Medcenter One Cancer Committee 2011 Annual Report

Transcription

1 Medcenter One Cancer Committee 211 Annual Report With a Focus on Non-Hodgkin s Lymphoma 21 CND Cancer Registry Statistics

2 Medcenter One Health Systems is proud to be recognized as an accredited cancer program, approved by the American College of Surgeons Commission on Cancer with Commendation. This award means that, in addition to meeting all 36 standards of care, Medcenter One was commended for exceeding the standards in multiple areas. The dedicated team of physicians, nurses and staff at Medcenter One Health Systems has set a series of goals designed to continue to improve this high level of cancer care.

3 Medcenter One Health Systems 211 Cancer Committee Physician Members: Edward Wos, DO. Chair & Cancer Liaison Physician. Hematology and Medical Oncology Douglas Berglund, MD. General Surgery Tarek Dufan, MD. Radiation Oncology Edward Fogarty III, MD. Diagnostic Radiology John Reynolds, MD. Hematology and Medical Oncology Mark Rodacker, MD. Pathology Thomas Thorson, MD. Family Medicine Anthony Tello, MD. Medical Director Jeanette Viney, MD. General Surgery John Watkins, MD. Radiation Oncology Non-Physician Members: Jan Kamphuis, PhD, CNO, VP of Patient Care Becky Bohrer, LSW Judy Carson, American Cancer Society Sara Doll, NP, Medical Oncology Ken Dykes, Executive Director, BCC Kari Edwards, RN, QRI Tamara Fischer, RN, OCN, Oncology Research Rev. Gary Heaton, Pastoral Care Jody Jahner, RN, Cancer Care Clinic Sheri Kost, RN, Oncology Shrikant Kubsad, PhD, Medical Physicist, BCC Mike Neff, PT & Rehab Jennifer Newman, OT, Lymphadema Clinic Barb Nies, RN, Oncology Director Tara Schilke, RN, BCC Oncology Program Coordinator Ashley Thompson, NP, Medical Oncology Mike Urbanec, Reg Pharmacist Mark Weichel, RN Oncology Research Tracy Wildeman, CTR, Central ND Cancer Registry Kim Welder, Home Health Hospi

4 Pathology and the Diagnosis of Non Hodgkin s Lymphoma Jason Meyer, MD Pathology Medcenter One Non-Hodgkin s lymphomas are a class of lymphoproliferative neoplasms which clinically range from chronic, slowly progressive entities, such as small lymphocytic lymphoma, to aggressive, highly proliferative diseases such as Burkitt lymphoma. Pathologists have a vital role in the diagnosis of these disorders. While the most common tissue samples submitted for evaluation for non-hodgkin s lymphoma are lymph node biopsies, the disease may initially present in virtually any organ. Regardless of the biopsy source, submission of fresh tissue (not yet placed in formalin) is preferred. This allows the pathologist the option of appropriately processing a portion of the specimen for ancillary studies such as flow cytometry or cytogenetic analysis. Flow cytometry studies utilize numerous fluorochrome labeled antibodies to specific antigens expressed by the cells analyzed. Evaluation of the patterns of such antigenic expression provides valuable diagnostic data. Cytogenetic studies utilize predominantly morphologic evaluation of the cells karyotype for possible additional classification. Other studies, including fluorescent in situ hybridization (FISH) and molecular studies, may also be obtained when evaluation for specific genetic abnormalities is required. After the appropriate samples have been collected for possible ancillary studies, additional tissue is processed and embedded in paraffin blocks and H&E stained slides are prepared. Morphologic assessment of these slides by the pathologist remains the cornerstone for diagnosis and is particularly essential for appropriate and effective utilization of ancillary studies. Immunohistochemical stains may also be performed on the paraffin embedded blocks as needed and may provide additional data about antigenic expression and differentiation. Working closely with the patient s clinician, pathologists coordinate and analyze the complex data necessary to diagnose non-hodgkin s lymphomas. As our knowledge and understanding of these disorders continues to advance and treatment strategies continue to evolve, pathologists will continue to have an essential role in the overall care of patients with non-hodgkin s lymphoma.

