Novel Biomarker-Targeted Therapies for Metastatic Colorectal Cancer

2021 ◽  
Author(s):  
Shimoli V. Barot ◽  
Suneel D. Kamath
Keyword(s):  
Colorectal Cancer ◽  
Growth Factor ◽  
Metastatic Disease ◽  
Targeted Therapies ◽  
Early Stage ◽  
Growth Factor Receptor ◽  
Precision Oncology ◽  
Dynamic Heterogeneity ◽  
Early Stage Disease ◽  
Stage Disease

AbstractColorectal cancer (CRC) is one of the most common and fatal malignancies worldwide. Screening, surgery, and adjuvant therapy have proved efficacious in improving outcomes for early-stage disease. Despite decades of research efforts, cytotoxic chemotherapy has been the mainstay of treatment for metastatic disease and the prognosis remains unsatisfactory. Compelling evidence suggests that a fundamental reason for the limited success is the cancer's inherent dynamic heterogeneity, which is more predominant in late-stage disease. As our understanding of this molecular blueprint of CRC has evolved, a new avenue of targeted therapies has emerged. Beginning with epidermal growth factor receptor and vascular endothelial growth factor inhibitors, numerous targeted agents have been developed and investigated in large, multicenter, prospective clinical trials. Testing for mutations in RAS (KRAS and NRAS), BRAF, and HER2 and for mismatch repair/microsatellite instability and NTRK fusions has now been incorporated in the management guidelines, with additional biomarkers rapidly surfacing. As we enter the latest paradigm of precision oncology in CRC, this article will provide an overview of the different molecular subsets of CRC and the current biomarker-targeted therapies in the management of metastatic disease.

scholarly journals Tumor Characteristics and Treatment Outcomes of Older Women with Breast Cancer in Jordan

2019 ◽  
Author(s):  
Hikmat Abdel-Razeq ◽  
Fadwa Abdel Rahman ◽  
Hanan Al-Masri ◽  
Hazem Abdulelah ◽  
Mahmoud Abu Nasser ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Treatment Outcomes ◽  
Metastatic Disease ◽  
Cox Regression ◽  
Early Stage ◽  
Poor Performance Status ◽  
Tumor Characteristics ◽  
Early Stage Disease ◽  
Node Positive ◽  
Stage Disease

Abstract Background : Less than 10% of newly diagnosed breast cancer in our region are diagnosed in women 70 years or older. Treatment plans of such patients is less clear and have poor outcomes. In this paper, we describe clinical presentation, tumor characteristics and treatment outcomes in such patients. Methods : Consecutive patients aged 65 years or older with pathologically-confirmed diagnosis of breast cancer were included. Medical records and hospital databases were searched for patients’ characteristics and treatment outcomes. Results : A total of 553 patients, median age 70 (range: 65-91) years, were included. On presentation, 114 (20.6%) patients had metastatic disease and was mostly visceral (81; 71.1%). Patients with non-metastatic disease had poor pathological features including node-positive in 244 (55.6%), GIII in 170 (38.7%) and lymphovascular invasion in 173 (39.4%). Patients were treated less aggressively; 144 (32.8%) patients with early-stage disease and 98 (86.0%) with metastatic disease never had chemotherapy. After a median follow up of 45 months, 5-year overall survival for the whole group was 67.6%. Survival was better for patients with non-metastatic disease (78.8% vs. 25.4%, P<0.001) and for those with node-negative compared to node-positive disease (85.4% vs. 74.1%, P=0.002). On Cox regression, only positive lymph nodes were associated with poor outcome in patients with non-metastatic disease (Hazard Ratio [HR], 1.75; 95% CI: 1.006-3.034, P=0.048). Conclusions : Older Jordanian women with breast cancer present with more aggressive features and advanced-stage disease that reflect poorly on treatment outcomes. Because of comorbidities and poor performance status, some patients were not aggressively treated.

