Is Restaging with Chest and Abdominal CT Scan after Neoadjuvant Chemoradiotherapy for Locally Advanced Rectal Cancer Necessary?

Background

There is no evidence regarding restaging of patients with locally advanced rectal cancer after a long course of neoadjuvant radiotherapy with or without chemotherapy. This study evaluated the value of restaging with chest and abdominal computed tomographic (CT) scan after radiotherapy.

Methods

Between January 2000 and December 2010, all newly diagnosed patients in our tertiary referral hospital, who underwent a long course of radiotherapy for locally advanced rectal cancer, were analyzed. Patients were only included if they had chest and abdominal imaging before and after radiotherapy treatment.

Results

A total of 153 patients who met the inclusion criteria and were treated with curative intent were included. A change in treatment strategy due to new findings on the CT scan after radiotherapy was observed in 18 (12 %) of 153 patients. Twelve patients (8 %) were spared rectal surgery due to progressive metastatic disease.

Conclusions

Restaging with a chest and abdominal CT scan after radiotherapy for locally advanced rectal cancer is advisable because additional findings may alter the treatment strategy.     

Locally Advanced Breast Cancer: Is Surgery Necessary?

Abstract: A retrospective analysis of the treatment of locally advanced breast cancer (LABC) was undertaken at Stanford Medical Center to assess the outcome of patients who did not undergo surgical removal of their tumors. Between 1981 and 1998, 64 patients with locally advanced breast cancer were treated with induction chemotherapy, radiation with or without breast surgery, and additional chemotherapy. Sixty-two (97%) patients received cyclophosphamide, doxorubicin, and 5-fluorouracil (CAF) induction chemotherapy. Induction chemotherapy was followed by local radiotherapy in 59 (92%) patients. Based on the clinical response to chemotherapy and patient preference, 44 (69%) patients received no local breast surgery. Radiotherapy was followed by an additional, non-doxorubicin-containing chemotherapy in all patients. The mean age of patients was 49 years. Of the 65 locally advanced breast cancers in 64 patients, 26 (41%) were stage IIIA, 35 (55%) were stage IIIB, and 4 (6%) were stage IV (supraclavicular lymph nodes only). Response to induction chemotherapy was seen in 59 patients (92%), with 29 (45%) achieving a complete clinical response and 30 (47%) a partial clinical response. With a mean follow-up of 51 months (range 7–187 months), 43 patients (67.2%) have no evidence of recurrent disease. Eight (12.5%) have recurred locally, and 21 (32.8%) have recurred with distant metastasis. Actuarial 5-year survival is 75%, disease-free survival is 58%, and local control rate is 87.5%. These data indicate that the routine inclusion of breast surgery in a combined modality treatment program for LABC does not appear necessary for the majority of patients who experience a response to induction chemotherapy.     

Sphincter-Preserving Operations Following Preoperative Chemoradiation: An Alternative to Abdominoperineal Resection for Lower Rectal Cancer?

BACKGROUND: Sphincter-preserving operations (SPO) for lower rectal cancer are on the rise. In the study reported here, we compared the oncologic outcomes of patients who underwent sphincter-preserving operations following preoperative chemoradiation for lower rectal cancer with the outcome for patients who underwent abdominoperineal resection (APR). METHODS: This prospective study included 87 patients who underwent proctectomy with curative intent for locally advanced rectal cancer that was located less than 6 cm from the anal verge. Forty-four patients had APR with no preoperative treatment. Forty-three patients underwent concurrent chemoradiation therapy (CCRT) consisting of preoperative 5-fluorouracil-based chemotherapy and pelvic radiation (4500-5040 cGy); this was followed 6 weeks later by surgery (SPO/CCRT). The oncologic outcomes between the two groups were compared, and factors affecting survival were evaluated. RESULTS: The median follow-up period was 56.2 months. The overall postoperative complication rates did not significantly differ between SPO/CCRT and APR (32.6% versus 34.2%; p = 0.879). Also, there were no significant differences in the overall recurrence rate (20.9% versus 20.5%; p = 0.956) and 5-year overall survival rate (70.8% versus 62.9%; p = 0.189) between the two groups. By multivariate analysis, only the pathologic N stage was significantly associated with overall survival (p < 0.001). CONCLUSIONS: Sphincter-preserving operation with CCRT could be another option for the treatment of locally advanced lower rectal cancer in patients who are clinically considered for APR, with no deterioration of oncologic outcomes. For patients undergoing curative resection for lower rectal cancer, the pathologic N stage can provide valuable prognostic information about survival.     

