scholarly journals Correlation between Prognostic Factors and the Histopathological Response to Neoadjuvant Chemotherapy in Osteosarcoma: A Retrospective Study

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Yogi Prabowo ◽  
Iwan Setiawan ◽  
Achmad Fauzi Kamal ◽  
Evelina Kodrat ◽  
Muhammad Luqman Labib Zufar
Keyword(s):  
Prognostic Factors ◽  
Neoadjuvant Chemotherapy ◽  
Tumor Size ◽  
Scoring System ◽  
Poor Responder ◽  
Grading System ◽  
Symptom Duration ◽  
Histopathological Response ◽  
Prognostic Features ◽  
Response To Neoadjuvant Chemotherapy

Background.Multimodality treatment, incorporating neoadjuvant chemotherapy and adjuvant chemotherapy, is the standard management plan for osteosarcoma that increases the overall survival (OS) rate. However, data regarding prognostic factors affecting the histopathological response following neoadjuvant chemotherapy is limited. Patients and Methods. We retrospectively reviewed patients diagnosed with osteosarcoma in our center between 2008 and 2018. We classified patient characteristics according to gender, age, tumor size, site and stage at diagnosis, site of metastasis, type of surgery, necrosis rate based on the Huvos grading system, and the number of neoadjuvant chemotherapy cycles. We divided response to neoadjuvant chemotherapy into poor responder for patients with Huvos grades 1 and 2 and good responder for patients with Huvos grades 3 and 4. We also documented patients’ survival and follow-up information. Results. We reviewed 64 patients within 5–65 years of age, dominated by men (62.5%). The distal femur (53.1%) was the most common site of osteosarcoma. Fifteen (23.4%) patients had a good response while 49 (76.6%) patients were poor responders to neoadjuvant chemotherapy based on the Huvos grading system. Based on multivariate analysis, gender ( p  = 0.012), age ( p  = 0.029), symptom duration ( p  = 0.004), and tumor enlargement after neoadjuvant chemotherapy ( p  < 0.001) were significantly associated with histopathological response. A scoring system was proposed integrating these significant variables (age > 20 years = 1 point, female gender = 1 point, symptom duration > 12 weeks = 1 point, and increased tumor size after neoadjuvant chemotherapy = 2 points). This scoring system divides patients into two groups with a total score of more than two predicting a poor responder to neoadjuvant chemotherapy. Conclusions. Age, gender, symptoms duration, and tumor size after neoadjuvant chemotherapy are the prognostic features that affect the histopathological response to neoadjuvant chemotherapy in patients with osteosarcoma.

Expression of BCRP/ABCG2 Protein in Invasive Breast Cancer and Response to Neoadjuvant Chemotherapy

2021 ◽  
Author(s):  
Yan Shou Zhang ◽  
Chao Yang ◽  
Lei Han ◽  
Lei Liu ◽  
Yun Jiang Liu
Keyword(s):  
Breast Cancer ◽  
Breast Carcinoma ◽  
Neoadjuvant Chemotherapy ◽  
Tumor Size ◽  
Hormone Receptor ◽  
Molecular Subtypes ◽  
Therapy Response ◽  
Luminal A ◽  
Luminal B ◽  
Response To Neoadjuvant Chemotherapy

Background: Breast cancer resistance protein (BCRP), or ABCG2 (ATP-binding cassette sub-family G member 2), is an ATP-binding cassette (ABC) transporter that mediates energy-dependent transport of substrate drugs out of the cell. Its overexpression may contribute to intrinsic drug resistance in vitro. However, the current literature has not yet clarified the clinical significance of BCRP/ABCG2 in invasive breast carcinoma. Objectives: The purpose of this study was to validate the expression of BCRP/ABCG2 in invasive breast carcinoma and its role in response to neoadjuvant chemotherapy. Methods: In this study, a pretherapeutic core biopsy was performed in 222 patients. BCRP/ABCG2 expression in carcinoma tissue was measured by immunohistochemistry. BCRP/ABCG2 expression correlations with clinicopathological features, molecular subtypes, and therapy response after neoadjuvant chemotherapy were investigated. Results: The results showed that BCRP/ABCG2 was expressed in different molecular subtypes. The proportions of patients with high BCRP/ABCG2 expression were similar in luminal A and luminal B tumors (Luminal B, 80%; Luminal A, 78%), compared with other molecular subtypes (Triple-negative, 63%; HER-2+, 58%. P=0.05). BCRP/ABCG2 expression and the number of lymphatic metastases (&#119875;=0.001) and tumor size (&#119875;=0.011) demonstrated a statistically significant correlation. Low BCRP/ABCG2 expression was associated with an increased pathological complete response (pCR) rate of 38%, higher than the 19% in tumors with high BCRP/ABCG2 expression (P=0.002). In multivariable analysis, BCRP/ABCG2 and hormone receptor (HR) expression were identified as independent risk factors of pCR (P=0.003, P=0.013. respectively). Conclusions: BCRP/ABCG2 is highly expressed in hormone receptor-positive breast cancer. High BCRP/ABCG2 expression is associated with lymphatic metastasis, tumor size, and poor pCR. BCRP/ABCG2 may be a novel potential biomarker that can predict clinical progression and therapy response after neoadjuvant chemotherapy.