5 Medical Oncology in Non-Hodgkin s Lymphoma Treatment Edward Wos, DO Hematology and Medical Oncology Medcenter One Cancer Committee Chairman Non-Hodgkin s lymphoma is a form of malignancy of the lymphatic system. It represents 4.6% of all cancers. It is the 5th most common malignancy in women and the 6th most common in men. The incidence increases with age. Non-Hodgkin s lymphoma can present in lymphatic tissue such as lymph nodes, spleen, and bone marrow. It may also arise in almost any organ of the body. The five year relative survival in the 195s was 28% and it rose to 63% from the years 199 to 24. This improvement in survival occurred mainly because of improvement in treatment of lymphomas with intermediate to high grade histologies. The cause of non-hodgkin s lymphoma is varied. It includes environmental factors such as pesticides, insecticides, solvents, and organic chemicals. Rarely viruses such as Epstein-Barr virus may play a role. Bacterial infections such as H. pylori may contribute to certain non-hodgkin s lymphoma. Immunosuppressive drugs can also lead to the development of non-hodgkin s lymphoma. Lifestyle and diet may also play a role. PRESENTATION Low-grade lymphoma such as follicular non-hodgkin s lymphoma grows slowly and patients may be asymptomatic for many years. They usually present with enlarged lymph nodes which may wax and wane over a period of time. The incidence of extranodal involvement in low-grade follicular lymphoma tends to not be as great as in high grade lymphomas. The patients often present with splenomegaly or cytopenias from bone marrow involvement. High to intermediate grade lymphomas have a more varied presentation. One-third of them are extranodal which may include involvement of the skin, the GI system, GU tract, thyroid, CNS, and bone marrow. B symptoms such as night sweats, fever, weight loss can occur with high to intermediate grade lymphomas. Oncologists will stage the lymphoma based on the extent of spread of the disease. Stage I is involvement of one single lymph node region. Stage II is two or more lymph node regions on the same side of the diaphragm. Stage III are lymph nodes which involve both sides of the diaphragm and stage IV involves disseminated disease. Patients with high grade lymphomas are graded on the international prognostic index. The adverse affects that are counted in this index include: Age greater than 6. Stage III to IV. Number of extranodal sites greater than or equal to 2. Performance status greater than or equal to ECOG2. At Medcenter One we see all types of non-hodgkin s lymphoma. We will limit this presentation to two of the most common: 1. Diffuse large B-cell lymphoma which represents the intermediate to high grade lymphomas. 2. Follicular lymphomas which represents the low-grade lymphomas.

6 DIFFUSE LARGE B-CELL LYMPHOMAS Patients with diffuse large B-cell lymphomas represent about 33% of all lymphomas in the country and 27% at Medcenter One. It may present with an enlarged peripheral lymph node. Often times patients are sent after a lymph node was biopsied by a surgeon and the pathology report had indicated the disease. Sometimes patients are seen when a CT scan ordered for other reasons displays enlarged lymph nodes. Needle biopsies are sometimes attempted when the lymph nodes are not assessable to palpation. Typically we ask the surgeon, after the specimen is obtained, to send the sample in saline as opposed to formalin so it can be sent out for flow cytometry and immunophenotypical studies can be done. Essentially work-up includes physical exam with attention to node bearing areas, examination of the liver, spleen, performance status, and the symptoms. We also look at lab results such as Complete Blood Count with differential, Lactic acid dehydrogenase (LDH), comprehensive metabolic panel, uric acid and radiological studies such as CT scan of the chest, abdomen, and pelvis with contrast and finally unilateral or bilateral bone marrow biopsy and aspirate. A lumbar puncture is done with large B-cell lymphoma if certain adverse features are present such as more than two extranodal sites, involvement of the paranasal sinuses or bone marrow involvement. PET CT may be done if there are any questions about lymph nodes on a CT scan. Based on the international prognostic indicators, progression free survival in patients are as follows: If none of the adverse factors are present, the patient has a 94% four year progression-free survival. If one or two of the factors are present, the patient has an 8% four year progression-free survival and if there are 3 to 5 of the factors present there is 55% progression-free survival in four years. The standard induction treatment is based on stage. Stage I or II can be further sub classified as bulky versus non bulky. Bulky includes lymph nodes greater than 1 cm. The drugs typically used to treat are rituximab which is an antibody against protein on the cells called CD2 and chemotherapy agents such as Cytoxan, vincristine, Adriamycin, and prednisone. If there is non bulky disease often 3 cycles of chemotherapy is given followed by radiation. Alternatively, R-CHOP x6 can be given with or without radiation. If bulky disease is present, 6 cycles are given, plus or minus radiation therapy. Stage III or IV disease is usually given with R-CHOP x6-8 cycles. Responses are seen in upwards of 8% of patients, 5% to 6% achieve complete remission and 5% of these patients are likely to be cured which is 3% to 5% overall. For patients who either do not have a complete remission or who relapse, alternative treatments are possible but long-term responses have mostly been with autologous peripheral stem cell transplants. Patients who do not have responsive disease prior to stem cell transplants generally do poorly. Peripheral stem cell transplants done in high risk patients done automatically after induction therapy remains controversial. Adriamycin, one of the chemotherapy agents included in R-CHOP is cardiotoxic, hence a 2D echo is often done to evaluate the ejection fraction prior to and post treatment to make sure that there is no effect on the heart. A complete remission has been achieved with no evidence of disease or disease-related symptoms on scans or physical exam. If the bone marrow is positive a repeat bone marrow must be negative. Following the completion of therapy restaging and documentation of complete remission, patients are seen on periodic intervals to monitor for treatment complications and assess for possible relapse. Frequency of the extent of these visits depends on the comfort level of the patient and the physician. A

