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The Aetiology of Delay to Commencement of Adjuvant Chemotherapy following Colorectal Resection  [PDF]
G. S. Simpson,R. Smith,P. Sutton,A. Shekouh,C. McFaul,M. Johnson,D. Vimalachandran
International Journal of Surgical Oncology , 2014, DOI: 10.1155/2014/670212
Abstract: Purpose. Timely administration of adjuvant chemotherapy following colorectal resection is associated with improved outcome. We aim to assess the factors which are associated with delay to adjuvant chemotherapy in patients who underwent colorectal resection as part of an enhanced recovery protocol. Method. A univariate and multivariate analysis of patient data collected as part of a prospectively maintained database of colorectal cancer patients between 2007 and 2012. Results. 166 patients underwent colorectal resection followed by adjuvant chemotherapy. Median postoperative hospital stay was 6 days, and time to commencement of adjuvant chemotherapy was 50 days. Longer inpatient stay correlated with increased time to adjuvant chemotherapy ( ). Factors found to be independently associated with duration of hospital stay and time to commencement of adjuvant chemotherapy included stoma formation ( ), anastaomotic leak ( ), and preoperative albumin ( ). The use of laparoscopic surgery was associated with shorter time to adjuvant chemotherapy but did not reach significance ( ). Conclusion. A number of independent variables associated with delay to adjuvant therapy previously not described have been identified. Further work may be required to elucidate the effect that these variables have on long-term outcome. 1. Introduction Colon and rectal cancer is a common malignancy worldwide, having the third highest incidence of all cancers with around 1 million diagnoses worldwide each year [1]. Multimodality treatment strategies are employed in the management of colorectal malignancy; with neoadjuvant and adjuvant treatments complimenting the mainstay of treatment-surgical resection. The use of adjuvant chemotherapy (AC) following surgical resection of colorectal cancer has been shown to improve outcome [2–5]. Adjuvant chemotherapy has been advocated in patients with stage II disease associated with adverse disease features including T4 disease, perforation or obstruction [6], and in all patients with stage III disease [7]. The timing of administration of adjuvant chemotherapy following surgical resection has been proposed as a factor that potentially affects overall outcome, although this has not been proven conclusively. Some studies have demonstrated that initiation of chemotherapy occurring more promptly following surgical resection is being associated with improved outcome [8–10]. A meta-analysis found poorer outcomes if chemotherapy is administered 8 weeks or more after surgery [11], whilst another meta-analysis has reported a decrease in overall survival of 14%
Late solitary testicular metastasis from rectal cancer  [cached]
Venkitaraman Ramachandran,George Mathew,Weerasooriya Suranga,Selva-Nayagam Sid
Journal of Cancer Research and Therapeutics , 2010,
Abstract: Isolated testicular metastasis from rectal cancer is rare. We describe the case of a patient who presented with a locally advanced rectal malignancy and underwent multimodality treatment with low anterior resection, postoperative radiotherapy and adjuvant chemotherapy. He developed a painless testicular nodule while on follow-up, five years after the diagnosis of primary rectal cancer. Histopathology and immunohistochemistry of orchidectomy specimen were compatible with a metastatic adenocarcinoma of rectal origin. We hypothesize that this phenomenon of isolated relapse in a sanctuary site could be due to the altered biology and pattern of metastasis as a result of effective adjuvant systemic chemotherapy. Treatment of late isolated relapse in the testis needs to be ascertained.
Neoadjuvant chemoradiotherapy plus adjuvant chemotherapy versus adjuvant chemoradiotherapy in the treatment of patients with resectable rectal adenocarcinoma: a single-center 6-year study  [cached]
A. Avgerinos,G.A. Nalmpantidis,H. Abuouda,I. Avramidis
Annals of Gastroenterology , 2010,
Abstract: The last 20 years have seen significant advances in the use of radiation and chemotherapy in the treatment of rectal cancer patients. Studies comparing preoperative chemoradiotherapy to postoperative chemoradiotherapy in Greek patients with resectable rectal adenocarcinoma are rare. Patients and Methods: We conducted a retrospective cohort study of 74 patients (48 men, 26 women, mean age 63,8 years) with resectable rectal stage II or III cancer. Eighteen patients received preoperative chemoradiotherapy and postoperative chemotherapy (group A). Fifty-six patients received postoperative chemoradiotherapy (group B). Chemotherapy consisted of Capecitabine alone or in combination with Oxaliplatin and 5-FU. Radiotherapy consisted of 25Gy (in 5 fractions in group A) or 45Gy (in 28 fractions in group B). Results: Overall 5-year survival was 69,7% (95% CI 50,3 - 89,1%). Median overall survival (OS) was 24,5 months. There was no statistically significant difference in survival curves and recurrence free survival (RFS) between the two treatment groups. Twelve patients (16,2%, 95% CI: 9,0 – 27,0%) developed recurrence. Total RFS was 22,5 months, 20,0 months in group A and 25,0 months in group B (N.S). Adverse effects of therapies were the same in both groups. Conclusions: Preoperative chemoradiotherapy did not enhance OS and RFS in stage II and III rectal carcinoma patients who received adjuvant chemotherapy.
