Mucinous colorectal cancer: Disease characteristics, treatment outcomes and the impact of metastasectomy.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 3586-3586
Author(s):  
Darren Cowzer ◽  
Emily Harrold ◽  
Jane Sze Yin Sui ◽  
Mairi Lucas ◽  
Helen M Fenlon ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
De Novo ◽  
Medical Oncology ◽  
Disease Free Survival ◽  
Stage Ii ◽  
Stage Iii ◽  
Metastatic Setting ◽  
Significant Difference ◽  
The Impact

3586 Background: Mucinous colorectal cancer (CRC) differs from adenocarcinoma with regard to clinical and histological features and is reported to have inferior outcomes when compared to non-mucinous CRC. This study aims to evaluate the clinical features and outcomes of patients with mucinous CRC at our institution. Methods: Medical records of patients with CRC that were referred to medical oncology between September 1999 and September 2018 were retrospectively reviewed. Mucinous histology was defined as those containing > 50% mucin identified on histology specimens. Statistical analysis was performed using Prism V9.0. Results: We identified 1,115 patients with CRC that were referred to medical oncology during this period. The tumours of 81 (7.3%) patients were classified as mucinous. Median age was 65 (28-94 years) and 45 (55.5%) were male. Forty-one patients (51%) had right sided tumours, 27 (33%) had left sided tumours and 13 (16%) had rectal tumours. Twenty-three (28.4%) had de novo metastatic disease. Eleven of 24 patients (46%) with stage II disease relapsed and 18 of 33 (55%) of those with stage III disease relapsed. Radiological surveillance identified 20/29 (69%) of relapsed disease, 5 (17%) were symptomatic and 4 (14%) had a rise in CEA. Median follow up for patients with stage II disease was 53 months and 3 year and 5-year disease free survival (DFS) was equal in both groups at 60.9%. For stage III disease 3- and 5-year DFS was 58.1% and 48.4% respectively with a median follow up of 43 months. In the metastatic setting, we observed no significant difference in overall survival (OS) between left and right sided tumours ( p = 0.550). Median OS for pts with stage IV mucinous CRC who received any treatment was 25 months. Metastasectomy was performed in 25/52 (48%) patients and was associated with a significant improvement in OS, 23 vs 51 months ( p < 0.005, HR 0.4). Conclusions: Mucinous CRC has been associated with inferior responses to treatment and worse overall outcomes compared to non-mucinous histologies. Survival in advanced-stage disease in our cohort is higher than what has been reported in the literature. With an effective multi-disciplinary approach and the increasing use of metastasectomy as a treatment option, survival in the advanced disease setting may be comparable to non-mucinous CRC.

The Addition of Gemtuzumab Ozogamicin to Induction Chemotherapy for AML Improves Disease Free Survival without Extra Toxicity: Preliminary Analysis of 1115 Patients in the MRC AML15 Trial.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 13-13 ◽  
Author(s):  
Alan K. Burnett ◽  
William J. Kell ◽  
Anthony H. Goldstone ◽  
Donald Milligan ◽  
Ann Hunter ◽  
...  
Keyword(s):  
Induction Chemotherapy ◽  
Preliminary Analysis ◽  
De Novo ◽  
Remission Rate ◽  
Pilot Trial ◽  
Disease Free Survival ◽  
Gemtuzumab Ozogamicin ◽  
Significant Difference ◽  
The Impact

