In this large study of colorectal-cancer screening, the endoscopist's rate of adenoma detection was associated with the risk of interval colorectal cancer after screening colonoscopy. Colorectal ...cancers were less likely to be diagnosed between screening examinations when colonoscopies were performed by endoscopists with an adenoma detection rate of 20% or more.
In this large study of colorectal-cancer screening, the endoscopist's rate of adenoma detection was associated with the risk of interval colorectal cancer after screening colonoscopy.
Although colonoscopy is widely used for colorectal-cancer screening,
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its miss rate for cancers and adenomatous polyps (benign premalignant tumors or adenomas), which is low but not negligible, remains a concern.
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It has been suggested that a high-quality examination that ensures the detection and removal of all neoplastic lesions is key for screening efficacy.
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In response, professional societies have proposed the use of various quality-assessment indicators. Of such indicators, the rates of adenoma detection and cecal intubation are the most commonly used.
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However, these measurements have never been validated, and it is not known whether an improvement . . .
The addition of cetuximab to irinotecan, fluorouracil, and leucovorin (FOLFIRI) as first-line treatment for metastatic colorectal cancer (mCRC) was shown to reduce the risk of disease progression and ...increase the chance of response in patients with KRAS wild-type disease. An updated survival analysis, including additional patients analyzed for tumor mutation status, was undertaken.
Patients were randomly assigned to receive FOLFIRI with or without cetuximab. DNA was extracted from additional slide-mounted tumor samples previously used to assess epidermal growth factor receptor expression. Clinical outcome according to the tumor mutation status of KRAS and BRAF was assessed in the expanded patient series.
The ascertainment rate of patients analyzed for tumor KRAS status was increased from 45% to 89%, with mutations detected in 37% of tumors. The addition of cetuximab to FOLFIRI in patients with KRAS wild-type disease resulted in significant improvements in overall survival (median, 23.5 v 20.0 months; hazard ratio HR, 0.796; P = .0093), progression-free survival (median, 9.9 v 8.4 months; HR, 0.696; P = .0012), and response (rate 57.3% v 39.7%; odds ratio, 2.069; P < .001) compared with FOLFIRI alone. Significant interactions between KRAS status and treatment effect were noted for all key efficacy end points. KRAS mutation status was confirmed as a powerful predictive biomarker for the efficacy of cetuximab plus FOLFIRI. BRAF tumor mutation was a strong indicator of poor prognosis.
The addition of cetuximab to FOLFIRI as first-line therapy improves survival in patients with KRAS wild-type mCRC. BRAF tumor mutation is an indicator of poor prognosis.
In a large, national program of colorectal-cancer screening in Poland, men were about twice as likely as women to have advanced neoplasia detected on colonoscopy. The yield of colonoscopy among men ...40 to 49 years of age was similar to that among women 55 to 59 years of age (in these differing age groups, one advanced neoplasia detected for every 23 men and 22 women screened).
In a large program of colorectal-cancer screening, men were about twice as likely as women to have advanced neoplasia detected on colonoscopy. The yield of colonoscopy among men 40 to 49 years of age was similar to that among women 55 to 59 years of age.
Colorectal cancer is the most frequent cancer in Europe
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and the second leading cause of death related to cancer in the United States.
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Screening can lead to decreased incidences of colorectal cancer and death owing to the detection of both precancerous lesions and cancers at early stages, respectively.
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Fecal occult-blood testing and flexible sigmoidoscopy can miss a substantial fraction of important lesions.
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Despite its risk, inconvenience, and cost, colonoscopy is a valid primary screening tool for colorectal cancer when performed every 10 years, beginning at 50 years of age in people who are at average risk.
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Whatever method . . .
To report the results of a planned safety analysis from a phase III trial comparing capecitabine plus oxaliplatin (XELOX) with bolus fluorouracil/leucovorin (FU/LV) as adjuvant therapy for stage III ...colon cancer.
Patients with stage III colon carcinoma were randomly assigned to receive either XELOX (intravenous oxaliplatin plus oral capecitabine; 3-week cycle for eight cycles) or standard intravenous bolus FU/LV administered as the Mayo Clinic (Mayo; Rochester, MN) or Roswell Park (RP; Buffalo, NY) regimen for a similar length of time. A total of 1,886 patients were randomly assigned.
