Survival Benefit of Chemotherapy According to 21-Gene Recurrence Score in Young Women with Breast Cancer.

BACKGROUND: Initial trials evaluating Oncotype DX, reported as a recurrence score (RS) from 0 to 100, were not powered to evaluate overall survival, and premenopausal women were underrepresented. The purpose of this study was to explore the benefit of chemotherapy according to RS among younger women eligible for oncotype testing. METHODS: Women aged 40-50, diagnosed with HR-positive, HER2-negative breast cancer between 2010 and 2017 were selected from the National Cancer Database (NCBD). Patients were grouped by age, RS, nodal status, and chemotherapy receipt. Kaplan-Meier curves were used to compare unadjusted overall survival (OS) between the groups, and log-rank tests were used to test for a difference between groups. Cox proportional hazards models were used to examine the association between select factors and OS. RESULTS: A total of 15,422 patients met inclusion criteria, 45.3% of whom received chemotherapy. Median follow-up time was 66.4 (50.6-86.6) months. Patients who received chemotherapy were more likely to have higher-stage and higher-grade tumors, tumors that were PR-negative, and have higher RS (p < 0.001 for all). RS was prognostic for OS regardless of nodal status. After adjustment, chemotherapy was associated with a significant improvement in OS only in the pN1 RS 31-50 subgroup (p = 0.02). CONCLUSIONS: RS retains its prognostic value in younger patients with early stage HR-positive, HER2-negative breast cancer. Chemotherapy survival benefit was limited to patients aged 40-50 with pN1 disease and RS of 31-50. Therefore, chemotherapy decision-making should be especially preference-sensitive in women aged 40-50 with intermediate RS, where it may not provide a survival benefit for many women.

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

BACKGROUND: Neoadjuvant chemotherapy (NACT) is often recommended for patients with node-positive invasive lobular carcinoma (ILC) despite unclear benefit in this largely hormone receptor-positive (HR+) group. We sought to compare overall survival (OS) between patients with node-positive ILC who received neoadjuvant endocrine therapy (NET) and those who received NACT. METHODS: Women with cT1-4c, cN1-3 HR+ ILC in the National Cancer Data Base (2004-2014) who underwent surgery following neoadjuvant therapy were identified. Kaplan-Meier curves and Cox proportional hazards modeling were used to estimate unadjusted and adjusted overall survival (OS), respectively. RESULTS: Of the 5942 patients in the cohort, 855 received NET and 5087 received NACT. NET recipients were older (70 vs. 54 years) and had more comorbidities (Charlson-Deyo score ≥ 1: 21.1% vs. 11.5%), lower cT classification (cT3-4: 44.2% vs. 51.0%), lower rates of mastectomy (72.5% vs. 82.2%), lower rates of pathologic complete response (0% vs. 2.5%), and lower rates of postlumpectomy (73.2% vs. 91.0%) and postmastectomy (60.0% vs. 80.8%) radiation versus NACT recipients (all p < 0.001). NACT recipients had higher unadjusted 10-year OS versus NET recipients (57.9% vs. 36.0%), but after adjustment, there was no significant difference in OS between the two groups (p = 0.10). CONCLUSIONS: Patients with node-positive ILC who received NET presented with smaller tumors, older age, and greater burden of comorbidities versus NACT recipients but had similar adjusted OS. While there is evidence from clinical trials supporting efficacy of NET in HR+ breast cancer, our findings suggest the need for further, histology-specific investigation regarding the optimal inclusion and sequence of endocrine therapy and chemotherapy in ILC.

Magnetic resonance imaging-guided core needle biopsy and needle localized excision of occult breast lesions.

BACKGROUND: Breast magnetic resonance imaging (MRI) has been reported to be twice as sensitive and three times more specific in detecting breast cancer. We report a series of MRI-guided stereotactic breast biopsies (SCNBB) and needle localized breast biopsies (NLBB) to evaluate MRI as a localization tool. METHODS: Forty-one breast lesions were identified in 39 patients who subsequently had SCNBB or NLBB. Suspicious areas of enhancement were stereotactically biopsied with 16-G core biopsy needles or localized with 22-G wires for excision under laser guidance. RESULTS: Forty-one breast lesions were identified from 1,292 breast MRIs. SCNBB identified three malignancies and two areas of atypia. Two additional cancers were found after NLBB. In patients having NLBB alone, five cancers and two areas of atypia were identified. CONCLUSIONS: In this initial series, breast MRI-guided SCNBB and NLBB were valuable tools in the management of patients with suspicious abnormalities seen only on MRI.

