Saint Francis Cancer Treatment Center

Oncology Update05I S S U E

J A N2 0 1 4

Dr. Melhem Jabbour • Dr. Ryan RamaekersDr. Doug Clark • Dr. M. Sitki Copur

GRAND ISLAND & HASTINGS, NEBRASKA

B r i n g i n g t h e b e s t c a n c e r c a r e t o y o u r c o m m u n i t i e s

2010 Outstanding Achievement Award

in this issue• Center for Translational Research:

Personalizing Cancer Research

• Xofigo now offered at Saint Francis

• Autologous Transplantation as Consolidation for Aggressive Non-Hodgkin’s Lymphoma

• Cancer-Related Brain Fog

Happy New Year and First Anniversary!January 2014 marks the one-year anniversary of the launch of our newsletter! We would like start our celebration by thanking you – our loyal readers and referring physicians. Your great support and precious feedback over the past year has been invaluable.

Cancer Care Continuum requires a team effort. Our team starts with you, our referring physicians, and includes all of the disciplines working closely with us; from schedulers, nurses, genetic counselors, nurse navigators, to physical therapy, rehabilitation, tumor registry, home health/hospice services and more.

This past year, we have tried to prioritize features involving this coordinated “Cancer Care Team” concept. In the New Year, we will continue to provide you with the most contemporary and potentially practice-changing data relevant to our day to day practice with the “Cancer Care Team” concept in mind.

As always, we welcome any particular subject or area of interest that you would like to see covered. Please don’t hesitate to contact us at mcopur@sfmc-gi.org, or emartinez@sfmc-gi.org. We would love to hear from you.

Cheers to a Healthy, Happy, Prosperous and Successful new year!

M. Sitki Copur, MD, FACP

The Catholic Health Initiatives (CHI) Center for Translational Research (CTR) was developed out of a need for innovation and growth in the face of a changing healthcare landscape. As one component of CHI’s Institute for Research and Innovation (CIRI), the CTR seeks to further the science of, and adoption of advanced diagnostics by directly engaging CHI hospitals, clinicians and researchers in system-wide programs.

One such program is the multi-site collection of consented patient biospecimens and accompanying clinical information. The CTR’s operational infrastructure — consisting of the CHI hospital network, dedicated research staff, translational research software and IRB-approved protocols for biospecimen procurement — and associated clinical data enables centrally coordinated, multi-site research studies.

Heather Benzel, a clinical research nurse with the CTR, is currently working on the biorepository project at Saint Francis Medical Center. She is collecting blood and tissue specimens from oncology patients who have been diagnosed with a malignancy. The tissues are being collected and stored at Saint Francis, but may eventually be used for academic, government, commercial and local research. Regardless of who uses the specimen in the future, its use must be in line with CHI’s ethical and religious directives.

The CTR is recruiting patients for the tissue procurement portion of the study if they have a solid tumor greater than 1.5 cm in diameter, are undergoing resection, are 19 years of age or older, able to provide written consent, and are not currently pregnant. Patients with a malignant diagnosis that are not undergoing a resection can also participate in the blood-only component of the project. The protocol will soon enroll any patient with a malignant diagnosis and collect archived paraffin embedded tissue as well.

To find potential subjects, Benzel screens the oncology and Operating Room (OR) schedules to identify eligible patients. Physicians are then notified and explained the process, and will determine if a patient is an appropriate candidate. If the physician feels that the patient is a match, he or she will be informed about the study, and given the choice to participate. Benzel also hopes to recruit help from physicians so they can also identify eligible patients and inform them about the study.

Participating patients’ tumor tissue is collected during the normal surgical procedure. Although she is in the OR at the time of resection, Benzel stresses that the collection of the tissue is designed to not interfere with current procedures.

“Our first priority is given to patient care and diagnostics,” Benzel said of the collection process. “I work very closely with the physicians, surgeons and pathologists to ensure that patient care is number one.”

She works closely with the pre-operative and surgical staff to coordinate the tissue collection and transport it to pathology, where it must be frozen within 30 minutes of collection.