Patient profile and treatment outcome of rectal cancer patients treated with multimodality therapy at a regional cancer center  [cached]
Deo Suryanarayana,Kumar Sunil,Shukla Nootan,Kar Madhabananda
Indian Journal of Cancer , 2004,
Abstract: BACKGROUND : Incidence of rectal cancer has wide geographical variation. Disease pattern in developing countries is different from developed countries as majority of the patients present in advanced stage because of delayed referral and lack of uniform treatment practices. AIMS : Present study describes the patient profile and treatment results from a tertiary care cancer center in India. SETTING AND DESIGN : Tertiary care Regional cancer center. Retrospective analysis 89 patients with rectal adenocarcinoma treated between 1995 and 2002 were analyzed. METHODS: Patients with adenocarcinoma rectum were evaluated in a G.I. Oncology clinic and were treated using multimodality protocols involving surgery, radiotherapy and adjuvant chemotherapy. STATISTICAL ANALYSIS : A descriptive analysis of patient and disease profile,treatment patterns and out come was performed. Survival analysis was performed using Kaplan-Meier method. RESULTS : Mean age of the patients was 45.4 years and majority of them had tumor in lower third of rectum with evidence of extrarectal spread. Seventy five percent of the patients underwent curative resection with abdominoperineal resection being the commonest procedure. Forty seven percent of patients were given short course preoperative radiotherapy and the remaining received postoperative radiotherapy. Sixty four percent of patients could complete planned adjuvant chemotherapy. Operative mortality was 2% and 23% had morbidity. Local recurrence rate was 8.9%. 5-year disease free and overall survival was 54% and 58% respectively. CONCLUSION : Majority of rectal cancer patients present with locally advanced and low rectal growths leading to low sphincter salvage rates. Despite the advanced stage of presentation optimal oncologic results can be obtained by using a good surgical techniques in combination with adjuvant radiotherapy and chemotherapy. Short course preoperative radiotherapy seems to be more feasible in Indian context. Timely referral and uniform treatment guidelines throughout the country are needed for optimal management of rectal cancer in India.
The Current State of Targeted Agents in Rectal Cancer  [PDF]
Dae Dong Kim,Cathy Eng
International Journal of Surgical Oncology , 2012, DOI: 10.1155/2012/406830
Abstract: Targeted biologic agents have an established role in treating metastatic colorectal cancer (CRC), and the integration of targeted therapies into the treatment of CRC has resulted in significant improvements in outcomes. Rapidly growing insight into the molecular biology of CRC, as well as recent developments in gene sequencing and molecular diagnostics, has led to high expectations for the identification of molecular markers to be used in personalized treatment regimens. The mechanisms of action and toxicities of targeted therapies differ from those of traditional cytotoxic chemotherapy. Targeted therapy has raised new insight about the possibility of tailoring treatment to an individual’s disease, the assessment of drug effectiveness and toxicity, and the economics of cancer care. This paper covers the last decade of clinical trials that have explored the toxicity and efficacy of targeted agents in locally advanced and metastatic CRC and how their role may benefit patients with rectal cancer. Future efforts should include prospective studies of these agents in biomarker-defined subpopulations, as well as studies of novel agents that target angiogenesis, tumor-stromal interaction, and the cell signaling pathways implicated in rectal cancer. 1. Introduction Over the past 30 years, the management of rectal cancer has undergone many significant changes. Until the 1980s, surgery was the mainstay of therapy for patients with rectal cancer confined to the bowel and regional lymph nodes [1]. However, local recurrence occurred in approximately 25% to 50% of patients with T3 or lymph node-positive rectal cancer [2]. These local failures, as well as distant metastases, were a serious problem in locally advanced rectal cancer (LARC). To reduce these high failure rates, multiple trials evaluated different strategies of adjuvant radiation and 5-fluorouracil- (5-FU-) based chemotherapy [1, 3, 4]. Trial results demonstrated postoperative adjuvant chemoradiotherapy improved local control and survival compared with surgery alone, leading to the routine integration of adjuvant combined modality therapy into standard practice. At the same time, total mesorectal excision (TME) was introduced and further decreased local failure rates to less than 10% [5]. Subsequently, the landmark trial conducted by the German Group established superior local control, reduced treatment-related toxicity, and an improved sphincter preservation rate with neoadjuvant chemoradiotherapy compared with adjuvant 5-FU-based chemoradiation [6]. Today, although not proven to provide survival
INTERSPHINCTERIC TOTAL PROCTECTOMY IN THE MANAGEMENT OF LOW RECTAL CANCER  [PDF]
A. Montori
Jurnalul de Chirurgie , 2007,
