Prognostic phenotypic subtypes to predict recurrence and response to adjuvant chemotherapy for colorectal cancer.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 205-205
Author(s):  
Antonia K. Roseweir ◽  
James Hugh Park ◽  
Sanne ten Hoorn ◽  
Arfon GMT Powell ◽  
Susan Aherne ◽  
...  

205 Background: Histological phenotypic subtypes have been proposed that stratify survival in a discovery cohort of patients with stage I-III colorectal cancer (CRC). However, clinical utility has not been validated nor associations with recurrence and chemotherapy assessed. Therefore, this study assessed prognostic value in patients with stage I-III CRC as well as predictive value for recurrence and chemotherapy response. Methods: Two independent stage I-III CRC patient cohorts were utilized to assess associations between phenotypic subtypes, survival, and recurrence. Stage II-III patients, from the SCOT adjuvant chemotherapy trial, were utilized to assess associations between phenotypic subtypes and adjuvant chemotherapy response. Log rank analysis compared immune and stromal subtypes. Results: In an 867-patient internal cohort, phenotypic subtype stratified patients by disease-free survival (DFS) (HR 2.18 95% CI 2.26-4.47, p < 0.001); independent of stage and location. The stromal subtype also predicted increased local and distant recurrence (p < 0.001). In a 146-patient external validation cohort, phenotypic subtype significantly stratified patients by DFS (HR 3.43 95% CI 1.60-7.35, p = 0.001). In 1343 SCOT trial patients, phenotypic subtype significantly stratified patients by DFS (HR 1.59 95% CI 1.13-2.25, p = 0.010). Furthermore, there was evidence that the effect of regimen depended on phenotypic subtype (p = 0.048), only significantly stratifying DFS in patients receiving FOLFOX (HR 3.73 95% CI 1.58-8.81, p = 0.003) but not CAPOX (HR 0.84 95% CI 0.56-1.26, p = 0.396) adjuvant chemotherapy. Interestingly, the immune subtype associated with improved DFS in patients receiving FOLFOX compared to CAPOX adjuvant chemotherapy (HR 3.40 95% CI 1.41-8.19, p = 0.006). Whereas patients with a stromal subtype trended towards improved DFS in patients receiving CAPOX compared to FOLFOX adjuvant chemotherapy (HR 0.72 95% CI 0.50-1.05 p = 0.088). Conclusions: Histological phenotypic subtypes are an effective independent prognostic classification for patients with stage I-III CRC that can predict response to FOLFOX adjuvant chemotherapy as well as the presence of local and distant recurrence.

2019 ◽  
Vol 26 (3) ◽  
pp. 619-631
Author(s):  
Abdullah Sakin ◽  
Nurgul Yasar ◽  
Suleyman Sahin ◽  
Serdar Arici ◽  
Saban Secmeler ◽  
...  

Background This study aimed to retrospectively investigate the efficacy and tolerability of adjuvant chemotherapy in ≥70-year-old patients with stage IIA (T3N0M0) colorectal cancer. Methods Lymphovascular invasion, perineural invasion, margin positivity, dissected lymph node count of <12, and presence of perforation/obstruction were accepted as risk factors. Those patients with at least one risk factor were regarded as having high risk. Results The study included 168 patients, among which 95 (56.5%) were male and 73 (43.5%) were female. The median age of patients was 73 years (range: 70–94). One hundred one (60.1%) patients were identified to have high risk. Eighty-one (87%) patients received 5-flourouracil+leucovorin and 12 (13%) patients received capecitabine regimens as adjuvant chemotherapy. The patients receiving capecitabine regimen had significantly higher rates of dose reduction at initiation and during the treatment. Among low-risk group, there was no statistically significant difference between patients with and without adjuvant chemotherapy in terms of disease-free survival or overall survival (p = 0.528 and p = 0.217, respectively). In high-risk group, patients receiving adjuvant chemotherapy significantly differed from those not receiving adjuvant chemotherapy in terms of median disease-free survival and overall survival (p = 0.009 and p < 0.001, respectively). While the grade, lymph node status, and adjuvant chemotherapy were identified as the most significant independent factors for disease-free survival, the most significant factors for overall survival were the age, Eastern Cooperative Oncology Group performance status, adjuvant chemotherapy, and recurrence. Conclusion The findings of our study showed improved disease-free survival and overall survival in high-risk ≥70-year-old patients who received adjuvant chemotherapy due to T3N0M0 colorectal cancer. We believe that 5-flourouracil+leucovorin or capecitabine regimens should be recommended for these older high-risk patients who could receive adjuvant chemotherapy regardless of age.


Author(s):  
Masatsune Shibutani ◽  
Kiyoshi Maeda ◽  
Hisashi Nagahara ◽  
Hiroshi Ohtani ◽  
Tetsuro Ikeya ◽  
...  

