Outcomes of Screening-Detected Ductal Carcinoma In Situ Treated with Wide Excision Alone

Background  

Ductal carcinoma in situ (DCIS) is commonly identified on screening mammography. Standard treatment for localized DCIS is wide local excision (WLE) and adjuvant radiotherapy. This approach represents overtreatment in many cases, where the DCIS would never have become clinically significant, or where less intensive treatment would have been satisfactory. We reviewed the medium-term outcome of a cohort of screen detected DCIS patients treated mainly with WLE without radiotherapy.     

The Clinical Utility of DCISionRT® on Radiation Therapy Decision Making in Patients with Ductal Carcinoma In Situ Following Breast-Conserving Surgery

Background

The role of radiation therapy (RT) following breast-conserving surgery (BCS) in ductal carcinoma in situ (DCIS) remains controversial. Trials have not identified a low-risk cohort, based on clinicopathologic features, who do not benefit from RT. A biosignature (DCISionRT^®) that evaluates recurrence risk has been developed and validated. We evaluated the impact of DCISionRT on clinicians’ recommendations for adjuvant RT.

Methods

The PREDICT study is a prospective, multi-institutional, observational registry in which patients underwent DCISionRT testing. The primary endpoint was to identify the percentage of patients where testing led to a change in RT recommendations.

Results

Overall, 539 women were included in this study. Pre DCISionRT testing, RT was recommended to 69% of patients; however, post-testing, a change in the RT recommendation was made for 42% of patients compared with the pre-testing recommendation; the percentage of women who were recommended RT decreased by 20%. For women initially recommended not to receive an RT pre-test, 35% had their recommendation changed to add RT following testing, while post-test, 46% of patients had their recommendation changed to omit RT after an initial recommendation for RT. When considered in conjunction with other clinicopathologic factors, the elevated DCISionRT score risk group (DS > 3) had the strongest association with an RT recommendation (odds ratio 43.4) compared with age, grade, size, margin status, and other factors.

Conclusions

DCISionRT provided information that significantly changed the recommendations to add or omit RT. Compared with traditional clinicopathologic features used to determine recommendations for or against RT, the factor most strongly associated with RT recommendations was the DCISionRT result, with other factors of importance being patient preference, tumor size, and grade.

     

Sentinel Lymph Node Biopsy: Is It Indicated in Patients With High-Risk Ductal Carcinoma-In-Situ and Ductal Carcinoma-In-Situ With Microinvasion?

Background: Axillary lymph node status is the strongest prognostic indicator of survival for women with breast cancer. The purpose of this study was to determine the incidence of sentinel node metastases in patients with high-risk ductal carcinoma-in-situ (DCIS) and DCIS with microinvasion (DCISM).Methods: From November 1997 to November 1999, all patients who underwent sentinel node biopsy for high-risk DCIS (n = 76) or DCISM (n = 31) were enrolled prospectively in our database. Patients with DCIS were considered high risk and were selected for sentinel lymph node biopsy if there was concern that an invasive component would be identified in the specimen obtained during the definitive surgery. Patients underwent intraoperative mapping that used both blue dye and radionuclide. Excised sentinel nodes were serially sectioned and were examined by hematoxylin and eosin and by immunohistochemistry.Results: Of 76 patients with high-risk DCIS, 9 (12%) had positive sentinel nodes; 7 of 9 patients were positive for micrometastases only. Of 31 patients with DCISM, 3 (10%) had positive sentinel nodes; 2 of 3 were positive for micrometastases only. Six of nine patients with DCIS and three of three with DCISM and positive sentinel nodes had completion axillary dissection; one patient with DCIS had an additional positive node detected by conventional histological analysis.Conclusions: This study documents a high incidence of lymph node micrometastases as detected by sentinel node biopsy in patients with high-risk DCIS and DCISM. Although the biological significance of breast cancer micrometastases remains unclear at this time, these findings suggest that sentinel node biopsy should be considered in patients with high-risk DCIS and DCISM.     

Inadequate Margins of Excision When Undergoing Mastectomy for Breast Cancer: Which Patients are at Risk?

Background

We analyzed the margin status and risk factors for inadequate margins among patients who underwent skin-sparing mastectomies (SSM) and traditional total mastectomies (TM).

Materials and Methods

Patients undergoing mastectomies from 2003 to 2009 were included. Margins of excision were considered positive if carcinoma was at an inked margin and were considered close if such disease was within 2 mm of an inked margin.