Hematoma-directed ultrasound-guided breast biopsy.

OBJECTIVE AND SUMMARY BACKGROUND DATA: The standard technique for removal of nonpalpable breast lesions is needle localization breast biopsy. Because traumatic hematomas can often be seen with ultrasound, the authors hypothesized that iatrogenically induced hematomas could be used to guide the excision of nonpalpable lesions using ultrasound. METHODS: Twenty patients with nonpalpable breast lesions detected by magnetic resonance imaging only were enrolled in this single-institution trial, approved by the institutional review board. A hematoma consisting of 2 to 5 mL of the patient's own blood was injected into the breast to target the nonpalpable lesion. Intraoperative ultrasound of the hematoma was used to direct the excisional biopsy. RESULTS: The average age of women was 53.8 +/- 10 years. Ninety-five percent of lesions detected by magnetic resonance imaging were localized by hematoma injection. All the hematomas used to recognize targeted lesions were identified at surgery by ultrasound and removed without complication. Eight (40%) of the lesions were malignant, with an average tumor size of 12 +/- 6 mm (range 4-25). The remaining 12 lesions (60%) comprised papillomas, sclerosing adenosis, radial scar, fibroadenoma, and areas of atypical ductal hyperplasia. CONCLUSION: The results of this pilot study show the effectiveness of hematoma-directed ultrasound-guided breast biopsy for nonpalpable lesions seen by magnetic resonance imaging. This new procedure is potentially more comfortable for the patient because no wire or needle is left in the breast. It is technically faster and easier because ultrasound is used to visualize directly the location of the hematoma at surgery and to confirm lesion removal in the operating room by specimen ultrasound. The hematoma can be placed several days before biopsy, easing scheduling, and without fear of the migration that may occur with needle localization. This method may have ready application to mammographically detected lesions.

Central venous catheter placement in patients with disorders of hemostasis.

BACKGROUND: Patients requiring central venous access frequently have disorders of hemostasis. The aim of this study was to identify factors predictive of bleeding complications after central venous catheterization in this group of patients. METHODS: A retrospective analysis of all central venous catheters placed over a 2-year period (1997 to 1999) at our institution were performed. The age, sex, clinical diagnosis, most recent platelet count, prothrombin international normalized ratio (INR), activated partial thromboplastin time (aPTT), catheter type, the number of passes to complete the procedure, and bleeding complications were retrieved from the medical records. RESULTS: In a 2-year period, 2,010 central venous catheters were placed in 1,825 patients. Three hundred and thirty placements were in patients with disorders of hemostasis. In 88 of the 330 patients, the underlying coagulopathy was not corrected before catheter placement. In these patients, there were 3 bleeding complications requiring placement of a purse string suture at the catheter entry site. In the remaining 242 patients, there was 1 bleeding complication. Of the variables analyzed, only a low platelet count (<50 x 10(9)/L) was significantly associated with bleeding complications. CONCLUSION: Central venous access procedures can be safely performed in patients with underlying disorders of hemostasis. Even patients with low platelet counts have infrequent (3 of 88) bleeding complications, and these problems are easily managed.

"The home infusion patient": patient profiles for the home infusion therapy market.

The authors review the relevant literature regarding home health care patient profiles. An empirical analysis is provided from archival data for a home infusion company servicing patients in urban and rural areas. The results are provided as a 2 x 2 matrix for patients in urban and rural areas seeing either a specialist or primary care physicians. A series of moderated regressions indicate that type of treating physician, patient's gender, geographic residence and level of acuity are cogent in predicting the complexity of prescribed infusion therapies. Managerial implications are provided for the home care marketer in segmenting patient markets for infusion services.

Role of breast magnetic resonance imaging in determining breast as a source of unknown metastatic lymphadenopathy.

