Abstract Background Adjuvant therapy for T3N0 rectal cancer was controversial with respect to both radiation and the use of a combined regimen of chemotherapy. We evaluated both clinical features and biomarkers and sought to determine risk factors for those patients retrospectively. Methods A total of 122 patients with T3N0 rectal cancer were analyzed in this study from January 2000 to December 2005. Clinicopathologic and biomarkers were used to predict local recurrence (LR), disease-free survival (DFS), and overall survival (OS). Results The median follow-up interval was 45.4 months. Five-year LR, DFS, and OS rates were 10.4%, 68.3%, and 88.7%. Having a lower tumor location and showing low P21 and high CD44v6 expression were identified as risk factors for LR: patients with two or three of these risk factors had a higher 5-year LR rate (19.3%) than did patients with none or one of these risk factors (6.8%) (p = 0.05). A poorer DFS was related to low P21 nor high CD44v6 expression but not to tumor location: the 5-year DFS rates were 79.3% for those with neither, 65.9% for those with either one or the other, and 16.9% for those with both (p = 0.00). Conclusions The prognostic model including tumor location, P21 and CD44v6 expressions could help to distinguish these patients with high risk T3N0 patients and determine whether adjuvant therapy was beneficial.
Purpose The aim of the study is to identify the risk factors of synchronous ILN metastasis for lower rectal cancer involving the anal canal. Methods Patients with lower rectal cancer who underwent radical resection at the Fudan University Shanghai Cancer Center were retrospectively analyzed. The synchronous ILN metastasis was defined as the metastasis occurring within 6 months after the diagnosis of rectal cancer. Patients' gender, age, tumor diameter, dentate line invasion, differentiation level, histological type, depth of invasion, perirectal LN metastasis, lymphovascular invasion or perineural invasion were analyzed in the study. The correlation between synchronous ILN involvement and clinicopathological features were analyzed with Chi-square test/fisher's exact test. Variables with p<0.05 in univariate analysis were then analyzed in a multivariate logistic model. Odds ratio (OR) along with 95% confidence intervals (95% CI) were calculated. Results A total of 325 patients (182 men and 143 women) with lower rectal cancer met the criteria and were enrolled in the study. Among them, 20 patients (6.2%) had synchronous ILN metastasis. Both univariate and multivariate analysis showed the invasion of the dentate line had a strong correlation with synchronous ILN metastasis with the odds ratio (OR) of 23.558 [95% confidence interval (CI) 6.380–86.982] (p<0.001). The presence of lymphovascular invasion also showed a significant correlation synchronous ILN metastasis with odds ratio (OR) of 5.260 [95% confidence interval (CI) 1.818–15.212] (p = 0.002). Conclusions The invasion of dentate line and lymphovascular invasion are two independent risk factors of inguinal lymph node metastasis for lower rectal cancer involving the anal canal.
Objective To assess the impact of respiratory motion on the displacement of target area and to analyze the discrimination between free breathing and active breathing control (ABC) in patients with gastric cancer treated with post-operative radiotherapy. Methods From January 2005 to November 2006, 22 patients with post-operatively confirmed gastric cancer were enrolled in this study. All diseases were T_3/ N +, staging Ⅱ - Ⅳ. Patients were CT scanned and treated by radiation with the use of ABC. Image J software was used in image processing, motion measurement and data analysis. Surgical clips were implanted as fiducial marks in the tumor bed and lymphatic drainage area. The motion range of each clip was measured in the resultant-projection image. Motions of the clips in superior-inferior (S-I), right-left (R-L) and anterior-posterior (A-P) directions were determined from fluoroscopy movies obtained in the treatment position. Results The motion ranges in S-I, R-L and A-P directions were 11.1 mam, 1.9 mm and 2.5 mm (F = 85.15, P = 0. 000) under free breathing, with 2.2 mm, 1.1 mm and 1.7 nun under ABC (F = 17.64, P = 0. 000), and the reduction of motion ranges was significant in both S-I and A-P directions (t = 4.36, P = 0. 000;t = 3.73,P = 0.000). When compared with under free-breathing, the motion ranges under ABC were kept unchanged in the same breathing phase of the same treatment fraction, while significant increased in different breathing phase in all three directions (t = - 4.36, P = 0. 000; t = - 3.52, P = 0.000; t =-3.79, P = 0. 000), with a numerical value of 3.7 mm, 1.6 mm and 2.8 mm, respectively (F = 19.46, P = 0. 000) . With ABC between different treatment fractions , the maximum displacements were 2.7 mm, 1.7 mm and 2.5 mm for the centre of the clip cluster (F =4.07,P =0. 019), and were 4.6 mm, 3.1 mm and 4.2 mm for the clips (F =5.17 ,P =0.007). The motion ranges were significant increased in all the three directions (t = - 4.09, P=0.000 ; t =-4.46, P = 0.000 ; t = - 3.45, P =0.000). Conclusions In the irradiation of post-operative gastric cancer, the maximum displacement of organ motions induced by respiration is in S-1 direction and the minimum in R-L direction under free breathing. The use of ABC can reduce the motions significantly in S-I and A-P directions, and the same changes exist in both inter-and intra-fraction treatment.