The safety population comprised 1,864 patients, of whom 938 received XELOX and 926 received FU/LV. Most treatment-related adverse events (AEs) occurred at similar rates in both treatment arms. However, patients receiving XELOX experienced less all-grade diarrhea, alopecia, and more neurosensory toxicity, vomiting, and hand-foot syndrome than those patients receiving FU/LV. Compared with Mayo, XELOX showed fewer grade 3/4 hematologic AE and more grade 3/4 gastrointestinal AE. Compared with RP, XELOX showed less grade 3/4 gastrointestinal AE and more grade 3/4 hematologic AE. As expected grade 3/4 neurosensory toxicity and grade 3 hand-foot syndrome were higher with XELOX. Treatment-related mortality within 28 days from the last study dose was 0.6% in the XELOX group and 0.6% in the FU/LV group.
XELOX has a manageable tolerability profile in the adjuvant setting. Efficacy data will be available within the next 24 months.
The standard combination of intravenous fluorouracil plus leucovorin for adjuvant treatment of colon cancer was compared with the oral fluoropyrimidine capecitabine in almost 2000 patients with ...resected colon cancer. With disease-free survival as the primary end point, capecitabine was at least as effective as fluorouracil plus leucovorin. The oral drug had fewer side effects than the intravenous combination.
With disease-free survival as the primary end point, capecitabine was at least as effective as fluorouracil plus leucovorin. The oral drug had fewer side effects than the intravenous combination.
Almost 1 million patients receive a diagnosis of colorectal cancer yearly, and half a million deaths from this neoplasm occur annually worldwide.
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Each year, approximately 230,000 patients with colon cancer are eligible for adjuvant chemotherapy.
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The benefits of fluorouracil-based adjuvant chemotherapy in reducing the risk of relapse and prolonging survival in patients with resected colon cancer are well established, particularly in stage III disease.
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Survival advantages were demonstrated with bolus intravenous fluorouracil plus leucovorin administered according to the Mayo Clinic regimen (five days, monthly, for six months) or the Roswell Park regimen (weekly bolus, six of every eight . . .
To compare 5 x 5 Gy preoperative radiotherapy with immediate surgery vs. preoperative chemoradiotherapy (50.4 Gy, 5-fluorouracil, leucovorin) with delayed surgery in a randomized trial for cT3-T4 ...low-lying rectal cancer. Despite the downstaging effect of chemoradiotherapy, similar long-term outcomes were observed in both groups.
The Cox model was used to evaluate the prognostic value of ypTN ("yp" denotes that pathologic classification was performed after initial multimodality therapy) categories and the surgical margin status in 291 patients.
Disease-free survival (DFS) (hazard ratio HR 1.05, 95% confidence interval CI, 0.73-1.51), distant metastases (HR, 1.17; 95% CI, 0.77-1.78), and local control (HR, 1.45; 95% CI, 0.74-2.84) were similar in both arms. The ypN status was the only independent prognostic factor for DFS (p < 0.001). An interaction (p = 0.016) between N stage and the assigned treatment was demonstrated. For ypN-negative patients, DFS was similar in both arms (HR, 0.83, 95% CI, 0.47-1.48); however, for ypN-positive patients, DFS was worse in the chemoradiotherapy arm (HR, 1.73; 95% CI, 1.07-2.77). The 4-year (median follow-up) DFS rate in N-positive patients was 51% in the 5 x 5-Gy arm vs. 25% in the chemoradiotherapy arm. The corresponding 4-year rates for the incidence of local recurrence and distant metastases were 14% vs. 27% (HR, 1.95; 95% CI, 0.78-4.86) and 38% vs. 68% (HR, 2.05; 95% CI, 1.21-3.48).
N-positive disease after chemoradiotherapy indicates radiochemoresistance. N-positive disease after 5 x 5 Gy RT includes both radiosensitive and radioresistant tumors, because the interval between radiotherapy and surgery was too short for radiosensitive cancer to undergo necrosis. Thus, the greater risk of distant metastases recorded in the chemoradiotherapy arm suggests that radiochemoresistance of nodal metastases from rectal cancer is associated with a high potential for developing distant metastases.
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GEOZS, IJS, NUK, OILJ, UL, UM, UPUK
Background
The primary end-point of our randomized trial was sphincter preservation. The secondary aim was to evaluate whether distal bowel clearance ≤1 cm is safe after radiation.
Methods
The study ...randomized 312 patients with cT3-4 resectable low-lying and mid-rectal cancer to receive either preoperative irradiation (5 × 5 Gy) with immediate total mesorectal excision (TME) or chemoradiation (50.4 Gy, bolus 5-fluorouracil and leucovorin) with delayed TME. After anterior resection, pathologists prospectively measured macroscopic and microscopic distal bowel clearance.