BACKGROUND: Occult primary breast cancer (OPBC) represents less than 1% of breast cancer. In only a third of cases, mammography identifies a primary tumor. We hypothesized that rotating delivery of excitation off-resonance breast magnetic resonance imaging (MRI) would identify or exclude the breast as a primary site in patients with OPBC. METHODS: In a retrospective review, 10 patients were identified with OPBC in which MRI was performed. Malignant appearing lesions were correlated with histopathologic findings at biopsy or surgery. RESULTS: MRI identified the primary site in 8 of 10 cases as breast (80%), and excluded it in 2 cases. The extent of disease and location was accurately predicted when compared with histopathologic specimen. CONCLUSIONS: As we continue to focus on a cure of early breast cancer, it is imperative that diagnostic images become more sensitive and specific. MRI accurately predicted OPBC in this subset of patients.

Use of touch preps for diagnosis and evaluation of surgical margins in breast cancer.

BACKGROUND: The best cosmetic results with conservative breast surgery are obtained at the time of initial excisional biopsy. The usefulness of the touch prep (TP) technique was evaluated for accuracy in diagnosis as well as in evaluation of margins at the time of original breast biopsy. METHODS: Four hundred twenty-eight consecutive patients with breast masses seen from January 1993 to December 1994 were evaluated prospectively using TP. RESULTS: Three hundred forty-five benign and 83 malignant tumors were evaluated. Tumors ranged in size from microscopic to 8 cm. Pathologic diagnosis was correct as compared to permanent section in 99.3%. The three carcinomas missed on TP were focal and in situ. Sensitivity was 96.39%, and specificity was 100%. Positive predictive value was 100%, and negative predictive value was 99.3%. For margin evaluation, the sensitivity and specificity were both estimated to be 100%. CONCLUSIONS: TP has the advantage of being a simple, quick (2 to 3 minutes), safe (no loss of diagnostic material), and accurate method for diagnosis and estimation of tumor margins at the time of the original surgery.

Effect of glutamine on methotrexate efficacy and toxicity.

OBJECTIVE: To examine the effect of oral glutamine (GLN) on the efficacy and toxicity of methotrexate (MTX). SUMMARY BACKGROUND DATA: The use of high-dose chemotherapy regimens is limited by the severity of their toxicities. Oral GLN has been shown to decrease the gut toxicity seen with MTX treatment while enhancing its tumoricidal effect. METHODS AND RESULTS: Studies were done in laboratory rats and in breast cancer outpatients. Fischer 344 rats were randomized to 48 hours of prefeeding with GLN (1 g/kg/day) or an isonitrogenous amount of glycine. Rats were killed 24 hours after receiving a 20-mg/kg intraperitoneal dose of MTX. In the GLN group, there was a threefold increase in total MTX in the tumor as compared with the control group, and this increase was in both the diglutamated and pentaglutamated MTX. Inversely, there was a significant decrease in the total polyglutamated MTX in the gut in the GLN group. Given the results of this preclinical study, the authors performed a phase I trial. Nine patients diagnosed with inflammatory breast cancer received GLN (0.5 g/kg/day) during MTX neoadjuvant therapy, escalating from doses of 40 mg/m2 to 100 mg/m2 weekly for 3 weeks, followed by a doxorubicin-based regimen. No toxicity of oral GLN was detected. No patient showed any sign of chemotherapy-related toxicity. One patient had a grade I mucositis. Except for one, all patients responded to the chemotherapy regimen. Median survival was 35 months. CONCLUSIONS: These studies suggest that GLN supplementation is safe in its administration to the tumor-bearing host receiving MTX. By preferentially increasing tumor retention of MTX over that of normal host tissue, GLN may serve to increase the therapeutic window of this chemotherapeutic age.

The role of the physician and the present and emerging health care channel.

The author examines the position of physicians in the health care channel on the basis of Transaction Cost Analysis. Propositions are offered that explain recent vertical integration. Moreover, a conceptual model of the future health care channel is offered for capitated pricing.

Assessing the strategy-performance paradigm: implications for organizational adaptation in discontinuous environments for home health care providers.

