (40% ypN+) still 25% of patients in the ypT1-2 group had a mean number of 2.2 residual LN metastases. 55% of these metastases were located afar from the primary lesion in the proximal mesorectum. No patient with ypT0 status had residual LN metastases. Conclusions: Even in patients with good response and tumors restricted only to the bowel wall (ypT1-2) after RCT there is a considerable risk for residual LN metastases. The majority of metastases were located clearly outside the tumor region. Local excision of residual rectal cancer would be accompanied by a higher rate of local failure and radical surgery with TME should remain the standard treatment in those patients.

Association of specific gene expression profiles with a pathologic complete response to neoadjuvant therapy in esophageal adenocarcinoma.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 51-51
Author(s):  
Patrick James McLaren ◽  
Anthony P Barnes ◽  
Willy Z Terrell ◽  
Gina M. Vaccaro ◽  
Jack Wiedrick ◽  
...  
Keyword(s):  
Gene Expression ◽  
Esophageal Cancer ◽  
Neoadjuvant Therapy ◽  
Esophageal Adenocarcinoma ◽  
Expression Profiles ◽  
Pathologic Complete Response ◽  
Gene Expression Profiles ◽  
Complete Response ◽  
Specific Gene ◽  
Specific Gene Expression

51 Background: Predicting prognosis in esophageal cancer remains an unrealized goal despite studies linking constellations of genes to therapeutic response. In this study, we analyzed specific predictor genes expressed in tumor specimens from our institutional repository. Our aim was to determine if specific gene expression profiles are associated with pathologic complete response (pCR) after neoadjuvant chemo-radiotherapy (CRT). Methods: We investigated eleven genes identified from prior studies (CCL28, SPARC, S100A2, SPRR3, SIRT2, NOV, PERP, PAPSS2, DCK, DKK3, ALDH1) that have significant association with esophageal cancer progression. Patients with esophageal adenocarcinoma treated with neoadjuvant CRT followed by esophagectomy at our institution between January 2011 and July 2015 were included. Quantitative real-time polymerase chain reaction was conducted on pre-treatment biopsy specimens to determine gene expression. Patients were classified into two groups: 1) pCR and, 2) no or poor response (NR) after CRT based on final pathology report. An omnibus test using Mahalanobis distance was applied to evaluate overall genetic expression differences between groups. Log-rank tests compared the differential expression of individual genes. Results: 29 patients (11 pCR and 18 NR) were analyzed. Overall, gene expression profiles were significantly different between pCR and NR patients (p < 0.01). In particular, CCL28 was over-expressed in pCR (Log-HR: 1.53, 95%CI: 0.46-2.59, p = 0.005), and DKK3-was under-expressed in pCR patients (Log-HR: -1.03 95%CI: -1.97, -0.10, p = 0.031). Conclusions: Esophageal adenocarcinoma patients with a pCR after neoadjuvant therapy have genetic profiles that are significantly different from typical NR profiles. In our population, the genes CCL28 and DKK3 are potential predictors of treatment response.

Circulating cell-free DNA (ctDNA) assessments before, during, and after neoadjuvant therapy (NAC) in nonmetastatic inflammatory breast cancer (IBC).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e12113-e12113
Author(s):  
Carolyn S. Hall ◽  
Salyna Meas ◽  
Vanessa Nicole Sarli ◽  
Anthony Lucci
Keyword(s):  
Breast Cancer ◽  
Pathologic Complete Response ◽  
Copy Number Variants ◽  
Residual Tumor ◽  
Complete Response ◽  
Single Nucleotide Variants ◽  
Single Nucleotide ◽  
Cell Free Dna ◽  
Free Dna ◽  
Circulating Cell Free Dna

