Michelle C. Specht

Predicting Nonsentinel Node Status After Positive Sentinel Lymph Biopsy for Breast Cancer: Clinicians Versus Nomogram

BackgroundWith increasing frequency, breast cancer patients and clinicians are questioning the need for completion axillary lymph node dissection (ALND) in the setting of a positive sentinel lymph node (SLN). We previously developed a nomogram to estimate the likelihood of residual disease in the axilla after a positive SLN biopsy result. In this study, we compared the predictions of clinical experts with those generated by the nomogram and evaluated the ability of the nomogram to change clinicians’ behavior.MethodsPathologic features of the primary tumor and SLN metastases of 33 patients who underwent completion ALND were presented to 17 breast cancer specialists. Their predictions for each patient were recorded and compared with results from our nomogram. Subsequently, clinicians were presented with clinical information for eight patients and asked whether they would perform a completion ALND before and after being presented with the nomogram prediction.ResultsThe predictive model achieved an area under the receiver operating characteristic curve of .72 when applied to the test data set of 33 patients. In comparison, the clinicians as a group were associated with an area under the receiver operating characteristic curve of .54 (P < .01 vs. nomogram). With regard to performing a completion ALND, providing nomogram results did not alter surgical planning.ConclusionsOur predictive model seemed to substantially outperform clinical experts. Despite this, clinicians were unlikely to change their surgical plan based on nomogram results. It seems that most clinicians can improve their predictive ability by using the nomogram to predict the likelihood of additional non-SLN metastases in a woman with a positive SLN biopsy result.

Therapy of alcohol withdrawal syndrome in intensive care unit patients following trauma: results of a prospective, randomized trial.

OBJECTIVES To assess the effect of three different alcohol withdrawal therapy regimens in traumatized chronic alcoholic patients with respect to the duration of mechanical ventilation and the frequency of pneumonia and cardiac disorders during their intensive care unit (ICU) stay. DESIGN A prospective, randomized, blinded, controlled clinical trial. SETTING A university hospital ICU. PATIENTS Multiple-injured alcohol-dependent patients (n=180) transferred to the ICU after admission to the emergency room and operative management. A total of 180 patients were included in the study; however, 21 patients were excluded from the study after assignment. INTERVENTIONS Patients who developed actual alcohol withdrawal syndrome were randomized to one of the following treatment regimens: flunitrazepam/clonidine (n=54); chlormethiazole/haloperidol (n=50); or flunitrazepam/haloperidol (n=55). The need for administration of medication was determined, using a validated measure of the severity of alcohol withdrawal (Revised Clinical Institute Withdrawal Assessment for Alcohol Scale). MEASUREMENTS AND MAIN RESULTS The duration of mechanical ventilation and major intercurrent complications, such as pneumonia, sepsis, cardiac disorders, bleeding disorders, and death, were documented. Patients did not differ significantly between groups regarding age, Revised Trauma and Injury Severity Score and Acute Physiology and Chronic Health Evaluation II score on admission. In all except four patients in the flunitrazepam/clonidine group, who continued to hallucinate, the Revised Clinical Institute Withdrawal Assessment for Alcohol Scale decreased to <20 after initiation of therapy. ICU stay did not significantly differ between groups (p=.1669). However, mechanical ventilation was significantly prolonged in the chlormethiazole/haloperidol group (p=.0315) due to an increased frequency of pneumonia (p=.0414). Cardiac complications were significantly (p=.0047) increased in the flunitrazepam/clonidine group. CONCLUSIONS There was some advantage in the flunitrazepam/clonidine regimen with respect to pneumonia and the necessity for mechanical ventilation. However, four (7%) patients had to be excluded from the study due to ongoing hallucinations during therapy. Also, cardiac complications were increased in this group. Thus, flunitrazepam/haloperidol should be preferred in patients with cardiac or pulmonary risk. Further studies are required to determine which therapy should be considered.