Key words:
Gastric neoplasms/radiotherapy; Radiotherapy, postoperative; Free breathing; Active breath control
In our previous dose-escalation study, we uncovered the maximum tolerated dose (MTD) of weekly irinotecan was escalated to 80 mg/m2 and 65 mg/m2 for UDP glucuronosyltransferase family 1 member A1 (UGT1A1) *1*1 and *1*28 rectal cancer patients in neoadjuvant chemoradiotherapy (nCRT). This is an expansion study for *1*1 patients.Patients with clinical stage T3-4, N0-2 rectal cancer eligible for preoperative chemoradiotherapy were screened for the UGT1A1*28 genotype. A total of 52 patients with the *1*1 genotype were enrolled. Whole-pelvic intensity-modulated radiation therapy was given in 50 Gy/25 fractions. Concurrently, irinotecan of 80 mg/m2 and capecitabine of 625 mg/m2 twice daily from Monday to Friday were administered weekly. Primary endpoint was toxicities; secondary endpoints included pathological complete response (pCR), tumour-regression grading, treatment compliance, overall survival, local recurrence and disease-free survival.All patients completed capecitabine-based radiotherapy as scheduled, and 42 (81%) patients completed more than three cycles of weekly irinotecan. Overall, grade 3/4 toxicities were observed in 20 cases, including 11 leucopenia, 10 neutropenia and 12 diarrhoea. Forty-three patients (83%) underwent a radical surgery, and 12 were evaluated as pCR. Another four patients accepted a watch-and-wait strategy because of clinical complete response (CCR).Our data demonstrated manageable toxicities and an encouraging CCR rate for UGT1A1 *1*1 genotype in an enhanced neoadjuvant therapy. A phase III trial is ongoing to evaluate the value of irinotecan in neoadjuvant therapy (CinClare) [ClinicalTrials.gov identifier: NCT02605265].
Objective To estimate the operative risk and outcomes of colorectal cancer patients 80 years of age and older. Methods Colorectal cancer resection was performed in 99 patients 80 years of age and older between Dec. 1987 and June 2005. The informations about clinical data, co-morbidity,complications, operative mortality and survival were retrospectively analyzed. The patients were followed-up for 45.12 months (range 1-136) months. Results Of 99 patients, co-morbidity was found in 43 patients (43.4% ) and complication in 10 patients (10.1%). No patient died of operation.Eighty patients completed the follow-up study. The overall 3-year survival rate and disease-free survival rate were 64.3% and 61.1%, respectively. Whereas the overall 5-year survival rate and disease-free survival rate were 52.8% and 52.1%, respectively. In univariate analysis, curative or palliative operation, tumor differentiation, cancer embolism in the vasculature, tumor staging and complications were proved to be significant prognostic factors. Multivariate survival analysis,however, showed that only the curative or palliative operation was independent factor for survival.Conclusions The high risk of co-morbidity for patients 80 years of age and older is not the obstacle to cancer resection.These patients will have satisfactory outcomes via optimal treatment and operation.
Key words:
Colorectal neoplasms; Surgery; Prognosis
This study investigated the local effect and acute toxicity of irinotecan and capecitabine with concurrent intensity-modulated radiation therapy (IMRT) for the treatment of recurrent rectal cancer without prior pelvic irradiation. Seventy-one patients diagnosed with recurrent rectal cancer who did not previously receive pelvic irradiation were treated in our hospital from October 2009 to July 2012. Radiotherapy was delivered to the pelvis, and IMRT of 45 Gy (1.8 Gy per fraction), followed by a boost of 10 Gy to 16 Gy (2 Gy per fraction), was delivered to the recurrent sites. The concurrent chemotherapy regimen was 50 mg/m2 irinotecan weekly and 625 mg/m2 capecitabine twice daily (Mon-Fri). Radical surgery was recommended for medically fit patients without extra-pelvic metastases. The patients were followed up every 3 months. Tumor response was evaluated using CT/MRIs according to the RECIST criteria or postoperative pathological findings. NCI-CTC 3.0 was used to score the toxicities. Forty-eight patients (67.6%) had confirmed recurrent rectal cancer without extra pelvic metastases, and 23 patients (32.4%) had extra pelvic metastases. Fourteen patients (19.7%) underwent radical resections (R0) post-chemoradiation. A pathologic complete response was observed in 7 of 14 patients. A clinical complete response was observed in 4 patients (5.6%), and a partial response was observed in 22 patients (31.0%). Only 5 patients (7.0%) showed progressive disease during or shortly after treatment. Of 53 symptomatic patients, clinical complete and partial symptom relief with chemoradiation was achieved in 56.6% and 32.1% of patients, respectively. Only 2 patients (2.8%) experienced grade 4 leukopenia. The most common grade 3 toxicity was diarrhea (16 [22.5%] patients). The median follow-up was 31 months. The cumulative local progression-free survival rate was 74.2% and 33.9% at 1 and 3 years after chemoradiation, respectively. The cumulative total survival rate was 80.1% and 36.5% at 1 and 3 years after chemoradiation, respectively. This study revealed that concurrent irinotecan and capecitabine with IMRT significantly relieves local symptoms and exhibits promising efficacy with manageable toxicities in recurrent rectal cancer without prior pelvic irradiation. Improving the rate of R0 resections will be investigated in a future study.