e12113 Background: : IBC is a rare and aggressive subtype of breast cancer. A significant number of IBC patients who achieve pathologic complete response (no residual tumor in breast and axillary nodes, pCR) relapse after NAC. We hypothesized that circulating cell-free DNA (ctDNA) identified in blood before, during, and after NAC would identify novel ctDNA targets. Methods: Plasma ctDNA was extracted from 43 non-metastatic IBC patients (IRB: LAB04-0698) pre, mid, and post-NAC. The Oncomine Pan Cancer ctDNA Assay (ThermoFisher) was used for library preparation, and high throughput next generation sequencing was performed on a GeneStudio S5XL System (ThermoFisher), following manufacturer’s directions. ThermoFisher Ion Reporter 5.10 Software was used to analyze single nucleotide variants (SNVs), and copy number variants (CNVs). Results: Seventeen patients had pre-NAC ctDNA assessments; 7/17 (41%) had PIK3CA SNVs; 5/7 also had MYC or FGFR2 CNVs. Five of 17 (29%) had TP53 SNVs; 2/5 also had FGFR2 CNVs. Ten patients had mid-NAC ctDNA assessments; 9/10 (90%) had PIK3CA SNVs; 5/9 also had FGFR2 CNVs, 2/9 had FGFR2 and FGFR3 CNVs, 2/9 also had TP53 SNVs, 1/9 had FGFR2 and ERB2 CNVs. Thirty-one patients had post-NAC ctDNA assessments; 5/31 (16%) had PIK3CA SNVs; 2/5 had FGFR2 CNVs, 1/5 also had a TP53 mutation and an FGFR2 CNV, 1/5 had FGFR2 CNV, and FGFR3 CNV. Six of 31 (19%) had TP53 SNVs, 1/6 had CCND1 CNVs, no CNVs were detected in 6 patients with TP53 SNVs. Six of 31 (19%) had MAP2K1 SNVs. Three of 31 (10%) had MET SNVs; 1/3 had CCND3 CNVs, no CNVs were detected in 2 patients with MET SNVs. No SNVs or CNVs were detected in 10/31 (32%) of patients post NAC. Conclusions: ctDNA assessments before, during, and after NAC identified novel targets that could be tested in future adjuvant therapies trials in IBC patients who remain at high risk for relapse.

Comparison of serum HER-2/neu between trastuzumab-based regimen and anthyracycline-based regimen during neoadjuvant chemotherapy in advanced primary breast cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e11582-e11582
Author(s):  
J. Lee ◽  
W. Min ◽  
S. Kim ◽  
B. Son
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Ductal Carcinoma ◽  
Pathologic Complete Response ◽  
Residual Tumor ◽  
Complete Response ◽  
Breast Cancers ◽  
Maximal Diameter ◽  
Her 2 ◽  
Positive Breast Cancer

e11582 Background: Serum Her-2/neu has been known as molecular surrogating marker of predicting treatment response in Her-2 positive breast cancer. We compare the change of serum Her-2/neu during neoadjuvant chemotherapy between trastuzumab(H) and anthyracyline(A) based treatment. Methods: All breast cancers were tested by immunohistochemical stain and FISH for Her-2/neu before treatment. Serum Her-2/neu was twice measured by Chemiluminescence immunoassay(ADVIA centaurTMsystem) before neoadjuvant chemotherapy and before operation. The cutoff value was 10.2 mg/ml according to previous study. Pathologic complete response (pCR) was considered as no residual tumor or remnant ductal carcinoma in situ, partial response (PR) was less than 50% decrease in maximal diameter in pathologic tumor size. Results: Serum Her-2/neu of trastuzumab group was more decreased than of anthyracyline group (H; 12.9 ± 14.5 ng/mL vs. A; 2.2 ± 1.2 ng/mL, p=0.024). In trastuzumab group, pCR was relatively correlated with decrease of serum Her-2/neu (PR: 0.8 ± 0.84 ng/ml vs. pCR: 21.1 ± 13.2 ng/ml, p=0.08). Conclusions: A decrease in serum Her-2/neu levels during treatment was associated with pathologic response in patients receiving neoadjuvant chemotherapy, particularly, trastuzumab-based regimen. Serum Her-2/neu levels may serve to monitoring neoadjuvant therapy in Her-2/neu positive breast cancer. No significant financial relationships to disclose.