The effects of low-dose dopamine on splanchnic blood flow and oxygen uptake in patients with septic shock

Objective:To assess the effects of low-dose dopamine on splanchnic blood flow and splanchnic oxygen uptake in patients with septic shock.Design:Prospective, controlled trial.Setting:University hospital intensive care unitPatients:11 patients with septic shock, diagnosed according the criteria of the 1992 American College of Chest Physicians/Society of Critical Care Medicine consensus conference, who required treatment with norepinephrine.Measurements and main results:Systemic and splanchnic hemodynamics and oxygen transport were measured before and during addition of low-dose dopamine (3 μg/kg per min). Low-dose dopamine had a marked effect on total body hemodynamics and oxygen transport. The fractional splanchnic flow at baseline ranged from 0.15 to 0.57. In 7 patients with a fractional splanchnic flow less than 0.30, low-dose dopamine increased splanchnic flow and splanchnic oxygen delivery and oxygen consumption. In 4 patients with a fractional splanchnic flow above 0.30, low-dose dopamine did not appear to change splanchnic blood flow.Conclusion:Low-dose dopamine has a potential beneficial effect on splanchnic blood flow and oxygen consumption in patients with septic shock, provided the fractional splanchnic flow is not already high before treatment.

Intercurrent complications in chronic alcoholic men admitted to the intensive care unit following trauma

ObjectiveA chronic alcoholic group following trauma was investigated to determine whether their ICU stay was longer than that of a non-alcoholic group and whether their intercurrent complication rate was increasedDesignProspective study.SettingAn intensive care unit.PatientsA total of 102 polytraumatized patients were transferred to the ICU after admission to the emergency room and after surgical treatment. Of these patients 69 were chronic alcoholics and 33 were allocated to the non-alcoholic group. The chronic-alcoholic group met the DSM-III-R and ICD-10 criteria for alcohol dependence or chronic alcohol abuse/harmful use. The daily ethanol intake in these patients was ≥60 g. Diagnostic indicators included an alcoholismrelated questionnaire (CAGE), conventional laboratory markers and carbohydrate-deficient transferrin.Measurement and resultsMajor intercurrent complications such as alcohol withdrawal syndrome (AWS), pneumonia, cardiac complications and bleeding disorders were documented and defined according to internationally accepted criteria. Patients did not differ significantly between groups regarding age, TRISS and APACHE score on admission. The rate of major intercurrent complications was 196% in the chronic alcoholic vs 70% in the non-alcoholic group (P=0.0001). Because of the increased intercurrent complication rate, the ICU stay was significantly prolonged in the chronic-alcoholic group by a median period of 9 days.ConclusionsChronic alcoholics are reported to have an increased risk of morbidity and mortality. However, to our knowledge, nothing is known about the morbidity and mortality of chronic alcoholics in intensive care units following trauma. Since chronic alcoholics in the ICU develop mor major complications with a significantly prolonged ICU stay following trauma than non-alcoholics, it seems reasonable to intensify research to identify chronic alcoholics and to prevent alcohol-related complications.

The Impact of Radiation Therapy on the Risk of Lymphedema After Treatment for Breast Cancer: A Prospective Cohort Study

PURPOSE/OBJECTIVE Lymphedema after breast cancer treatment can be an irreversible condition with a negative impact on quality of life. The goal of this study was to identify radiation therapy-related risk factors for lymphedema. METHODS AND MATERIALS From 2005 to 2012, we prospectively performed arm volume measurements on 1476 breast cancer patients at our institution using a Perometer. Treating each breast individually, 1099 of 1501 patients (73%) received radiation therapy. Arm measurements were performed preoperatively and postoperatively. Lymphedema was defined as ≥10% arm volume increase occurring >3 months postoperatively. Univariate and multivariate Cox proportional hazard models were used to evaluate risk factors for lymphedema. RESULTS At a median follow-up time of 25.4 months (range, 3.4-82.6 months), the 2-year cumulative incidence of lymphedema was 6.8%. Cumulative incidence by radiation therapy type was as follows: 3.0% no radiation therapy, 3.1% breast or chest wall alone, 21.9% supraclavicular (SC), and 21.1% SC and posterior axillary boost (PAB). On multivariate analysis, the hazard ratio for regional lymph node radiation (RLNR) (SC ± PAB) was 1.7 (P=.025) compared with breast/chest wall radiation alone. There was no difference in lymphedema risk between SC and SC + PAB (P=.96). Other independent risk factors included early postoperative swelling (P<.0001), higher body mass index (P<.0001), greater number of lymph nodes dissected (P=.018), and axillary lymph node dissection (P=.0001). CONCLUSIONS In a large cohort of breast cancer patients prospectively screened for lymphedema, RLNR significantly increased the risk of lymphedema compared with breast/chest wall radiation alone. When considering use of RLNR, clinicians should weigh the potential benefit of RLNR for control of disease against the increased risk of lymphedema.

