A Brief Historical Perspective of Cancer Rehabilitation and Contributions From the National Institutes of Health.

People who have cancer diagnoses often need care throughout their lives through all stages of their illness. These stages include diagnosis, primary treatment, survivorship, and end of life. The management of people with cancer, now a common and chronic illness with long-term survival improving, is complex, challenging, and rapidly changing. Rehabilitation for people with cancer diagnoses is a new specialty and is charged with providing care throughout the trajectory of illness and wellness to maximize potential for function and mitigate disability. Rehabilitation interventions include the application of physical and occupational therapeutics, speech and language interventions, and physical medicine in order to help patients reach their individual goals and to promote life satisfaction. The Department of Rehabilitation in the Clinical Center of the National Institutes of Health has pioneered this field through research and clinical care models over the past 40 years. Staff of this department has supported clinical research investigators at the National Institutes of Health in their exploration of new treatments using chemotherapies, surgery, radiation, and psychosocial interventions. They have also engaged in research specific to rehabilitation to devise and improve functional outcome measures, design exercise interventions, devise orthotics, and prosthetic devices for adaptation to functional loss. Collectively, the staff has published widely in oncology textbooks and professional journals in order to share findings and improve the quality of cancer rehabilitation treatment across the continuum of care.

Predictors of functional shoulder recovery at 1 and 12 months after breast cancer surgery.

The objective of this study are (1) to determine if upper extremity function, as represented by shoulder ROM, self-reported symptoms and upper extremity functional limitations in activities of daily living could be predictively related to demographic and cancer characteristics post-surgery for breast cancer. And (2) to examine if variables related to early onset impairment contribute to late onset impairments in women after breast cancer surgery. Subjects were assessed preoperatively and 1, 3, 6, 9, and 12+ months post breast cancer surgery for impairments and symptoms and at 12+ months for shoulder functional limitations using a physical therapy surveillance model. Body weight, shoulder ROM, manual muscle testing, and upper limb volume were recorded. At 12+ months, the Harvard Alumni Health Study Physical Activity Questionnaire, and an Upper Limb Disability Questionnaire were administered. Symptoms and ROM impairments were compared by functional limitations. Characteristics significantly associated with early ROM impairment (but not later impairment) were axillary lymph node dissection, removal of ≥15 nodes, mastectomy surgery and stage II breast cancer. Positive nodes, older age, and BMI≥25 were significantly associated with reduced shoulder ROM at 12+ months. At 12+ months, only 10 % of the patients experienced ROM impairments while rates of self-reported symptoms in the affected upper extremity at 12+ months were as follows: pain-49%, weakness-47.1%, numbness-55.9%, feeling tired-42.5%. The majority of patients used the affected upper extremity for reaching without limitation, but ≥35% reported limitation with household chores, carrying and lifting. Difficulty carrying and lifting could be predicted by BMI≥25 and use of the dominant affected upper limb. Different factors are associated with early versus later ROM loss. Symptoms reported by breast cancer survivors are frequently associated with functional limitations in upper extremity tasks and warrant intervention. Physical therapy using a prospective surveillance model of care may reduce severity of ROM loss, symptoms and functional upper extremity limitations 1 year after breast cancer surgery.

Racial disparities in physical and functional domains in women with breast cancer.

INTRODUCTION: African-American women are more likely than white women to have functional impairments after breast cancer (BC) surgery; however, no differences were found in self-reported health status surveys at 12+ months postsurgery. PURPOSE: This analysis compared white and African-American BC survivors' (BCS) health status, health-related quality of life, and the occurrence of physical impairments after BC treatment. METHODS: One hundred sixty-six women (130 white, 28 African-American, 8 other) were assessed for impairments preoperatively and at 1, 3, 6, 9, and 12+ months postsurgery. Health status was assessed at 12+ months using the Short Form Health Survey (SF36v2™). Analysis of variance estimated differences between groups for health status and impairment occurrence. RESULTS: No differences were found between groups for BC type, stage, grade, or tumor size; surgery type; or number of lymph nodes sampled. African-American BCS had more estrogen/progesterone receptor-negative tumors (p < 0.001; p = 0.036) and received radiation more frequently (p = 0.03). More African-American BCS were employed (p = 0.022) and reported higher rates of social activities (p = 0.011) but less recreational activities (p = 0.020) than white BCS. African-American BCS had higher rates of cording (p = 0.013) and lymphedema (p = 0.011) postoperatively. No differences were found in self-reported health status. CONCLUSION: In a military healthcare system, where access to care is ubiquitous, there were no significant differences in many BC characteristics commonly attributed to race. African-American women had more ER/PR-negative tumors; however, no other BC characteristics differed between racial groups. African-American women exhibited more physical impairments, although their BC treatment only differed regarding radiation therapy. This suggests that African-American BCS may be at higher risk for physical impairments and should be monitored prospectively for early identification and treatment.