scholarly journals Beyond IDH-Mutation: Emerging Molecular Diagnostic and Prognostic Features in Adult Diffuse Gliomas

Cancers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1817 ◽  
Author(s):  
Kanish Mirchia ◽  
Timothy E. Richardson
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Prognostic Factors ◽  
The United States ◽  
Molecular Diagnostic ◽  
Grading System ◽  
Diffuse Glioma ◽  
Prognostic Features ◽  
Molecular Features ◽  
Diffuse Gliomas

Diffuse gliomas are among the most common adult central nervous system tumors with an annual incidence of more than 16,000 cases in the United States. Until very recently, the diagnosis of these tumors was based solely on morphologic features, however, with the publication of the WHO Classification of Tumours of the Central Nervous System, revised 4th edition in 2016, certain molecular features are now included in the official diagnostic and grading system. One of the most significant of these changes has been the division of adult astrocytomas into IDH-wildtype and IDH-mutant categories in addition to histologic grade as part of the main-line diagnosis, although a great deal of heterogeneity in the clinical outcome still remains to be explained within these categories. Since then, numerous groups have been working to identify additional biomarkers and prognostic factors in diffuse gliomas to help further stratify these tumors in hopes of producing a more complete grading system, as well as understanding the underlying biology that results in differing outcomes. The field of neuro-oncology is currently in the midst of a “molecular revolution” in which increasing emphasis is being placed on genetic and epigenetic features driving current diagnostic, prognostic, and predictive considerations. In this review, we focus on recent advances in adult diffuse glioma biomarkers and prognostic factors and summarize the state of the field.

Development of a Prognostic Scoring System for Secondary Acute Myeloid Leukemia (sAML) Arising from Myelodysplastic Syndromes (MDS), Myeloproliferative Disorders (MPD), or Therapy-Related AML (t-AML).

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 921-921 ◽  
Author(s):  
Sanjay R. Mohan ◽  
Paul Elson ◽  
Cristina Rodriguez ◽  
Rachid Baz ◽  
Matt Kalaycio ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Induction Chemotherapy ◽  
Scoring System ◽  
Cleveland Clinic ◽  
Myeloproliferative Disorders ◽  
Risk Groups ◽  
Complete Response ◽  
Remission Induction ◽  
Prognostic Features ◽  
Multivariable Analyses

Abstract Background: Patients (pts) with sAML are evaluated together in large AML trials regardless of whether their sAML arises from antecedent MDS vs. from MPD vs. t-AML. Prognostic factors and outcomes may differ among these subgroups, and a prognostic scoring system would be helpful in determining which patients would benefit from induction chemotherapy. Methods: We conducted a retrospective review of all pts with newly diagnosed, pathologically-confirmed AML at Cleveland Clinic between 1997 and 2007 to identify sAML pts treated with cytarabine-based induction chemotherapy. Data on known prognostic factors (age, white blood cell count (WBC) at diagnosis, cytogenetic risk groups (as defined by CALGB 8461), and AML etiology) were collected as baseline characteristics and controlled for in stepwise multivariable analyses. Complete response (CR) and overall survival (OS) were analyzed. A prognostic scoring system for OS was developed based on the number of poor prognostic features present, derived from significant multivariable factors. Pts received 1 point for adverse cytogenetics, 1 point for having 1-10% peripheral blasts, and 1 point for AML arising from MDS or MPD. Pts with 0 points were favorable, 1 point intermediate, 2 or more points unfavorable. Results: Of 584 AML pts identified, 361 were treated with remission induction therapy, of whom 90 had AML arising from MDS, MPD, or t-AML. Thirty-nine (43%) had antecedent MDS, 21 (23%) an MPD, and 30 (33%) had t-AML, and 47% were female. Pts with AML arising from MDS were older at AML diagnosis (median of 67 years) vs. from MPD (61 years) and t-AML (60 years) (p=.02) but a shorter time from antecedent diagnosis/event (7 months, vs. 47 and 37 months, respectively (p<0.001)). Cytogenetic risk categories were favorable in 9 pts (10%), intermediate in 38 (42%), adverse in 27 (30%), and unknown in 16 (18%) and were similar among groups (p=.28). Median WBC at AML diagnosis was also lower for pts with AML from MDS (3.7k/uL, vs. 9.9 k/uL for AML from MPD and 8.9 k/uL for t-AML, p=.04), as were peripheral blasts (11%, vs. 29% for AML from MPD and 23% for t-AML, p=.01). The overall CR rate was 51% and was qualitatively lower for pts with AML from MDS (38%) than from MPD (62%) or t-AML (60%), but not significantly (p=0.11). The overall reinduction rate was 21% and did not differ among groups (p=.76). Median OS was significantly longer for pts with t-AML (15 months) vs. AML from MDS (8 months) or from MPD (11 months, p=.02). Available SNP karyotyping data on a subset of pts (6 from MDS, 1 from MPD, 4 with t-AML) did not reveal any shared or cryptic lesions that would distinguish responders from non-responders. In multivariable analyses, secondary AML etiology remained non-predictive of CR but was an independent prognostic factor for OS. Pts with t-AML had improved OS compared to AML from MDS (p=.01) or from MPD (p=.08). Favorable- or intermediate-risk cytogenetics, compared to adverse, were significant predictors of CR (p<.001) and OS (p<.001). Age <60 years (compared to 360 years) was a significant predictor of CR (p=.02), but not OS. Patients with 1–10% peripheral blasts had worse OS vs. 0% or >10% blasts (p=.01). Using the prognostic scoring system described above, favorable pts (n=16) had a median OS of 40 months vs. 12 months for intermediate pts (n=33) and 4 months for unfavorable patients (n=27, p<.001). Conclusions: Among sAML patients undergoing induction chemotherapy, pts with t-AML have a longer OS than AML from MDS or from MPD. Other important predictors of CR or OS were cytogenetics, age, and peripheral blast %. The sAML prognostic scoring system distinguished patients with improved survival from induction chemotherapy.

