Multiple myeloma is a malignant plasma cell neoplasm that affects more than 20,000 people each year and is the second most common hematologic malignancy. It is part of a spectrum of monoclonal plasma ...cell disorders, many of which do not require active therapy. During the past decade, considerable progress has been made in our understanding of the disease process and factors that influence outcome, along with development of new drugs that are highly effective in controlling the disease and prolonging survival without compromising quality of life. Identification of well-defined and reproducible prognostic factors and introduction of new therapies with unique modes of action and impact on disease outcome have for the first time opened up the opportunity to develop risk-adapted strategies for managing this disease. Although these risk-adapted strategies have not been prospectively validated, enough evidence can be gathered from existing randomized trials, subgroup analyses, and retrospective studies to develop a working framework. This set of recommendations represents such an effort—the development of a set of consensus guidelines by a group of experts to manage patients with newly diagnosed disease based on an interpretation of the best available evidence.
Abstract
Background: Breast conserving surgery (BCS) and radiotherapy (RT) reduce the risk of breast cancer recurrence, but can cause various functional deficits in breast cancer survivors. Side ...effects to the shoulder can include pain, stiffness, and restricted mobility, which are difficult to objectively assess in the clinic.
Methods: The mechanical integrity of the shoulder and the pectoralis major (PM) was assessed in patients at least 1 year post-treatment with BCS and RT. Nine patients with node-negative breast cancer were treated with 2 RT fields to the breast alone after BCS and sentinel node biopsy (Group 1). Nine patients with node-positive breast cancer were treated with ≥3 RT fields to the breast and draining lymphatics after BCS and axillary lymph node dissection (ALND) (Group 2). Nodal RT was delivered to the supraclavicular and infraclavicular (level III axillary) nodes in 9/9 patients, the internal mammary nodes in 6/9 patients, and the full axilla (levels I, II, and III) in 1/9 patient. Nine age-matched healthy controls (mean age 54) with no history of breast cancer or shoulder injury were also examined. The mechanical integrity of the shoulder was objectively quantified using robot-assisted biomechanical measures of shoulder stiffness. The shear elastic modulus, or 'stiffness', of the clavicular and sternocostal fiber regions of PM was assessed using ultrasound shear wave elastography. Participants were examined while they were relaxed or actively contracting force with their shoulder muscles. Linear mixed effect models with Bonferroni-corrected multiple comparisons were used to determine if shoulder stiffness or PM shear elastic modulus differed between the two breast cancer groups and controls.
Results: Patients in Groups 1 (mean age 54) and 2 (mean age 57) were an average (SD) 754(111) and 988(163) days since initiating RT (p=0.003). Shoulder stiffness did not differ between the 2 groups and healthy controls (F2,27=0.76, p=0.48), There was a significant group difference in PM shear elastic modulus (F2,27=8.33, p=0.0015), with Group 2 patients exhibiting an average greater stiffness of 14-21% in the sternocostal and 12-28% in the clavicular regions of the PM versus Group 1 patients (p<0.001) and healthy controls (p =0.021). There was no difference between patients treated with Group 1 and controls (p=0.29).
Conclusions: Although power is limited due to small sample size, this study provides the first evidence that the mechanical integrity of the shoulder remains intact in patients who receive ALND combined with a supraclavicular field (generally without full axillary radiotherapy). The observation of altered PM function without subsequent changes to shoulder stiffness in patients treated with ALND and ≥3 RT fields suggests these patients likely develop new neuromuscular strategies to stabilize the shoulder joint to compensate for the PM. Future work is needed to appreciate whether certain muscle strategies are associated with poorer quality of life in breast cancer survivors, and to prospectively monitor the impact of breast cancer treatments on PM mechanical properties.
Citation Format: Lipps DB, Leonardis JM, Lehmann S, Dess RT, McGinnis G, Strauss JB, Hayman JA, Pierce LJ, Jagsi R. Mechanical properties of the shoulder and pectoralis major in women undergoing breast conserving therapy with axillary dissection and regional nodal radiotherapy versus sentinel node biopsy and radiotherapy to the breast alone abstract. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-12-18.
Multiple myeloma is a neoplastic plasma cell dyscrasia that on a yearly basis affects nearly 17,000 individuals and kills more than 11,000. Although no cure exists, many effective treatments are ...available that prolong survival and improve the quality of life of patients with this disease. The purpose of this consensus is to offer a simplified, evidence-based algorithm of decision making for patients with newly diagnosed myeloma. In cases in which evidence is lacking, our team of 18 Mayo Clinic myeloma experts reached a consensus on what therapy could generally be recommended. The focal point of our strategy revolves around risk stratification. Although a multitude of risk factors have been identified throughout the years, including age, tumor burden, renal function, lactate dehydrogenase, β2 -microglobulin, and serum albumin, our group has now recognized and endorsed a genetic stratification and patient functional status for treatment.
