Residual Lymph Node Disease After Neoadjuvant Chemotherapy Predicts an Increased Risk of Lymphedema in Node-Positive Breast Cancer Patients

Background

Axillary lymph node dissection (ALND) is recommended for patients with clinically node-positive breast cancer and carries a risk of lymphedema >30 %. Patients with node-positive breast cancer may consider neoadjuvant chemotherapy, which can reduce node positivity. We sought to determine if neoadjuvant chemotherapy reduced the risk of lymphedema in patients undergoing ALND for node-positive breast cancer.

Methods

The 229 patients who underwent unilateral ALND and chemotherapy were divided into two groups: 30 % (68/229) had neoadjuvant and 70 % (161/229) had adjuvant chemotherapy. Prospective arm volumes were measured via perometry preoperatively and at 3- to 7-month intervals after surgery. Lymphedema was defined as relative volume change (RVC) ≥10 %, >3 months from surgery. Kaplan–Meier curves and multivariate regression models were used to identify risk factors for lymphedema.

Results

Fifteen percent (10/68) of neoadjuvant patients compared with 23 % (37/161) of adjuvant patients developed RVC ≥10 % (hazard ratio = 0.76, p = 0.39). For all patients, body mass index was significantly associated with lymphedema (p = 0.0003). For neoadjuvant patients, residual lymph node disease after chemotherapy was associated with a ninefold greater risk of lymphedema compared to those without residual disease (p = 0.038).

Conclusions

Patients who underwent neoadjuvant chemotherapy did not have a statistically significant reduction in risk of lymphedema. Among patients who receive neoadjuvant chemotherapy, residual lymph node disease predicted a greater risk of lymphedema. These patients should be closely monitored for lymphedema and possible early intervention for the condition.     

Preoperative Combined Radiotherapy and Chemotherapy for Middle and Lower Rectal Cancer: Preliminary Results

Background: Adjuvant treatment for rectal cancer is still controversial. This study reports on overall survival and disease-free survival, toxicity, downstaging, and surgical morbidity in rectal cancer patients who received combined chemoradiation therapy followed by curative surgery.Methods: Between 1993 and 1998, 51 patients (31 males and 20 females; median age, 60 years; range, 33–73 years) underwent chemoradiation therapy followed by radical surgery for middle and lower rectal adenocarcinoma. Criteria for giving preoperative radiotherapy (total 45 Gy in 25 fractions of 1.8 Gy/day for 5 weeks) and chemotherapy (5-fluorouracil 350 mg/m2/day and leucovorin 10 mg/m2/day, bolus on days 1–5 and 29–33) were an age younger than 75 years; an Eastern Cooperative Oncology Group performance status score of 0 to 2; and clinical preoperative stage II–III. Forty-three low anterior and eight abdominoperineal resections were performed. Median follow-up time was 29 (range, 3–63) months.Results: Although grade 3 to 4 toxicity occurred in 14 cases (27.4%), all patients completed the planned adjuvant therapy. At pathology, a complete response was found in eight (15.7%) cases. Of the remaining 43 cases, 22 were stage I, 12 were stage II, and 9 were stage III. Five-year actuarial disease-free survival and overall survival rates were 86.4% and 85.5%, respectively. Whereas no local recurrences were found, 4 patients had distant metastases. Three patients died (1 of cancerrelated causes), 45 are alive and disease free, and 3 are alive with disease.Conclusions: The combined preoperative chemoradiation approach used by us seems to improve the disease-free survival and overall survival of selected patients with rectal cancer. However, a longer follow-up time is required to confirm these preliminary results.Presented at the 52nd Annual Meeting of Society of Surgical Oncology, Orlando, Florida, March 4–7, 1999.     

Preoperative versus Postoperative Radiotherapy for Rectal Cancer in a Decision Analysis and Outcome Prediction Model

Purpose

Reduction of local recurrences has been achieved by radiotherapy, but also by improved surgical technique (total mesorectal excision). Radiotherapy has adverse effects and cannot exceed local dose limits. Neoadjuvant radiotherapy may result in overtreatment. We aimed to define the minimum local benefit that would have to be postulated for radiotherapy in order to bring a benefit to the overall cohort. We hypothesized that saving radiotherapy as treatment for a subset of patients with high-risk tumors and local recurrences improves the outcome of the overall cohort. We sought to simulate preoperative versus postoperative radiotherapy in theoretical decision analysis model based on published recurrence rates, with overall survival being the primary end point.

