Clinical Insights: September 2014

Article

CE lesson worth 1.0 contact hours that are intended for advanced practice nurses, registered nurses, and other healthcare professionals who care for cancer patients.

STATEMENT OF NEED

The overall goal is to update the healthcare professional’s knowledge of cancer detection and prevention and to understand current and new research regarding state-of-the-art care for those with or at risk for cancer.

TARGET AUDIENCE

Intended for advanced practice nurses, registered nurses, and other healthcare professionals who care for cancer patients.

OVERALL EDUCATIONAL OBJECTIVES

Upon completion, participants should be able to:

  • Describe new preventive options and treatments for cancer patients
  • Identify options for individualizing the treatment for cancer patients
  • Review new evidence to facilitate survivorship and supportive care for cancer patients

ACCREDITATION STATEMENT

Dannemiller is approved by the California Board of Registered Nursing, Provider Number 4229, for 1.0 contact hour. CBRN credit is not accepted by the Michigan and Utah State licensing boards.

DISCLOSURES

The planners and authors of this CE activity have disclosed no relevant financial relationships with any commercial companies pertaining to this activity.

METHOD OF PARTICIPATION

  • Read the articles in this section in its entirety.
  • Go to www.dannemiller.com/onn-sept-2014
  • Complete and submit the CE posttest and activity evaluation.
  • Print your Certificate of Credit.

This activity is provided free of charge to participants.

Breast Cancer

Nurse Navigation Increases Uptake of Antiestrogen Therapy, Study Finds

New research has found that high risk and minority women receive better cancer care if they are paired with a patient navigator.

The study, published online July 28, 2014 in the Journal of Clinical Oncology, found that navigated participants were more likely than non-navigated participants to receive antiestrogen therapy, which is considered the gold standard in treatment for certain types of breast cancer.

“This study gave us a glimpse of the potential benefit of patient navigation but there’s a lot more research to be done,” said Naomi Ko, MD, MPH, instructor of medicine in the Section of Hematology Oncology at Boston University School of Medicine and a practicing breast oncologist at Boston Medical Center. “At this point we still need to understand how or why patient navigation works.”

Using a subset of data from 8 of 10 research centers participating in the NCI-funded national Patient Navigation Research Program (PNRP), researchers sought to identify the possible benefits of assigning patient navigators to women recently diagnosed with breast cancer. All PNRP centers had navigation interventions in place to assist patients in receiving their treatment in a timely way.

To be included in the study reported here, participants had either received an abnormal cancer screening result, detection of an abnormality in the breast, or a breast cancer diagnosis. The impact of navigation versus non-navigation in these patients was then examined according to initiation of three treatments: antiestrogen therapy, postlumpectomy radiation, and chemotherapy in women younger than age 70 with triple-negative tumors larger than 1 cm.

The study is the first national study to show a relationship between navigators and the initiation of certain recommended treatments for breast cancer, the researchers noted. The results showed that among participants eligible for antiestrogen therapy, navigated participants (n = 380) had a statistically significant higher likelihood of receiving antiestrogen therapy compared with non-navigated controls (n = 381; odds ratio [OR], 1.73; P = .004) in a multivariable analysis.

“Although we are able to report a positive association between navigation and receipt of antiestrogen therapy,” the authors noted, “our study cannot elucidate the process or mechanism behind how patient navigation may be effective.”

The results of the analysis also found that navigated participants eligible for radiation therapy after lumpectomy (n = 255) were no more likely to receive radiation (OR, 1.42; P = .22) than control participants (n = 297).

In interpreting this finding, the study authors posited that barriers addressed in radiation therapy, “may require a different set of actions compared with assistance in obtaining antiestrogen therapy,” such as help with managing transportation issues and work schedules.

“Understanding where patient navigation is most beneficial in cancer care, in order to help the neediest patients, is a rich topic for future research,” Ko said.

Nurse Perspective

A. Nicole Spray, APRN

Hays Med Breast Center Hays, KS

Cancer patients experience many complexities with cancer, beginning from the time of diagnosis, to treatment, and into survivorship. Many times a cancer patient will need multiple doctors, tests, and treatments at various facilities to manage their care.