Neuroendocrine carcinoma of the cervix: A single institution’s experience.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e15585-e15585
Author(s):  
Megan Preston ◽  
Georgia Anne-Lee McCann ◽  
David M. O'Malley ◽  
Christina Boutsicaris ◽  
Larry J. Copeland ◽  
...  
Keyword(s):  
Adjuvant Therapy ◽  
Metastatic Disease ◽  
Survival Data ◽  
Early Stage ◽  
Stage I ◽  
Stage Ii ◽  
Advanced Stage ◽  
Single Institution ◽  
Early Stage Disease ◽  
Stage Disease

e15585 Background: Neuroendocrine carcinomas (NEC) of the cervix comprise only 2% of all cervical cancers. As a result, prospective data is limited and treatment guidelines rely on literature from lung NEC. The objective of this study was to examine and report on our experience in the management of this rare, aggressive disease. Methods: This was an IRB-approved, single-institution, retrospective review. Study criteria included patients with cervical NEC diagnosed between 1990-2011. Demographic, treatment and survival data was collected. Progression-free survival (PFS) and overall survival (OS) was defined as the time from date of initial treatment until progression or death respectively, or date of last contact. Results: A total of 24 patients met inclusion criteria. The median age at diagnosis was 43. Median PFS was 13.6 months and median OS was 16.4 months. The majority of patients had advanced-stage disease (61% stage II-IV, 39% stage I). Of the 9 patients with stage I disease, 4 were treated with platinum + etoposide-based neoadjuvant chemotherapy and 5 were treated with initial radical surgery. Seven of the 9 patients had post-operative adjuvant therapy consisting of chemotherapy, chemo-radiation or radiation only. Seven of the 9 patients (78%) were alive at last follow-up. Of the two patients who were deceased, one had metastatic disease found at surgery and the other declined adjuvant therapy and died of recurrence. Patients with stage II-IV disease (n=15) had a median PFS and OS of 11.5 and 12.1 months, respectively. Only 2 had no evidence of disease at last encounter. The remainder died without achieving remission. Patients with metastatic disease had significantly worse survival when compared to those with loco-regional disease with a median OS of 8 vs. 28 months (p = .03), respectively. Conclusions: We report one of the largest single-institution experiences of neuroendocrine cervical cancer. Advanced-stage patients had a poor prognosis regardless of therapy. However, multi-modality therapy in early-stage disease resulted in an excellent prognosis (78% survival) for these rare, highly aggressive tumors. These findings support the goal of curative intent for early-stage disease using multi-modality therapy.

scholarly journals Immunotherapies and Targeted Therapies in the Treatment of Metastatic Colorectal Cancer

2019 ◽  
Vol 7 (8) ◽  
pp. 83 ◽  
Author(s):  
Prashanth Rawla ◽  
Adam Barsouk ◽  
Andreas V. Hadjinicolaou ◽  
Alexander Barsouk
Keyword(s):  
Colorectal Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Targeted Therapies ◽  
Checkpoint Inhibitors ◽  
Growth Factor Receptor ◽  
Her2 Positive ◽  
Cancer Hallmarks ◽  
Epidermal Growth

Colorectal cancer (CRC) is the third leading cause of cancer deaths, and while mortality has largely improved in the developed world, five-year survival for metastatic disease remains dismally low at only 15%. Fortunately, nearly a dozen targeted therapies and immunotherapies have been FDA approved in the past decade for certain patient profiles with metastatic CRC (mCRC), and many others are under development. Checkpoint inhibitors such as pembrolizumab have proven effective at extending survival for mismatch repair (MMR)-deficient and high microsatellite instability (MSI) mCRC patients. In combination with chemotherapy in first- and second-line treatment, antiangiogenic (anti-vascular endothelial growth factor (anti-VGEF)) agent bevacizumab has been shown to increase mCRC survival. Anti-epidermal growth factor receptor (anti-EGFR) agents panitumumab and cetuximab, in combination with chemotherapy, have also prolonged survival among KRAS and all RAS wild-type mCRC patients. Among these patients, anti-EGFR therapy has been found to be more efficacious than bevacizumab. Improved selectivity has allowed small-molecule receptor tyrosine kinase (RTK) inhibitors to target VEGF and EGFR with greater efficacy and tolerability. Combinations of immunotherapies, RTKs, monoclonal antibodies, and cytotoxic drugs are being investigated to provide broad-spectrum protection against relapse by simultaneously targeting many cancer hallmarks. Lastly, human epidermal growth factor receptor 2 (HER2) therapy has shown promise for HER2-positive mCRC patients, though larger clinical trials are required to secure FDA approval.

