scholarly journals Tumor-Infiltrantig Lymphocytes Density as Determinant in Early Stage Colorectal Cancer Prognosis: A Single Centre Pilot Study

2019 ◽  
pp. 1-5
Author(s):  
Cristiana Lo Nigro ◽  
Vincenzo Ricci ◽  
Teresa Fabozzi ◽  
Daniela Vivenza ◽  
Mirella Fortunato ◽  
...  
Keyword(s):  
Decision Making ◽  
Early Stage ◽  
Tumor Infiltrating Lymphocytes ◽  
Cancer Prognosis ◽  
Stage Ii ◽  
Stage Iii ◽  
High Risk Population ◽  
Published Data ◽  
Decision Making Process ◽  
Prognostic Tool

Stage II colon cancer (CC) is a heterogeneous disease with different clinical behaviour. There is a high degree of uncertainty in recommending adjuvant chemotherapy, which is usually suggested in the high-risk population on the basis of TNM, stage and key biological markers. Published data suggest that specific tumor-infiltrating lymphocytes (S-TILs) (CD3+, CD8+, CD45RO+) may represent a valuable prognostic tool to drive the decision-making process. We performed an analysis on 13 cases of stage II and III CC that relapsed, and on 15 cases that did not. We analyzed the density of CD3+, CD8+ and CD45RO+ in the surgical samples after radical surgery by IHC in the center of the tumor (CT) and in its invasive margin (IM). For each marker, we identified two grading of staining, high density (HD) or low density (LD), where the cut-off was the median value observed. This analysis was carried out stratifying patients in two cohorts: stage II (12 patients) and stage III (16 patients). Density of CD3+, CD8+ and CD45RO+ in CT did not affect DFS and OS, except for OS in stage II pts for CD3+ (P=0.012). Conversely HD of CD3+, CD8+ and CD45RO+ in IM showed significant benefit in DFS compared to LD (P=0.001, P=0.013 and P=0.001 respectively) in stage II patients and, only for CD3+, also in stage III patients (P=0.048). Similarly, we observed a significant gain in OS in pts with HD CD3+ and CD45RO+ (P=0.05 and P=0.003) but not CD8+ (P=0.25) in IM for stage II patients. S-TILs might represent a valuable prognostic tool to drive the decision-making process especially for stage II CC disease, with a more pronounced role of S-TILs in IM compared to CT. Our results will be verified in ongoing large prospective study.

scholarly journals A mid-term follow-up of Koutsogiannis’ osteotomy in adult-acquired flatfoot stage II and “early stage III”

SICOT-J ◽  
2017 ◽  
Vol 3 ◽  
pp. 24
Author(s):  
Camilla Arvinius ◽  
Elena Manrique ◽  
Antonio Urda ◽  
Zulema Cardoso ◽  
Jose Enrique Galeote ◽  
...  
Keyword(s):  
Early Stage ◽  
Stage Ii ◽  
Stage Iii

Predictors of adjuvant chemotherapy (AT) decision-making in referred patients (pts) with stage II and III colon cancer (CC)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15070-e15070
Author(s):  
D. S. Ksienski ◽  
M. Levesque ◽  
S. Gill
Keyword(s):  
Decision Making ◽  
Colon Cancer ◽  
High Risk ◽  
Marital Status ◽  
Univariate Analysis ◽  
Stage Ii ◽  
Stage Iii ◽  
Low Grade ◽  
Delayed Presentation ◽  
To Receive