Breast cancer-related lymphedema: comparing direct costs of a prospective surveillance model and a traditional model of care.

Secondary prevention involves monitoring and screening to prevent negative sequelae from chronic diseases such as cancer. Breast cancer treatment sequelae, such as lymphedema, may occur early or late and often negatively affect function. Secondary prevention through prospective physical therapy surveillance aids in early identification and treatment of breast cancer-related lymphedema (BCRL). Early intervention may reduce the need for intensive rehabilitation and may be cost saving. This perspective article compares a prospective surveillance model with a traditional model of impairment-based care and examines direct treatment costs associated with each program. Intervention and supply costs were estimated based on the Medicare 2009 physician fee schedule for 2 groups: (1) a prospective surveillance model group (PSM group) and (2) a traditional model group (TM group). The PSM group comprised all women with breast cancer who were receiving interval prospective surveillance, assuming that one third would develop early-stage BCRL. The prospective surveillance model includes the cost of screening all women plus the cost of intervention for early-stage BCRL. The TM group comprised women referred for BCRL treatment using a traditional model of referral based on late-stage lymphedema. The traditional model cost includes the direct cost of treating patients with advanced-stage lymphedema. The cost to manage early-stage BCRL per patient per year using a prospective surveillance model is $636.19. The cost to manage late-stage BCRL per patient per year using a traditional model is $3,124.92. The prospective surveillance model is emerging as the standard of care in breast cancer treatment and is a potential cost-saving mechanism for BCRL treatment. Further analysis of indirect costs and utility is necessary to assess cost-effectiveness. A shift in the paradigm of physical therapy toward a prospective surveillance model is warranted.

Segmental limb volume change as a predictor of the onset of lymphedema in women with early breast cancer.

OBJECTIVE: To demonstrate that segmental changes along the upper extremity occur before the onset of breast cancer-related lymphedema (BCRL). These changes may be subclinical in nature and may be predictive of the onset of chronic lymphedema. DESIGN: A retrospective subset analysis of a larger prospective cohort trial. PATIENT COHORT: A total of 196 patients provided consent and were enrolled in the prospective study. Subclinical lymphedema developed in 46 of these patients. Limb volume data were available for 45 of these 46 patients from visits before the onset of lymphedema and were used in this analysis. We compared this group with an age-matched control group without BCRL from the same cohort (n = 45). SETTING: Military hospital outpatient breast care center. METHODS: Women were enrolled and assessed preoperatively. Baseline measures of limb volume were obtained with the use of optoelectronic perometry, and reassessment was conducted at 1, 3, 6, 9, and 12 months postoperatively. BCRL was identified in 46 of 196 women at an average of 6.9 months postoperatively. A retrospective analysis was conducted in which we examined volume changes over four 10-cm segments of the limb at the visits before the onset of BCRL. By using repeated-measures multivariate analysis of variance, we compared segmental volumes between groups at preoperative baseline, time of diagnosis of BCRL, and time of follow-up after early intervention. Linear regression analysis was performed to determine the strength of the relationship between total limb volume change with segmental volumes at the time of diagnosis of BCRL. MAIN OUTCOME MEASUREMENTS: We hypothesized that segmental volume changes occur and can be measured in the limb before the onset of lymphedema. RESULTS: At arm segments 10-20 cm (P = .044) and 20-30 cm (P <.001), a significant volume increase was noted before the diagnosis of subclinical BCRL. Segmental volume changes correlated to the total limb volume (TLV) change. At segments 20-30 cm, the coefficient of determination was r(2) = 0.952, and at 10-20 cm it was r(2) = 0.845, suggesting that these segments predicted TLV changes. CONCLUSION: Serial interval assessment of limb volume segments may be an important clinical tool to detect early-onset lymphedema before TLV changes.