Abstract The MRC AML15 Trial is primarily for patients with any form of AML who are under 60 years. One of the questions addressed was whether the addition of the immunoconjugate, Gemtuzumab Ozogamicin (GO) to induction (course 1) and/or consolidation (course 3) is beneficial. In induction patients are randomised to receive either DA (Daunorubicin/Ara-C) or ADE (Ara-C/Daunorubicin/Etoposide) or FLAG-Ida (Fludarabine/Ara-C/Idarubicin/G-CSF) and in consolidation either MACE (Amsacrine/Etoposide) or HD Ara-C (3.0g/m2 or 1.5g/m2 per dose). Our prior pilot trial had shown that GO 3mgs/m2 could be safely added to day 1 of each of these treatments (Kell et al Blood102, 4277–4283). Here we report the preliminary results of the effect of combining GO with induction chemotherapy. This randomisation achieved its recruitment target and was closed on 30 June 2006. All other comparisons in the trial, including GO in consolidation, remain open. Patients: A total of 1115 patients were randomised between July 2002 and June 2006. The median age was 49 (range 0–71) years: 53% of patients were male: 92% (n=1027) had de novo disease: 95% had WHO performance score of &lt;2: 43% received DA, 43% FLAG-Ida, and 14% ADE. (Recruitment to ADE+GO opened in June 2005). Patients with WBC &gt; 30 x 109/l and LFT’s &gt; normal were initially excluded but admitted from March 2004. APL patients were not eligible for entry. 15% of patients with data had favourable 71% intermediate, and 14% adverse cytogenetics. Over 83% were CD33 positive. Results: The overall remission rate was 85% with no differences between the arms for GO vs no GO in CR (85% vs 85%) induction death (8% vs 7%) or resistant disease (7% vs 8%). There was a modest increase in mucositis on the GO arm in course 1 only (p=0.04) and increased AST and Alt toxicity in C1 (p=.002; p=.03) but no difference in bilirubin grades. GO patients used more platelets (19 vs 14; p&lt;0.0001), but not red cells, and had more days on IV antibiotics (20.6 vs 18.6 p=0.001). The haemopoietic recovery and days in hospital were similar. With a median follow-up of 15 months (range 0–45), there is no significant difference in deaths in CR (GO vs no GO): 36 vs 45 (HR 0.75; CI.49–1.16 p=0.2), but relapse was reduced: 37% vs 52% at 3 years (HR 0.70 (0.52–0.92) p=0.01) resulting in an improved DFS: 51% vs 40% at 3 years (HR 0.72 (0.56–0.91) p=0.008). There is so far no significant difference in OS (53% vs 46% at 3 years; HR 0.91(0.73–1.14) p=0.4). Conclusion: This preliminary analysis of 1115 randomised patients indicates that the addition of GO to induction chemotherapy can reduce the relapse risk without adding significant extra toxicity and this has significantly improved the DFS in the GO arm. Longer follow up is required to determine the impact on survival.

SCOT: Tumor sidedness and the influence of chemotherapy duration on DFS.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 558-558 ◽  
Author(s):  
Mark P. Saunders ◽  
James Paul ◽  
Jana Crosby ◽  
Gordon Brown ◽  
Timothy Iveson ◽  
...  
Keyword(s):  
High Risk ◽  
Disease Free Survival ◽  
Stage Ii ◽  
Stage Iii ◽  
Contributing Factors ◽  
Significant Difference ◽  
N Stage ◽  
Stage Ii Colorectal Cancer ◽  
Meta Analyses ◽  
The Impact