7 majority of relapses occur during the first two years after completion of treatment. Relapses are usually symptomatic and are rarely identified on the basis of routine imaging. If relapse is picked up a few weeks earlier because of intense monitoring it is unlikely to improve outcome. When planning the post treatment surveillance, care should be taken in the limited number of CT scans done particularly in young individuals. There is no role for routine PET or PET CT imaging on longitudinal followup of asymptomatic patients after response assessment. One way of doing CT scans at month 6, 12, 18, 24, 3, and 36 and then yearly until 5 years after attainment of complete remission. No more imaging is performed after 5 years unless abnormalities suggest the possibility of relapse. Medcenter One does participate in the NCCTG clinical trials regarding many different cancers involving non-hodgkin s lymphoma. Some of the road blocks to effective treatment include side effects of chemotherapy. We have improved the management of the side effects with improved antiemetics, side effect monitoring and IV hydration. The future at this time for the treatment of diffuse large cell lymphoma includes improving survival and also identifying those high risk patients that may benefit from addition of novel agents or consolidative autologous stem cell transplant as opposed to waiting for relapse. FOLLICULAR NON-HODGKIN S LYMPHOMA Follicular non-hodgkin s lymphoma is seen in about 24, cases annually in the United States. This represents approximately 21% of the cases of non-hodgkin s lymphoma at Medcenter One. The clinical course of follicular lymphoma is typically indolent with many patients surviving for years without treatment. Other patients may suffer an aggressive course by developing aggressive disease or transforming into a high grade non-hodgkin s lymphoma. About 85% to 95% of these patients exhibit advanced stage disease at diagnosis and are considered incurable even with modern therapies. Patients with stage I or II disease, however, may be cured with radiation. Risk factors are not well established in this disease but may include immunodepressive therapies after organ transplantation, inherited immune disease and rheumatoid arthritis. Oftentimes patients with follicular lymphoma are diagnosed incidentally while undergoing imaging for other reasons. Many patients note the presence of painless lymphadenopathy. Patients with advanced stage disease (III/IV) disease may note fever, drenching night sweats or weight loss. Anorexia and fatigue are also not uncommon. Patients may have anemia if bone marrow involvement is present. If the follicular lymphoma transforms into a diffuse large B cell lymphoma, they will have a sudden onset of night sweats, fever, weight loss and enlargement of lymph nodes. Patients with localized disease, stage I or II, typically manifest with palpable lymph nodes that are mobile with rubbery consistency. Patients with advanced disease may exhibit pallor or diffuse adenopathy, loss of appetite, increased lymph nodes over a short interval of time. Diagnostic staging includes excisional node biopsy evaluated by a hematopathologist. Fine needle aspirate is inadequate, but a core biopsy may be utilized if an excisional biopsy is not safe or practical. Again a CT scan of the chest, neck, abdomen and pelvis is essential for staging. PET scans are not standard in all patients but may be useful on occasion. Hepatitis B status is again useful because hepatitis B maybe reactivated by the use of rituximab. Routine chemistries and CBC, beta-2 microglobulin and bone marrow biopsy and aspirates are done to exclude marrow involvement. The prognostic indicators of follicular lymphoma are as follows: Age greater than 6, stage III or IV disease, hemoglobin less than 12, serum LDH greater than normal and involvement of greater than or

