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Monday, October 23, 2017

By Monica Hubbert, MOT, OTR/L, CLT

 Lymphedema can be a major and long-term concern for many cancer patients, but good communication and collaboration among the patient, the treating oncologist, and supportive-care professionals can lessen these impacts and help patients to move forward with good quality of life.

Lymphedema is a protein-rich edema that results from trauma to the lymphatic system—including damage caused by necessary interventions such as sentinel-node biopsy, node-bed dissection, and radiation therapy — and reflects a mechanical insufficiency of the lymphatic system. It typically occurs in one or more of the limbs and may also involve other body parts, such as the corresponding trunk quadrant, breast, head and neck, or genitalia.

The body continues to produce its normal lymphatic load, but some anatomical change has caused a reduction in the system's ability to accommodate and transport lymph fluid. The accumulation of lymph fluid that results from this insufficiency can lead to considerable pain and discomfort for patients, and significantly limit their mobility and ability to complete physical tasks that used to be routine.

Early referral of all patients experiencing or at high risk for developing lymphedema to a certified lymphedema therapist as soon as possible is advised, but this option is not always readily available. There are many steps an oncologist can take to help patients understand and manage lymphedema, either in collaboration with a certified lymphedema therapist or before a specially trained therapist has been engaged.

Advising Patients on Risk & What to Expect

Education is one of the most important things that clinicians can provide to patients, and to all staff members who have direct contact with the patient. Good communication and flow of information among all these parties throughout a patient's journey enables appropriate triage and is likely to improve the patient's long-term outcomes.

While lymphedema in cancer patients typically develops within the first 2-3 years after treatment, that is just the most common range of onset; patients receiving the treatment interventions outlined above are at lifelong risk of developing lymphedema. The highest incidence of lymphedema occurs in patients with breast cancer, sarcomas, gynecologic cancers, melanoma, genitourinary cancer, and head/neck cancers.

Good education for patients starts before they have surgery to remove lymph nodes or other treatments that can impact their lymphatic system. Patients should be informed of how many nodes will be removed, their location, and what parts or sections of the body are at risk for developing lymphedema, as well as the anatomy, physiology, and pathophysiology of the lymphatic system—what the function and capacity of their lymphatic system was before surgery and what they can expect post-operatively. They should be advised they are at a lifelong risk of developing lymphedema and will have to monitor for symptoms for the rest of their life.

Education for patients who are at risk for lymphedema—all patients who are undergoing a change to their lymphatic system—should include guidance on maintaining a healthy and active lifestyle, how to avoid classic risk factors such as needle sticks or having blood pressure taken on an at-risk limb, when to be concerned about subjective symptoms of heaviness or fullness of the limb, and whom to contact if they suspect that they are experiencing lymphedema. It's especially important that patients in the highest risk group—those with BMI greater than 25, those undergoing or who have undergone radiation therapy, and those who had lymph nodes or node beds removed—be advised at time of treatment that they are at high risk for developing lymphedema. Patients who evidenced infection after surgery or during the acute treatment period are also at higher risk for developing lymphedema.

Practitioners and patients should be aware of the services that may be available through a certified lymphedema therapist. This professional has undergone training in caring for patients with lymphedema at a specialist level, and can be an occupational therapist, physical therapist, nurse, physician, massage therapist, etc. These professionals will perform a lymphedema-specific evaluation and formulate an individualized treatment plan.

Monitoring for lymphedema

A surveillance model should be implemented as part of standard care for patients at risk of developing lymphedema. Every interaction with the patient is an opportunity for the clinical team to monitor for signs of lymphedema. An initial assessment should be performed 1 month following the treatment intervention, and then in 3-month intervals after that for at least the first year.

One of the most valuable sources of information to support this surveillance is the patient's subjective input regarding experiences of sensation of fullness, limb heaviness, achiness, or feeling that clothing or jewelry is becoming tighter, and patients should be urged to not delay reporting these symptoms. A good way to collect and track this input is through either a pre-visit written questionnaire or in person as part of the individual's check-in process.