558 Background: Patients with R-sided tumours who develop metastatic disease have a worse prognosis compared to patients with L-sided tumours. The latter may also have a greater benefit from treatment with EGFR inhibitors. In general, registry studies and meta-analyses have shown that patients with loco-regional R-sided tumours have a worse overall survival (OS). This has recently been confirmed by the PETACC8 study but only after they had relapsed. There was not a significant difference in disease free survival (DFS). Methods: The SCOT study showed that 3-months of oxaliplatin-containing adjuvant chemotherapy (OxFp) was non-inferior to 6-months for patients with stage III and high-risk stage II colorectal cancer. Here we divide the population into left and right-sided tumours to see whether sidedness had an impact on DFS. We also evaluated whether sidedness impacted on the 3 vs. 6-months comparison in SCOT. Results: 6088 patients with Stage III/high risk Stage II cancers or the colon or rectum were randomised between March 27, 2008 and November 29, 2013 from 244 centres (164 UK, 32 Australia, 19 Spain, 14 Sweden, 10 Denmark and 5 New Zealand). In February 2017 (3-years FU) information on sidedness was available for 3219 patients (1207 R-sided, 2012 L-sided). Characteristics: Right: median age: 65, Male: 53%, T4 41%, Stage II: 17%; Left: median age: 65, Male: 66%, T4 24%, Stage II: 21%). Patients with R-sided tumours had a significantly worse DFS (3-year DFS right: 73% (se=1%), left: 80% (se=1%). HR 1.401 (95% CI 1.216-1.615; p=0.000004). Adjusting for T and N-stage reduced the HR to 1.215 (95% ci 1.051-1.404, p=0.009). The data did not suggest that sidedness affected the impact of chemotherapy duration on 3-year DFS (R: HR (3 month/6 month) 1.049 (0.849 -1.296) L: 0.910 (0.753-1.099). Test for homogeneity, p=0.327). Further sub-set analysis was limited due to cohort size. Conclusions: This is the first study to show that unselected patients with R-sided tumours had a worse DFS compared to L-sided tumours. This implies that prognosis is influenced primarily by greater recurrence rather than the contributing factors that influence OS. Tumour sidedness did not impact on the 3-months vs. 6-months comparison in SCOT. Clinical trial information: ISRCTN59757862.

scholarly journals Evaluation of the introduction of a standardised protocol for the staging and follow-up of colorectal cancer on resection rates for liver metastases

2010 ◽  
Vol 92 (3) ◽  
pp. 225-230 ◽  
Author(s):  
J Tiernan ◽  
CD Briggs ◽  
GRB Irving ◽  
MT Swinscoe ◽  
M Peterson ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Liver Resection ◽  
Liver Metastases ◽  
Disease Free Survival ◽  
District Hospitals ◽  
Significant Difference ◽  
Specialist Centre ◽  
The Uk ◽  
The Impact

INTRODUCTION In 2004, an audit in our unit demonstrated wide variation in liver resection rates for colorectal cancer (CRC) metastases within the cancer network. Subsequently, a network-wide CT-based follow-up and referral policy was introduced for all patients. A second audit was performed to assess the impact of the guidelines on liver resection rates. SUBJECTS AND METHODS Analysis of prospective liver resection database between 1997 and 2004 and after the introduction of standardised guidelines between January 2005 and April 2008. RESULTS A total of 362 patients underwent liver resection for CRC metastases between 1997 and 2008, 237 prior to the introduction of the referral guidelines and 125 after. Liver resection rates according to referring hospital varied from 0.92 to 2.32 per 100,000 population before guidelines were introduced. After 2005, resection rates from the four district hospitals standardised (1.68–1.84 per 100,000 population), but the central unit rate (Sheffield) remained significantly higher (2.67 per 100,000 population). No significant difference in 1-year disease-free survival between patients from Sheffield and the outlying hospitals was found (P = 0.553). CONCLUSIONS Introduction of a referral protocol standardised resection rates from the four district hospitals, but these remain lower compared to the specialist centre. The wide-spread adoption of a policy to discuss all patients with liver metastases at an advanced disease multidisciplinary team meeting, in the presence of hepatobiliary specialists, may further increase resection rates across the UK.

Preoperative hepatic and regional arterial chemotherapy in the prevention of liver metastasis after colorectal cancer surgery

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4090-4090
Author(s):  
J. Xu ◽  
Y. Zhong ◽  
W. Niu ◽  
X. Qin ◽  
Y. Wei ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Liver Metastasis ◽  
Disease Free Survival ◽  
Stage Ii ◽  
Stage Iii ◽  
Control Group ◽  
Free Survival ◽  
Significant Difference ◽  
Disease Free