8 equal to 5 nodal areas. Patients with lower scores experience longer survival and patients with higher scores experience shorter survival and increased risk for transformation. The FLIPI-2 substitutes bone marrow involvement for stage, elevated Beta 2-microglobulin for LDH and largest nodal diameters > 6 cm for number of nodal sites > 4. The same staging used for diffuse large B cell lymphoma is used for follicular lymphoma. Treatment paradigms for follicular lymphoma are stage and grade dependent. Patients with grade 3 follicular lymphoma are treated like diffuse large B cell lymphoma. Patients with grade 1-2 follicular lymphoma are treated according to extent of disease. Stage I or II patients are typically treated with potentially curative radiation. Stage III or IV advanced stage disease may be observed or treated with systemic therapies depending on patient's age, comorbidity symptoms and organ dysfunction. Because patients with nonaggressive extensive follicular lymphoma may progress very slowly or at times experience spontaneous regression, immediate treatment is not always indicated. Early treatment with chemotherapy regimens does not improve survival for asymptomatic patients. Options for treatment include rituximab alone or in combination with CVP or CHOP. R-CHOP gives about a 5% to 7% response rate. Single agent rituximab may be useful for elderly symptomatic patients who would not tolerate chemotherapy. Imaging is usually done after 2 cycles and completion to identify those with lack of response or progression. Other first line therapies include rituximab in combination of fludarabine-based regimens or rituximab monotherapy. Second line salvage regimens include rituximab, fludarabine or radioimmune therapy with tositumomab or ibritumomab. Relapse or refractory follicular lymphoma may be treated with chemotherapy plus rituximab regimens autologous stem cell transplant. Maintenance rituximab following chemotherapy in patients who have received R-CHOP or CHOP prolong disease free survival. Bendamustine and rituximab recently demonstrated longer progression free survival than R-CHOP. Complications of treatment include nausea, vomiting, diarrhea, fatigue, rhinitis, neurotoxicity, peripheral neuropathy, constipation, alopecia, photosensitivity, cardiac complications. Fludarabine can get prolonged risk of CMV reactivation, herpes virus, Pneumocystis or fungal infection. Prophylaxis against Pneumocystis is often advised for 3-6 months following fludarabine therapy. Ongoing surveillance following treatment of follicular lymphoma is important because most patients do eventually relapse despite monochemotherapy and immunotherapy. This includes physical exam of nodal areas every 3 months for 2 years and every 6 months for 2-3 years and then at least annually. CT every 6-12 months for 2 years following treatment is reasonable and then as symptoms and signs dictate. Routine PET should be not be obtained. The follicular lymphoma international prognostic score is as follows. A -1 factor gives a 5-1 year survival of 91% and 71% respectively; intermediate risk, which is 2 factors, give a 5-1 year survival of 78% and 51% respectively and high risk, which is greater than 2 factors, gives 5 and 1 year overall survival of 53% and 36% respectively. Patients with only localized stage I or II disease treated with radiation can have a 1-year overall survival approaching 8%.