Results
Macroscopic and microscopic distal bowel clearance, distal intramural spread, sphincter preservation, local control, disease-free survival, and overall survival did not differ in the two randomized groups. Pooled analysis of the two groups showed that the incidence of local recurrence at 4 years (median follow-up) for patients with macroscopic clearance ≤1 cm (
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= 42) and >1 cm (
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= 124) was 11.3% and 15.4%, respectively (
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= 0.514); the hazard ratio (HR) was 0.70, and the 95% confidence interval (CI) was 0.23–2.07. The corresponding values for patients with microscopic clearance ≤1 cm (
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= 51) and >1 cm (
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= 101) were 9.6% and 17.6% (
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= 0.220; HR 0.51; 95% CI 0.17–1.53).
Conclusion
After preoperative radiotherapy, distal bowel clearance ≤1 cm did not compromise local control.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
According to common conviction rectal tumour shrinkage after preoperative radio(chemo)therapy increases the likelihood of anterior resection (AR). In order to verify this belief, we performed a ...systematic review of randomised trials.
We identified 10 randomised trials encompassing altogether 4596 patients in whom preoperative radio(chemo)therapy resulted in tumour shrinkage in the experimental arm as compared to the control arm.
Tumour shrinkage observed in the experimental groups did not result in a statistically significant higher ARs rate in any study when we performed an analysis of all the randomised cases. Subgroups of patients considered to be candidates for abdominoperineal resection before randomisation were identified in three trials. A statistically significantly higher rate of ARs was demonstrated in the experimental arm of the CAO/ARO/AIO 94 study. However, in that study, sphincter preservation was a secondary endpoint and some features of the trial may bias the estimation of the effect. The benefit of sphincter preservation was not confirmed by subgroup analyses performed in the Lyon R90-01 study and in the Polish study, which were originally designed to evaluate the sphincter preservation issue.
The body of evidence gathered from randomised trials does not support the concept of a beneficial effect of preoperative radiotherapy on the ARs rate.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Abstract Background and purpose Patients ( N = 316) with resectable cT3-4 low-lying and mid-rectal cancer were randomised to receive either preoperative 5 × 5 Gy irradiation with subsequent surgery ...performed within 7 days or chemoradiation (50.4, 1.8 Gy per fraction plus boluses of 5-fluorouracil and leucovorin) followed by surgery after 4–6 weeks. No differences were found in sphincter preservation, survival, local control and late complications. Early complications were less frequent in the short-course group. The aim of this report is to find out whether large doses per fraction of short-course schedule result in more severe anorectal and sexual dysfunction and quality of life (QoL) impairment. Materials and method Patients who were free of disease were asked to answer the QLQ-C30 and those without stoma were, additionally, asked to fill in a questionnaire of anorectal (19 items) and sexual function (1 item). Results Two hundred and twenty-two patients (86% response rate) completed the QLQ-C30 and 118 (86% response rate) the anorectal–sexual function questionnaire. The median time from surgery to filling in the QLQ-C30 questionnaire was 12 months, and to filling in the anorectal–sexual function questionnaire – 13 months. We did not find significant differences between the randomised groups regarding QoL and the anorectal and sexual functions. Approximately two-thirds of patients had anorectal function impairment. Approximately 20% of patients stated that this considerably influenced their QoL. Conclusions QoL and the anorectal and sexual functioning did not differ in patients receiving short-course radiotherapy, as compared to those receiving chemoradiation.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Abstract Background and purpose To report an early analysis of prospective study exploring preoperative radiotherapy and local excision in rectal cancer. Materials and methods Mucosa at tumour edges ...was tattooed. Patients with cT1-3N0 tumour <3-4 cm were treated with either 5 × 5 Gy + 4 Gy boost ( N = 31) or chemoradiation (50.4 Gy + 5.4 Gy boost, 1.8 Gy per fraction + 5-fluorouracyl and leucovorin; N = 13). Thirteen patients from the short-course group were unfit for chemotherapy. The interval from radiation to full-thickness local excision was 6 weeks. The protocol called for conversion to a transabdominal surgery in case of ypT2-3 disease or positive margin. Results The postoperative complications requiring hospitalization were recorded in 9% of patients. The rate of pathological complete response was 41%. The rate of patients requiring conversion was 34%; however, 18% actually underwent conversion and the remaining 16% refused or were unfit. During the 14 months of median follow-up, local recurrence was detected in 7% of patients and all underwent salvage surgery. Of 19 patients in whom initially anterior resection was likely, 16% had abdominoperineal resection performed for a conversion or as a rescue procedure. Conclusion Our study suggests that the short-course radiation prior to local excision is a treatment option for high-risk patients.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