Abstract: The management of lower rectal cancer is still controversial. A multidisciplinary approach is recommended. There are a lot of surgical techniques for lower rectal cancer (abdomino-perineal rectal resection, nerve sparing technique, total mesorectal excision, intersphincteric total proctectomy, trans-anal anastomosis etc.). In this paper it is presented the intersphincteric total proctectomy. The key points for sphincter preservation surgery are: a good knowledge of anal function pathophysiology, 2 cm distal adequate margin (or 1 cm for neo-adjuvant treated patients), total mesorectal excision, colo-anal anastomosis, nerve sparing proctectomy. The colo-anal anastomosis is the last step of the intersphincteric total proctectomy. Neo-adjuvant therapy is also indicated. The selection criteria and the technique of intersphincteric total proctectomy is presented. Between 1987-2002 this procedure was made at 120 patients with lower rectal cancer. The postoperative specific complications were: pelvic peritonitis (n=1) and anal stenosis (n=4). No anastomotic leak was encountered. 9 patients were classified in stage 0, 48 in stage I, 26 in stage II and 37 in stage III (UICC clasification). The 5 years survival rate was 97.4% for stages 0 and I, 71.3% for stages II and III. The functional results revealed a good continence in 77.5%, incontinence of liquid stools in 12.5%, incontinence for flatus in 7.5%, local recurrence in 2.5% and sexual or urological disfunction in 5%. Conclusions: Preoperative radiotherapy and sphincter preservation surgery (intersphincteric proctectomy ) provide good control of distal rectal cancer. Combined radiotherapy and chemotherapy seems to improve oncologic results with minimal additional morbidity. Our 6-8 week post-radiotherapy interval maximizes tumor shrinkage reducing the risks of radiation-induced complications. Intersphincteric proctectomy according to our experience reduces post-operative complications and risk of local recurrences. Use of diverting ileostomy/colostomy is mandatory in cases of colo-anal anastomosis. The quality of life is well accepted by the patients.
Video-assisted thoracoscopic surgery is more favorable than thoracotomy for administration of adjuvant chemotherapy after lobectomy for non-small cell lung cancer
Guanchao Jiang, Fan Yang, Xiao Li, Jun Liu, Jianfeng Li, Hui Zhao, Yun Li, Jun Wang
World Journal of Surgical Oncology , 2011, DOI: 10.1186/1477-7819-9-170
Abstract: One hundred and ten NSCLC patients underwent lobectomy and adjuvant chemotherapy from June 2004 to June 2010 was analyzed. The baseline characteristic criteria, variables related to surgery and accomplishing status of chemotherapy were analyzed.All 110 patients underwent lobectomy through VATS (n = 54) or thracotomy (n = 56) and adjuvant chemotherapy. There was no significant difference in patients' age, preoperative pulmonary function, co-morbidity, pathologic staging between the two groups, whereas, blood loss, operation time and postoperative complications, chest tube duration and length of stay were less in VATS group. There were no significant differences in time to initiation chemotherapy. Cases in VATS group received more cycles of chemotherapy (3.6 vs. 3.0, p = 0.002). A higher proportion of patients received full dose on schedule in VATS group (57.4% vs. 33.9%, p = 0.013) and a higher proportion of patients completed ≥75% planed dose, (88.9% vs. 71.4%, p = 0.022); slightly higher proportion of patients in thoracotomy group had grade 3 or more toxicity (20.4% vs. 35.7%, p = 0.074).Patients underwent lobectomy by VATS have better compliance and fewer delayed or reduced dose on adjuvant chemotherapy than those by thoracotomy.Adjuvant cisplatin-based chemotherapy is recommended for patients with stages II, IIIA, and a subgroup of IB non-small cell lung cancer (NSCLC), based on the positive results of several large randomized trials and a meta-analysis [1-4]. Among these studies, the JBR10 study reported that postoperative chemotherapy increased 15 percent at 5 years survival rate in lung cancer patients (mainly for patients with stage II disease) [2]; ANITA study reported that the absolute overall survival benefit with adjuvant chemotherapy was 8.6 percent at five years and 8.4 percent at seven years (mainly for patients with stage II and IIIA disease) [3]. Subgroup analysis of CALGB 9633 indicated that lung cancer patients in stage IB with tumor diameter more
Timing of Adjuvant Chemotherapy and Survival in Patients with Stage II/III Rectal Cancer  [PDF]
Isac S. F. Lima, Yutaka Yasui, Andrew Scarfe, Marcy Winget
Journal of Cancer Therapy (JCT) , 2012, DOI: 10.4236/jct.2012.326122
Abstract: Background: Treatment guidelines in the 1990s established surgery followed by chemoradiotherapy as the standard treatment for stage II/III rectal cancer. Our aim was to investigate the association between the timing of adjuvant treatment and patient survival in practice and identify demographic/clinical factors associated with treatment patterns. Methods: All residents of Alberta diagnosed with stage II/III rectal adenocarcinoma in 2000-2005 who had surgery were included in the study. Demographic and clinical data were obtained from the Alberta Cancer Registry and linked to hospital data and socioeconomic data from the 2001 Canadian Census. Overall and cancer-specific hazard ratios of death were estimated using Cox proportional hazards models. Results: 1243 patients were included in the study; 636 (51%) patients received treatment consistent with guidelines. Patients who received adjuvant chemotherapy 12 - 16 weeks after surgery or more than 16 weeks/ did not receive it had a 43% and 58% higher risk of rectal cancer death, respectively, compared to those who received it within 8 weeks of surgery. Conclusion: Adjuvant chemotherapy for stage II/III rectal cancer should be initiated within 12 weeks after surgery to maximize treatment benefits. Efforts to increase the proportion of patients treated within 12 weeks after surgery are needed.