e15070 Background: Randomized clinical trials have demonstrated a robust survival benefit of AT for node positive (stage III) CC patients; similar evidence for node-negative (stage II) patients is lacking. While guidelines recommend AT for stage III colon cancer but AT is not a routine recommendation for stage II. Actual practice of the evidence varies and suggests the interplay of additional variables. We sought to identify factors associated with practice patterns which vary from conventional AT guidelines, ie no AT in stage III CC and receipt of AT in.stage II CC. Methods: Data pertaining to pt demographics, tumor characteristics, and treatment for pts with resected stage II (n=176) and III CC (n=235) referred to the British Columbia Cancer Agency in 2004 was collected by retrospective chart review. One-sided Fisher's exact test was used to assess statistical significance (p<0.05) by univariate analysis. Results: 28% (n=49) of stage II pts received AT. Compared to untreated pts, stage II pts who received AT were significantly more often younger than 66 years (57% vs 21%), lived in a city with a regional cancer center (71% vs 51%), had T4 disease (33% vs 9%), vascular invasion (22% vs 5%), perineural invasion (10% vs 2%) and high grade (26% vs 2%). Marital status, ethnicity, lymphatic invasion and high CEA were not associated with AT in stage II. 29% (n=69) of stage III pts did not receive AT. Compared to treated pts, stage III pts who did not receive AT were significantly more often older than 65 years (91% vs 51%), had low grade disease (96% vs 84%) and presented for oncology consultation greater than 42 days from surgery (29% vs 11%). Marital status, ethnicity, residence, T4 status or N2 status were not associated with no AT in stage III. Conclusions: For pts with stage II CC, subgroups associated with high risk for relapse were more likely to receive AT although the majority of stage II pts in this cohort remained untreated. For stage III disease, almost one-third of referred pts did not receive AT. Older age and delayed presentation were strongly associated with failure to receive AT. Within the limitations of a retrospective review, these data highlight the significant and commonly observed implications of factors other than stage in AT decision-making for high risk resected CC. No significant financial relationships to disclose.

Association of time to adjuvant chemotherapy (TTAC) and overall survival among patients with rectal cancer treated with preoperative radiation.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 461-461
Author(s):  
Gillian Gresham ◽  
Caroline Speers ◽  
Ryan Woods ◽  
Winson Y. Cheung ◽  
Kimberly Schaff ◽  
...  
Keyword(s):  
Adjuvant Chemotherapy ◽  
Cox Regression ◽  
Early Stage ◽  
Time Frame ◽  
Stage Ii ◽  
Stage Iii ◽  
Significant Prognostic Factor ◽  
Preoperative Radiation ◽  
Cut Point ◽  
Point Analysis

461 Background: Studies suggest that delayed adjuvant chemotherapy (AC) beyond 8 weeks is associated with inferior survival in early-stage colon cancer (CA). The optimal TTAC in rectal CA remains unclear. The objective of this study was to determine the prognostic effect of TTAC in stage II and III rectal CA treated with standard preoperative (op) chemoradiation. Methods: Patients with stage II/III rectal CA treated with pre-op chemoradiation, received post-op AC, and referred to the British Columbia Cancer Agency between 1999 and 2008 were included. Univariate and multivariate analyses were conducted using Kaplan Meier and Cox regression methods to evaluate the association between TTAC and outcomes. X-tiles cut-point analysis was performed to determine the optimal TTAC. Results: A total of 327 eligible patients were identified: median age 61 (range 22-85), 70% male, and 75% stage III. In terms post-op AC, 51% received 5-fluorouracil (5-FU), 32% received capecitabine, 12% received 5-FU and oxaliplatin, and 5% received other chemotherapy. Median TTAC was 7.0 weeks (wks) (range 1.6-33.3 wks). Cut-point analysis revealed the optimal TTAC to be 5.6 wks (HR: 0.42, 95%CI 0.22-0.82, p=0.0087). Initiation of AC within optimal TTAC (5.6 wks) and 6 wks from date of surgery (sx) was associated with a significant survival benefit while no significant effect was seen at 8 wks. TTAC of ≤ 6 wkswas found to be a significant prognostic factor in multivariate analysis (p=0.047) adjusted for ECOG, age, sex, stage, margin status, and grade. In stratified analysis by stage, patients with stage III disease benefited from AC (p=0.018) while those with stage II did not (p=0.71). Conclusions: In this study, the optimal TTAC was 6 weeks or less. Initiation of AC within this time frame was associated with improved OS. This is less than the optimal timeframe indicated in the literature for colon CA. [Table: see text]

Personalizing Colon Cancer Adjuvant Therapy: Selecting Optimal Treatments for Individual Patients

2015 ◽  
Vol 33 (16) ◽  
pp. 1787-1796 ◽  
Author(s):  
Rodrigo Dienstmann ◽  
Ramon Salazar ◽  
Josep Tabernero
Keyword(s):  
Colon Cancer ◽  
Early Stage ◽  
Tumor Staging ◽  
Predictive Biomarkers ◽  
Postoperative Chemotherapy ◽  
Stage Ii ◽  
Stage Iii ◽  
Molecular Characteristics ◽  
Early Stage Disease ◽  
Metastatic Setting