Baseline data can significantly improve the team's ability to monitor for and diagnose lymphedema. Patients who are at high risk for lymphedema should have baseline circumferential measurements taken at standardized points prior to intervention and intermittently throughout the follow-up process. Bioimpedance devices, if available, can be used to document these measurements and track any changes.

Self-monitoring is a necessary skill for every person at risk of developing lymphedema. Patients should be instructed on how to monitor for subjective signs and symptoms, as well as for intermittent episodes of edema throughout their lifetime. It's also important for patients to know whom to contact when they identify these signs, and for the clinic to have an established protocol for triaging these patients.

Treatment options

A holistic approach to treatment can help empower patients and encourage them to follow through with all the steps involved in managing the symptoms associated with this chronic condition.

When a difference of greater than 1 cm in circumferential measurements between the affected extremity and the non-affected extremity occurs 3 months or more after the initial surgical intervention, a patient may benefit from conservative management. This approach will vary depending on the stage of lymphedema, and may include any or all of the following interventions: fitting the patient with a compression garment, offering skilled instruction on performance of self-manual lymph drainage, performing targeted exercises with compression, education on skin and nail care, and use of multilayered short-stretch compression bandages.

Compression garments may be used prophylactically with a lymphedema that is latent or at the beginning stages of development. These garments should only be provided by individuals who understand compression garments and how to fit for them. Patients are often provided with a compression garment immediately after treatment, when post-traumatic edema is present and fluctuation of weight may still be occurring. Poor-fitting compression garments can contribute to lymphedema symptoms. Another difficulty is that compression garments are given and then worn at a later date when changes to the body composition have occurred. Compression garments should be provided only when there is a source to monitor them for fit and form.

When conservative management is not sufficient for managing the symptoms of lymphedema, complete decongestive therapy (CDT) performed by a certified lymphedema therapist is likely indicated. CDT involves skin care with specific lotions and soaps, wound care, compression bandaging or garments, lymphedema-specific exercises, and manual lymph drainage.


Patients should be educated on the importance of meticulous skin and nail care (including avoiding nail salons or patronizing only highly scrutinized establishments) to reduce the potential for cellulitis or other infections of the skin. Assessment and treatment for nail fungus and/or infections of skin folds should occur prior to referral for lymphedema management; multiple episodes of cellulitis may indicate the presence of an untreated lymphedema. Patients should also be educated on limiting or avoiding the use of lotions or skin products with fragrance or high alcohol content, as these products tend to dry skin and may lead to creases or microcracks.

Patients should be educated on the importance of exercise as part of a healthy lifestyle. When the patient or care team is unsure about whether it's safe for the patient to resume normal activities, "low and slow" is a good mantra—low weight with low repetitions and slow progression.

Pain management and psychosocial support are also critical for patients with lymphedema and should be integrated into each patient's treatment plan.

Connecting With a Therapist

Every member of the clinical team can play an important role in providing guidance, direction, and hope to patient who have or may develop lymphedema.

Organizations such as the National Lymphedema Network and Lymphedema Association of North America are good resources for those looking to locate a certified lymphedema therapist. If you are not able to find one in your area, another option is to reach out to your local therapy resources to discuss your patients' needs. You may also consider creating a position in your clinic or sponsoring an employee for training through a program accredited by the North American Lymphedema Education Association.

Monica Hubbert, MOT, OTR/L, CLT, is an Occupational Therapist at Roswell Park Cancer Institute, Buffalo, N.Y.




Wednesday, October 18, 2017

Yokohama, Japan—As non-small cell lung cancer (NSCLC) survival rates have increased over time, new research sheds light on how NSCLC outcomes are significantly influenced by the type of treatment facility where patients undergo care. Bhagirathbhai Dholaria, MBBS, of the Moffitt Cancer Center in Tampa, Fla., presented these findings at the International Association for the Study of Lung Cancer (IASLC) 2017 World Conference on Lung Cancer (WCLC).