Methods

Computerized literature search for studies published between 1996 and 2011, supplemented by manual review of the retrieved reference lists.

Results

Postoperative radiotherapy evolved as preferred strategy with cure rates of 65.6?% vs. 63.7?% for postoperative and neoadjuvant radiotherapy, respectively, and a decrease of radiation exposure to 42.9?% of the cohort. The system was sensitive to (1) the fraction of stage I cancers included in the cohort, (2) the difference between local recurrence rates (LRR) for neoadjuvant radiotherapy, adjuvant radiotherapy, or surgery-only approach, and (3) the compliance with the postoperative radiotherapy. If the surgery-only recurrence was set to the published 10?%, 13?%, and 27?%, respectively, adjuvant radiotherapy had to achieve LRR below the threshold values of 6.3?%, 8.5?%, and 18.3?% to reverse the impact of compliance.

Conclusions

Radiotherapy only improves cancer-specific survival of the cohort if there is a large difference in LRR with versus without it. Routine treatment may therefore be inferior to a tailored radiotherapy regimen.     

Prognostic Significance of the Metastatic Lymph Node Ratio in Node-Positive Rectal Cancer

Background  The purpose of the study was to evaluate the prognostic value of metastatic lymph node ratio (LNR) in node-positive rectal cancer. Methods  A retrospective review was performed in 318 rectal cancer patients who received curative anterior resection in a single institution. Clinicopathological variables including LNR were studied in univariate and multivariate analyses by Cox regression. LNR was further studied when stratified by quartiles. Survival analyses were performed using the Kaplan–Meier method and log-rank test. Results  With median follow-up of 41 months, the 5-year disease-free survival (DFS) rate, overall survival (OS) rate, and local recurrence (LR) rate were 56.82%, 59.8%, and 11%, respectively. Multivariate analysis revealed that LNR as a continuous variable was the most significant prognostic factor for DFS, OS, and LR. On quartiles, LNR was stratified into three groups: <0.14, 0.14–0.49, and 0.5–1. The 5-year DFS rate was 72.57%, 58.54%, and 34.75% (P = 0.0001) and the 5-year OS rate was 72.19%, 61.92%, and 38.47% (P = 0.002) in the three groups, respectively. Five-year LR rate was significantly higher with LNR between 0.14 and 1 (3.6% in LNR<0.14 versus 15.6% in LNR 0.14–1, P = 0.019). Conclusions  LNR is an important prognostic factor for node-positive rectal cancers. With a cutoff of 0.14 and 0.5, node-positive rectal cancer patients could be categorized into three subsets with significant different outcomes.     

直肠癌术前放疗的研究进展

目的总结近年来直肠癌术前放化疗的研究进展。方法复习近年来国内、外有关直肠癌术前放化疗的相关文献报道。结果术前放疗的远期局部复发率较术后放化疗明显降低,无瘤生存期明显延长;在Ⅲ期直肠癌患者,术前短程放疗比术前常规放疗具有更高的局部复发率,而在Ⅱ期直肠癌患者二者的局部复发率差异无统计学意义;p53、CEA、Cox-2、EGFR、VEGF等生物学因子是判断直肠癌术前放疗效果的敏感指标。结论直肠癌的术前放疗方案倾向于选择术前常规放疗,多种敏感因子的广泛研究及基因表达谱、基因芯片的发展为直肠癌术前放疗个体化方案的制定提供了更多的筛选指标。     

Risk Factor Analysis of Postoperative Complications After Robotic Rectal Cancer Surgery

Background  

The robotic system has been adopted as the new modality for minimally invasive surgery for rectal cancer. However, analysis of risk factors for complications after robotic rectal cancer surgery (RRS) has been limited. This study aimed to identify the risk factors for complications after RRS.     