Is Rectal Washout Necessary in Anterior Resection for Rectal Cancer? A Prospective Clinical Study

Background Implantation of exfoliated malignant cells has been suggested as a possible mechanism of tumor recurrence in colorectal anastomoses that might be prevented by cytocidal washout. The aim of our study was to assess whether malignant cells are likely to be collected by a circular stapler introduced transanally to perform an anastomosis and to observe local recurrences during follow-up, with special attention to the washout status of patients. Methods Between May 1999 and March 2004, 96 patients with carcinoma of the rectum and distal sigmoid colon undergoing anterior resection under the care of three surgeons (only one of whom routinely performed rectal washout) were prospectively studied. While 38 patients had rectal washout with 5% povidone-iodine before anastomosis, 58 patients did not. A circular stapler was used for anastomosis, and the stapler was immediately rinsed in 100 ml of saline. The fluid was then classified as “acellular,” “malignant cells identified,” or “benign cells identified” by pathologists. Results Malignant cells were collected from the circular stapler after use in 3 patients (8%) on whom rectal washout was performed and in 2 (3%) patients who did not have rectal washout performed (P = 0.631). Three patients (8%) in the washout group developed local recurrence, and 2 patients (3.4%) in the no-washout group had local recurrence (one was anastomotic recurrence) (P = 0.338). The median follow-up time was 23 (range: 9–70) months. Conclusions There were no differences in terms of the number of patients who had malignant cells collected from the circular stapler and local recurrence rates between the two groups. Although this is not a randomized study and size and mean follow-up time of the study were not sufficient, our results did not offer rational arguments in support of intraoperative rectal washout when a circular stapler is used after low anterior resection for carcinoma. Because of the limitations of our study, however, we are unable to arrive at a definite conclusion regarding rectal washout. There is a need for a randomized, controlled, large-scale, multicenter trial to establish the clinical relevance of intraoperative rectal washout. This paper was presented at the American Society of Colon and Rectal Surgeons Annual Meeting, June 21–26, 2003, New Orleans, LA (in the Resident/Fellow Presentations as the presentation of International Scholarship Winner).     

Preoperative Chemoradiotherapy with Capecitabine and Oxaliplatin in Locally Advanced Rectal Cancer. A Phase I–II Multicenter Study of the Dutch Colorectal Cancer Group

Background We studied the maximum tolerated dose (MTD) and efficacy of oxaliplatin added to capecitabine and radiotherapy (Capox-RT) as neoadjuvant therapy for rectal cancer. Methods T3-4 rectal cancer patients received escalating doses of oxaliplatin (day 1 and 29) with a fixed dose of capecitabine of 1000 mg/m² twice daily (days 1–14, 25–38) added to RT with 50.4 Gy and surgery after 6–8 weeks. The MTD, determined during phase I, was used in the subsequent phase II, in which R0 resection rate (a negative circumferential resection margin) was the primary end point. Results Twenty-one patients were evaluable. In the phase I part, oxaliplatin at 85 mg/m² was established as MTD. In phase II, the main toxicity was grade III diarrhea (18%). All patients underwent surgery, and 20 patients had a resectable tumor. An R0 was achieved in 17/21 patients, downstaging to T0-2 in 7/21 and a pCR in 2/21. Conclusion Combination of Capox-RT has an acceptable acute toxicity profile and a high R0 resection rate of 81% in locally advanced rectal cancer. However the pCR rate was low.     