With treatment of NSCLC rapidly advancing, Dholaria and his team decided to explore the role of novel therapeutic treatment and initial treatment at academic centers, which provide greater access to advanced technologies and clinical trials, in NSCLC outcome trends. Based on data of NSCLC incident cases between 2004 and 2013 from the National Cancer Database, the researchers plotted overall survival (OS) by year of diagnosis and type of treatment facility. The study included more than 1 million NSCLC patients, separated by initial treatment facility type (academic: 31.5%, non-academic: 68.5%).

The researchers found that NSCLC treatment at academic centers was associated with reduced risk of death when compared to non-academic centers. Four-year OS for academic and non-academic cohorts was 25 percent and 19 percent, respectively (p<0.001). They also found that the survival difference between academic and community centers was greater among non-metastatic compared to metastatic NSCLC.

This difference remained significant even after adjusting for age, race, income, education, geographic location, insurance status, TNM stage, and treatment modalities. These findings highlight the importance of ensuring easier access to facilities with multidisciplinary expertise and training programs. This approach has potential to increase survival of NSCLC patients.

Additionally, the researchers determined that the median OS for patients diagnosed from 2010 to 2013 (14.8 months) was significantly higher when compared to patients diagnosed from 2004 to 2009 (12.4 months), which points to major treatment advances for NSCLC (p<0.001).

Community centers, which remain an important resource for cancer care, should be provided with resources to improve quality of care and access to clinical trials, said Dholaria. Additionally, collaboration between academic and community centers should be encouraged to improve access to specialty care for socioeconomically disadvantaged patients in rural areas. We hope our results will inform policymakers in ​

Wednesday, October 4, 2017

Researchers conducted an analysis that included nearly 10,000 women with the BRCA1 or BRCA2 genetic mutations to estimate the age-specific risk of ovarian or breast cancer for women with these mutations, according to a study published by JAMA (2017; doi:10.1001/jama.2017.7112).

The optimal clinical management of women with BRCA1 and BRCA2 mutations depends on accurate age-specific cancer risk estimates. These can be used to estimate the absolute risk reduction from preventive strategies and inform decisions about the age at which to begin cancer screening. Antonis C. Antoniou, PhD, of the University of Cambridge, England, and colleagues included 6,036 BRCA1 and 3,820 BRCA2 female carriers (5,046 unaffected and 4,810 with ovarian or breast cancer or both at study entry) in the analysis.

During a median follow-up of 5 years, 109 women were diagnosed with ovarian cancer, 426 with breast cancer, and 245 with contralateral breast cancer. Among the findings of the researchers:

  • The cumulative ovarian cancer risk to age 80 years was 44 percent for BRCA1 and 17 percent for BRCA2 carriers.
  • Cancer risk varied by mutation location within the BRCA1 or BRCA2 gene.
  • The cumulative breast cancer risk to age 80 years was 72 percent for BRCA1 and 69 percent for BRCA2 carriers.
  • For contralateral breast cancer, the cumulative risk 20 years after breast cancer diagnosis was 40 percent for BRCA1 and 26 percent for BRCA2 carriers.
  • Breast cancer risk increased with increasing number of first- and second-degree relatives diagnosed as having breast cancer for both BRCA1 and BRCA2 carriers.

Limitations of the study include that, although there was variation in the cancer risks for mutation carriers by cancer family history, the study sample was not identified through population screening of unaffected women; therefore, the overall estimates may not be directly applicable to such women.

"The results indicate that family history is a strong risk factor for mutation carriers and that cancer risks vary by mutation location, suggesting that individualized counseling should incorporate both family history profiles and mutation location," the authors concluded.


Wednesday, October 4, 2017

Almost all ovarian cancer patients enrolled in PRO-002, a phase Ib trial, benefited from the combination of NUC-1031, a first-in-class nucleotide analogue, plus carboplatin, according to data presented at the ESMO 2017 Congress in Madrid (Abstract 968P).

Researchers administered NUC-1031 in a dose-escalation schedule as a 30-minute infusion on days 1 and 8 with carboplatin on day 1, every 3 weeks for 6 cycles.