Preoperative Chemotherapy Alone and Combined with Preoperative Radiotherapy in Small-Size Breast Cancer

Abstract: Breast conservation surgery is an effective and safe treatment for many breast carcinomas. It may be possible to further limit the extent of resection (or expand the indication for breast conservation) by the application of preoperative chemotherapy and radiotherapy. We explored the feasibility of this in a pilot study.
Seventy-three patients (mean age 48, 63% premenopausal) with confirmed breast cancer, less than 2.5 cm, received chemotherapy (Group A) or chemotherapy plus radiotherapy (Group B) prior to limited resection (tumorectomy). Axillary dissection was always performed. Results: In 6/31 (19%) Group A and 17/42 (40%) Group B patients the tumor was not palpable after preoperative treatment, with complete pathological remission in 1 and 3 cases respectively. Histologic grading, mitosis, cellular alteration, and cellularity evaluations indicated a consistently greater therapeutic effect with chemoradiotherapy than with chemotherapy alone.
In conclusion, radiotherapy appears useful in the preoperative treatment of breast cancer and its use in association with various drug combinations should be further explored.     

Lymph Node Retrieval after Preoperative Chemoradiotherapy for Rectal Cancer

Background

Current guidelines recommend the assessment of at least 12 lymph nodes for rectal cancer staging. Preoperative chemoradiotherapy may affect lymph node yield in this malignancy. This study investigated the impact of neoadjuvant chemoradiotherapy on the number of lymph nodes retrieved from rectal cancer patients.

Methods

An analysis of 162 rectal cancer patients who underwent curative surgery between 2005 and 2010. Seventy-one patients with stage II or III tumors received preoperative chemoradiotherapy. Using multivariate analysis, we assessed the correlation between clinicopathologic variables and number of retrieved lymph nodes. We also evaluated the association between survival and number of lymph nodes obtained.

Results

On multivariate analysis, preoperative chemoradiotherapy was the only variable to independently affect the number of lymph nodes obtained. The mean number of lymph nodes was 14.2 in patients treated with preoperative chemoradiotherapy and 19.4 in those not treated (P?P?=?0.003). After chemoradiation, the number of retrieved lymph nodes was inversely correlated with tumor regression grade. Results showed that 5-year overall and disease-free survival were similar whether the patient had 12 or more nodes retrieved or not.

Conclusions

Preoperative chemoradiotherapy reduces the lymph node yield in rectal cancer. The number of retrieved lymph nodes is affected by degree of histopathologic response of the tumor to chemoradiation. Thus, number of lymph nodes should not be used as a surrogate for oncologic adequacy of resection after neoadjuvant chemoradiotherapy for rectal cancer.     

Sentinel Lymph Node Biopsy Performed After Neoadjuvant Chemotherapy is Accurate in Patients with Documented Node-Positive Breast Cancer at Presentation

Background The optimal strategy for incorporating lymphatic mapping and sentinel lymph node biopsy into the management of breast cancer patients receiving neoadjuvant chemotherapy remains controversial. Previous studies of sentinel node biopsy performed following neoadjuvant chemotherapy have largely reported on patients whose prechemotherapy, pathologic axillary nodal status was unknown. We report findings using a novel comprehensive approach to axillary management of node-positive-patients receiving neoadjuvant chemotherapy. Methods We evaluated 54 consecutive breast cancer patients with biopsy-proven axillary nodal metastases at the time of diagnosis that underwent lymphatic mapping with nodal biopsy as well as concomitant axillary lymph node dissection after receiving neoadjuvant chemotherapy. All cases were treated at a single comprehensive cancer center between 2001 and 2005. Results The sentinel node identification rate after delivery of neoadjuvant chemotherapy was 98%. Thirty-six patients (66%) had residual axillary metastases (including eight patients that had undergone resection of metastatic sentinel nodes at the time of diagnosis), and in 12 cases (31%) the residual metastatic disease was limited to the sentinel lymph node. The final, post-neoadjuvant chemotherapy sentinel node was falsely negative in three cases (8.6%). The negative final sentinel node accurately identified patients with no residual axillary disease in 17 cases (32%). Conclusions Sentinel lymph node biopsy performed after the delivery of neoadjuvant chemotherapy in patients with documented nodal disease at presentation accurately identified cases that may have been downstaged to node-negative status and can spare this subset of patients (32%) from experiencing the morbidity of an axillary dissection.     