Benzel says the goal of this project is to keep CHI hospitals on the cutting edge of what cancer research is moving toward -- looking at tumor tissues at a genetic level.

“One of our goals is to figure out why two people can come in with the same diagnosis and have the same treatment, yet have different outcomes,” Benzel said. “What we’re really doing is taking a proactive approach to research so that we can more efficiently enable researchers to identify how genes affect the growth and development of cancerous tumors. From there, we can help manage and gain a more personalized approach to cancer treatment, management and care.”

Currently the CTR’s biorepository project is only studying oncology patients, but other disease states are forthcoming. For more information on the Center for Translational Research, please visit http://www.chiresearch.org/CTR. v

Center for Translational Research:Personalizing Cancer Research

To learn more about the Center for Translational R e s e a r c h or referring patients to the biorepository p r o j e c t , please contact

Heather Benzel, BSN, RN, CCRP at (308) 398-8925 or hbenzel@sfmc-gi.org.

Clinicopathologic Predictors of Sentinel Lymph Node Metastasis in Thin Melanoma

Indications for sentinel lymph node biopsy (SLNB) for thin melanoma are continually evolving.

A large multi-institutional study evaluated the factors predictive of sentinel lymph node (SLN) metastasis in thin melanoma. Retrospective review of the Sentinel Lymph Node Working Group database from 1994 to 2012 identified 1,250 patients who had a SLNB and thin melanoma (< 1 mm) were reported in November 2013 issue of Journal of Clinical Oncology. Clinicopathologic characteristics of patients were correlated with SLN status and outcome. SLN metastases were detected in 65 (5.2%) of 1,250 patients. On univariable analysis, rates of Breslow thickness equal to or more than 0.75 mm, Clark level equal to or more than IV, ulceration, and absence of regression differed significantly between positive and negative SLN groups (all P < .05). These four variables and mitotic rate were used in multivariable analysis, which demonstrated that Breslow thickness equal to or more than 0.75 mm (P< .03), Clark level equal to or more than IV (P< .05), and ulceration (P< .01) significantly predicted SLN metastasis with 6.3%, 7.0%, and 11.6% of the patients with these respective characteristics having SLN disease. Melanomas< 0.75 mm had positive SLN rates of < 5% regardless of Clark level and ulceration status. Median follow-up was 2.6 years. Melanoma-specific survival was significantly worse for patients with positive versus negative SLNs (P= .001). Breslow thickness equal to or more than 0.75 mm, Clark level equal to or more than IV, and ulceration significantly predicted SLN disease in thin melanoma. By using a 5% metastasis risk threshold, SLNB is indicated for melanomas equal to or more than 0.75 mm, but further study is needed to define indications for SLNB in melanomas < 0.75mm.

Reference: Jonathan DH et al. Clinicopathologic Predictors of Sentinel Lymph Node Metastasis in Thin Melanoma, J Clin Oncol 2013; 51:1114

Potentially PracticeChanging Data

Xofigo Now Offered at Saint FrancisSaint Francis Cancer Treatment Center has recently begun offering a new radioactive medicine to patients with widespread metastatic prostate cancer. The drug, Xofigo, was approved by the FDA in May 2013, and has been shown to prolong survival with minimum toxicities.

Xofigo is an intravenous (IV) injection of radioactive radium 223. It is used to treat prostate cancer that has spread to the bone that is also resistant to other medical treatments. In addition, to qualify for treatment, patients must meet certain blood count criteria.

The treatment works by essentially undermining the growth of tumors. Xofigo is absorbed by the bones much like calcium and targets areas of bone metastasis. The radioactive substance damages cancer’s DNA and prevents it from spreading further. Xofigo produces a radioactive alpha particle with short range and thus limits damage to surrounding healthy tissue.

A full course of treatment consists of six injections administered once a month for six months. Labs are drawn three weeks after each treatment to ensure the patient’s blood counts qualify the patient for the next injection. After the initial injection, each of the five follow-up labs needs to show an ANC of at least 1.0, hemoglobin of 10 and platelets of 50.