Therapeutic Targets and Opportunities in Endometrial Cancer: Update on Endocrine Therapy and Nonimmunotherapy Targeted Options

2020 ◽  
pp. 245-255
Author(s):  
Helen J. MacKay ◽  
Victor Rodriguez Freixinos ◽  
Gini F. Fleming
Keyword(s):  
Endometrial Cancer ◽  
Endocrine Therapy ◽  
Metastatic Disease ◽  
Early Stage ◽  
Treatment Options ◽  
Treatment Strategies ◽  
Targeted Treatment ◽  
Early Stage Disease ◽  
New Era ◽  
Stage Disease

Worldwide, the incidence of endometrial cancer is increasing. Although the prognosis remains good for patients diagnosed with early-stage disease, for those diagnosed with recurrent or metastatic disease, options have been limited, and prognosis is short. Optimizing and identifying new well-tolerated treatments for women living with endometrial cancer is a top priority. A new era is dawning where we are starting to see the integration of clinically relevant genomic and pathologic data to inform and refine treatment strategies for women with endometrial cancer. Here, we focus on reviewing nonimmunotherapy-based targeted treatment options and emerging directions for women with endometrial cancer.

Tumor Characteristics and Treatment Outcomes of Older Patients with Breast Cancer in Jordan

2020 ◽  
Author(s):  
Hikmat Abdel-Razeq ◽  
Fadwa Abdel Rahman ◽  
Hanan Al-Masri ◽  
Hazem Abdulelah ◽  
Mahmoud Abu Nasser ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Treatment Outcomes ◽  
Metastatic Disease ◽  
Older Patients ◽  
Cox Regression ◽  
Early Stage ◽  
Tumor Characteristics ◽  
Early Stage Disease ◽  
Node Positive ◽  
Stage Disease

Abstract Background: Less than 10% of newly diagnosed breast cancer cases in Jordan are diagnosed in women 70 years or older. Treatment plans of such patients is less clear and could result in poor outcomes. In this paper, we describe clinical presentation, tumor characteristics and treatment outcomes in this population of breast cancer patients.Methods: Consecutive patients aged 65 years or older with pathologically-confirmed diagnosis of breast cancer were included. Medical records and hospital databases were searched for patients’ characteristics and treatment outcomes.Results: A total of 553 patients, mean age ± SD (71± 5.1) years, were included. On presentation, 114 (20.6%) patients had metastatic disease and was mostly visceral (81; 71.1%). Patients with non-metastatic disease had poor pathological features including node-positive in 244 (55.6%), high grade (grade III) in 170 (38.7%) and lymphovascular invasion in 173 (39.4%). Patients were treated less aggressively; 144 (32.8%) patients with early-stage disease and 98 (86.0%) with metastatic disease never had chemotherapy. After a median follow up of 45 months, 5-year overall survival for the whole group was 67.6%. Survival was better for patients with non-metastatic disease (78.8% vs. 25.4%, P<0.001) and for those with node-negative compared to node-positive disease (85.4% vs. 74.1%, P=0.002). On Cox regression, only positive lymph nodes were associated with poor outcome in patients with non-metastatic disease (Hazard Ratio [HR], 1.75; 95% CI: 1.006-3.034, P=0.048).Conclusions: Older Jordanian patients with breast cancer present with more aggressive features and advanced-stage disease that reflect poorly on treatment outcomes. Older patients were treated less aggressively with less than a third received any chemotherapy.

Prevalence of delay to seeking medical attention in patients with synovial sarcoma and association with inferior outcomes.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e23556-e23556
Author(s):  
Tiffany Seto ◽  
Meena Song ◽  
Elisabeth Russell ◽  
Danny Sam ◽  
Minggui Pan
Keyword(s):  
Synovial Sarcoma ◽  
Metastatic Disease ◽  
Median Duration ◽  
Early Stage ◽  
Young Patients ◽  
Medical Attention ◽  
Early Stage Disease ◽  
Palpable Mass ◽  
Presenting Symptoms ◽  
Stage Disease