Serum Markers and Prognosis in Locally Advanced Breast Cancer

2005 ◽  
Vol 91 (6) ◽  
pp. 522-530 ◽  
Author(s):  
Javier Martínez-Trufero ◽  
Abigail Ruíz de Lobera ◽  
Juan Lao ◽  
Teresa Puértolas ◽  
Angel Artal-Cortés ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Prognostic Factors ◽  
Neoadjuvant Chemotherapy ◽  
Locally Advanced Breast Cancer ◽  
Locally Advanced ◽  
Serum Levels ◽  
Serum Markers ◽  
Baseline Serum ◽  
Ca 15.3 ◽  
Response To Neoadjuvant Chemotherapy

Background Locally advanced breast cancer (LABC) represents a heterogeneous subgroup of breast cancer with an often dismal outcome. Identifying prognostic factors has acquired great significance for the selection of optimal treatment in individual patients. Methods Between January 1993 and December 1997, 103 patients were treated in our institution with multimodality treatment consisting of neoadjuvant chemotherapy followed by surgery, adjuvant chemotherapy and radiotherapy; tamoxifen was added in hormone receptor-positive cases. In the search for prognostic factors well-established parameters (clinical, pathological and treatment-related) as well as new features with potential value (c-erbB-2, baseline serum levels of CA 15.3 and CEA) were included in the univariate and multivariate analysis. Results At a median follow-up of 92 months (range, 8-130), the estimated five-year cancer-specific overall survival (OS) and disease-free survival (DFS) were 71.34% and 57.7%, respectively. Among the 22 different variables studied, only 10 were significantly correlated with OS and DFS. In multivariate analysis five retained independent prognostic value for both OS and DFS: tumor grade, serum markers, features of inflammatory breast cancer (IBC), response to neoadjuvant chemotherapy and lymph node status. With cutoff values of 35 U/mL for CA 15.3 and 5 ng/mL for CEA, the probability of five-year OS (Cox hazard ratio 3.91, P = 0.0009) and DFS (Cox hazard ratio 2.40, P = 0.02) decreased from 78% to 52% and from 68% to 47%, respectively, when at least one of these markers was abnormal. Conclusions Baseline serum levels of CEA and CA 15.3 emerged from this study as strong independent predictors of outcome in LABC, whose value adds to other established prognostic factors such as postoperative nodal status, IBC, histological grade and response to neoadjuvant chemotherapy.