“We are very excited to be able to offer a cutting-edge therapy like Xofigo to our patients,” said Doug Clark, MD, Radiation Oncologist at Saint Francis Cancer Treatment Center. “Our goal is to stay on the forefront of technology so that cancer patients in central Nebraska can receive the treatment they need close to home.”

Saint Francis Cancer Treatment Center is currently the only facility west of Lincoln that offers Xofigo. To learn more about this treatment, please contact Radiation Oncologist Doug Clark, MD, or Radiation Therapy Manager Marlene Hinrichs, MA (R)(T) at (308) 398-5450. v

Efficacy and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early HER2-positive breast cancer (NeoSphere): a randomized multicenter, open-label, phase 2 trial.

Studies with pertuzumab, a novel anti-HER2 antibody, show improved

efficacy when combined with the established HER2-directed antibody trastuzumab in breast cancer therapy. In a multicenter, open-label, phase 2 study, treatment-naive women with HER2-positive breast cancer were randomly assigned (1:1:1:1) centrally and stratified by operable, locally advanced, and inflammatory breast cancer, and by hormone receptor expression to receive four neoadjuvant cycles of: trastuzumab plus docetaxel every 3 weeks; group A) or pertuzumab plus docetaxel (group B) or pertuzumab and trastuzumab (group C) or pertuzumab plus docetaxel (group D). The primary endpoint was pathological complete response in the breast. Of 417 eligible patients, 107 were randomly assigned to group A, 107 to group B, 107 to group C, and 96 to group D. Patients given pertuzumab and trastuzumab plus docetaxel (group B) had a significantly improved pathological complete response rate

(49 of 107 patients; 45.8% compared with those given trastuzumab plus docetaxel (group A; 31 of 107; 29.0% p=0.0141). 23 of 96 (24.0%) women given pertuzumab plus docetaxel (group D) had a pathological complete response, as did 18 of 107 (16.8%) given pertuzumab and trastuzumab (group C). The number of serious adverse events was similar in groups A, B, and D. Patients given pertuzumab and trastuzumab plus docetaxel (group B) had a significantly improved pathological complete response rate compared with those given trastuzumab plus docetaxel, without substantial differences in tolerability. Pertuzumab and trastuzumab without chemotherapy eradicated tumors in a proportion of women and showed a favorable safety profile. These findings justify further exploration in adjuvant trials and support the neoadjuvant approach for accelerating drug assessment in early breast cancer.Reference: Gianni L et al. Efficacy and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early HER2-positive breast cancer (NeoSphere): a randomised multicentre, open-label, phase 2 trial. Lancet Oncol. 2012;13:25-32.

Potentially PracticeChanging Data

The prognosis for patients with pancreatic cancer is poor, even after resection with curative intent. Gemcitabine-based chemotherapy is standard treatment for advanced

pancreatic cancer, but its effect on survival in the adjuvant setting has not been demonstrated.CONKO-001 (Charité Onkologie 001), a multicenter, open-label, phase 3 randomized trial evaluated the efficacy and toxicity of gemcitabine in patients with pancreatic cancer after complete tumor resection. Patients with macroscopically completely removed pancreatic cancer entered the study between July 1998 and December 2004 in 88 hospitals in Germany and Austria. Follow-up ended in September 2012. After stratification for tumor stage, nodal status, and resection status, patients were randomly assigned to either adjuvant gemcitabine treatment (1g/m2 d 1, 8, 15, q 4 weeks) for 6 months or to observation alone. The primary end point was disease-free survival. Secondary end points included treatment safety and overall survival, with overall survival defined as the time from date of randomization to death. A total of 368 patients were randomized, and 354 were eligible for intention-to-treat-analysis. By September 2012, 308 patients (87.0% ) had relapsed and 316 patients (89.3%) had died. The median follow-up time was 136 months. The median disease-free survival was 13.4 months in the treatment group compared with 6.7 months in the observation group P < .001). Patients randomized to adjuvant gemcitabine treatment had prolonged

overall survival compared with those randomized to observation alone P = .01), with 5-year overall survival of 20.7% vs 10.4%, respectively, and 10-year overall survival of 12.2% vs 7.7% . Among patients with macroscopic complete removal of pancreatic cancer, the use of adjuvant gemcitabine for 6 months compared with observation alone resulted in increased overall survival as well as disease-free survival. These findings provide strong support for the use of gemcitabine in this setting.