术前新辅助化疗联合同步放化疗对局部进展期直肠癌预后及血清标志物影响

目的:探讨术前同步放化疗联合氟尿嘧啶+亚叶酸钙+奥沙利铂(FOLFOX4)新辅助化疗对局部进展期直肠癌患者血清血清脂肪酸合成酶(FAS)、肿瘤型M2丙酮酸激酶(Tu M2-PK)表达的影响,为直肠癌的临床治疗方案提供参考.方法:选取100例进展期直肠癌患者为研究对象,以抽签法随机分为试验组和对照组,各50例.试验组术前...     

术前,术后放疗的直肠癌治疗中作用的评估和比较

目的：评估和比较辅助性术前、术后放疗在直肠癌治疗中的作用。方法：１９８８年２月～１９９５年２月收治经病理证实的直肠癌１７６例,配合手术分别采用术前单次放疗、术前常规放疗和术后放疗。术前单次放疗组３８例,剂量为５Ｇｙ,并于放疗后４８ｈ内手术;术前４０Ｇｙ常规放疗组４３例,多为临床晚期（Ｔ３～４占６０．５％）,中位剂量４０Ｇｙ,放疗后休４周再行手术;术后放疗组９５例,以病变晚期和淋巴结阳性为主（Ｔ３～４占６２．１％,Ｔ２～４Ｎ＋占８１．１％）,采用中位剂量５４Ｇｙ常规分割,疗程约６周,手术后３～４周开始接受放疗。结果：全部病例平均随访８４个月,Ｋａｐｌａｎ－Ｍｅｉｅｒ法计算生存率。术前单次放疗组３年、５年局部复发率分别为７８．９％和５０．０％,常规术前４０Ｇｙ放疗组为６７．４％和５１．１％;术后放疗组为５８．９％和     

Neoadjuvant Chemoradiation Versus Hyperfractionated Accelerated Radiotherapy in Locally Advanced Rectal Cancer

Background Neoadjuvant therapy is increasingly used in resectable locally advanced rectal cancer. The exact role of the addition of chemotherapy is not established. We compared neoadjuvant therapy using chemoradiation (CRT) or hyperfractionated accelerated radiotherapy (HART). Methods Clinical, pathological, and survival data were obtained from patients with resectable stage II or III rectal cancer within 7 cm from the anal verge. A group of 50 patients was treated with a preoperative dose of 41.6 Gy of radiotherapy (RT) in two daily fractions of 1.6 Gy over 13 days immediately followed by surgery (HART). A second group of 96 patients received 45 Gy of conventionally fractionated RT in 25 daily fractions of 1.8 Gy combined with 5-fluorouracil–based chemotherapy followed by surgery within 4 to 6 weeks (CRT). Both groups were compared in terms of morbidity, pathological downstaging, local recurrence, and survival. Results Both groups were comparable in terms of preoperative clinicopathological variables. The mean distance from the anal verge was 5.8 cm (HART) versus 4.9 cm (CRT). Sphincter preservation was possible in 74% (HART) versus 83.5% (CRT) of patients (P = .013). The clinical anastomotic leak rate was 2% (HART) versus 2.2% (CRT). Pathological complete response was observed in 4% (HART) versus 18% (CRT) of the resected specimens (P = .002). A pelvic recurrence developed in 6% (HART) versus 4.4% (CRT) of patients (P = .98). Overall 5-year survival was 58% (HART) versus 66% (CRT) (P = .19); disease-free 5-year survival was 51% (HART) versus 62% (CRT) (P = .037). Conclusions Compared with preoperative HART followed by immediate surgery, preoperative CRT followed by a 6-week waiting period enhances pathological response and increases sphincter preservation rate. This could be explained by the addition of chemotherapy or the longer interval between neoadjuvant therapy and surgery. No statistically significant difference was observed in local control or overall survival.     