For more than three decades, postoperative chemotherapy—initially fluoropyrimidines and more recently combinations with oxaliplatin—has reduced the risk of tumor recurrence and improved survival for patients with resected colon cancer. Although universally recommended for patients with stage III disease, there is no consensus about the survival benefit of postoperative chemotherapy in stage II colon cancer. The most recent adjuvant clinical trials have not shown any value for adding targeted agents, namely bevacizumab and cetuximab, to standard chemotherapies in stage III disease, despite improved outcomes in the metastatic setting. However, biomarker analyses of multiple studies strongly support the feasibility of refining risk stratification in colon cancer by factoring in molecular characteristics with pathologic tumor staging. In stage II disease, for example, microsatellite instability supports observation after surgery. Furthermore, the value of BRAF or KRAS mutations as additional risk factors in stage III disease is greater when microsatellite status and tumor location are taken into account. Validated predictive markers of adjuvant chemotherapy benefit for stage II or III colon cancer are lacking, but intensive research is ongoing. Recent advances in understanding the biologic hallmarks and drivers of early-stage disease as well as the micrometastatic environment are expected to translate into therapeutic strategies tailored to select patients. This review focuses on the pathologic, molecular, and gene expression characterizations of early-stage colon cancer; new insights into prognostication; and emerging predictive biomarkers that could ultimately help define the optimal adjuvant treatments for patients in routine clinical practice.

A new prognostic and predictive tool to enhance shared decision making in stage III colon cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 4010-4010 ◽  
Author(s):  
Alberto F. Sobrero ◽  
Alberto Puccini ◽  
Qian Shi ◽  
Axel Grothey ◽  
Thierry Andre ◽  
...  
Keyword(s):  
Decision Making ◽  
Colon Cancer ◽  
Shared Decision Making ◽  
Therapeutic Option ◽  
Stage Iii ◽  
Accurate Information ◽  
Decision Making Process ◽  
Shared Decision ◽  
Predictive Tool ◽  
Stage Iii Colon Cancer

4010 Background: Survival outcomes in patients with stage III colon cancer varies widely according to T-N sub-stages. The ability to estimate the benefit of each therapeutic option (surgery alone, fluoropyrimidines alone, oxaliplatin-based doublet for either 3 or 6 months) in each T-N subgroup within stage III, may provide more accurate information helping doctors and patients in the complex shared decision-making process surrounding adjuvant therapy. Methods: Theoutcomedata of 12,834 patients with stage III colon cancer enrolled in the IDEA trial served as our database. Patients were categorized in 16 sub-stages, based on the T-N categories. We created a meta-regression model to predict the expected 3-year DFS within each T-N sub-stage and hence the 5-year DFS rates were projected. We then evaluated the efficacy of each therapeutic option in every sub-stage, working backward by subtraction, using an average of the HRs reported in the pertinent trials publication as conversion factor. Results: Large differences in 3-year DFS rate were observed among the subgroups, ranging from 95% (T1N1a) to 29% (T4N2b) in the overall population. The contribution to outcome of each therapeutic option in this setting varied widely across sub-stages. According to our model, patients with T1N1a cancers have a projected 5-year DFS of 85% with surgery alone. Adjuvant fluoropyrimidine alone results in 4.2% absolute DFS gain; an additional 1.7% and 0.6% gain is seen with oxaliplatin for 3 and 6 months, respectively. Patients with T4N2b cancers show a 4.7% 5-year DFS with surgery alone, and a 7.1%, 5.0%, 2.1% increase with the aforementioned adjuvant options, respectively. Conclusions: The resulting overlay bar graph gives patients and doctors the projected relative benefit of each treatment option and may substantially help the shared decision-making process.

scholarly journals ‘I treat it but I don’t know what this disease is’: a qualitative study on noma (cancrum oris) and traditional healing in northwest Nigeria