This study was designed to evaluate the efficacy and toxicities of concomitant boost intensity-modulated radiation therapy (IMRT) along with capecitabine and oxaliplatin, followed by a cycle of Xelox, in neoadjuvant course for locally advanced rectal cancer. Patients with histologically confirmed, newly diagnosed, locally advanced rectal adenocarcinoma (cT3-T4 and/or cN+) located within 12 cm of the anal verge were included in this study. Patients received IMRT to the pelvis of 50 Gy and a concomitant boost of 5 Gy to the primary tumor in 25 fractions, and concurrent with oxaliplatin (50 mg/m2 d1 weekly) and capecitabine (625 mg/m2 bid d1–5 weekly). One cycle of Xelox (oxaliplatin 130 mg/m2 on d1 and capecitabine 1000 mg/m2 twice daily d1–14) was given two weeks after the completion of chemoradiation, and radical surgery was scheduled eight weeks after chemoradiation. Tumor response was evaluated by tumor regression grade (TRG) system and acute toxicities were evaluated by NCI-CTC 3.0 criteria. Survival curves were estimated using the Kaplan-Meier method and compared with Log-rank test. A total of 78 patients were included between March 2009 and May 2011 (median age 54 years; 62 male). Seventy-six patients underwent surgical resection. Twenty-eight patients underwent sphincter-sparing lower anterior resection and 18 patients (23.7%) were evaluated as pathological complete response (pCR). The incidences of grade 3 hematologic toxicity, diarrhea, and radiation dermatitis were 3.8%, 10.3%, and 17.9%, respectively. The three-year LR (local recurrence), DFS (disease-free survival) and OS (overall survival) rates were 14.6%, 63.8% and 77.4%, respectively. Initial clinical T stage and tumor regression were independent prognostic factors to DFS. An intensified regimen of concomitant boost radiotherapy plus concurrent capecitabine and oxaliplatin, followed by one cycle of Xelox, can be safely administered in patients with locally advanced rectal cancer, and produces a high rate of pCR. A prognostic score model is helpful to distinguish different long-term prognosis groups in early stage.
Abstract Background This study was designed to explore whether an intensified chemoradiotherapy (CRT) led to a better clinical outcome in locally advanced rectal cancer. Methods Patients with stage II/III rectal cancer were randomly allocated to receive either pelvic intensity-modulated radiation therapy (IMRT) of 50 Gy/25Fx concurrently with capecitabine and oxaliplatin (Arm A), or pelvic radiation of 50 Gy/25Fx with a concomitant boost of 5 Gy to the primary lesion, followed by a cycle of XELOX 2 weeks after the end of CRT (Arm B). All patients were planned to receive a definitive operation 8 weeks after the completion of CRT and a total of six perioperative chemotherapy cycles of capecitabine and oxaliplatin regardless of pathological result. Pathological complete response (ypCR) was the primary endpoint. Results From February 2010 to December 2011, 120 patients from three centers were enrolled in this study. Ninety-five percent patients completed a full-dose chemoradiotherapy as planning. Then 53 and 57 patients received a radical surgery, and 8 and 14 cases were confirmed as ypCR in two groups ( P = 0.157). The other 10 patients failed to receive a definitive resection because of unresectable disease. Similar toxicities were observed between two groups and more incision healing delay were found in Arm B (3 vs.13, P = 0.011). No statistical differences were observed in local-regional control ( P = 0.856), disease-free survival ( P = 0.349) and overall survival ( P = 0.553). Mesorectal fascia (MRF) involvement was an independent prognostic factor for survival in multivariate analysis. Conclusions A concomitant boost to oxalipatin-combined preoperative chemoradiotherapy demonstrated a slightly higher pCR rate but delayed incision healing after surgery. The impact of MRF involvement on survival merits further investigations. Trial registration NCT01064999 (ClinicalTrials.gov).
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