Reference: Oettle H, et al. Adjuvant chemotherapy with gemcitabine and long-term outcomes among patients with resected pancreatic cancer: the CONKO-001 randomized trial JAMA. 2013;310:1473-81.

The efficacy of autologous stem-cell transplantation during the first remission in patients with diffuse, aggressive non-Hodgkin’s lymphoma classified as high-intermediate risk or high risk on the International Prognostic Index remains controversial and is untested in the rituximab era. October 2013 issue of New England Journal of medicine reported the results of 397 patients who had aggressive diffuse non-Hodgkin’s lymphoma with an age-adjusted classification of high risk or high-intermediate risk. After initial five cycles of cyclophosphamide, doxorubicin,

vincristine, and prednisone (CHOP) or CHOP plus rituximab, patients with a response were randomly assigned to receive three additional cycles of induction chemotherapy (control group) or one additional cycle of induction chemotherapy followed by autologous stem-cell transplantation (transplantation group). The primary efficacy end points were 2-year progression-free survival and overall survival. Of 370 induction-eligible patients, 253 were randomly assigned to the transplantation group (125) or the control group (128). Forty-six patients in the transplantation group and 68 in the control group had disease progression or died, with 2-year progression free survival rates of 69 and 55%, respectively P = 0.005. Thirty-seven patients in the transplantation group and 47 in the control group died, with 2-year overall survival rates of 74 and 71%, respectively; P = 0.30. Exploratory analyses showed a differential treatment effect according to risk level for both progression-free survival (P = 0.04 for interaction) and overall survival (P = 0.01 for interaction). Among high-risk patients, the 2-year overall survival rate was 82% in the transplantation group and 64% in the control group. Early autologous stem-cell transplantation improved progression-free survival among patients with high-intermediate-risk or high-risk disease who had a response to induction therapy.

Reference: Stiff PJ et al. Autologous Transplantation as Consolidation for Aggressive Non-Hodgkin’s Lymphoma. N Engl J Med 2013;369:1681-1690.

Autologous Transplantation as Consolidation for Aggressive Non-Hodgkin’s Lymphoma

Adjuvant chemotherapy with gemcitabine and long-term outcomes among patients with resected pancreatic cancer: the CONKO-001 randomized trial.

Potentially PracticeChanging Data

Potentially PracticeChanging Data

Cancer-Related Brain FogMany people joke about “chemo brain,” but the mental fog that often plagues cancer patients is a very real phenomenon.

During cancer treatment, many patients experience a mental cloudiness that affects their memory and cognition. Although it is often referred to as “chemo brain,” a cancer patient may still experience cognitive distress without having received chemotherapy. Several factors, including anxiety or depression from the cancer diagnosis itself, the impact of medication and anesthesia, and sleep problems or fatigue may contribute to mild loss of brain function.

For many patients, these cognitive changes are subtle and short-lived, but for others long-term changes may occur. Fortunately, for brain fog unrelated to chemotherapy, the symptoms tend to subside after the underlying problems are treated or go away.

Dr. Colin Sanner, a general neurologist with Saint Francis Medical Center’s Department of Neurology, has this to say about cognitive impairment associated with cancer treatment:

“’Chemo brain’—residual cognitive impairment following cancer treatment—is well recognized but poorly understood. It stems from

multiple problems associated with life changes in cancer survivors. Some of these problems are related to treatment itself: direct toxic effect of chemotherapy agents, metabolic derangements from vomiting & diarrhea or loss of appetite, release of toxic chemicals or rapid shift in electrolyte balance from rapidly killing tumor cells, toxic effect on supporting cells of central nervous system disrupting the normal physiology of the brain, among others.