Home health care agencies are on the brink of experiencing prospective payment systems which will prove to be a major environmental shift. What will be the best strategy to offset the effects of prospective payment systems? Longitudinal studies of hospitals facing similar pressures may offer the best solution. This paper offers an attempt to address whether proactive or low cost strategies will provide home health agencies with higher firm performance after prospective payment systems.

A quality tool for health insurers. A new scale measures "quality orientation" from the customer's point of view.

This study defines a company's quality orientation as "all process-related activities that can be discerned by customers." This even includes certain processes internal to the company that can be seen and evaluated by customers. One significant contribution this study provides is scale development centered on customer rather than employee perceptions. To generate scale items, input was gathered from experts involved in the study, senior managers employed with the target company, focus groups of employees working on the front line with customers, and users of the services. Because the sale measures customer perceptions of quality in comparison with the firm's closest competitor, it provides managers with information for benchmarking performance relative to others in the marketplace.

Risk factors for requiring cataract surgery following total body irradiation.

In order to determine the incidence of cataract surgery following total body irradiation (TBI), questionnaires were mailed to 173 surviving patients who had received single fraction TBI for haematological malignancies. All patients had undergone bone marrow transplantation at the Royal Marsden Hospital, Surrey, between 1977 and 1991. Replies were received from 135 patients (78%). Fifty-four patients had required cataract surgery. The probability of requiring surgery for cataract at 2, 5 and 10 years post TBI was 5%, 39% and 58%, respectively. No cataract surgery was performed at less than 2 years after the time of TBI, and 12 years is the longest interval, prior to surgery, recorded so far. From a number of potential risk factors, those found to predict independently for cataract surgery, and their relative risk (RR) factors, were: cranial radiotherapy preceding TBI (RR 4.2 for patients irradiated in year prior to TBI, 3.3 for others irradiated); skull dose (RR 2.3 for patients over 25 years at time of TBI); TBI dose rate (RR 2.1 for dose rate > 3.5 cGy/min). An additional 31 patients (22%) reported the presence of cataracts which had not yet required surgery.

Prevention of chronic radiation enteropathy by dietary glutamine.

BACKGROUND: Nearly 50% of all cancer patients receive therapeutic radiation during the course of their disease. The risk of late complications is the main dose-limiting factor in the delivery of radiation therapy. The small intestine, the major site of chronic radiation enteropathy, is also the principal organ of glutamine consumption. We therefore hypothesized that the provision of supplemental glutamine may have a protective effect on the development of chronic radiation enteropathy. METHODS: This study evaluated the effects of supplemental oral glutamine on the development of chronic radiation (XRT) enteropathy. After scrotalization of a loop of small intestine, rats were randomized to receive 1 g/kg/day glutamine (GLN) or glycine (GLY) by gavage. After 2 days of prefeeding, rats were randomized to 1 of 4 groups: GLN + XRT (n = 10), GLY + XRT (n = 10), GLN only (n = 10), GLY only (n = 10). Twenty Gy was delivered to the scrotalized bowel in the GLN + XRT and GLY + XRT groups via a collimated beam. Gavage was continued for 10 days. Animals were then pair-fed chow. Rats were killed at 2 months postirradiation. Chronic radiation injury was assessed microscopically. RESULTS: Injury scores in GLN + XRT were similar to those of unirradiated bowel and significantly different from GLY + XRT (1.89 +/- 0.48 in XRT + GLN vs. 6.42 +/- 1.55 in the XRT + GLY, p < 0.01). Elevated Injury Scores in the XRT + GLY group correlated with gross thickening and fibrosis, a 10-fold decrease in gut GLN extraction (1.40 +/- 4.3% in GLY + XRT vs. 16.0 +/- 5.1% in GLN + XRT, p < 0.05), and a 30% decrease in glutathione content (2.46 +/- 0.19 and GLY + XRT vs. 3.17 +/- 0.17 GLN + XRT, p < 0.05). CONCLUSIONS: Provision of GLN during abdominal/pelvic XRT may prevent XRT injury and decrease the long-term complications of radiation enteropathy.

Glutamine facilitates chemotherapy while reducing toxicity.