Several barriers may exist for patients receiving cancer care, including financial limitations, transportation issues, language barriers, and mental health issues which can make it difficult for them to understand treatment plans

For those of us who have had the privilege to work with patient navigators, their impact on patient care is undebatable. It seems clear, from a qualitative standpoint, the positive impact navigators have in providing communication and coordination of care to cancer patients. Quantitative data regarding the benefit of patient navigators is lacking, as well as where in the cancer trajectory they have the greatest impact

As we move into a time of healthcare reform and tight economics, it is imperative to have both qualitative and quantitative data to support the efforts of patient navigators and expand this specialty area to maximize effective services offered to cancer patients.

Better Communication May Ease Patients’ Fear of Breast Reconstruction

Even though universal coverage for postmastectomy breast reconstruction is mandated, a new study has found that the majority of women are deciding not to undergo breast reconstruction surgery following a mastectomy.

The study, published online August 20, 2014, in JAMA Surgery, found that 58.4% of 485 patients surveyed decided not to undergo breast reconstruction surgery, citing such reasons as not wanting to have additional surgery (48.5%), it wasn’t important (33.8%), fear of implants (36%), and a concern of possible complications (33.6%).

“There has always been a lot of concern because breast reconstruction rates in the United States have persistently been that only about 30% to 40% of women who get a mastectomy undergo reconstruction,” said Monica Morrow, MD, FACS, lead author of the study and chief of breast surgery services at Memorial Sloan Kettering Cancer Center. “This has raised concerns that doctors aren’t offering women reconstruction or talking about reconstruction.”

The authors used Surveillance, Epidemiology, and End Results registries from Los Angeles and Detroit to identify women aged 20 to 79 years with specific types of breast cancer. Eligible women were asked to complete a survey. The analytic sample for the authors’ study included 485 patients who initially reported having a mastectomy and 4 years later reported remaining disease free.

Of the 485 patients, 146 patients underwent reconstruction at the time of mastectomy, 76 patients had their breast reconstruction surgeries later, and 263 patients did not undergo breast reconstruction.

According to the study results, only 18% of the patients who chose not to have breast reconstruction after mastectomy were unaware that reconstruction was an option, whereas 11.8% didn’t have insurance coverage. Women also cited trouble finding a surgeon (5.6%) or that their surgeon did not take their insurance (7.8%) as other reasons.

Although the study found that only 13.3% of women reported being dissatisfied with the decision- making process, it also showed that nonwhite women, older women, women with a lower education level, or women with a major coexisting illness and chemotherapy were all less likely to undergo breast reconstruction surgery

Ethnic minority groups were less prone to indicate a desire to avoid additional surgery as a reason for forgoing reconstruction (70% for nonblack, non-Latina patients vs 39.7% and 34.1% for black and Latina patients, respectively; P <.001) and less likely to suggest that reconstruction was not important (42.4% for nonblack, non-Latina patients vs 21.6% and 31.3% for black and Latina patients, respectively; P = .04).

The study also showed that more Latina patients were worried about interference with cancer detection or complications of the procedure as well as not being able to take time off from work or family. More black and Latina patients also attributed their decision to the systems barrier of having no insurance coverage. Morrow said that these women were also more likely to be dissatisfied with the decision-making process. “It does suggest that there are potentially some additional barriers in women with lower educational attainment and lower socioeconomic status.”

Many misunderstandings surrounding breast reconstruction surgery persist, Morrow noted. “We did find evidence that there is misunderstanding that having a reconstruction may interfere with detection of cancer recurrence, and so I think that’s something that can clearly be communicated to people when offering them the option of reconstruction,” she said, adding that some residual fear of breast implants remains, a worry that could be eased through improved patient education and clinician communication.

Nurse Perspective

Deirdre Kiely, MS, MPA, RN, ANP

Nurse Practitioner Perlmutter Cancer Center NYU Langone Medical Center New York, NY

The diagnosis and management of breast cancer has evolved over the past three decades. The advent of the Comprehensive Breast Center as a model of care in the 1980s and all of the advances that have occurred within its multidisciplinary specialties have changed the face of breast cancer care.

These changes include offering to patients breast-conserving approaches to surgical management of early-stage breast cancer and a variety of breast reconstruction options when mastectomy is performed. The study reported here by Morrow and colleagues, however, suggests that the majority of women who are undergoing mastectomy surgery—whether based on medical necessity or personal choice&mdash;are declining reconstruction.