Surgically Proven Complete Response of Stage III Non-Small Cell Lung Cancer after Cisplatin-Enhanced Radiotherapy. Clinical Implications and Long-Term Results

2003 ◽  
Vol 89 (1) ◽  
pp. 16-19
Author(s):  
Amedeo Vittorio Bedini ◽  
Luca Tavecchio ◽  
Vincenzo Delledonne ◽  
Stefano Michele Andreani
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Pathologic Complete Response ◽  
Complete Response ◽  
Small Cell ◽  
Stage Iii ◽  
Clinical Implications ◽  
Small Cell Lung

Aims and Background Pathologic complete response in locally advanced non-small cell lung cancer is the main end point of combined therapies (chemotherapy and/or radiotherapy). Surgery after an induction treatment can improve local control, allowing the histologic assessment of treatment activity by means of resection or extensive biopsies. Methods Thirty patients surgically assessed without viable tumor after concurrent radiotherapy and continuous infusion of low-dose cisplatin, owing to an initially unresectable stage III non-small-cell lung cancer, were the object of evaluation to assess clinical implications, short- and long-term surgical results. Results The specificity rate of the preoperative restaging was 36.6%. The surgical procedures consisted of 22 resections and of extensive biopsies in 8 cases. The operative mortality was 4% (1/25) for procedures other than right pneumonectomy (3/5). No patient received postoperative chemotherapy. Eleven distant progressions, 4 local recurrences, and 4 new primary tumors were assessed as initial failures. The 8-year overall survival was 36%. Conclusions Pathologic complete response after cisplatin-enhanced radiotherapy cannot be satisfactorily assessed by clinical means. Surgery is required to obtain a reliable evaluation; however, right pneumonectomy should be contraindicated because of prohibitive risk. Although an effective local treatment can cure patients with advanced stage III disease, the addition of chemotherapy seems advisable to improve tumor relapse control.

scholarly journals Targeted Androgen Pathway Suppression in Localized Prostate Cancer: A Pilot Study

2014 ◽  
Vol 32 (3) ◽  
pp. 229-237 ◽  
Author(s):  
Elahe A. Mostaghel ◽  
Peter S. Nelson ◽  
Paul Lange ◽  
Daniel W. Lin ◽  
Mary Ellen Taplin ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Pathologic Complete Response ◽  
Specific Antigen ◽  
Serum Testosterone ◽  
Residual Tumor ◽  
Complete Response ◽  
Dehydroepiandrosterone Sulfate ◽  
Primary Outcome Measure ◽  
Androgen Synthesis

Purpose Ligand-mediated activation of the androgen receptor (AR) is critical for prostate cancer (PCa) survival and proliferation. The failure to completely ablate tissue androgens may limit suppression of PCa growth. We evaluated combinations of CYP17A and 5-α-reductase inhibitors for reducing prostate androgen levels, AR signaling, and PCa volumes. Patients and Methods Thirty-five men with intermediate/high-risk clinically localized PCa were randomly assigned to goserelin combined with dutasteride (ZD), bicalutamide and dutasteride (ZBD), or bicalutamide, dutasteride, and ketoconazole (ZBDK) for 3 months before prostatectomy. Controls included patients receiving combined androgen blockade with luteinizing hormone-releasing hormone agonist and bicalutamide. The primary outcome measure was tissue dihydrotestosterone (DHT) concentration. Results Prostate DHT levels were substantially lower in all experimental arms (0.02 to 0.04 ng/g v 0.92 ng/g in controls; P < .001). The ZBDK group demonstrated the greatest percentage decline in serum testosterone, androsterone, and dehydroepiandrosterone sulfate (P < .05 for all). Staining for AR and the androgen-regulated genes prostate-specific antigen and TMPRSS2 was strongly suppressed in benign glands and moderately in malignant glands (P < .05 for all). Two patients had pathologic complete response, and nine had ≤ 0.2 cm3 of residual tumor (defined as a near-complete response), with the largest numbers of complete and near-complete responses in the ZBDK group. Conclusion Addition of androgen synthesis inhibitors lowers prostate androgens below that achieved with standard therapy, but significant AR signaling remains. Tissue-based analysis of steroids and AR signaling is critical to informing the search for optimal local and systemic control of high-risk prostate cancer.

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