Lateral Pelvic Node Metastasis in Locally Advanced Rectal Cancer: Are We Exaggerating or Ignoring?

Annals of Surgical Oncology -     

Thumbprinting Locally Advanced Pancreatic Cancer: Have We Developed the Optimal Staging System?

Annals of Surgical Oncology -     

Is There an Optimal Definition for a Positive Circumferential Resection Margin in Locally Advanced Esophageal Cancer?

Annals of Surgical Oncology -     

Factors Associated with Local–Regional Failure After Definitive Chemoradiation for Locally Advanced Esophageal Cancer

Background

Locally advanced esophageal cancer is often treated with a trimodality approach. While a substantial proportion of such patients initially achieve a clinical complete response (cCR) after chemoradiation, only a small proportion achieve durable control. We analyzed patients who reached cCR after definitive chemoradiation for esophageal cancer to identify clinical predictors of local disease recurrence.

Methods

We identified 141 patients who obtained initial cCR after definitive chemoradiation without surgery for esophageal cancer from 2002 through 2009. The initial response to treatment was assessed by endoscopic evaluation and biopsy results, with cCR defined as having no evidence of disease present. Patterns of failure were categorized as in-field (within the planned treatment volume [PTV]), outside the radiation treatment field, or both.

Results

At a median follow-up of 22 months (range, 6–87 months), 77 patients (55 %) had experienced disease recurrence (local or both). Of first failures, 32 (23 %) were outside the radiation field, followed by 30 (21 %) within the field, and 15 (11 %) were both. By multivariate analysis, in-field failure after cCR was associated with a pretreatment standardized uptake value on positron emission tomography of >10 (subhazard ratio [SHR] 3.31, p = 0.023) and poorly differentiated tumors (SHR 3.69, p = 0.031). All failures, in-field and out-of-field, correlated with non-Caucasian ethnicity (SHR 2.55, p = 0.001), N1 disease (SHR 2.05, p = 0.034), T3/T4 disease (SHR 3.56, p = 0.011), and older age (SHR 0.96, p = 0.008).

Conclusions

Our data suggest that selected clinical characteristics can be used to predict failure patterns after definitive chemoradiation. Such risk-assessment strategies can help individualize therapy.     

What is the Significance of the Circumferential Margin in Locally Advanced Rectal Cancer After Neoadjuvant Chemoradiotherapy?

Background

The circumferential resection margin (CRM) is highly prognostic for local recurrence in rectal cancer surgery without neoadjuvant treatment. However, its significance in the setting of long-course neoadjuvant chemoradiotherapy (nCRT) is not well defined.

Methods

Review of a single institution’s prospectively maintained database from 1998 to 2007 identified 563 patients with locally advanced rectal cancer (T3/T4 and/or N1) receiving nCRT, followed after 6 weeks by total mesorectal excision (TME). Kaplan-Meier, Cox regression, and competing risk analysis were performed.

Results

The authors noted that 75 % of all patients had stage III disease as determined by endorectal ultrasound (ERUS) and/or magnetic resonance imaging (MRI). With median follow-up of 39 months after resection, local and distant relapse were noted in 12 (2.1 %) and 98 (17.4 %) patients, respectively. On competing risk analysis, the optimal cutoff point of CRM was 1 mm for local recurrence and 2 mm for distant metastasis. Factors independently associated with local recurrence included CRM ≤1 mm, and high-grade tumor (p = 0.012 and 0.007, respectively). CRM ≤2 mm, as well as pathological, nodal, and overall tumor stage are also significant independent risk factors for distant metastasis (p = 0.025, 0.010, and <0.001, respectively).

Conclusion

In this dataset of locally advanced rectal cancer treated with nCRT followed by TME, CRM ≤1 mm is an independent risk factor for local recurrence and is considered a positive margin. CRM ≤2 mm was associated with distant recurrence, independent of pathological tumor and nodal stage.     

