Changes in tumor proliferation of rectal cancer induced by preoperative 5-fluorouracil and irradiation

1998 ◽  
Vol 41 (1) ◽  
pp. 62-67 ◽  
Author(s):  
Christopher G. Willett ◽  
Michael Hagan ◽  
William Daley ◽  
Gretchen Warland ◽  
Paul C. Shellito ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Tumor Proliferation

36 Tumor proliferation in rectal cancer following pre-operative irradiation

1995 ◽  
Vol 32 ◽  
pp. 159 ◽  
Author(s):  
Christopher G. Willett ◽  
Gretchen Warland ◽  
Michael P. Hagan ◽  
William J. Daly ◽  
John Coen ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Tumor Proliferation

Factors of local immunity in patients with rectal cancer after prolonged radiotherapy.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15164-e15164
Author(s):  
Oleg Ivanovich Kit ◽  
Aleksandr V. Snezhko ◽  
Elena Yu. Zlatnik ◽  
Inna A. Novikova ◽  
Nabil Al-haj ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Neoadjuvant Treatment ◽  
Proliferation Index ◽  
Tumor Proliferation ◽  
Immunological Study ◽  
Dna Cytometry ◽  
Local Immunity ◽  
Cd8 Cells ◽  
Group 2 ◽  
Group 1

e15164 Background: Immunological study of the blood and tumor tissues was performed in patients with rectal cancer receiving neoadjuvant chemoradiotherapy. Methods: 30 patients with rectal cancer (13 women and 17 men aged 37-68 years with stage II-III adenocarcinomas G1-G3) were divided into groups according to results of DNA cytometry and their response to neoadjuvant treatment. When tumor proliferative activity was stable for 4 weeks of treatment, patients received surgery on time (group 1), while patients with verified inhibition of tumor proliferation (the index decrease by 1.5 times and more) continued treatment for 6-8 weeks and then were operated on (group 2). The immune status of patients (T, B, NK, DN, Tregs) was assessed during treatment. Homogenates of tumor tissue samples obtained during surgery were studied for the levels of lymphocytes (flow cytometry) and cytokines TNF-α, IL-1ß, IL-1RA, IL-6, IL-8, IFN-α, IFN-γ (ELISA); tumor proliferation index was assessed by DNA cytometry. Results were analyzed by Statistica 10.0 program. Results: The dynamics of parameters of the cellular immunity was different in patients of two groups. In group 1, percentage of T lymphocytes in blood decreased (from 66.7±3.3 to 50.4±1.6%), as well as their main subsets (CD4+ and CD8+ cells: from 33.6±2.7 to 27.0±1.7% and from 26.7±2.4 to 20.7±1.7% respectively). Patients of group 2 developed an increase in levels of NK cells from 10.1±1.2 to 15.3±2.2%, and levels of CD3+, CD4+ and CD8+ cells were significantly higher than in group 1: 35.0±1.8% for CD4+ and 28.3±2.9% for CD8+ (p < 0.05). The groups also differed in indices of local immunity: DN cells levels in group 2 were lower than in group 1 (5.8±1.0 vs. 18.4±5.4%) and CD4+ were higher (36.6±3.3 vs. 26.2±3.1%; p < 0.05). Patients of group 2 showed lower levels of IL-1ß, IL-6, IL-10, while IFNγ was elevated by 5.4 times, indicating a more favorable local cytokine status of the patients, compared to group 1. Conclusions: In rectal cancer patients with effect confirmed by DNA cytometry, prolongation of chemoradiotherapy to 6-8 weeks provides the formation of a more favorable immunological microenvironment of the tumor, and in such cases it is considered appropriate.

Rectal cancer: The influence of tumor proliferation on response to preoperative irradiation

1995 ◽  
Vol 32 (1) ◽  
pp. 57-61 ◽  
Author(s):  
Christopher G. Willett ◽  
Gretchen Warland ◽  
John Coen ◽  
Paul C. Shellito ◽  
Carolyn C. Compton
Keyword(s):  
Rectal Cancer ◽  
Preoperative Irradiation ◽  
Tumor Proliferation

Tumor proliferation in rectal cancer following preoperative irradiation.