4090 Background: To investigate whether preoperative hepatic and regional arterial chemotherapy are able to prevent liver metastasis and improve overall survival in patients receiving curative colorectal cancer resection. Methods: Patients with Stage II or Stage III colorectal cancer (CRC) were randomly assigned to receive preoperative hepatic and regional arterial chemotherapy (PHRAC group, n=256) or surgery alone (control group, n=253). The primary endpoint was disease-free survival, whereas the secondary endpoints included liver metastasis-free survival and overall survival. Results: There were no significant differences in overall morbidity between PHRAC and Control groups. During the follow-up period (median, 42 months), the median liver metastasis time for patients with stage III CRC was significantly longer in the PHRAC group (16±3 months v.s. 8±1 months, P=0.01). In stage III patients, there was also significant difference between the two groups with regard to the incidence of liver metastasis (18.9% vs 27.3%, P=0.01), 5-year disease-free survival (70.2% vs 52.0%, P=0.0076), 5-year overall survival (80.3% vs 69.5%, P=0.020) and the median survival time (40.1± 4.6 months vs 36.3 ± 3.2 months, P=0.03). In the PHRAC arm, the risk ratio of recurrence was 0.63 (95% CI, 0.51–0.79, P=0.0001), of death was 0.50(95% CI, 0.32–0.67; P=0.005), and of liver metastasis was 0.70 (95% CI, 0.52–0.86; p=0.01). In contrast, PHRAC seemed to be no benefit for stage II patients. Toxicities, such as hepatic toxicity and leucocyte decreasing, were mild and could be cured with medicine. Conclusions: Preoperative hepatic and regional arterial chemotherapy, in combination with surgical resection, could be able to reduce and delay the occurrence of liver metastasis and therefore improve survival rate in patients with stage III colorectal cancer. No significant financial relationships to disclose.

The impact of primary tumor sidedness on survival in early-onset colorectal cancer by stage: A National Veterans Affairs retrospective analysis.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 31-31
Author(s):  
Ibrahim Azar ◽  
Nada Almasalmeh ◽  
Saghi Esfandiarifard ◽  
Gurjiwan Virk ◽  
Wissam Kiwan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Primary Tumor ◽  
Early Onset ◽  
Stage Iv ◽  
Response To Therapy ◽  
Stage Ii ◽  
Metastatic Setting ◽  
Significant Difference ◽  
The Impact ◽  
Early Onset Colorectal Cancer

31 Background: The incidence of early-onset colorectal cancer (EOCRC) is rising. Left-sided colorectal cancer (LCC) is associated with better survival and response to therapy compared to right-sided colon cancer (RCC) in the metastatic setting. Current NCCN guidelines recommend the addition of EGFR inhibitors to KRAS/NRAS wild-type metastatic CRC originating from the left-side only. Whether primary tumor sidedness impacts survival in loco-regional disease and in EOCRC is of clinical interest. Methods: Data from the National VA Cancer Cube Registry was studied. 65,940 cases of CRC were diagnosed between 2001 and 2015. EOCRC (2,096 cases) was defined as CRC diagnosis at age <50 years. ICD codes C18 to C20 were used to delineate patients with RCC vs. LCC. RCC was defined as cancer from the cecum to the hepatic flexure (C18.0-C18.3), LCC from the splenic flexure to the rectum (C18.5-18.CRC; C19 & C20). Transverse cancer (C18.4), overlapping and unidentified sites (C18.8; C18.9) were excluded. Results: EOCRC is more likely to originate from the left-side (66.65% LCC in EOCRC vs. 58.77% in the whole CRC dataset). Overall, LCC has better 5-year OS than RCC in Stage I, III and better 1-year OS in stage IV (Table). Stage II RCC has better 5-year OS than LCC (RC 53.39% vs LC 49.28%). In EOCRC, there is no statistically significant difference between LCC and RCC in Stages I-III. Stage IV EOCRC patients with LCC and RCC have a 1-year OS of 73.23% and 59.84%, respectively. Conclusions: EOCRC is more likely than CRC to originate from the left side. In EORCRC patients, LCC is associated with better OS than RCC only in patients with metastatic disease. In the overall population, LCC is associated with better OS in all states except Stage II. The better prognosis of Stage II RCC might be due to the reported high incidence of MSI-high tumors in this subpopulation. [Table: see text]