Results

A total of 426 patients were identified. The mean age was 60 years and 90% were white. Mean tumor size was 2.6 cm and 44% had multiple ipsilateral carcinomas. Of 426 patients, 177 (42%) underwent SSM with reconstruction and 249 (58%) TM. The rate of positive or close margins on the initial specimen was 29% for SSM vs. 12% for TM (P < 0.01), and the rate of reoperation for margins was 7% for SSM vs. 2% for TM (P < 0.01). Logistic regression analysis revealed that independent risk factors for initial close or positive margins included SSM (odds ratio 2.36, 95% confidence interval [95% CI] 1.05–5.30), multiple ipsilateral tumors (OR 2.12, 95% CI 1.05–4.24), and upper-inner quadrant location (OR 2.58, 95% CI 1.07–6.19). Mean follow-up time was 28 months, and the local recurrence rate was 0.9%. Local recurrence rates were not different for those undergoing SSM (1.1%) vs. TM (0.8%, P = NS).

Conclusions

Mastectomy patients undergoing SSM, with multiple ipsilateral tumors, and/or upper-inner quadrant disease are at significantly higher risk for inadequate margins of excision. These patients warrant more vigilant intraoperative attention to margin status to ensure adequate margins at the end of the first operation.     

What is the Incidence of Suicide in Patients with Bone and Soft Tissue Cancer?

Clinical Orthopaedics and Related Research® - Patients with cancer in the United States are estimated to have a suicide incidence that is approximately twice that of the general population....     

Radiation Pneumonitis in Breast Cancer Patients Treated with Taxanes: Does Sequential Radiation Therapy Lower the Risk?

Taxanes are now routinely used in conjunction with radiation therapy (RT) as adjuvant therapy for breast cancer. Recent publications have reported several cases of radiation pneumonitis (RP) in patients receiving RT and taxane chemotherapy, thus raising concern as to the safety of this combination. To decrease the potential risk of RP, we sequenced RT after taxane chemotherapy with a target interval of 3-4 weeks in two consecutive institutional breast protocols. Forty patients were treated on two adjuvant systemic protocols consisting of modified radical mastectomy (n = 9) or breast-conserving surgery (n = 31), followed by adjuvant doxorubicin, cyclophosphamide, and a sequential taxane (ACT), followed by RT. All patients had either node-positive or high-risk node-negative breast cancer and were treated between October 2000 and September 2002. Postmastectomy, a median dose of 5040 cGy was delivered to the chest wall. After breast-conserving surgery, a median dose of 4680 cGy was delivered to the breast plus a 1400 cGy boost to the surgical cavity. Information regarding RP was gathered retrospectively by reviewing patient records. With a median follow-up of 28 months (range 6-42 months), no cases of clinical RP were identified and no local failures had occurred. The median time interval for all patients between the completion of chemotherapy and the initiation of RT was 34 days (range 5-70 days). At the latest follow-up, 2 patients were diagnosed with metastatic disease and 38 patients were without evidence of disease. Sequencing of RT after taxane therapy with a target interval of 3-4 weeks does not appear to result in increased pulmonary toxicity and is associated with good local control.     

Screening for Recurrences in Patients Treated with Breast-Conserving Surgery: Is there a Role for MRI?

Background Although it has been shown that magnetic resonance imaging (MRI) is more sensitive than mammography in the detection of breast cancer in high-risk populations, there is little data on the use of MRI as a screening tool to detect recurrence after breast-conserving surgery. Our objective was to determine the potential role of MRI in the screening of breast cancer patients treated with breast-conserving surgery. Methods Retrospective chart review of all patients undergoing margin-negative lumpectomy and adjuvant radiation therapy for infiltrating breast carcinoma between 1^st January 1993 and 1^st January 2004. Patients were followed for recurrence in the ipsilateral or contralateral breast by physical exam and mammography. Results Four hundred and seventy-six primary tumor excisions were performed. Patients were followed for a median of 5.4 years. Ipsilateral breast recurrences developed in eight patients (1.7%) with a mean diameter of 1.6 cm. All of these women are alive and free of metastases. Contralateral cancers developed in 11 patients (2.3%) with a mean diameter of 1.5 cm. Ten of these 11 women are alive and free of disease. Conclusions In a contemporary patient population the risk of local recurrence after lumpectomy and radiation therapy is very low. If screening MRI had been a part of annual follow-up, a total of 2570 MRIs would have been performed. Given the small tumor size at detection and the excellent survival of those who recurred, annual screening MRI would have incurred significant cost and would have been unlikely to improve overall survival.     