Factors predicting clinically significant fatigue in women following treatment for primary breast cancer.

Cancer-related fatigue is common, complex, and distressing. It affects 70-100% of patients receiving chemotherapy and a significant number who have completed their treatments. We assessed a number of variables in women newly diagnosed with primary breast cancer (BrCa) to determine whether biological and/or functional measures are likely to be associated with the development of clinically significant fatigue (CSF). Two hundred twenty-three women participated in a study designed to document the impact of the diagnosis and treatment of primary breast cancer on function. Forty-four had complete data on all variables of interest at the time of confirmed diagnosis but prior to treatment (baseline) and ≥ 9 months post-diagnosis. Objective measures and descriptive variables included history, physical examination, limb volume, hemoglobin, white blood cell count, and glucose. Patient-reported outcomes included a verbal numerical rating of fatigue (0-10, a score of ≥ 4 was CSF), five subscales of the SF-36, Physical Activity Survey, and Sleep Questionnaire. At baseline, the entire cohort (n = 223) and the subset (n = 44) were not significantly different for demographic, biological, and self-reported data, except for younger age (p = 0.03) and ER+ (p = 0.01). Forty-five percent had body mass index (BMI) ≥ 25, 52% were post-menopause, and 52% received modified radical mastectomy, 39% lumpectomy, 52% chemotherapy, 68% radiation, and 86% hormonal therapy. Number of patients with CSF increased from 1 at baseline to 11 at ≥ 9 months of follow-up. CSF at ≥ 9 months significantly correlated with BMI ≥ 25, abnormal white blood cell count, and increase in limb volume and inversely correlated with vigorous activity and physical function (p < 0.05). Fatigue increases significantly following the treatment of BrCa. Predictors of CSF include high BMI and WBC count, increase in limb volume, and low level of physical activity. These are remediable.

Pre-operative assessment enables early diagnosis and recovery of shoulder function in patients with breast cancer.

In order to determine the extent and time course of upper limb impairment and dysfunction in women being treated for breast cancer (BC), and followed prospectively, a novel physical therapy surveillance model post-treatment was used. Subjects included adult women with newly diagnosed, untreated, unilateral, Stage I to III BC, and normal physiological and biomechanical shoulder function. Subjects were excluded if they had a previous history of BC, or prior injury or surgery of the affected upper limb. Measurements included body weight, shoulder ranges of motion (ROM), manual muscle tests, pain levels, upper limb volume, and an upper limb disability questionnaire (ULDQ). Measurements were taken at baseline (pre-surgery), and 1, 3-6, and 12 months post-surgery. All subjects received pre-operative education and exercise instruction and specific physical therapy (PT) protocol after surgery including ROM and strengthening exercises. All measures of function were significantly reduced 1 month post-surgery, but most recovered to baseline levels by 1-year post-surgery. Some subjects developed signs of lymphedema 3-12 months post-surgery, but this did not compromise function. Shoulder abduction, flexion, and external rotation, but not internal rotation ROM, were associated with the ULDQ. Most women in this cohort undergoing surgery for BC who receive PT intervention may expect a return to baseline ROM and strength by 3 months. Those who do not reach baseline, often continue to improve and reach their pre-operative levels by 1-year post-surgery. Lymphedema develops independently of shoulder function 3-12 months post-surgery, necessitating continued monitoring. A prospective physical therapy model of surveillance allows for detection of early and later onset of impairment following surgery for BC in this specific cohort of patients.

Preoperative assessment enables the early diagnosis and successful treatment of lymphedema.

BACKGROUND: The incidence of breast cancer (BC)-related lymphedema (LE) ranges from 7% to 47%. Successful management of LE relies on early diagnosis using sensitive measurement techniques. In the current study, the authors demonstrated the effectiveness of a surveillance program that included preoperative limb volume measurement and interval postoperative follow-up to detect and treat subclinical LE. METHODS: LE was identified in 43 of 196 women who participated in a prospective BC morbidity trial. Limb volume was measured preoperatively and at 3-month intervals after surgery. If an increase>3% in upper limb (UL) volume developed compared with the preoperative volume, then a diagnosis of LE was made, and a compression garment intervention was prescribed for 4 weeks. Upon reduction of LE, garment wear was continued only during strenuous activity, with symptoms of heaviness, or with visible swelling. Women returned to the 3-month interval surveillance pathway. Statistical analysis was a repeated-measures analysis of variance by time and limb (P

Long-term treatment of hypoparathyroidism: a randomized controlled study comparing parathyroid hormone-(1-34) versus calcitriol and calcium.