The nurse’s role as a member of a multidisciplinary healthcare team is multifaceted, providing each patient diagnosed with breast cancer personalized, informative care from diagnosis through to survivorship. The nurse is also instrumental in supporting the reconstruction decision-making process by identifying patient learning needs and potential barriers in access to cancer care, as well as in developing a comprehensive plan of care.

In this study, 43.2% of patients who chose not to have reconstruction had limited access for various reasons. The 13.3% of women who were noted to be dissatisfied with the decision-making process would potentially be patients subject to disparities in access to healthcare services who could benefit from a navigation program.

The role of the nurse as patient navigator offers individualized assistance to patients to overcome barriers in the healthcare system while supporting individual choices and preferences. This is a model based upon shared, informed decision-making to optimize patient outcomes. There are additional studies that show quality-of-life benefits of reconstruction, including psychological, physical, and sexual well-being, which should be shared with patients considering reconstruction options. The provision of complete and accurate information with full access to services assists a patient to frame the choices based on individual circumstances and make the right individual choice. The nurse can be instrumental in identifying and addressing patient needs to support shared decision-making regarding breast reconstruction options.

Evidence-Based Information Should Guide Prophylactic Mastectomy Decisions

One of the first studies to prospectively examine women’s breast surgery preferences has revealed that newly diagnosed women with breast cancer who decide to undergo contralateral prophylactic mastectomy aren’t relying on evidence-based information, highlighting the need for interdisciplinary patient education and communication. Results of the study were presented at the ASCO Breast Cancer Symposium held September 4-6, 2014 in San Francisco. Abstract 71

“There is so much information about breast cancer that it’s easy for patients to get overwhelmed. As doctors, we have to be aware of each patient’s knowledge level and the concerns and worries he or she has,” said lead study author Katharine Yao, MD, director of the breast surgical program at NorthShore University HealthSystem, Evanston, Illinois, and a clinical associate professor of surgery at the Pritzker School of Medicine, University of Chicago. “And we need to do a better job of educating patients that the risk of developing contralateral breast cancer is actually low and that breast cancer can come back in other parts of their body no matter what type of surgery they have.”

Researchers administered a 55-item survey to 150 newly diagnosed breast cancer patients at two institutions prior to their surgery—but after they had made their decision as to type of procedure&mdash; to compare patient knowledge, perception, and anxiety factors among those who considered a CPM versus those who did not

Eighty-three patients (58%) wanted or considered a CPM upon initial diagnosis, whereas 35 patients (24.6%) knew that they did not want a CPM upon initial diagnosis. Sixteen patients (11.3%) said that they knew about CPM but did not think it was an option for them, and 8 patients (5.6%) did not have any knowledge of CPM.

Patients were asked a knowledge-based question: Does removing a healthy breast reduce the chance that the cancer will come back? Thirtytwo percent of the patients who considered CPM and 53% of patients who did not consider CPM said that this statement was correct. Another question measured anxiety levels and asked patients: How much do you worry about getting cancer elsewhere in your body? Forty-three percent of women considering CPM responded that they were very much/extremely worried about this, versus 11% of those not considering CPM.

“These data demonstrate that this complex decision is often the result of higher anxiety levels and worry about recurrence,” Yao said. “These are certainly valid concerns, but as oncologists we need to make certain that we are educating each patient about her individual risk for the future.”

Lung Cancer

Promising Findings for Afatinib—Cetuximab Combo in Previously Treated EGFR-Mutant Lung Cancer

Results of an early-phase study have shown the combination of afatinib and cetuximab has utility in EGFR-mutant lung cancer patients who have developed resistance to gefitinib and erlotinib, with the afatinib—cetuximab regimen eliciting a 29% response in patients receiving the combination (Cancer Discov. 2014. doi:10.1158/2159-8290.CD-14-0326).

“Treatment with erlotinib and gefitinib leads to dramatic tumor regression and has improved survival for patients with EGFR-mutant lung adenocarcinoma,” said Yelena Y. Janjigian, MD, assistant attending physician at Memorial Sloan Kettering Cancer Center and assistant professor of medicine at Weill Cornell Medical College. “Unfortunately, these cancers invariably acquire resistance to these drugs, and the patient’s disease progresses.”