Four dose cohorts of NUC-1031 (500, 625, and 750 mg/m2) with carboplatin (AUC4 or 5) were studied, according to study authors. Recommended phase II dose (RP2D) was the primary endpoint, while secondary endpoints included safety, RECIST response, progression-free survival, and PK/PD.

The study included 25 patients with a median age of 64 years. All patients in the study were previously treated with an average of three prior chemotherapy regimens. Of the evaluable participants, 17 were either refractory or resistant to their last platinum-containing regimen.

Results showed that the combination was well-tolerated and demonstrated clinical activity in women with recurrent platinum-resistant and platinum-sensitive ovarian cancer. 

An overall response rate of 39 percent was observed among the 23 evaluable patients, including one who achieved a complete response, eight with partial responses, and 13 with stable disease that lasted at least 12 weeks. This yielded an overall disease control rate of 96 percent (22 patients). The responses were durable, with an average progression-free survival of 7.4 months.

The most common adverse events across all dose levels were neutropenia, leukopenia, and thrombocytopenia. No unexpected adverse events were observed with the combination to date.

"The RP2D was 500 mg/m2 NUC-1031 on days 1 and 8 with AUC5 carboplatin day 1, q21d," study authors wrote. "The efficacy and synergy of this schedule and the ability to deliver carboplatin at AUC5 makes this an attractive therapeutic combination."

"The fact that the [NUC-1031] combination with carboplatin achieved these results in heavily pre-treated and platinum-resistant patients clearly demonstrates [NUC-1031] is a very active agent," concluded Sarah Blagden, MBBS, PhD, Associate Professor of Experimental Cancer Medicine at the University of Oxford and Chief Investigator of the study. "Importantly, the favorable toxicity profile of [NUC-1031] enabled us to combine it with carboplatin at AUC 5, whereas with gemcitabine, carboplatin has to be given at AUC 4. Thus, we are able to deliver both [NUC-1031] and carboplatin at their optimal dose."




Wednesday, October 4, 2017

Blocking a protein found on the surface of ovarian cancer cells could prevent or reduce the spread of the disease to other organs, according to new research at the University of Illinois at Chicago.

The American Cancer Society estimates that 22,440 women in the U.S. will receive a new diagnosis of ovarian cancer this year. About 15,000 will die from the disease, which ranks fifth in cancer deaths among women and No. 1 among cancers of the female reproductive system. It is often diagnosed in a late stage, after the cancer has spread to other organs, making it incurable to currently available treatment options.

Symptoms of ovarian cancer include bloating, pelvic or abdominal pain, feeling of fullness, or urinary tract complaints. The cancer mainly develops in older women, after menopause—about half are 63 or older. A woman's lifetime risk of getting ovarian cancer is about one in 75.

"The greatest barrier to our ability to treat cancer in this stage is that we know very little about the molecules that cause the disease to spread," said Maria Barbolina, PhD, Associate Professor of Biopharmaceutical Sciences and lead researcher of the study. "The goal of our research is to identify key molecules that govern metastasis and use them as targets for the development of new drugs."

Barbolina and her colleagues hypothesized that biomolecules successfully targeted with drugs in other cancers might also be targets in metastatic ovarian cancer. In earlier research, Barbolina discovered that a fractalkine receptor—a protein found on the cell surface—is expressed in the majority of ovarian cancer cases. It could help the cancer spread to other organs throughout the body when stimulated by another protein that binds to it.

In her latest findings, published in the journal Oncogene, Barbolina demonstrated in a mouse model that, by lowering production of the fractalkine receptor, tumors did not metastasize to nearby sites of the peritoneal wall, bowel, or liver (2017; doi:10.1038/onc.2016.456).

Nearly a third of all cancer drugs target G protein-coupled receptors, of which fractalkine is one, so "we reasoned that blocking it may prevent or reduce ovarian cancer metastasis, because it's expressed in 64 percent of metastatic ovarian carcinoma specimens," Barbolina explained.