Hypoparathyroidism is one of the few remaining hormonal insufficiency states for which replacement therapy is unavailable. Previous short-term controlled trials have shown PTH to be a safe and effective treatment of hypoparathyroidism. In this randomized, parallel group, open-label trial, we compared synthetic human PTH-(1-34) (PTH) with conventional therapy, calcitriol and calcium, over a 3-yr period. Twenty-seven patients with confirmed hypoparathyroidism, aged 18-70 yr, were randomized to either twice daily sc PTH or oral calcitriol and calcium. The primary end points were calcium levels in serum and urine. Secondary end points were creatinine clearance, markers of bone turnover, and bone mineral density. Throughout the 3-yr study period, serum calcium levels were similar in both treatment groups within or just below the normal range. Mean urinary calcium excretion was within the normal range from 1-3 yr in PTH-treated patients, but remained above normal in the calcitriol group. Bone mineral content and bone mineral density showed no significant between-group differences over the 3-yr study period. We conclude that treatment with twice daily sc PTH provides a safe and effective alternative to calcitriol therapy and is able to maintain normal serum calcium levels without hypercalciuria for at least 3 yr in patients with hypoparathyroidism.

The grading of lymphedema in oncology clinical trials.

Lymphedema is a common late toxicity of cancer therapy. This article describes the rationale and process utilized by the Lymphedema Working Group for the revision and expansion of the Common Toxicity Criteria version 2 (CTC v2.0) lymphedema criteria to produce the CTC v3.0 lymphedema criteria. Established clinician-based rating scales and quantitative instruments are reviewed in this article. None of the extant rating scales have been formally validated, nor has their reliability been assessed. Drawbacks of current scales were considered in formulating CTC v3.0 criteria. Most rely exclusively on volume to diagnose and grade lymphedema. This imposes significant clinical limitations, particularly in the assessment of toxicity in oncology clinical trials. Volume-based rating scales are of little value in rating the severity of bilateral limb and nonlimb edema. Problems with nonvolumetric staging systems (eg, CTC v2.0) include insufficient detail to permit useful discrimination of severity among the majority of lymphedema patients. Technologies for objectively quantifying lymphedema have been developed and validated. Although these are briefly reviewed, it is recognized that cost and access issues limit their widespread clinical utility and, as such, were not considered in developing the CTC v3.0 criteria. The CTC v3.0 lymphedema criteria adopted several innovations. Principle among these was the decision to generate separate criteria for volumetric increase, dermal changes, and subcutaneous fibrosis. We anticipate the use of the new CTC v3.0 lymphedema criteria to begin in mid-2003 for grading the key clinical features of this disorder in oncology clinical trials. The purpose of this article is to familiarize the reader with (1) background on the clinical features of lymphedema, (2) information on established lymphedema rating systems, (3) the consensus process and rationale of the Lymphedema Working Group, (4) the new CTC v3.0, and (5) quantitative techniques for assessment of lymphedema.

Lymphedema management.

Lymphedema, defined as the abnormal accumulation of protein rich fluid dysfunction of the lymphatic system, is a common sequela of cancer therapy. The incidence is highest among patients who have undergone resection and irradiation of a lymph node bed. Recently, increased attention has been focused on the modification of anticancer therapies in an effort to minimize lymphatic compromise. Sentinel lymph node biopsy is an example of a surgical procedure developed to preserve lymphatic function. Concurrent with the development of less invasive treatments, the field of lymphedema management has evolved rapidly over the past decade. Combined manual therapy, often referred to as complex decongestive physiotherapy (CDP), has emerged as the standard of care. CDP combines compression bandaging, manual lymphatic drainage (a specialized massage technique), exercise, and skin care with extensive patient education. Case series collectively describing a mean 65% volume reduction in over 10,000 patients attest its efficacy. Pneumatic compression pumps were historically widely used to control lymphedema. Their use as an isolated treatment modality is now rare. Reliance on pumps diminished with the recognition that they may exacerbate truncal and genital lymphedema, as well as injure peripheral lymphatics when applied at high pressures. Many noncompressive approaches, particularly the use of benzopyrone medications and liposuction, continue to be used abroad.