Proton therapy for breast cancer after mastectomy: early outcomes of a prospective clinical trial.

PURPOSE Dosimetric planning studies have described potential benefits for the use of proton radiation therapy (RT) for locally advanced breast cancer. We report acute toxicities and feasibility of proton delivery for 12 women treated with postmastectomy proton radiation with or without reconstruction. METHODS AND MATERIALS Twelve patients were enrolled in an institutional review board-approved prospective clinical trial. The patients were assessed for skin toxicity, fatigue, and radiation pneumonitis during treatment and at 4 and 8 weeks after the completion of therapy. All patients consented to have photographs taken for documentation of skin toxicity. RESULTS Eleven of 12 patients had left-sided breast cancer. One patient was treated for right-sided breast cancer with bilateral implants. Five women had permanent implants at the time of RT, and 7 did not have immediate reconstruction. All patients completed proton RT to a dose of 50.4 Gy (relative biological effectiveness [RBE]) to the chest wall and 45 to 50.4 Gy (RBE) to the regional lymphatics. No photon or electron component was used. The maximum skin toxicity during radiation was grade 2, according to the Common Terminology Criteria for Adverse Events (CTCAE). The maximum CTCAE fatigue was grade 3. There have been no cases of RT pneumonitis to date. CONCLUSIONS Proton RT for postmastectomy RT is feasible and well tolerated. This treatment may be warranted for selected patients with unfavorable cardiac anatomy, immediate reconstruction, or both that otherwise limits optimal RT delivery using standard methods.

Comparison of the performance of SAPS II, SAPS 3, APACHE II, and their customized prognostic models in a surgical intensive care unit

BACKGROUND The Simplified Acute Physiology Score (SAPS) 3 has recently been developed, but not yet validated in surgical intensive care unit (ICU) patients. We compared the performance of SAPS 3 with SAPS II and the Acute Physiology and Chronic Health Evaluation (APACHE) II score in surgical ICU patients. METHODS Prospectively collected data from all patients admitted to a German university hospital postoperative ICU between August 2004 and December 2005 were analysed. The probability of ICU mortality was calculated for SAPS II, APACHE II, adjusted APACHE II (adj-APACHE II), SAPS 3, and SAPS 3 customized for Europe [C-SAPS3 (Eu)] using standard formulas. To improve calibration of the prognostic models, a first-level customization was performed, using logistic regression on the original scores, and the corresponding probability of ICU death was calculated for the customized scores (C-SAPS II, C-SAPS 3, and C-APACHE II). RESULTS The study included 1851 patients. Hospital mortality was 9%. Hosmer and Lemeshow statistics showed poor calibration for SAPS II, APACHE II, adj-APACHE II, SAPS 3, and C-SAPS 3 (Eu), but good calibration for C-SAPS II, C-APACHE II, and C-SAPS 3. Discrimination was generally good for all models [area under the receiver operating characteristic curve ranged from 0.78 (C-APACHE II) to 0.89 (C-SAPS 3)]. The C-SAPS 3 score appeared to have the best calibration curve on visual inspection. CONCLUSIONS In this group of surgical ICU patients, the performance of SAPS 3 was similar to that of APACHE II and SAPS II. Customization improved the calibration of all prognostic models.

Long-term cosmetic outcomes and toxicities of proton beam therapy compared with photon-based 3-dimensional conformal accelerated partial-breast irradiation: a phase 1 trial.