Adjuvant chemotherapy with uracil-tegafur (UFT) for stage III colorectal cancer: Final results of randomized trials by the National Surgical Adjuvant Study of Colorectal Cancer (NSAS-CC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4049-4049 ◽  
Author(s):  
T. Hamaguchi ◽  
K. Shirao ◽  
Y. Moriya ◽  
S. Yoshida ◽  
S. Kodaira ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Rectal Cancer ◽  
Colon Cancer ◽  
Adjuvant Chemotherapy ◽  
Hazard Ratio ◽  
Stage Iii ◽  
Control Group ◽  
Significant Difference ◽  
Resected Stage

4049 Background: In the latter 1990s, no consensus was reached as to whether adjuvant chemotherapy was standard treatment for completely resected stage III colorectal cancer in Japan. At that time, we started two randomized controlled trials to clarify the role of adjuvant chemotherapy of stage III colon and rectal cancer in the same time. Methods: Patients with completely resected stage III cancer of the colon or rectum (PS, 0 to 2; age, 20 to 75 years; no other adjuvant therapy) were eligible for these trials. Patients were registered within 6 weeks after surgery and were randomly assigned to receive surgery alone (control group) or surgery followed by treatment with UFT (400 mg/m2/day), given for 5 consecutive days per week for 1 year (UFT group). The target number of patients was 500 for colon cancer and 400 for rectal cancer (hazard ratio = 0.67, one-sided a= 0.05, β= 0.2). The primary endpoint was relapse-free survival (RFS), and the secondary end point was overall survival (OS). Results: Between October 1996 and April 2001, a total of 334 patients with colon cancer and 276 with rectal cancer were enrolled. Four ineligible patients were excluded; data from the remaining 332 patients with colon cancer and 274 with rectal cancer were analyzed. The patients’ characteristics were similar in the groups. Analysis of the results of follow-up until March 2006, at least 5 years after surgery in all patients (median follow-up period, 6.2 years), showed no significant difference in RFS or OS in colon cancer. In rectal cancer, however, RFS and OS were significantly better in the UFT group than in the control group. The only grade 4 toxicity was diarrhea, occurring in 1 patient with colon cancer and 1 patient with rectal cancer. Conclusions: Postoperative adjuvant chemotherapy with UFT is well tolerated and improved RFS and OS in patients with stage III rectal cancer. In colon cancer, the expected benefits were not obtained (hazard ratio = 0.67). [Table: see text] No significant financial relationships to disclose.

Retrospective assessment of adherence to ASCO Surveillance Guidelines following treatment for stage II and III colorectal cancer (CRC)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e17517-e17517
Author(s):  
J. M. Davies ◽  
S. Lupichuk ◽  
E. Batuyong ◽  
R. J. Hilsden ◽  
J. Easaw
Keyword(s):  
Ct Scan ◽  
Adjuvant Treatment ◽  
Laboratory Data ◽  
Primary Care Providers ◽  
Stage Ii ◽  
Stage Iii ◽  
Care Providers ◽  
Cancer Centre ◽  
The Impact