9 Radiation Oncology in Non-Hodgkin s Lymphoma Treatment Tarek Dufan, MD Radiation Oncology Bismarck Cancer Center Non-Hodgkin s Lymphoma is one of the most common hematological cancers in our practice. As a radiation oncologist, I see multiple non- Hodgkin s lymphoma patients throughout the year. These patients are typically young, usually between 3 and 5 years old. The most common presentation is usually a large lymph node which is changing from time to time, getting bigger and smaller, depending on the necrosis inside it. It is also associated with night sweats, drenching, fever and weight loss. Often, the disease is diagnosed through screening studies for other reasons in an asymptomatic patient. The patient is sometimes self-referred, but the majority of the patients are referred to radiation oncology by medical oncologists, primary physicians and surgeons. The equipment used in the diagnosis of non-hodgkin s lymphoma is mainly a biopsy, CT scan, and PET CT scan. Also, diagnostic bone marrow aspiration, usually done through medical oncology, is important to complete the staging for this cancer. Proper staging is very important. Staging is done prior to treatment. It determines the course of treatment and the options available to the patient and physician. The outcome is also often dependent on the stage of the disease at diagnosis. Usually there are two modality treatments for this kind of disease. This includes systemic therapy with chemotherapy, sometimes including hormone therapy, or targeted therapy with radiation treatment. The stage of the disease is the basis for deciding whether the patient is treated with a single or combined modality treatment. In Bismarck, we have all the staging investigations needed to stage non- Hodgkin s cases properly and we have the expertise to treat non- Hodgkin s lymphoma with medical oncology, radiation oncology and appropriate surgery. An anticipated advance in treatment of non-hodgkin s lymphoma cases in our facility is the plan to implement a permanent PET CT scanner, which helps in the diagnosis. Also, our oncology group is associated with North Central Tumor Group. We participate in many studies with this group, mainly with chemotherapy and radiation. In the next five to ten years, I expect that more targeted therapy and more understanding of the natural history of disease and genetic background will be discovered. I believe these advances will improve our outcomes significantly.

10 Statistical Analysis of Cancer Diagnosis and Treatment At Medcenter One Health Systems With a Focus on Non-Hodgkin s Lymphoma Based on Central North Dakota Cancer Registry Data The Central North Dakota Cancer Registry is the data gathering and analysis arm of the cancer treatment program for Medcenter One Health Systems. The CNDCR reports de-identified data concerning the diagnosis, treatment and outcomes of cancer to physicians and researchers as well as state and national cancer data bases. Organized in 1983 as a joint venture of Medcenter One and St. Alexius medical centers, the registry has been located in the Bismarck Cancer Center since The registry also coordinates multidisciplinary tumor conferences for both hospitals. In 21, Medcenter One conducted 17 general tumor conferences, with 68 individual cases discussed by pathologists, diagnostic radiologists, surgeons, medical oncologists, radiation oncologists and other physicians involved in the care of those patients. Medcenter One also initiated tumor conferences specific to breast cancer in June, 21, and held 11 additional breast cancer focused conferences, with 3 more cases presented. The registry has recorded information about more than 5 patients who have been diagnosed or treated for cancer at Medcenter One since 22. A vital component of registry activity is producing reports on the success of the treatment of cancer at the 3 institutions in Bismarck: Medcenter One, St. Alexius and the Bismarck Cancer Center for the respective institutions and their physicians. The incidence of cancer diagnoses in the Medcenter One service area has grown by 19% from 22 to 21. The number of tumors diagnosed or treated peaked at 633 patients in 26, when both men and women saw a 2% spike during the calendar year and then a return to the normal growth trend the following year. The 549 cases diagnosed or treated in 21 was slightly below the growth average of the previous years. 1 This could be attributed to normal statistical ebbs and flows, rather than a decline in the overall number of cancer patients identified annually in the Bismarck area. 8 Cancer Diagnosed or Treated at Medcenter One Male Female

11 TOP SITES The four most commonly diagnosed tumors in Bismarck and the US are breast, colorectal, lung and prostate. Lymphoma, the most common neoplasm of the circulatory system, is the sixth most common cancer in the country and the fifth most frequently discovered cancer at Medcenter One. Top Sites MC1 1 MC1 % MC1 1 MC1 % MC1 1 MC1 % US 2 US % Breast Colorectal Lung Prostate Lymphoma Bladder Skin Leukemia Gynecological It is estimated that 75,19 men and women (4,88 men and 34,31 women) will be diagnosed with lymphoma and 2,62 men and women will die of lymphoma in the United States in GENDER Lymphoma occurs in men (54%) slightly more frequently than in women (46%), both nationwide and at Medcenter One. 1,2 In 21, however, 53% of the lymphomas diagnosed at Medcenter One were in women, as illustrated below. This can be due to the statistical inconsistencies of the relatively small number of lymphoma patients at Medcenter One. Male Female Lymphoma Patients Diagnosed or Treated at Medcenter One between Male Hodgkin Male Non-Hodgkin Female Hodgkin Female Non-Hodgkin