The phase Ib trial enrolled patients across six centers in the Netherlands and the United States. All participants had received prior erlotinib or gefitinib for a median of 1 year (range, 1 month to 7 years) before study entry. Of the 201 enrolled patients, 126 were treated with the maximum-tolerated dose of oral afatinib (40 mg daily) plus intravenous cetuximab (500 mg/m2 every 2 weeks).

Thirty-seven patients (29%) treated with the maximum-tolerated dose had a confirmed objective response (OR) with an overall median duration of confirmed OR of 5.7 months, Of those patients, 22 had their tumors shrink by 50% or more.

This level of tumor shrinkage is clinically significant because it results in regression of cancerrelated symptoms and improvement in the patient’s quality of life, noted Janjigian.

“Our study shows that a combination of afatinib and cetuximab can yield durable and robust clinical responses in the setting of acquired resistance, although larger, randomized trials are needed to confirm the results,” Janjigian continued. “Importantly, the afatinib—cetuximab combination benefited patients whether or not their cancer had acquired resistance to erlotinib or gefitinib as a result of a secondary mutation in EGFR called T790M.”

The status for EGFR-sensitizing mutations was known for all patients. Exon 19-deletion, found in 78 patients, was the most frequent EGFR mutation detected, followed by L858R-positive (n = 41). Of the 124 patients whose baseline T790M mutation status was known, 71 patients were T790M positive, whereas 53 patients were T790M negative.

OR rates were not statistically different for patients with and without the EGFR T790M mutation in their tumors: 32% and 25%, respectively. The median durations of the responses were 5.6 months for patients with EGFR T790M—positive tumors and 9.5 months for those with EGFR T790M–negative tumors.

Nearly all patients (99%) experienced treatmentrelated adverse events, the most common of which were rash (90%), diarrhea (71%), nail effects (57%), stomatitis (56%), fatigue (47%), and nausea (42%). The most common grade 3 events were rash (20%) and diarrhea (6%); grade 4 events (fatigue, pneumonitis, and lung infiltration) occurred in two patients.

Colorectal Cancer

Active Maintenance Improves Progression-Free Survival in mCRC

Two active maintenance regimens following disease stabilization with standard induction therapy demonstrated superior disease-free outcomes compared with no treatment in patients with metastatic colorectal cancer (mCRC), according to findings of a phase III trial (AIO KRK 0207) presented at the 2014 World Congress on Gastrointestinal Cancer held in Barcelona. Patients who received maintenance treatment with fluoropyrimidines plus bevacizumab or bevacizumab monotherapy experienced progression-free survival (PFS). Abstract O-0027

The optimal strategy for maintenance with bevacizumab following combination chemotherapy has remained unsettled. Dirk Arnold, MD, Director, Department of Medical Oncology, Tumour Biology Centre in Freiburg, Germany, and colleagues evaluated whether maintenance with no therapy or maintenance with bevacizumab monotherapy was noninferior to fluoropyrimidines plus bevacizumab following successful induction treatment

“Progression-free survival was improved with active maintenance treatment but it is too soon to tell if there is an effect on overall survival,” said Arnold.

The trial enrolled 840 patients with mCRC who received 24 weeks of induction treatment with fluoropyrimidines, oxaliplatin, and bevacizumab. After completing this treatment, 473 patients who did not experience disease progression were randomized into one of the following arms: Arm A, standard maintenance treatment with fluoropyrimidines and bevacizumab (n = 141); arm B, bevacizumab monotherapy (n = 153); or arm C, no treatment (n = 153). The initial induction therapy regimen would be readministered if any patients exhibited disease progression.

The primary endpoint of the trial was time to failure of strategy (TFS), which included the time of first induction treatment and duration of maintenance until disease progression. Secondary endpoints included time to first progression (PFS1) and overall survival (OS).

Following initial induction therapy, the response rate (RR: complete response [CR] + partial response [PR]) was 60% in arm A and B versus 59% in arm C. The best response of stable disease was reported for 40% of patients in arms A and B versus 41% of patients in arm C.

After being assigned to a maintenance strategy, patients achieved median PFS1 in arms A, B, and C of 6.2, 4.8, and 3.6 months, respectively. PFS1 from start of induction was 11.7 months, 10.2 months, and 9 months in arms A, B, and C, respectively.