Abstract Objective: The aim of this retrospective study was to evaluate the prognostic significance of lymphopenia associated with chemotherapy in patients with colorectal cancer who received adjuvant chemotherapy after undergoing potentially curative surgery. Summary of background data: Lymphocyte plays an important role in anti-tumor immunity. Lymphopenia is sometimes induced during the period of adjuvant chemotherapy after potentially curative surgery for colorectal cancer. However, the prognostic significance of lymphopenia associated with chemotherapy is unknown. Methods: One hundred and fifteen patients who received adjuvant chemotherapy after potentially curative surgery for stage II/III colorectal cancer were enrolled in this study. All patients were classified into two groups, the lymphopenia group and the normal group, according to minimum lymphocyte count during the period of adjuvant chemotherapy. Lymphopenia was defined as a lymphocyte count of less than 1,000/Ã&#x8e;¼l. Lymphopenia associated with chemotherapy was found in 17 of the 115 patients (14.8%). Results: Lymphopenia was associated with a worse disease-free survival (p=0.018). Moreover, in a multivariate analysis, lymphopenia associated with chemotherapy was identified to be an independent prognostic factor.


2008 ◽  
Vol 14 (9) ◽  
pp. 2749-2755 ◽  
Author(s):  
Antonello Di Paolo ◽  
Monica Lencioni ◽  
Federica Amatori ◽  
Samantha Di Donato ◽  
Guido Bocci ◽  
...  

2020 ◽  
Vol 30 (5) ◽  
pp. 664-669 ◽  
Author(s):  
Dan Wang ◽  
Shan Zhu ◽  
Congwei Jia ◽  
Dongyan Cao ◽  
Ming Wu ◽  
...  

ObjectiveThe standard treatment for young patients with stage I malignant ovarian germ cell tumors, except stage I dysgerminoma and stage IA G1 immature teratoma, is unilateral salpingo-oophorectomy with complete staging surgery followed by platinum-based chemotherapy. However, the role of complete staging surgery and adjuvant chemotherapy remains controversial. The aim of this study was to investigate the role of complete staging surgery and adjuvant chemotherapy in patients with early-stage pure immature teratoma after fertility-sparing surgery.MethodsPatients with stage I pure immature teratoma who underwent fertility-sparing surgery between January 1986 and June 2018 were reviewed retrospectively. Fertility-sparing surgery was defined as preservation of the uterus and at least one adnexa. The inclusion criteria were age >18 years, stage I disease (confined to one ovary), and diagnosis of pure immature teratoma. Patients with distant metastasis or mixed ovarian germ cell tumor were excluded. Complete staging surgery was defined as peritoneal cytology examination, peritoneal biopsy, omentectomy, or omental biopsy with or without lymph node dissection. Patients designated with stage I disease without complete staging surgery were categorized as stage X. Disease-free survival was defined as the interval from the date of surgery to the date of recurrence or censoring. Disease-free survival curves were calculated using the Kaplan–Meier method and compared using the log-rank test.ResultsA total of 75 patients were included in the analysis, with a median age of 26 years (range 18–40): 26 (34.7%) patients had received complete staging surgery; 51 (68%) patients received postoperative adjuvant chemotherapy while 24 (32%) underwent surgery alone; and 4 patients (5.3%) had recurrent disease during a median follow-up time of 80.2 months (range 13.7–261). The recurrence rates in the chemotherapy group and surveillance groups were 3.9% and 8.3%, respectively (p=0.46). All patients were successfully salvaged, except for one death. Tumor relapse occurred in patients with all grades of immature teratoma (G1: 1/35; G2: 2/25; G3: 1/15). Univariate analysis revealed that complete staging surgery, adjuvant chemotherapy, and tumor grade were not associated with 5 year disease-free survival (p=0.69, p=0.46, p=0.7, respectively). The 5 year disease-free survival rate was 94.6% and the overall survival rate was 98.7%.ConclusionAdult patients with stage I pure immature teratoma had 98.7% overall survival and recurrence rates were low after fertility-sparing surgery.


2000 ◽  
Vol 15 (1) ◽  
pp. 51-55 ◽  
Author(s):  
A.I. Behbehani ◽  
H. Al-Sayer ◽  
M. Farghaly ◽  
N. Kanawati ◽  
A. Mathew ◽  
...  