12 AGE There are over thirty different types of lymphomas, and each has unique characteristics requiring treatment highly dependent on the type and stage of the disease. Two basic divisions of Lymphoma are Hodgkin s Lymphoma and non-hodgkin s Lymphoma. Non-Hodgkin s Lymphoma is the more common and more often discovered in adults, while Hodgkin s Lymphoma is more often diagnosed in younger people, as shown in the accompanying chart. 1,2 # of Medcenter One Cases Age at Diagnosis MC1 HL ('1) MC1 NHL ('1) US HL ('8) US NHL ('8) # of US Cases HISTOLOGY 28 different histologies of lymphoma have been diagnosed in the Medcenter One Health Systems between 22 and 21. The most often identified lymphomas diagnosed here in 21 were B-Cell Chronic Lymphocytic Lymphoma, Malignant Large B-Cell diffuse lymphoma or Follicular Lymphoma. 1 Follicular Lymphoma All other lymphomas T-cell Lymphoma Lymphoma, marginal zone B- cell Burkitt lymphoma Malignant Lymphoma, diffuse large B- cell Histology of Lymphoma Medcenter One B-cell Chronic Lymphocytic Lymphoma/ small lymphocyte lymphoma Hodgkin lymphoma, nodular sclerosis other Hodgkin Lymphomas Malignant Lymphoma, small B-cell lymphocytic

13 FIRST COURSE TREATMENT Lymphoma is a systemic disease. In most cases, the first course of treatment of lymphoma at Medcenter One is chemotherapy or chemotherapy combined with hormone therapy. Radiation therapy may be used when the disease is confined to a small area. Surgery is rarely a first course of treatment of lymphoma, but may sometimes be used as a diagnostic tool or for treatment of a specific area. In approximately one-fourth of the cases, watchful waiting was determined to be the most appropriate course of action at the time of diagnosis. 1 First Course Treatment No Treatment Chemotherapy Hormone Therapy Radiation Therapy Surgery SURVIVAL 1,2 Medcenter One has an outstanding overall record in the treatment of cancer. This graph shows that Medcenter One, when all cancers are compared, has a greater survival rate than the US by as much as four and a half percent. In other words, 4 more Medcenter One cancer patients out of every 1 are alive one, two and three years after their diagnosis than in the rest of the country, 3% more after four years and 2 more patients out of every 1 are still alive after five years Observed Survival - All Cancers US MC1

14 1 5 Breast Breast cancer is the most frequently diagnosed tumor in the US and at Medcenter One. The survival at Medcenter One follows the national rate very closely. US MC1 1 5 Colorectal The second leading cancer diagnosis at Medcenter One, for colorectal patients, has a seven percent better rate of success in the first year and more than eight percent better in the second year. The advantage is still four percent after five years. US MC1 1 5 Lung Lung cancer is the most deadly cancer. Again, Medcenter One has a greater rate of success than the rest of the country in treating this disease. 16% more Medcenter lung patients are alive after the first year than in the rest of the country. That advantage remains over 8% after 5 years. US MC1 1 5 Prostate Of the four most common tumors, prostate cancer is the only diagnosis where the national statistics are ahead of the Medcenter One survival rates US MC1

15 1 Lymphoma Hodgkin & Non-Hodgkin US MC1 Five year survival of all lymphoma patients at Medcenter One is over 4 percent ahead of the national averages. For every 1 lymphoma patients diagnosed at Medcenter One since 22, there are five more survivors after one year than in the country as a whole. After 2, 3, 4 or 5 years, there are 4 more Medcenter lymphoma survivors than in the rest of the country for every 1 patients diagnosed. 1 Non-Hodgkin Lymphoma Survival US MC1 Among Non-Hodgkin s Lymphoma patients, the survival rate is approximately the same, with better than 5 more survivors among every 1 non-hodgkin s patients than in the rest of the country the first year. The advantage is still four more surviving in subsequent years. There are many factors influencing the favorable statistics for cancer patients in the Medcenter One Health Systems. From early detection to cutting edge medical oncology and world class radiation oncology treatments to a multidisciplinary approach of treating the disease, Medcenter One is ahead of the country in the success of cancer care, including lymphoma. The average overall survival of lymphoma cancer patients at Medcenter One is better than 4% higher than the country as a whole, and Medcenter One s outstanding programs are working to increase that advantage. 1 Central North Dakota Cancer Registry, Medcenter One Data Base 2 National Cancer Data Base 3