“Some other problems are unrelated to the chemotherapy, but are associated with cancer diagnosis: Emotional stress, financial stress, relationship stress, physical & mental fatigue, and so on. Because it is impossible to separate the effects of life circumstances from effects of treatment itself, all of these are lumped together as contributing factors to the syndrome ‘chemo brain’.

“Cognitive impairment looks different from one person to the next. Some common patterns of cognitive impairment in ‘chemo brain’ include:

1. Distractibility, impaired attention & concentration2. Impaired working memory & recall3. Word finding difficulty4. Executive dysfunction, difficulty prioritizing and carrying

out multistep tasks5. Impaired visual spatial skills, getting lost easily.”

To help cancer patients who are experiencing these problems, two Cancer Treatment Center staff members have completed Cancer-Related Brain Fog leader training. Mary Ann Kalinay, MS, LMHP, who is the Patient and Family Counselor, and Courtney Fuller, RN, OCN, the Breast Cancer Nurse Navigator, attended the three-day program presented by Dr. Heather Palmer. Dr. Palmer is a neuropsychologist and the Director of Cognitive Rehabilitation at Maximum Capacity, headquartered in Bradford, Ontario. Maximum Capacity is an evidence-based program for cognitive enhancement, and helps individuals improve or maintain their cognitive abilities.

The Cancer-Related Brain Fog leader training is based on Dr. Palmer’s research and is designed to address the brain fog which may be associated with having a cancer diagnosis. The objective of the program is to teach affected cancer survivors techniques and strategies to utilize their individual strengths, and to learn new ones to compensate for areas of change and/or weakness in order to maximize thinking capacity.

The first eight-week Cancer-Related Brain Fog class will begin Tuesday, January 21 and will be held weekly in the Telehealth conference room at Memorial Health Center from 5-6:30pm. For more information about the class or to refer a patient, please contact Mary Ann Kalinay at (308) 398-6517 or Courtney Fuller at (308) 398-3218. v

Dr. Colin Sanner

“Coping with Brain Fog”class facilitators

Mary Ann Kalinay, MS, LMHP

Courtney Fuller, RN, OCN

Interim Cosmetic and Toxicity Results From RAPID: A Randomized Trial of Accelerated Partial Breast Irradiation Using Three-Dimensional Conformal External Beam Radiation Therapy

FDA Hematology/Oncology Drug Approvals

Interim cosmetic and toxicity results of a multicenter randomized trial comparing accelerated partial-breast

irradiation (APBI) using three-dimensional conformal external beam radiation therapy (3D-CRT) with whole-breast irradiation (WBI) were reported in November 2013 issue of the Journal of Clinical Oncology. After breast-conserving surgery, women age 40 years and older with invasive or in situ breast cancer of less than 3 cm, were randomly assigned to 3D-CRT APBI (38.5 Gy in 10 fractions twice daily) or WBI (42.5 Gy in 16 or 50 Gy in 25 daily fractions and boost irradiation). The primary outcome was ipsilateral breast tumor recurrence (IBTR). Secondary outcomes were cosmesis and toxicity. Adverse cosmesis was defined as a fair or poor global cosmetic score. After a planned interim cosmetic analysis, the data, safety, and monitoring committee recommended release of results. Between 2006 -2011, 2,135 women were randomly assigned to 3D-CRT

APBI or WBI. Median follow-up was 36 months. Adverse cosmesis at 3 years was increased among those treated with APBI compared with WBI as assessed by trained nurses (29% v 17%; P < .001), by patients (26% v 18%; P< .0022), and by physicians reviewing digital photographs (35% v 17%; P < .001). Grade 3 toxicities were rare in both treatment arms (1.4% v 0%), but grade 1 and 2 toxicities were increased among those who received APBI compared with WBI (P< .001). 3D-CRT APBI increased rates of adverse cosmesis and late radiation toxicity compared with standard WBI. Clinicians and patients are cautioned against the use of 3D-CRT APBI outside the context of a controlled trial.

Reference: Olivotto IA et al. Interim Cosmetic and Toxicity Results From RAPID: A Randomized Trial of Accelerated Partial Breast Irradiation Using Three-Dimensional Conformal External Beam Radiation Therapy J Clin Oncol 2013; 31:4038-4045.