We report on the feasibility of outpatient transplant in 716 patients undergoing autologous stem cell transplant for multiple myeloma at Mayo Clinic's site in Rochester, MN, from January 1, 2000, ...through October 31, 2007. We also report on the development and effect of a multidisciplinary quality initiative implemented by the Mayo Clinic Blood and Marrow Transplant Program involving physicians, nurses, pharmacists, dietitians, and financial specialists for outpatient management of patients undergoing stem cell transplant. This approach uses an electronic ordering system for diagnostic tests and chemotherapy to minimize medical errors. Analysis of hospitalization trends since inception of the program showed that 278 (39%) of the 716 patients treated completed the transplant procedure as outpatients. The median duration of hospitalization for all patients was 4 days; age and serum creatinine levels were predictive of the need for and duration of hospitalization. We also assessed recent treatment-related mortality rates during a 33-month period after implementation of the program (between January 1, 2005, and October 1, 2007). The 100-day survival rate was 99.5% for patients with low-risk myeloma (transplant during first plateau; n=201) and 97.2% for patients with high-risk myeloma (refractory, relapsing or second or greater plateau; n=71). The overall 100-day survival rate was 98.9%. Our experience shows that outpatient transplant is feasible for all patients with multiple myeloma and results in shorter hospital stays and low treatment-related mortality rates.
Waldenström macroglobulinemia is a B-cell malignancy with lymphoplasmacytic infiltration in the bone marrow or lymphatic tissue and a monoclonal immunoglobulin M protein (IgM) in the serum. It is ...incurable with current therapy, and the decision to treat patients as well as the choice of treatment can be complex. Using a risk-adapted approach, we provide recommendations on timing and choice of therapy. Patients with smoldering or asymptomatic Waldenström macroglobulinemia and preserved hematologic function should be observed without therapy. Symptomatic patients with modest hematologic compromise, IgM-related neuropathy that requires therapy, or hemolytic anemia unresponsive to corticosteroids should receive standard doses of rituximab alone without maintenance therapy. Patients who have severe constitutional symptoms, profound hematologic compromise, symptomatic bulky disease, or hyperviscosity should be treated with the DRC (dexamethasone, rituximab, cyclophosphamide) regimen. Any patient with symptoms of hyperviscosity should first be treated with plasmapheresis. For patients who experience relapse after a response to initial therapy of more than 2 years' duration, the original therapy should be repeated. For patients who had an inadequate response to initial therapy or a response of less than 2 years' duration, an alternative agent or combination should be used. Autologous stem cell transplant should be considered in all eligible patients with relapsed disease.
Aim
The aim of our study was to assess the presence and risk of waterborne pathogens in the drinking water of outdoor facilities in New Zealand and track potential sources of microbial contamination ...in water sources.
Methods and results
A serial cross‐sectional study with a risk‐based sample collection strategy was conducted at 15 public campgrounds over two summer seasons (2011–2012 and 2012–2013). Drinking water supplied to these campgrounds was not compliant with national standards, based on Escherichia coli as an indicator organism, in more than half of the sampling occasions. Campylobacter contamination of drinking water at the campgrounds was likely to be of wild bird origin. Faecal samples from rails (pukeko and weka) were 35 times more likely to return a Campylobacter‐positive result compared to passerines. Water treatment using ultraviolet (UV) irradiation or a combination of filtration and UV irradiation or chemicals was more likely to result in water that was compliant with the national standards than water from a tap without any treatment. The use of filters alone was not associated with the likelihood of compliance.
Conclusions
Providing microbiologically safe drinking water at outdoor recreational facilities is imperative to avoid gastroenteritis outbreaks. This requires an in‐depth understanding of potential sources of contamination in drinking water sources and the installation of adequate water treatment facilities.
Significance and Impact of the Study
Our study provides evidence that drinking water without treatment or filter‐only treatment in public campgrounds is unlikely to comply with national standards for human consumption and extra water treatment measures such as UV irradiation or chemical treatment are needed.
Patients with multiple myeloma progressing on current therapies have limited treatment options. Pomalidomide (CC4047), an immunomodulatory drug, has significant activity in relapsed myeloma and ...previous studies suggest activity in lenalidomide refractory disease. To better define its efficacy in this group, we treated a cohort of lenalidomide refractory patients. Pomalidomide was given orally (2 mg) daily, continuously in 28-day cycles along with dexamethasone (40 mg) given weekly. Responses were assessed by the International Myeloma Working Group Criteria. Thirty-four patients were enrolled. The best response was very good partial response in 3 (9%), partial response (PR) in 8 (23%), best responses (MR) in 5 (15%), stable disease in 12 (35%) and progressive disease in 6 (18%), for an overall response rate of 47%. Of the 14 patients that were considered high risk, 8 (57%) had responses including 4 PR and 4 MR. The median time to response was 2 months and response duration was 9.1 months, respectively. The median overall survival was 13.9 months. Toxicity was primarily hematologic, with grade 3 or 4 toxicity seen in 18 patients (53%) consisting of anemia (12%), thrombocytopenia (9%) and neutropenia (26%). The combination of pomalidomide and dexamethasone (Pom/dex) is highly active and well tolerated in patients with lenalidomide-refractory myeloma.
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