PURPOSE To present long-term outcomes of a prospective feasibility trial using either protons or 3-dimensional conformal photon-based (accelerated partial-breast irradiation [APBI]) techniques. METHODS AND MATERIALS From October 2003 to April 2006, 98 evaluable patients with stage I breast cancer were treated with APBI (32 Gy in 8 fractions given twice daily) on a prospective clinical trial: 19 with proton beam therapy (PBT) and 79 with photons or mixed photons/electrons. Median follow-up was 82.5 months (range, 2-104 months). Toxicity and patient satisfaction evaluations were performed at each visit. RESULTS At 7 years, the physician rating of overall cosmesis was good or excellent for 62% of PBT patients, compared with 94% for photon patients (P=.03). Skin toxicities were more common for the PBT group: telangiectasia, 69% and 16% (P=.0013); pigmentation changes, 54% and 22% (P=.02); and other late skin toxicities, 62% and 18% (P=.029) for PBT and photons, respectively. There were no significant differences between the groups in the incidences of breast pain, edema, fibrosis, fat necrosis, skin desquamation, and rib pain or fracture. Patient-reported cosmetic outcomes at 7 years were good or excellent for 92% and 96% of PBT and photon patients, respectively (P=.95). Overall patient satisfaction was 93% for the entire cohort. The 7-year local failure rate for all patients was 6%, with 3 local recurrences in the PBT group (7-year rate, 11%) and 2 in photon-treated patients (4%) (P=.22). CONCLUSIONS Local failure rates of 3-dimensional APBI and PBT were similar in this study. However, PBT, as delivered in this study, led to higher rates of long-term telangiectasia, skin color changes, and skin toxicities. We recommend the use of multiple fields and treatment of all fields per treatment session or the use of scanning techniques to minimize skin toxicity.

Breast cancer diagnosis in women ≤ 40 versus 50 to 60 years : Increasing size and stage disparity compared with older women over time

BackgroundWomen ≤ 40 years account for 5% of new breast cancer diagnoses. Although there is increased awareness of genetic and other breast cancer risk factors, it is not clear whether this has resulted in earlier diagnosis in young women.MethodsA database review identified 8892 women treated for breast cancer from 1980 to 2002. We compared 925 women aged ≤ 40 years with 2362 women aged 50 to 60 years. The mean and median tumor size and lymph node status were determined for each group.ResultsThere were significant differences in tumor size and lymph node status in younger versus older women. From 1980 to the mid 1990s, tumor size and nodal status did not differ. Since the mid 1990s, tumor size has decreased more rapidly for women aged 50 to 60 years than for those ≤ 40 years. In 1998 to 2002, the mean tumor size reached a plateau of 1.8 cm in women 50 to 60 years, compared with a plateau of 2.4 cm in women ≤ 40 years (P < .001). The median tumor size in 1998 to 2002 was 1.4 cm in women 50 to 60 years compared with 1.9 cm in women ≤ 40 years (P < .001). Lymph node status was also significantly different during 1998 to 2002: 23.9% positive in women 50 to 60 years versus 35.2% in women ≤ 40 years (P < .001).ConclusionsSince the 1980s, women aged 50 to 60 years have enjoyed a greater decrease in tumor size and percentage with positive nodes. These data could be the result of ineffective screening of younger women or of more aggressive tumor biology. Further study is required to determine whether more effective identification and screening of young, high-risk women can result in earlier detection.

Sentinel Node Biopsy is Important in Mastectomy for Ductal Carcinoma In Situ

BackgroundThere is uncertainty about the utility of sentinel node biopsy (SNB) for ductal carcinoma in situ (DCIS) and its potential to avoid axillary lymph node dissection (ALND) in patients undergoing mastectomy for DCIS.MethodsA review was conducted of 179 patients who underwent mastectomy with sentinel node biopsy for DCIS without invasion or microinvasion on premastectomy pathology review.ResultsThe sentinel node identification rate was 98.9% (177/179). Twenty (11.3%) of 177 mastectomies for DCIS had a positive SNB: two micrometastasis (pN1mi) and 18 isolated tumor cells [pN0(i+)]. Unsuspected invasive cancer was found in 20 (11.2%) of 179 mastectomies, eight T1mic, five T1a, three T1b, and four T1c tumors. Sentinel nodes were identified in 19 of 20 patients with invasive cancer and four were positive: one pN1mi and three pN0(i+). Eighteen of 19 patients with unsuspected invasive cancer were able to avoid axillary dissection on the basis of SNB results. Of the 159 patients whose final pathology revealed DCIS without invasion, a sentinel node was identified in 158 (99.4%). The SNB was positive in 16 patients (10.1%): one pN1mi and 15 pN0(i+). Three patients underwent ALND on the basis of positive SNBs and in each the SNB was the only positive node.Conclusions11% of patients undergoing mastectomy for DCIS were found to have invasive cancer on final pathology. The use of SNB during mastectomy for DCIS allowed nearly all such patients to avoid axillary dissection. These results support routine use of SNB during mastectomy for DCIS.