1995 ◽  
Vol 13 (6) ◽  
pp. 1417-1424 ◽  
Author(s):  
C G Willett ◽  
G Warland ◽  
M P Hagan ◽  
W J Daly ◽  
J Coen ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Proliferative Activity ◽  
Rectal Wall ◽  
Locally Advanced ◽  
Advanced Rectal Cancer ◽  
Nuclear Antigen ◽  
High Dose ◽  
Preoperative Irradiation ◽  
Tumor Proliferation ◽  
Ki 67

PURPOSE This study examines the effect of preoperative irradiation on tumor proliferation in rectal cancer. PATIENTS AND METHODS One hundred twenty-two patients with locally advanced rectal cancer received 45 to 50 Gy of preoperative irradiation followed by surgery. Pretreatment tumor biopsies and postirradiation surgical specimens were scored for proliferative activity by assaying the extent of Ki-67 and proliferating-cell nuclear antigen (PCNA) immunostaining and the number of mitoses per 10 high-power fields (hpf). Preirradiation and postirradiation proliferative activity was determined and correlated to clinical outcome. RESULTS There was an overall reduction in the tumor proliferative activity of rectal cancer after irradiation compared with its preirradiation state. Decreases in the activity of all three markers of tumor proliferation (Ki-67 and PCNA immunostaining, and mitotic counts) were observed in irradiated tumors compared with pretreatment biopsies. Postirradiation tumor proliferative activity was associated with pathologic tumor stage. A high level of proliferative activity was observed in tumors downstaged to the rectal wall (T1-2) compared with tumors that retained transmural penetration (T3-4). Multivariate analysis indicated that postirradiation proliferative activity and stage were independently associated with survival following surgery. Patients with tumors that exhibited elevated proliferative activity postirradiation had improved survival compared with patients with tumors that showed less proliferative activity. CONCLUSION Moderate- to high-dose preoperative irradiation decreases both the tumor size and proliferative activity of rectal cancers. Elevated postirradiation tumor proliferative activity correlates strongly with improved survival. This may aid in identifying high-risk patients following preoperative irradiation and surgery.

Surgery, Radio- and Chemo- therapy for Multimodal Treatment of Rectal Cancer

Swiss Surgery ◽  
2001 ◽  
Vol 7 (6) ◽  
pp. 256-274 ◽  
Author(s):  
Link ◽  
Staib ◽  
Kornmann ◽  
Formentini ◽  
Schatz ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Multimodal Treatment ◽  
Local Relapse ◽  
Phase Iii ◽  
Neoadjuvant Radiotherapy ◽  
Term Survival ◽  
Primary Tumors ◽  
Impact On Survival ◽  
Relapse Rates

The possibilities and results of multimodal treatment in rectal cancer were reviewed with respect to the results of surgical treatment only. Based on the results of 4 studies, reducing local relapse rates and increasing long term survival rates significantly, postoperative radiochemotherapy (RCT) + chemotherapy (CT) should remain the recommended standard for R0 resected UICC II and III rectal cancers. The addition of RT to adjuvant CT reduces local relapses without significant impact on survival (NSABP R-02). Vice versa, the addition of CT to RT or an improved CT in the RCT-concept prolongs survival. Preoperative neoadjuvant radiotherapy (RT) reduced local relapse rates in 9 studies, and extended survival in one study that evaluated all eligible patients. Preoperative RT reduced local relapse rates in addition to total mesorectal excision (TME) but did not extend survival. The preoperative RCT + CT downstages resectable and nonresectable tumors and induces a higher sphincter preservation rate. Phase III data justifying its routine use in all UICC II + III stages are not yet available. This treatment may be routinely applied in nonresectable primary tumors or local relapses. Preoperative RCT (or RT) may evolve as standard, if the patient selection is improved and postoperative morbidity and long term toxicity reduced. Intraoperative RT could be added to this concept or be used together with preoperative/postoperative RT at the same indications. Postoperative adjuvant RT reduced local relapses significantly in a single trial, and no impact on survival time is reported. Since postoperative RT is inferior to preoperative RT, this treatment cannot be recommended, if RT is chosen as a single treatment modality in adjunction to surgery. The results of local tumor excisions may be improved with pre- or postoperative RCT + CT. In the future, multimodal treatment of rectal cancer might be more effective, if individualized according to prognostic factors.

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