e17517 Background: The 2005 ASCO guidelines for surveillance following adjuvant therapy for CRC outlined recommended surveillance tests and their frequencies including history and physical examination, CEA testing, CT scan and colonoscopy. The purpose of this study was to assess the impact of these guidelines post treatment of stage II and III CRC in the Calgary Health Region (CHR) before and after implementation of a computer generated, personalized discharge letter (DL). Methods: Cohort 1 patients completed adjuvant chemotherapy or radiotherapy for stage II and III CRC between September 1, 2006, and November 30, 2007, prior to implementation of the DL. Cohort 1 was retrospectively identified from the Alberta Cancer Registry. Registry data was collated with laboratory data and diagnostic imaging data is forthcoming. Adherence to the guidelines at 1-year follow-up in cohort 1 was measured. Prospective data collection on patients who completed adjuvant treatment after implementation of the DL (cohort 2) is ongoing. Comparison of adherence rates to surveillance testing between the two cohorts will be reported upon study completion. Results: For cohort 1, 209 of 238 patients referred to the cancer centre were from the CHR and hence included in the analysis. The average age was 65 and 53% were male. Most patients (136/209) had stage III CRC. 1/209 had a local recurrence only. 27/209 progressed to metastatic disease during the 1-year follow-up period, of which 23 of these patients were initially diagnosed with stage III CRC. CEA adherence (≥4 tests taken within 1-year follow-up period) was 38.3% (95% CI 31.7–44.9). CT scan adherence and use of “inappropriate” surveillance testing for cohort 1 will be available at the meeting. Conclusions: This study assesses compliance with the 2005 ASCO CRC surveillance guidelines at 1-year follow-up post adjuvant treatment at a tertiary cancer centre. Analysis of cohort 1 reveals that adherence to CEA testing is suboptimal. The next phase of this study will assess the impact of a DL, sent to patients and primary care providers outlining recommended surveillance tests and dates, on adherence rates. No significant financial relationships to disclose.

Effect of preoperative hepatic and regional arterial chemotherapy on metachronous liver metastasis after curative colorectal cancer resection: A prospective, multicenter, randomized controlled trial.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 511-511
Author(s):  
Jianmin Xu ◽  
Jianguo Xia ◽  
Yan Gu ◽  
Jianjiang Lin ◽  
Kefeng Ding ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Liver Metastasis ◽  
Adjuvant Therapy ◽  
Disease Free Survival ◽  
Stage Ii ◽  
Stage Iii ◽  
Metachronous Liver Metastasis ◽  
Colorectal Cancer Resection ◽  
Multicenter Randomized Controlled Trial ◽  
Metastasis Rate

511 Background: To evaluate the addition of preoperative hepatic and regional arterial chemotherapy (PHRAC) on prognosis for stage II and III colorectal cancer in a multicenter setting. Methods: Patients with clinical stage II or stage III colorectal cancer (CRC) were randomly assigned to receive PHRAC plus adjuvant therapy (PHRAC arm) or adjuvant therapy alone (control arm). The primary end point was disease free survival (DFS). Second end points were incidence of metachronous liver metastasis, overall survival (OS) and safety. Results: A total of 688 patients from 5 centers of China were randomly assigned to each arm. Five-year DFS were 75% for PHRAC arm and 61% for control arm (HR 0.60; 95% CI, 0.45 to 0.80; p<0.001). Five-year liver-metastasis rate was 8% and 18% in PHRAC arm and control arm, respectively (HR 0.39; 95% CI, 0.24 to 0.64; p<0.001). Five-year OS was 81% in PHRAC arm and 72% in control arm (HR 0.59; 95% CI, 0.42 to 0.84; p=0.003). There were no significant differences in morbidity or mortality between two arms. The results of eligible patients were barely changed. Subgroup analysis shows differences of DFS, liver-metastasis rate and OS were significant in stage III patients, but not in stage II patients. Conclusions: Additional PHRAC could reduce the incidence of metachronous liver metastasis and improve DFS and OS in patients with stage III CRC, without compromising patient safety. Clinical trial information: NCT00643877.

scholarly journals Folate pathway genes linked to mitochondrial biogenesis and respiration are associated with outcome of patients with stage III colorectal cancer

Tumor Biology ◽  
2019 ◽  
Vol 41 (6) ◽  
pp. 101042831984623 ◽  
Author(s):  
Elisabeth Odin ◽  
Arvid Sondén ◽  
Göran Carlsson ◽  
Bengt Gustavsson ◽  
Yvonne Wettergren
Keyword(s):  
Colorectal Cancer ◽  
Cancer Patients ◽  
Mitochondrial Biogenesis ◽  
Disease Free Survival ◽  
Stage Iii ◽  
Free Survival ◽  
Folate Pathway ◽  
Colorectal Cancer Patients ◽  
Disease Free