e23556 Background: Synovial sarcoma is an aggressive soft tissue sarcoma that predominantly affects young patients with high rate of relapse and mortality. Systemic study of patients’ presenting symptoms and possible delay of seeking medical attention is lacking. Methods: We retrospectively reviewed the electronic records of all patients diagnosed with synovial sarcoma from 2005 to 2016 within Kaiser Permanente Northern California to identify the pattern of presenting symptoms and its correlation with outcomes. Results: Of the 77 patients with synovial sarcoma, 64 had early stage disease and 13 had metastatic disease at diagnosis, with median age at diagnosis of 47 years. Anatomically, 48 patients had primary disease at the extremity, 12 trunk, and 17 visceral. Median duration of follow up is 40 months. The median time from symptom to first medical appointment (TTM) is 3 months (range 0.1 to 180 months). Nine out of 13 patients who presented with metastatic disease were visceral primary. For the 60 patients with an extremity/trunk primary, patients who presented with pain without a palpable mass had a median duration of TTM of 12 months, compared to the TTM of 3 months for patients who presented with a palpable mass. The relapse rate (RR) and disease-free survival (DFS) for patients with an extremity/trunk primary who presented with pain but without a palpable mass were significantly worse when compared to patients who presented with a palpable mass (RR 50% vs. 26.5%, and DFS 27 vs. 42.5 months, p < 0.005). TTM was inversely correlated with DFS for the 64 cases with early stage disease and for the 60 cases with extremity/trunk primary (p < 0.00000001). Of the 11 patients with a foot primary, a similar pattern of TTM and DFS was also observed. Conclusions: Patients with synovial sarcoma who presented with pain but without a palpable mass had longer TTM, worse DFS and higher RR compared to patients who presented with a palpable mass. Longer TTM was associated with worse DFS.

scholarly journals L1CAM expression in colorectal cancer identifies patients prone to metastasis already in early-stage disease

2019 ◽  
Vol 30 ◽  
pp. iv60
Author(s):  
A. Tampakis ◽  
E. Tampaki ◽  
A. Nonni ◽  
E. Patsouris ◽  
M. von Flüe ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Early Stage ◽  
Early Stage Disease ◽  
Stage Disease ◽  
L1cam Expression

Prognostic Significance of DNA Aneuploidy and p21ras Oncoprotein Expression in Colorectal Cancer and Their Role in the Determination of Treatment Modalities

2001 ◽  
Vol 16 (2) ◽  
pp. 97-104 ◽  
Author(s):  
N.H. Karelia ◽  
D.D. Patel ◽  
N.S. Desai ◽  
H.V. Mehta ◽  
P.K. Yadav ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Dna Ploidy ◽  
Early Stage ◽  
Prognostic Significance ◽  
S Phase ◽  
Response To Therapy ◽  
Phase Fraction ◽  
Treatment Modalities ◽  
Early Stage Disease ◽  
Stage Disease

The purpose of the present study was to investigate the prognostic significance of DNA ploidy, S-phase fraction and p21ras oncoprotein expression in patients with colorectal cancer and to correlate these factors with the clinical behavior of the tumors and their response to therapy. Of 79 patients with colorectal cancer 57% (45/79) had early stage disease. Forty-one percent (32/79) had aneuploid tumors while 30% (24/79) of the tumors had a high (>10%) S-phase fraction. p21ras oncoprotein expression was detected in 38% (30/79) of tumors. Patients with aneuploid tumors had a worse prognosis than patients with diploid tumors (p=0.0002). Similarly, patients with high S-phase fraction tumors had a shorter survival than those with low S-phase fraction tumors (p=0.005). No such difference was found between p21ras-positive and p21ras-negative tumor subgroups. In early stage colorectal cancer, aneuploidy was closely correlated with disease outcome (p=0.029). Early stage patients with diploid tumors who received radiotherapy and chemotherapy had a better prognosis than patients with aneuploid tumors. In conclusion, DNA ploidy is a significant and independent prognostic factor in colorectal cancer. Aneuploidy and genetic alteration of the p21ras oncoprotein are important in determining the biological aggressiveness of colorectal cancer. Furthermore, DNA ploidy may identify those subgroups of patients with early stage disease who may benefit from more aggressive treatment.

scholarly journals L1CAM expression in colorectal cancer identifies a high-risk group of patients with dismal prognosis already in early-stage disease

2019 ◽  
Vol 59 (1) ◽  
pp. 55-59 ◽  
Author(s):  
Athanasios Tampakis ◽  
Ekaterini Christina Tampaki ◽  
Afroditi Nonni ◽  
Gerasimos Tsourouflis ◽  
Alberto Posabella ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
High Risk ◽  
Risk Group ◽  
Early Stage ◽  
High Risk Group ◽  
Early Stage Disease ◽  
Dismal Prognosis ◽  
Stage Disease ◽  
L1cam Expression
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