TFS favored arm A over arm C (HR = 1.22; 95% CI, 0.96-1.57; P = .11), but did not reach statistical significance. A statistically significant difference was not observed between arms A and B in TFS (HR = 0.98; 95% CI, 0.76-1.28; P = .85).

Few patients terminated maintenance because of unacceptable toxicity: 8%, 5% and 1% of patients in arms A, B, and C, respectively. However 58%, 79%, and 86%, of patients in arms A, B, and C, respectively, discontinued because of disease progression.

The reinduction rate was low overall at 37%; upon first progression; only 24% of patients in arm A and 47 % of patients in arms B and C received reinduction.

Rates for grades 1, 2, and 3 toxicity during maintenance were similar across all three arms.

After 200 documented events, preliminary OS was 23.4 months from randomization, without significant difference between treatment arms (P = .69).

The researchers concluded that bevacizumab alone is noninferior to bevacizumab combined with fluoropyrimidines as maintenance, but no active maintenance is inferior to combination maintenance. In addition, immediate reinduction rates upon first progression were too low to accept this strategy.

“I suspect, but we do not know, that irinotecan toxicity was a factor in patients’ decisions to forgo reinduction therapy,” Arnold remarked.

Nurse Perspective

Laura Metcalfe, MSN, RN, APN-C, AOCNS

John Theurer Cancer Center Hackensack, NJ

Whether to continue chemotherapy or give a treatment holiday in the disease-stable mCRC patient has long been an area of concern—both to the patients and to clinicians. Historically, we have offered the patients both options. Some patients opt for the treatment break, fully understanding that when the disease becomes active again treatment will be resumed. Others opt to continue treatment citing concerns about disease progression. Traditionally this has been a discussion between the patient and the physician, looking at the pros and cons of each decision, and ultimately with the patient making the final decision.

The researchers in this study compared maintenance with no therapy (ie, “observation”) versus either maintenance with bevacizumab monotherapy or fluoropyrimidines plus bevacizumab. They concluded that bevacizumab alone is noninferior to bevacizumab combined with fluoropyrimidines as maintenance; however, no active maintenance is inferior to combination therapy.

This study may take some of the debate out of the conversation regarding what to do in the mCRC patient with disease stabilization. The only question remaining may be bevacizumab alone or plus a fluoropyrimidine. Tolerance of the therapy may be the deciding factor. In our practice, we have been offering patients capecitabine plus bevacizumab as maintenance, based on the results of the CAIRO3 trial which found that maintenance with capecitabine plus bevacizumab significantly delayed disease progression, compared to observation. Given that capecitabine is an oral therapy, many patients find this option more appealing than continuing the 46-hour intravenous fluorouracil treatment every 2 weeks. In addition, the bevacizumab can be given once every 3 weeks, leading to fewer and shorter visits to the oncology clinic.

Given that patients with mCRC are often living a long time with their disease, defining the appropriate treatment, including maintenance, remains vital. This new study has added some needed clarity to the issue.

Pancreatic Cancer

Prognostic Scale Developed for Survival in Locally Advanced Pancreatic Cancer

Four independent prognostic factors for improved overall survival (OS) in patients with locally advanced pancreatic cancer (LAPC) emerged from an analysis of the LAP 07 phase III trial presented at the 2014 World Congress on Gastrointestinal Cancer. Based on these factors, a risk scale was developed that could be useful for stratifying and treating patients. Abstract O-0002

Lead author Dewi Vernerey, MSc, Methodological and Quality of Life in Oncology Unit, University Hospital, Besançon, France, discussed the grim reality of pancreatic cancer, noting that 30% of patients present with disease that is locally advanced. He added that pancreatic cancer disease mortality in Europe increased from 73,439 deaths in 2009 to 82,300 deaths in 2014, an increase of approximately 12%.

Vernerey presented results from a data analysis from LAP 07, an international multicenter, randomized phase III trial. In LAP 07, investigators evaluated whether continued chemoradiotherapy improved OS in patients with inoperable LAPC whose tumors were determined to be controlled following 4 months of induction gemcitabine- based chemotherapy. LAP 07 found no advantage for continued chemotherapy versus no treatment in OS or progression-free survival.

In Vernerey et al’s analysis, 35 baseline characteristics from demographic, radiologic, disease history, and biologic parameters of 370 patients from LAP 07 comprised the variables evaluated by univariate and multivariate analysis to identify independent factors prognostic for OS.