Risk Factors for Mortality and Postoperative Complications After Gastrointestinal Surgery

Background Predictors of a poor surgical outcome are numerous, of which some are well-defined. We aimed to assess risk factors predictive of poor surgical outcome across different gastrointestinal operations related to the patient, the disease, the treatment, and the organization of care. Methods Data from 5,255 unselected patients undergoing open gastrointestinal surgery from 1995 through 1998 was prospectively recorded in a clinical database and validated. The database embraced variables related to patient history, preoperative clinical condition, operative findings and complexity, and the surgeon’s training. Variables predictive of mortality and complications occurring within 30 days after surgery were assessed by multiple logistic regression analysis. Results After elective operation, the 30-day mortality was 2.8% and major complications occurred in 11.5% of the patients. The corresponding figures in emergency surgery were 13.8% and 30.1%. Independent of elective or emergency surgery, dependent functional status, and type of operation were associated with postoperative mortality. Comorbidity, type of operation, blood loss, and reoperation were predictors of complications regardless of elective or emergency operation. In elective surgery, predictors of poor surgical outcome were high age, comorbidity, malignancy, and the surgeons training, whereas abnormal vital signs values and peritonitis were predictors of poor outcome after emergency surgery. Conclusion Premorbid factors, characteristics of the disease, the patients’ preoperative condition, operative factors, and the surgeon’s training are all associated with surgical outcome across different gastrointestinal operations and should be assessed when auditing surgical outcome.     

Neoadjuvant Endocrine Therapy Versus Neoadjuvant Chemotherapy in Node-Positive Invasive Lobular Carcinoma

Annals of Surgical Oncology - Neoadjuvant chemotherapy (NACT) is often recommended for patients with node-positive invasive lobular carcinoma (ILC) despite unclear benefit in this largely hormone...     

Effects of Postoperative Adjuvant Radiotherapy on Recurrence and Survival in Stage III Rectal Cancer

Background  

The aim of this study is to evaluate whether the addition of radiotherapy to chemotherapy would enhance the benefits obtained with chemotherapy alone, in stage III rectal cancer in the era of preoperative chemoradiotherapy and total mesorectal excision (TME).     

The Role for Sentinel Lymph Node Dissection after Neoadjuvant Chemotherapy in Patients who Present with Node-Positive Breast Cancer

Background

Sentinel lymph node (SLN) dissection has been investigated after neoadjuvant chemotherapy and has shown mixed results. Our objective was to evaluate SLN dissection in node-positive patients and to determine whether postchemotherapy ultrasound could select patients for this technique.

Methods

Between 1994 and 2010, 150 patients with biopsy proven axillary metastasis underwent SLN dissection after chemotherapy and 121 underwent axillary lymph node dissection (ALND). Clinicopathologic characteristics were analyzed before and after chemotherapy. Statistical analyses included Fisher??s exact test for nodal response and multivariate logistic regression for factors associated with false-negative events.

Results

Median age was 52?years. Median tumor size at presentation was 2?cm. The SLN was identified in 93?% (139/150). In 111 patients in whom a SLN was identified and ALND performed, 15 patients had a false-negative SLN (20.8?%). In the 52 patients with normalized nodes on ultrasound, the false-negative rate decreased to 16.1?%. Multivariate analysis revealed smaller initial tumor size and fewer SLNs removed (<2) were associated with a false-negative SLN. There were 63 (42?%) patients with a pathologic complete response (pCR) in the nodes. Of those with normalized nodes on ultrasound, 38 (51?%) of 75 had a pCR. Only 25 (33?%) of 75 with persistent suspicious/malignant-appearing nodes had a pCR (p?=?0.047).

Conclusions

Approximately 42?% of patients have a pCR in the nodes after chemotherapy. Normalized morphology on ultrasound correlates with a higher pCR rate. SLN dissection in these patients is associated with a false-negative rate of 20.8?%. Removing fewer than two SLNs is associated with a higher false-negative rate.     

Despite Equivalent Outcomes,Men Receive Neoadjuvant Chemotherapy Less Often Than Women for Lymph Node-Positive Breast Cancer

Annals of Surgical Oncology - Neoadjuvant chemotherapy (NAC) downstages breast cancer and provides prognostic information. Males with breast cancer are known to receive less treatment overall and...