CORR Insights®: What is the Incidence of Suicide in Patients with Bone and Soft Tissue Cancer?

Clinical Orthopaedics and Related Research® -     

Increased Incidence of Renal Cysts in Patients with Abdominal Aortic Aneurysms: A Common Pathogenesis?

We have empirically observed that patients with abdominal aortic aneurysms (AAAs) seem to have an increased incidence of renal cysts on computed tomography (CT). In order to evaluate this possible association, a retrospective cohort study was conducted comparing the incidence of renal cysts on CT scan in 100 patients with AAA to 100 patients without AAA (matched by age and gender). Univariate analysis and multiple logistic regression were performed to evaluate the association of AAAs and other risk factors with the presence of renal cysts. Of patients with AAAs, 54% had renal cysts compared to only 30% in the control group (p = 0.0006, relative risk = 2.73). The AAA group had a higher incidence of chronic obstructive pulmonary disease (COPD, 14% vs. 1%), hypertension (76.6% vs. 46.5%), coronary artery disease (38.3% vs. 12%), and hypercholesterolemia (41.5% vs. 9.1%) compared to the non-AAA group. There was a significant linear correlation between renal cysts and COPD (p = 0.011), the presence of AAA (p = 0.0005), and age (p = 0.019), whereas hypercholesterolemia (p = 0.059) and diabetes (p = 0.063) approached significance. On multivariate analysis, there were three independent predictors of renal cysts: COPD (p = 0.051), age (p = 0.01), and AAA (p = 0.028). In conclusion, there is a significantly higher incidence of renal cysts in patients with AAA compared to patients without AAA. To our knowledge, this association has not previously been reported. Future studies are needed to determine whether this correlation is the result of a commonality in the pathogenesis of AAA and renal cysts.     

Is the Quality of Life Better in Patients with Colostomy than Patients with Fecal Incontience?

Background A colostomy offers definitive treatment for individuals with fecal incontinence (FI). Patients and physicians remain apprehensive regarding this option because the quality of life (QOL) with a colostomy is presumably worse than living with FI. The aim of this study, therefore, was to compare the QOL of colostomy patients to patients with FI. Methods A cross-sectional postal survey of patients with FI or an end colostomy was undertaken. QOL measures used included the Short Form 36 General Quality of Life Assessment (SF-36) and the Fecal Incontinence Quality of Life score (FIQOL). Results The colostomy group included 39 patients and the FI group included 71 patients. The average FI score for FI group was 12 ± 4.9 (0 = complete continence, 20 = severe incontinence). In the colostomy group the average colostomy function score was 12.9 ± 3.8 (7 = good function, 35 = poor function). Analysis of the SF-36 revealed higher social function score in the colostomy group compared to the FI group. Analysis of the FIQOL revealed higher scores in the coping, embarrassment, lifestyle scales, and depression scales in the colostomy group compared to the FI group. Conclusion A colostomy is a viable option for patients who suffer from FI and offers a definitive cure with improved QOL.     

Does the Mechanism of Lymph Node Invasion Affect Survival in Patients with Pancreatic Ductal Adenocarcinoma?

Background  

Lymph node metastases are prognostically significant in pancreatic ductal adenocarcinoma. Little is known about the significance of direct lymph node invasion.     

Reviews: Should the Target Hemoglobin for Patients with Chronic Kidney Disease Treated with Erythropoietic Replacement Therapy be Changed?