Preoperative CEA and CA 19–9 levels have been used in the past as prognostic indicators in colorectal cancer, but Dukes’ stage is still considered to be the most important prognostic factor. Recent survival estimates may have been influenced by the fact that in the last decade adjuvant chemotherapy and postoperative irradiation have been included in the routine management of advanced-stage disease. In a heterogeneous Kuwaiti population higher reference levels (95th percentile) of CEA and CA 19–9 have been found than those usually employed. In the present study 62 patients with Dukes’ stage B + C could be analyzed for two-year disease-free survival (DFS). Relapse was observed in 19 patients, 28 patients were disease free and 15 patients with censored observations were included. No significant difference in DFS was observed in Dukes’ B (69%) versus Dukes’ C (48%) patients (p=0.09). On the other hand, Dukes’ stage B+C patients with elevated preoperative levels of CEA or CA 19–9 had a significantly poorer DFS than patients with normal levels. For CEA levels below or above the cutoff the DFS was 74% versus 23% (p=0.003); for CA 19–9 levels below or above the cutoff the DFS was 71% versus 33% (p=0.004). In 54 patients with Dukes’ stage B+C for whom preoperative levels of both CEA and CA 19–9 were available multivariate analysis revealed a decreasing risk of relapse in the following order: CEA and/or CA 19–9 elevated (chi-square 7.09; p=0.008), CA 19–9 elevated (chi-square 6.27; p=0.01), CEA elevated (chi-square 5.47; p=0.02), and Dukes’ C (chi-square 2.08; p=0.15 n.s.). Hence, novel treatment protocols may have improved the disease-free survival, but the use of adjuvant chemotherapy and/or radiotherapy is of questionable benefit in patients who have elevated levels of CEA and/or CA 19–9 prior to treatment.


2012 ◽  
Vol 27 (3) ◽  
pp. 203-211 ◽  
Author(s):  
Yao Chen ◽  
Cuihua Yi ◽  
Lian Liu ◽  
Bei Li ◽  
Yawei Wang ◽  
...  

Background Although many studies have investigated the prognostic effect of thymidylate synthase (TS) in colorectal cancer, no consensus has been reached. The aim of this meta-analysis was to obtain a more precise estimate of the prognostic significance of TS expression in localized cancers treated by curative resection and adjuvant chemotherapy. Materials and method Seventeen eligible studies reporting survival in 2,893 patients stratified by TS expression were pooled using a fixed- or random-effects model. The main outcome measure was hazard ratio (HR). Results The overall HR for overall survival was 1.01 (95% CI 0.74–1.39, p=0.947), with an I2 of 64.4%. The total HR for disease-free survival was 1.36 (95% CI 0.97–1.89, p=0.072), with an I2 of 75.8%. In the TS protein-tested subgroup, the total HR for disease-free survival was 1.72 (95% CI 1.02–2.89, p=0.042), with an I2 of 81.3%. Conclusion Our meta-analysis showed that, in the adjuvant setting, TS expression does not predict a poorer disease-free survival or a worse overall survival. Therefore, we believe that it is inappropriate to regard TS expression as a prognostic factor for patients with stage II and stage III colorectal cancer treated by surgery and adjuvant chemotherapy.


1997 ◽  
Vol 15 (6) ◽  
pp. 2432-2441 ◽  
Author(s):  
A Zaniboni

PURPOSE The rationale for using adjuvant chemotherapy in colorectal cancer is to achieve better disease control and thus reduce the high rates of tumor recurrence and mortality in patients who undergo curative surgery. The current literature, including relevant abstracts, on clinical trials of fluorouracil (5-FU) in combination with high-dose leucovorin as adjuvant chemotherapy for colorectal cancer is reviewed. The intent is not to present new data, but to present the reader with a broad perspective and larger patient experience on which to base well-reasoned treatment decisions. DESIGN Published clinical trials and abstracts presented at the 1996 American Society of Clinical Oncology (ASCO) meeting that assessed 5-FU in combination with high-dose leucovorin as adjuvant chemotherapy for colorectal cancer were surveyed. End points of interest were disease-free survival (DFS), overall survival, and toxicity. RESULTS In randomized trials that used high-dose leucovorin at doses that ranged from daily-times-five 200 mg/m2 to weekly 500 mg/m2 in combination with 5-FU, significant improvements in both DFS and overall survival were observed over surgery alone (control). In patients treated with high-dose leucovorin/5-FU, DFS rates ranged from 71% to 77% compared with control (58% to 64%). A similar trend was seen in overall survival, with a range of 75% to 84% compared with control (63% to 77%). Toxicities observed for high-dose leucovorin administered on a weekly or daily-times-five schedule were diarrhea, stomatitis, myelosuppression, and nausea. CONCLUSION Overall, the results of these randomized trials support the use of high-dose leucovorin/5-FU as adjuvant therapy for colorectal cancer. Longer follow-up studies are needed to compare the benefits of these different regimens in terms of survival and to characterize adverse effects, especially those that may not be immediately evident. Adjuvant therapy with high-dose leucovorin/5-FU is an effective regimen that is well tolerated by many patients with colorectal cancer.


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