Do MRI Reports Contain Adequate Preoperative Staging Information for End Users to Make Appropriate Treatment Decisions for Rectal Cancer?

Purpose

This study was designed to elicit end-user opinions regarding the importance and diagnostic accuracy of MRI for T-category, threatened or involved circumferential margin (CRMi), and lymph node involvement (LNi) for preoperative staging of rectal cancer and to determine completeness of MRI reports for these elements on a population based level.

Methods

The first part of this study was a mailed survey of surgeons, radiation oncologists, and medical oncologists to elicit their opinions regarding the importance and diagnostic accuracy of T-category, CRMi, and LNi on MRI. The second part of the study was an audit of MRI reports issued for pre-operative staging of rectal cancer to assess the completeness of these reports for T-category, CRMi, and LNi.

Results

Although T-category, CRMi, and LNi were considered essential by 97, 94, and 77 % of respondents, respectively, the MRI report audit showed that only 40 % of MRI reports captured all of these elements. The majority of end users reported moderate diagnostic accuracy on MRI for T-category and CRMi and low diagnostic accuracy for LNi (52.3, 43, and 48.5 % respectively). Multivariate analysis showed that specialty was the only independent predictor of correct reporting of the diagnostic accuracy for each of the MRI elements.

Conclusions

While end users consider T-category, CRMi and LNi essential for preoperative staging of rectal cancer, less than 40 % of MRI reports captured all of these elements. Therefore, strategies to improve communication between radiologists and end users are critical to improve the overall quality of care for rectal cancer patients.     

Current Status of Combined Radiation Therapy and Androgen Suppression in Locally Advanced Prostate Cancer: What Is the Way Forward?

ContextAndrogen-deprivation therapy (ADT) as an adjuvant to radiation therapy (RT) is an established treatment for locally advanced prostate cancer (PCa).ObjectiveTo examine the established clinical evidence on the use of short-term and/or long-term adjuvant ADT plus external irradiation and discuss recent data devoted to the duration of ADT with RT.Evidence acquisitionDuring the 2010 Annual Congress of the European Association of Urology (EAU) in Barcelona, Spain, a satellite symposium was held on the individualised management of patients with PCa. This paper is based on one of the presentations given at the symposium. Data were retrieved from recent review articles, original articles, and abstracts on the use of ADT in the neoadjuvant and/or concomitant and adjuvant settings with RT in patients with locally advanced PCa.Evidence synthesisA number of studies have evaluated the survival benefits of short-term and long-term adjuvant ADT with RT in locally advanced PCa. European Organisation for Research and Treatment of Cancer (EORTC) study 22863 demonstrated that immediate androgen suppression given during and for 3 yr after external irradiation improved disease-free survival (DFS) and overall survival (OS) of patients with locally advanced PCa out to 10 yr. The OS benefits of long-term adjuvant ADT with RT were subsequently shown in Radiation Therapy Oncology Group (RTOG) protocols 85-31 and 92-02. More recently, EORTC study 22961 provided a definitive observation that 6-mo androgen suppression in association with three-dimensional conformal RT (3D-CRT) resulted in inferior survival compared with RT and 3 yr of ADT in the treatment of locally advanced PCa. Not only was OS improved but there was a significant improvement in all parameters of progression-free survival (PFS).ConclusionsLocally advanced PCa should be managed with 3D-CRT plus concomitant and adjuvant 3-yr androgen suppression.     