Recombinant human erythropoietin (rHuEPO, epoetin) revolutionized the treatment of anemia in patients with chronic kidney disease (CKD) when it was approved for use in the United States in 1989. Among dialysis patients, the mean hemoglobin (Hb) in patients undergoing dialysis rose from 7-8 g/dl prior to 1989 to 11-12 g/dl today. Among patients with CKD not on dialysis, epoetin use has not been as broadly applied as among dialysis patients, and although the mean Hb level in this patient population has increased, the impact has been less than in patients on dialysis. The optimal treatment target for epoetin remains controversial. Consistent with clinical practice guidelines, current practice in dialysis patients in the United States aims to maintain a target Hb of 11-12 g/dl, a level that is still well below the normal range. Debate centers on whether the current Hb target is too low and whether the target range is too narrow. Quality of life clearly improves in many individuals as Hb rises into the normal range from lower levels. In retrospective studies, higher Hb levels have been associated with lower risks of hospitalization and mortality. However, one large, prospective clinical trial has raised concern about normalizing Hb in hemodialysis patients with cardiac disease, and other prospective studies have not yet provided convincing evidence of significant benefits from normalizing Hb in dialysis-dependent and non-dialysis-dependent patients with CKD. A relative lack of information on non-dialysis-dependent patients with CKD and changes in fiscal policies regulating reimbursement for epoetin have contributed to uncertainty as to the best practices for anemia management in patients with CKD. There is increasing interest in the potential benefits of broadening the current target Hb range or eliminating an upper limit altogether and instead establishing a minimum Hb goal. While some extension of the upper limit of the currently recommended target Hb range might appear to be reasonable, the extent to which this should be extended, the benefits, risks, and costs of maintaining higher Hb levels in patients with CKD, and whether target Hb levels should be different in different CKD patient groups remains to be determined. Future efforts are likely to focus on selecting patient populations most likely to benefit from normalizing Hb, while adjusting the range of a subnormal Hb target for others.     

Is Axillary Lymph Node Dissection Necessary After Sentinel Lymph Node Biopsy in Patients with Mastectomy and Pathological N1 Breast Cancer?

Background

The American College of Surgeons Oncology Group (ACOSOG) Z0011 trial reported that axillary lymph node dissection (ALND) did not change the recurrence and overall survival (OS) rates in patients with lumpectomy and one to two positive nodes detected by sentinel lymph node biopsy (SLNB). The aim of this study was to determine whether patients with mastectomy and pathological N1 disease found by SLNB could forego ALND.

Materials and Methods

This is a retrospective study of 214 patients diagnosed with primary invasive breast cancer who were treated by mastectomy and lymph node staging surgery (SLNB or ALND) at the Revlon/UCLA Breast Center between January 2002 and December 2010. Patients with pathological N1 disease were separated by their first nodal surgery into SLNB (subgroups: observation, radiation, and additional ALND with or without radiation) and ALND groups (subgroups: ALND with or without radiation).

Results

After a median follow-up of 43.6 months, the OS and systemic relapse-free survival (RFS) rate of the radiation group and additional ALND group were significantly better than the observation group (p = 0.031 and 0.046, respectively). Human epidermal growth factor receptor 2 (HER2) expression was found to predict OS and patients’ age, histological grade and HER2 expression predicted systemic recurrence. Compared with the SLNB group, pain (p = 0.021) and lymphedema (p = 0.043) occurred more frequently in the ALND group.

Conclusion

Radiation was as effective as ALND in patients with mastectomy and N1 disease for OS and RFS rates, yet radiation after SLNB had fewer side effects than ALND. SLNB followed by radiation could replace ALND in patients with mastectomy and pathological N1 breast cancer identified by SLNB.     

Results of Surgical Therapy in Patients with Barrett’s Adenocarcinoma

The incidence of adenocarcinoma arising from Barretts esophagus is dramatically increasing in Western countries. The purpose of this study was to report our experience in the surgical management of these patients. Between November 1992 and December 2000, 330 consecutive patients with adenocarcinoma of the esophagogastric junction were observed in our institution. Of these, 105 (31.8%) had Barretts carcinoma. In 12 individuals (11.4%) adenocarcinoma was discovered during endoscopic surveillance for Barretts esophagus. Twelve patients with doubtful cleavage planes at preoperative investigation were treated with neoadjuvant chemotherapy. Overall, 80 patients (76.2%) underwent esophagectomy without operative mortality. The Ivor Lewis approach was used in 70 patients; of these, 31 underwent extended mediastinal lymph node dissection. Seventy-four patients (92.5%) had R0 resection. The overall 5-year survival rate was 48%. Survival was significantly associated with stage, lymph node status, and completeness of resection. Early diagnosis remains the prerequisite for curative treatment of esophageal carcinoma. An extended mediastinal lymphadenectomy does not increase morbidity, allows precise tumor staging, and may prove effective in preventing local recurrences. Neoadjuvant therapy requires major improvement before it can be unconditionally recommended outside clinical trials.