Prospective phase II study of preoperative short-course radiotherapy for rectal cancer with twice daily fractions of 2.9 Gy to a total dose of 29 Gy - Long-term results
Matthias Guckenberger, Joern Wulf, Andreas Thalheimer, Daniel Wehner, Arnulf Thiede, Gottfried Müller, Marco Sailer, Michael Flentje
Radiation Oncology , 2009, DOI: 10.1186/1748-717x-4-67
Abstract: 118 patients (median age 64 years; male : female ratio 2.5 : 1) with pathological proven rectal cancer (clinical stage II 50%, III 41.5%, IV 8.5%) were treated preoperatively with twice daily radiotherapy of 2.9 Gy single fraction dose to a total dose of 29 Gy; surgery was performed immediately in the following week with total mesorectal excision (TME). Adjuvant 5-FU based chemotherapy was planned for pathological stage UICC ≥ II.After low anterior resection (70%) and abdominoperineal resection (30%), pathology showed stage UICC I (27.1%), II (25.4%), III (37.3%) and IV (9.3%). Perioperative mortality was 3.4% and perioperative complications were observed in 22.8% of the patients. Adjuvant chemotherapy was given in 75.3% of patients with pathological stage UICC ≥ II. After median follow-up of 46 months, five-year overall survival was 67%, cancer-specific survival 76%, local control 92% and freedom from systemic progression 75%. Late toxicity > grade II was observed in 11% of the patients.Preoperative short-course radiotherapy, total mesorectal excision and adjuvant chemotherapy for pathological stage UICC ≥ II achieved excellent local control and favorable survival.Multimodality treatment for rectal cancer is well established for more than 20 years after adjuvant radiochemotherapy has shown to improve overall survival [1]. Significant progress has been made in surgical, radiation and medical therapy: total mesorectal excision (TME) has become a surgical standard [2] and neoadjuvant radiotherapy (± chemotherapy) improved outcome compared to postoperative treatment.However, there is considerable debate regarding the best approach to preoperative therapy. The CAO/ARO/AIO-94 trial reported improved local control with decreased toxicity after preoperative compared to postoperative radiochemotherapy [3]: this so-called long-course treatment delivers conventionally fractionated radiotherapy of 45 Gy to 50 Gy and delayed surgery is performed to allow for tumor regression. S
The role of radiotherapy in rectal cancer  [cached]
H. Athanassiou, E. Fotopoulou, N. Zamboglou2
Annals of Gastroenterology , 2007,
Abstract: SUMMARY Radiotherapy, and more recently radiochemotherapy, has been extensively used together with surgery in the management of rectal cancer. Pelvic radiotherapy can decrease local failure rates when it is used before or after surgery in resectable cancers, even when administered to patients who underwent total mesorectal excision (TME) surgery. Preoperative and postoperative adjuvant radiotherapy have both been proved effective but there is not yet a randomised trial proving the superiority of either of the two methods through direct comparison. Although the survival advantage of postoperative radiation therapy does not seem to be great, the data suggests that there may be a greater survival benefit with preoperative therapy. Preoperative radio(chemo)therapy has also been increasingly used in resectable low-lying tumours in order to facilitate a sphincter- preserving procedure by decreasing tumour size. The incidence of sphincter preservation varies between 23% and 70% and this conservative approach may be an alternative to abdominoperitoneal resection, with good functional outcome, in selected patients. In patients, with primarily unresectable cancer, preoperative radiotherapy is usually administered to cause tumour regression and allow radical surgery. Intraoperative radiation therapy (IORT) and the addition of systemic chemotherapy have been used in order to improve the results of preoperative radiotherapy. In patients with advanced unresectable rectal cancer, and also in elderly patients, pelvic radiotherapy can provide very effective palliation of the symptoms.
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