Dose intensification of chemotherapy is thought to increase survival. With recent advances in hemopoietic cell modulators such as granulocyte colony stimulating factor, the limiting toxicity of intensifying chemotherapeutic regimens has become the severity of the associated enterocolitis. In animal models, glutamine protects the host from methotrexate-induced enterocolitis. This study evaluates the effects of a glutamine-supplemented diet on the tumoricidal effectiveness of methotrexate. Sarcoma-bearing Fisher 344 rats (n = 30) were pair-fed an isocaloric elemental diet containing 1% glutamine or an isonitrogenous amount of glycine beginning on day 25 of the study. Rats from each group received two intraperitoneal injections of methotrexate (5 mg/kg) or saline on days 26 and 33 of the study. On day 40, rats were killed, tumor volume and weight were recorded, and tumor glutaminase activity and tumor morphometrics were measured. Blood was taken for arterial glutamine content, complete blood count, and blood culture. The gut was processed for glutaminase activity and synthesis phase of the deoxyribonucleic acid. In rats receiving methotrexate, the tumor volume loss was nearly doubled when glutamine was added to the diet. Significant differences in tumor glutaminase activity and morphometrics were not detected. The toxicity to the host was ameliorated. Significantly increased synthesis phase of deoxyribonucleic acid of the whole jejunum, decreased bacteremia, "sepsis," and mortality were demonstrated. Glutamine supplementation enhances the tumoricidal effectiveness of methotrexate while reducing its morbidity and mortality in this sarcoma rat model.

Effect of supplemental dietary glutamine on methotrexate concentrations in tumors.

This study evaluated the effects of supplemental dietary glutamine (GLN) on methotrexate sodium concentrations in tumors and serum of sarcoma-bearing rats following the initiation of methotrexate. After randomization to a GLN diet (+GLN) or GLN-free diet (-GLN), tumor-bearing rats received 20 mg/kg of methotrexate sodium by intraperitoneal injection. The provision of supplemental GLN in the diet increased methotrexate concentrations in tumor tissues at 24 and 48 hours (38.0 +/- 0.20 nmol/g for the +GLN group vs 28.8 +/- 0.10 nmol/g for the -GLN group and 35.6 +/- 0.18 nmol/g for the +GLN group vs 32.5 +/- 0.16 nmol/g for the -GLN group, respectively). Arterial methotrexate levels were elevated only at 48 hours (0.147 +/- 0.007 microns/L for the +GLN group vs 0.120 +/- 0.006 microns/L for the -GLN group). Tumor morphometrics were not different between the groups but significantly greater tumor volume loss was seen even at 24 hours (-2.41 +/- 1.3 cm3 for the +GLN group vs -0.016 +/- 0.9 cm3 for the -GLN group). Tumor glutaminase activity was suppressed in both groups at 48 hours, but more so in the +GLN group (0.94 +/- 0.13 mumol/g per hour for the +GLN group vs 1.47 +/- 0.22 mumol/g per hour for the -GLN group). This study suggests that GLN may have therapeutic as well as nutritional benefit in oncology patients.

Advantages of the Papillon protocol in the preoperative treatment of rectal carcinoma.

Standard treatment for advanced rectal carcinoma currently includes surgery, radiotherapy, and chemotherapy. Although there are theoretic advantages to preoperative irradiation, it is often not performed because of the prolonged delay of surgery and the purported increase in perioperative complications. A pilot study was undertaken at our institution to evaluate a treatment protocol advocated by Dr. Papillon that offers a shorter treatment time and less patient morbidity than conventional preoperative therapy for rectal carcinoma. Twenty patients with rectal cancer underwent the preoperative regimen that consisted of 3,000 cGy delivered in 10 fractions over 12 days with concomitant 5-fluorouracil and mitomycin-C. Complications were acceptable. Local recurrence was lower than in most reported trials, and survival rates were comparable. Additional benefits of the protocol include lower radiation morbidity to the patient and a decreased delay between diagnosis and surgery.

Stockless inventory systems for the health care provider: three successful applications.

Three large hospital-based stockless inventory systems are described. First, the method of stockless inventory is described in some detail and differentiated from the just-in-time (JIT) method of inventory management. Second, three hospital case studies involving successful stockless systems are summarized and evaluated. Finally, some important implications for the implementation of stockless inventory systems are summarized for hospital management.