2019 ◽  
Vol 12 (1) ◽  
pp. 28-35 ◽  
Author(s):  
Elise Farley ◽  
Hussaina Muhammad Bala ◽  
Annick Lenglet ◽  
Ushma Mehta ◽  
Nura Abubakar ◽  
...  
Keyword(s):  
Decision Making ◽  
Thematic Analysis ◽  
Early Stage ◽  
Traditional Healers ◽  
Traditional Healing ◽  
Decision Making Process ◽  
Health Seeking ◽  
Cancrum Oris ◽  
The Face ◽  
Depth Interviews

Abstract Background Noma, a neglected disease mostly affecting children, with a 90% mortality rate if untreated, is an orofacial gangrene that disintegrates the tissues of the face in &lt;1 wk. Noma can become inactive with early stage antibiotic treatment. Traditional healers, known as mai maganin gargajiya in Hausa, play an important role in the health system and provide care to noma patients. Methods We conducted 12 in-depth interviews with caretakers who were looking after noma patients admitted at the Noma Children's Hospital and 15 traditional healers in their home villages in Sokoto state, northwest Nigeria. We explored perceptions of noma, relationship dynamics, healthcare practices and intervention opportunities. Interviews were audiorecorded, transcribed and translated. Manual coding and thematic analysis were utilised. Results Traditional healers offered specialised forms of care for specific conditions and referral guidance. They viewed the stages of noma as different conditions with individualised remedies and were willing to refer noma patients. Caretakers trusted traditional healers. Conclusions Traditional healers could play a crucial role in the early detection of noma and the health-seeking decision-making process of patients. Intervention programmes should include traditional healers through training and referral partnerships. This collaboration could save lives and reduce the severity of noma complications.

scholarly journals Transcriptional Subtyping and CD8 Immunohistochemistry Identifies Patients With Stage II and III Colorectal Cancer With Poor Prognosis Who Benefit From Adjuvant Chemotherapy

2018 ◽  
pp. 1-15 ◽  
Author(s):  
Wendy L. Allen ◽  
Philip D. Dunne ◽  
Simon McDade ◽  
Enya Scanlon ◽  
Maurice Loughrey ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Adjuvant Chemotherapy ◽  
Tumor Infiltrating Lymphocytes ◽  
Standard Of Care ◽  
Classification Systems ◽  
Stage Ii ◽  
Stage Iii ◽  
Clinical Value ◽  
Transcriptomic Profiling ◽  
Infiltrating Lymphocytes

Purpose Transcriptomic profiling of colorectal cancer (CRC) has led to the identification of four consensus molecular subtypes (CMS1 to 4) that have prognostic value in stage II and III disease. More recently, the Colorectal Cancer Intrinsic Subtypes (CRIS) classification system has helped to define the biology specific to the epithelial component of colorectal tumors; however, the clinical value of these classification systems in the prediction of response to standard-of-care adjuvant chemotherapy remains unknown. Patients and Methods Using samples from four European sites, we assembled a novel cohort of patients with stage II and III CRC (n = 156 samples) and performed transcriptomic profiling and targeted sequencing and generated a tissue microarray to enable integrated multiomics analyses. We also accessed data from two published cohorts of patients with stage II and III CRC: GSE39582 and GSE14333 (n = 479 and n = 185 samples, respectively). Results The epithelial-rich CMS2 subtype of CRC benefitted significantly from treatment with adjuvant chemotherapy in both stage II and III disease ( P = .02 and P < .001, respectively), whereas the CMS3 subtype significantly benefitted in stage III only ( P = .001). After CRIS substratification of CMS2, we observed that only the CRIS-C subtype significantly benefitted from treatment with adjuvant chemotherapy in stage II and III disease ( P = .0081 and P < .001, respectively), whereas the CRIS-D subtype significantly benefitted in stage III only ( P = .0034). We also observed that CRIS-C patients with low levels of CD8+ tumor-infiltrating lymphocytes were most at risk for relapse in both stage II and III disease (log-rank P = .0031; hazard ratio, 12.18 [95% CI, 1.51 to 98.58]). Conclusion Patient stratification using a combination of transcriptional subtyping and CD8 immunohistochemistry analyses is capable of identifying patients with poor prognostic stage II and III disease who benefit from adjuvant standard-of-care chemotherapy. These findings are particularly relevant for patients with stage II disease, where the overall benefit of adjuvant chemotherapy is marginal.

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