An Interval >7 Weeks between Neoadjuvant Therapy and Surgery Improves Pathologic Complete Response and Disease–Free Survival in Patients with Locally Advanced Rectal Cancer

Background  We assessed whether the time interval between neoadjuvant therapy and surgery affects the operative and postoperative morbidity and mortality, the pathologic complete response (pCR) rate, and disease recurrence in locally advanced rectal cancer. Methods  One–hundred and thirty-two patients with locally advanced low– and mid–rectal cancer underwent neoadjuvant chemoradiation followed by radical resection (October 2000 to December 2006). Data on the neoadjuvant regime, neoadjuvant–surgery interval, final pathology, type of operation, operative time, intraoperative blood transfusions, postoperative complications, length of hospital stay, disease recurrence, and mortality were reviewed. The patients were divided into two groups according to the neoadjuvant–surgery interval: ≤7 weeks (group A, n = 48), and >7 weeks (group B, n = 84). Results  The groups were demographically comparable except for the group A patients being younger at operation. The median interval between chemoradiation and surgery was 56 days (range 13–173 days). Thirty-seven patients (28%) had a pCR and near pCR. Fifty three patients (40%) had complications. There was no in-hospital mortality. Surgery type, operative time, number of intraoperative blood transfusions, postoperative complications, and length of hospitalization were not influenced by the interval length. The pCR and near pCR rates were higher with longer interval: 17% in group A, 35% in group B (P = 0.03). Patients operated at an interval >7 weeks had significantly better disease–free survival (P = 0.05). Conclusions  A neoadjuvant–surgery interval >7 weeks was associated with higher rates of pCR and near pCR, decreased recurrence and improved disease–free survival.     

Does Local Therapy Affect Survival Rates in Breast Cancer?

Background: The goal of this study was to challenge the hypothesis that local recurrence of breast cancer does not affect survival rates, by determining whether survival rates differ for conservative and radical surgical policies. Methods: This study used prospective long-term follow-up monitoring of two contemporaneous groups of patients, within a single unit, who were treated identically except for the one variable of local treatment policy, i.e., conservative or radical. A total of 451 patients with operable breast cancer were chosen from 567 consecutive patients with breast cancer who were treated between 1970 and 1979 in the University Department of Surgery. The rate of survival 132 months after treatment was used as an outcome measure.Results: Two hundred forty-one patients were treated using a conservative approach and 210 were treated using a radical approach. At 132 months, the survival rate (58% vs. 42%) and median survival time (>132 vs. 100 months) were significantly improved for the radically treated group (P < .01). The treatment groups were comparable in terms of age, menopausal status, tumor size, histologic grading, and Nottingham Prognostic Index values. The advantage of the radical policy persisted when examined in relation to each of these prognostic factors.Conclusions: Use of radical local treatment yielded a highly significant survival benefit (comparable to that obtained with adjuvant therapy), compared with a conservative approach. This was related to a reduced locoregional recurrence rate and provides evidence that local therapy influences long-term outcomes for patients with breast cancer. High-quality locoregional control should be emphasized, as is systemic therapy, in management policies. Assessment of surgical techniques, particularly in relation to locoregional recurrence rates, should be included in all studies in which surgery is a component of therapy.     

What Is the Minimum Number of Examined Lymph Nodes After Neoadjuvant Therapy in Rectal Cancer?

Background

To date, no guidelines have standardized the number of examined lymph nodes (eLNs) after neoadjuvant treatment. This study investigated the minimum number of eLNs required for patients with rectal cancer (RC) who received neoadjuvant treatment.

Material and Methods

This study was based on data from the Surveillance, Epidemiology, and End Results (SEER)-Medicare-linked database. We included 2173 patients with RC who received neoadjuvant therapy. Restricted cubic spline was used to analyze the association between eLNs and lymph node metastasis (LNM).

Results

The number of eLNs was an independent predictive factor for the presence of LNM (odds ratio 1.033; 95% confidence interval 1.020–1.046; P?<?0.001). When the number of eLN?≤?16, 10 and 11 eLNs had the highest rates of positive LNM. Analysis of the restricted cubic spline method found that when number of eLNs was <?10, the LNM rate increased rapidly, but this increase was not so obviously when there were >?10 eLNs.

Conclusions

Among RC patients who receive neoadjuvant therapy, the minimum number of eLNs may be 10 to ensure pathological quality.