5-fluorouracil in combination with the folate leucovorin is the cornerstone in treatment of colorectal cancer. Transport of leucovorin into cells, and subsequent metabolic action, require expression of several genes. The aim was to analyze if tumoral expression of genes putatively involved in leucovorin transport, polyglutamation, or metabolism was associated with outcome of patients with stage III colorectal cancer treated with adjuvant chemotherapy. A total of 363 stage III colorectal cancer patients who received adjuvant bolus 5-fluorouracil + leucovorin alone, or in combination with oxaliplatin according to Nordic bolus regimes were included. Expression of 11 folate pathway genes was determined in tumors using quantitative real-time polymerase chain reaction and related to disease-free survival. The median follow-up time was 5 years. During follow-up, 114 (31%) patients suffered from recurrent disease. A high tumoral expression of the genes SLC46A1/PCFT, SLC19A1/RFC-1, ABCC3/MRP3, GGH, and MTHFD1L, which are involved in folate transport, polyglutamation, or metabolism, was associated with longer disease-free survival of the patients. Each of these genes either encodes mitochondrial enzymes or is being regulated by mitochondrial transcription factors. Expression of the SLC46A1/PCFT gene was most strongly associated with disease-free survival, regardless of treatment regimen. In conclusion, the results show that expression of folate pathway genes are associated with outcome of colorectal cancer patients treated with adjuvant 5-fluorouracil in combination with leucovorin. A prospective study needs to be conducted to determine if expression of these genes can be used to predict response to leucovorin and other folates that are now being tested in clinical studies. Moreover, there seems to be a link between folate metabolism and mitochondrial biogenesis and respiration that deserves further exploration.

Adjuvant methotrexate escalated to toxicity for resectable stage III and IV squamous head and neck carcinomas--a prospective, randomized study.

1987 ◽  
Vol 5 (2) ◽  
pp. 278-285 ◽  
Author(s):  
R E Rentschler ◽  
D W Wilbur ◽  
G H Petti ◽  
G D Chonkich ◽  
D A Hilliard ◽  
...  
Keyword(s):  
Overall Survival ◽  
Head And Neck ◽  
Statistical Significance ◽  
Randomized Study ◽  
Disease Free Survival ◽  
Stage Iii ◽  
Hematologic Toxicity ◽  
Head And Neck Carcinomas ◽  
Significant Difference

To determine if adjuvant methotrexate (MTX), escalated weekly to toxicity, could improve disease-free survival (DFS) and overall survival by preventing recurrent disease, 60 patients with potentially resectable stage III or IV squamous head and neck carcinomas were stratified by primary site, stage, and nutritional status, then randomized by pairs to receive or not receive adjuvant MTX. All received standard surgery and postoperative radiation therapy. Five patients were taken off study because of unresectability at the time of surgery, leaving 55 evaluable patients. There were no statistically significant imbalances in known prognostic factors between the two treatment arms. MTX was begun at 40 mg/m2 and escalated 10 mg/m2 weekly (four doses preoperatively; four doses postoperatively, preradiation therapy; eight doses postradiation therapy) to mucosal or hematologic toxicity. The median peak MTX dose achieved was 80 mg/m2. Although three patients were hospitalized with MTX toxicity, none died of MTX toxicity. No patient receiving MTX had disease progression during treatment, and there was no increase in postoperative complications. Thirty-two patients died (median survival, 19 months); 23 patients are alive with median follow-up of 43 months. There was no statistically significant difference in actuarial DFS (P = 1.0) or overall survival (P = .61). Although patients on the MTX arm appeared to have less local and regional recurrences at first recurrence (thus more distant metastases), this did not reach statistical significance (P = .06). There was no significant difference between the sites of recurrence at death or last follow-up (P = .38).

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