Potentially PracticeChanging Data

• FDA granted regular approval for crizotinib (Xalkori, Pfizer, Inc.) capsules for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors are anaplastic lymphoma kinase (ALK)-positive as detected by an FDA-approved test. November 20, 2013

• FDA granted accelerated approval to Ibrutinib (IMBRUVICA, Pharmacyclics, Inc.) for the treatment of patients with mantle cell lymphoma (MCL) who have received at least one prior therapy. November 13, 2013

• FDA approved obinutuzumab (GAZYVA injection, for intravenous use, Genentech, Inc.; previously known as GA101) for use in combination with chlorambucil for the treatment of patients with previously untreated chronic lymphocytic leukemia (CLL). November 1, 2013

• FDA granted accelerated approval to pertuzumab injection (PERJETA, Genentech, Inc.) for use in combination with trastuzumab and docetaxel for the neoadjuvant treatment of patients with HER2-positive, locally advanced, inflammatory, or early stage breast cancer (either greater than 2 cm in diameter or node positive) as part of a complete treatment regimen for early breast cancer. September 30, 2013

Kicking the habitSaint Francis Cancer Treatment Center offers tobacco cessation classes to its patients, and anyone in the community who wants to quit using tobacco.

The Freedom From Smoking® program was developed by the American Lung Association, and teaches participants how to quit in a supportive setting.

The seven-week, eight-session program is led by Cancer Treatment Center staff members Ann Tvrdy, MSN, CRNI, and Connie Hameloth, RN, who are both certified facilitators.

“Freedom From Smoking® was developed by a team of physicians, psychologists and health educators,” Hameloth said. “Over the past 25 years, it has been continually tested, updated and improved, so participants can feel confident that they are receiving the best possible assistance from a top-rated program.”

If you have a patient who is interested and could benefit from this program, please contact Ann or Connie at (308) 398-5450 for information on upcoming classes.

C O N TAC T I N F O R M AT I O N Saint Francis Cancer Treatment Center2116 West Faidley AvenueGrand Island, NE 68803(308) 398-5450ht tp : / / sa in t f ranc i sg i . o rg

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Oncology Update Issue 05 January 2014

Providers:M. Sitki Copur, MD, FACP

Medical Director of OncologyMelhem Jabbour, MD

Ryan Ramaekers, MDDoug Clark, MDDeborah Nelson, APRN, AOCNPMonica McDonald, APRNMegan Schriner, PA

Clinical Trials:Sarah Einspahr, RNMary Gulzow, CRA, CCRPRebecca Hadenfeldt, BSNJennifer Scott, BSN, OCNAlicia Wicht, CRA

Center for Translational Research Heather Benzel, RN, CCRP

Pharmacists:Angie Obermiller, PharmD

Oncology Pharmacy SupervisorJon Olsen, PharmDMark Tharnish, PharmD

Navigators:Courtney Fuller, RN, OCN

Breast Cancer Nurse NavigatorAshley Wissing, MA

Colorectal Cancer Navigator

NutritionistMaureen Hilderbrand, RD, LMNT

Genetic Counselor:Kim Brussow, CGC

Tumor RegistryLeslie Mlinar, CTRPatty Tripp, CTR, RHIT

Patient & Family Counselor:Mary Ann Kalinay, MS, LMHP

Oncology Project CoordinatorAnn Tvrdy, MSN, CRNI

Certified Tobacco Cessation Facilitator

Community Outreach CoordinatorConnie Hameloth, RN

Certified Tobacco Cessation Facilitator

Management:Max Norvell, PharmD

Director of OncologyMary Mickey, RN, OCN

Clinical Manager, Medical OncologyMarlene Hinrichs, MA (R) (T)

Clinical Manager, Radiation Therapy

Meet our team

Locations:

Saint Francis Cancer Treatment Center2116 West Faidley AvenueGrand Island, NE 68803(308) 398-5450

Saint Francis Cancer Treatment Center2nd Street & Marian RoadHastings, NE 68901(402) 461-5588

Visit us online:

SaintFrancisGI.org