Univariate analysis narrowed the characteristics to WHO tumor status 2, age at diagnosis, blood pressure, ASAT, albumin, the presence of pain, tumor size, and poorly differentiated histology grade as potential prognostic variables.

Upon multivariate analysis, age, tumor size, increased albumin, and the presence of pain emerged as independent prognostic factors of OS. Using these four variables, a prognostic score scale for risk of death in patients with LAPC was devised, with scale scores ranging from 0 to 4. Based on the scale, three risk groups for death were identified: lower risk (0, 1), intermediate risk (1, 2), and higher risk (2, 3).

Patients were stratified using the scale, with 17, 166, and 187 patients identified for the lower, intermediate, and higher risk groups, respectively. By global rank test, the three risk groups were associated with a median OS of 18.8, 13.4, and 11.8 months, respectively.

“Nomogram development and this simple score should allow patient stratification that can direct treatment management and design of future clinical trials,” said Vernerey. He added that external validation of this score using a cohort from the large ARCAD (Aide et Recherche en Cancérologie Digestive) database is ongoing.

Ruxolitinib Combo Improves Outcomes in Metastatic Setting Pancreatic Cancer

Adding ruxolitinib to capecitabine as a second-line treatment for patients with metastatic pancreatic cancer significantly improved survival for a subgroup with a high degree of local and systemic inflammation compared with capecitabine plus placebo, according to phase II trial results presented at the 2014 World Congress on Gastrointestinal Cancer. Abstract O-0026

The results from the RECAP trial confirm the role of inflammation in promoting cancer and the importance of the JAK-STAT pathway, which ruxolitinib inhibits, as a therapeutic target in metastatic pancreatic cancer, said lead author Herbert I. Hurwitz, MD, in presenting the findings at the conference.

Ruxolitinib, which is supplied in tablet form, inhibits JAK1/JAK2 kinases and blocks signaling mediated by many proinflammatory cytokines. Initially approved by the FDA in 2011, ruxolitinib is indicated for treatment of patients with intermediate- or high-risk myelofibrosis.

Two phase III clinical trials, JANUS 1 and JANUS 2, are evaluating ruxolitinib among patients with pancreatic cancer with inflammation scores of 1 or 2 as measured by the modified Glasgow Prognostic Score (mGPS), according to Hurwitz, a Professor of Medicine at Duke University School of Medicine. He said mGPS also is being used as a selection criterion in trials evaluating ruxolitinib in colorectal, non—small cell lung, and breast cancers.

The RECAP trial enrolled 127 patients who progressed after treatment with gemcitabine; all patients were treated with 1000 mg/m2 of capecitabine twice daily on days 1 through 14 of a 21-day cycle. A cohort of 64 patients also received 15-mg doses of ruxolitinib twice daily on days 1 through 21, and 63 patients received placebo.

The primary endpoint was overall survival (OS), and secondary endpoints included progression- free survival (PFS) and objective response rate (ORR). In the overall patient population, a trend toward improved OS at 12 months favoring the ruxolitinib combination over capecitabine/ placebo that did not reach statistical significance was seen, with a similar trend in PFS. The confirmed ORR was 7.8% in the ruxolitinib arm compared with 0% in the placebo arm.

However, preplanned subgroup analysis of data from patients with high serum C-reactive protein (CRP) and albumin levels told a stronger story. Subgroup analysis of a cohort of 60 patients with CRP levels greater than the group median of 13 mg/L showed statistically significant OS improvement and a trend toward improved PFS among the 31 patients receiving ruxolitinib. Patients with CRP ≤13 mg/L who received ruxolitinib also showed improved OS and PFS, but the differences between arms did not reach statistical significance. The subgroup analysis also revealed improved survival rates at 3 months and 6 months of 48% and 42%, respectively, in the ruxolitinib arm, compared with 29% and 11%, respectively, in the placebo arm.

Adverse events of grade 3 or grade 4 severity were reported by 75% of patients in the ruxolitinib arm compared with 82% of patients in the placebo arm. Grade 3/4 anemia was observed more often with ruxolitinib than with placebo (15.3% vs 1.7%), respectively, and grade 3/4 neutropenia and thrombocytopenia occurred in 1.7% of ruxolitinib-treated patients versus 0% of patients receiving placebo.

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