Prognostic value of response assessed by RECIST and WHO criteria to neoadjuvant chemotherapy in locally advanced gastric cancer patients

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15647-e15647
Author(s):  
S. R. Park ◽  
J. S. Lee ◽  
Y. W. Kim ◽  
I. J. Choi ◽  
K. W. Ryu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Advanced Gastric Cancer ◽  
Tumor Size ◽  
Tumor Response ◽  
Locally Advanced ◽  
R0 Resection ◽  
Who Criteria ◽  
Locally Advanced Gastric Cancer ◽  
Response To Neoadjuvant Chemotherapy

e15647 Background: In metastatic gastric cancer, the response to chemotherapy is assessed by RECIST or WHO criteria according to the change of tumor size. There are no data, however, on the usefulness of those criteria in evaluating tumor response in the setting of neoadjuvant chemotherapy. The aim of this study was to evaluate the relationship between tumor response to neoadjuvant chemotherapy-as assessed by RECIST and WHO criteria-and clinical outcome in locally advanced gastric cancer (LAGC) patients. Methods: This study recruited LAGC patients who, from January 2003 through November 2005, entered the neoadjuvant arm of prospective randomized phase II trials comparing neoadjuvant chemotherapy to adjuvant chemotherapy. LAGC was defined as stage III or IV (M0) disease based on computed tomography (CT) according to the Japanese Classification of Gastric Carcinoma. Patients with measurable lesions received 3 cycles of neoadjuvant chemotherapy consisting of docetaxel (36 mg/m2) and cisplatin (40 mg/m2) on days 1 and 8 every 3 weeks, followed by surgery. Results: After chemotherapy, 40 (95%) patients underwent surgery and the remaining 2 patients showed new distant metastasis on CT scan. Thirty-five (83%) patients had curative R0 resection. Twenty-eight (67%) patients had a clinical response to neoadjuvant chemotherapy according to RECIST/WHO criteria. Although R0 resection rate (93% vs 64%, P = 0.03), median relapse-free survival (RFS) (43.2 vs 7.5 months, P = 0.14), and overall survival (OS) (not reached vs 27.0 months, P = 0.10) were better in responders than non-responders, they did not differ significantly in the subgroup that subsequently underwent surgery. When we redefined the decrease in tumor size judged as a response by RECIST (≥60% rather than ≥30%) and WHO (≥75% rather than ≥50%) criteria, response correlated significantly with both RFS (P = 0.03) and OS (P = 0.02). Conclusions: In the neoadjuvant setting, which frequently involves smaller measurable lesions than the metastatic setting, larger changes in tumor size than those specified by RECIST and WHO criteria are needed to predict postoperative outcome. No significant financial relationships to disclose.

A population model to predict progression free survival in breast cancer patients treated with neoadjuvant chemotherapy ñ vaccines based on tumour growth inhibition metrics.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e12114-e12114
Author(s):  
Belen P.Solans ◽  
Diego Salas ◽  
Marta Abengozar ◽  
Luis Javier Pina ◽  
Arlette Elizalde ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Prognostic Factors ◽  
Neoadjuvant Chemotherapy ◽  
Tumor Growth ◽  
Growth Inhibition ◽  
Neoadjuvant Therapy ◽  
Tumor Size ◽  
Clinical Benefit ◽  
Progression Free Survival ◽  
Free Survival

e12114 Background: Breast cancer (BC) is the most commonly diagnosed malignancy in women. Neoadjuvant chemotherapy selects patients with optimal pathological responses and increases tumorectomy versus total mastectomy. Changes in tumor size (CTS) are related to an early clinical benefit and to Progression Free Survival (PFS) and Overall Survival (OS) in BC patients. Thus, the identification of new prognostic factors in the neoadjuvant scenario is crucial. Objectives:To assess the link between tumor growth inhibition metrics (TGI) and progression free survival (PFS) based on data obtained from BC patients with neoadjuvant therapy Methods: Data were obtained from 218 patients with BC treated at the University Clinic of Navarra, diagnosed from January 2008 to February 2016, with a median age of 49 years (range 25 to 84). Classification of molecular subtypes was based on IHC and found as follows: Her2 (6%), LA ( 23%), LB ( 36%), LB-Her2 (10%) and TN ( 25%). Patients were treated with ddECx 4 followed Docetaxel x 4. Her2 patients had therapy with Trastuzumab. 18% of the patients (LB and TN) received vaccination with dendritic cells. Data were analysed under the population approach with NONMEN 7.3. A model accounting for the dynamics of tumor growth and antitumor effect of the neoadjuvant therapy was developed. The model describes tumor size as the sum of the longest diameters of target lesions as a function of time and drug exposure. A PFS model was developed to describe the PFS time distribution as a function of covariates Results: The TGI was able to individually and accurately describe the tumor shrinkage. Vaccinated patients had an increased shrinkage rate of 36% (p < 0.001) than those who were not (p < 0.001). PFS (months) was best described by a Weibull model, and greater tumor size at diagnosis (p < 0.05), smaller CTS (p < 0.05) and TN subtype (p < 0.001) were identified as poor prognostic factors Conclusions: A PFS model that uses a model-based estimate of tumor growth to predict the PFS of BC patients receiving neoadjuvant therapy has been developed. This model helps to gain early understanding of potential clinical benefit to facilitate go/no-go decision making.

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