Lung Cancer: An Overview

Transcription

1 VOL. I Issue Lung Cancer: An Overview By Matthew F. Koscielski, M.D. Lung cancer is the most common cause of cancer mortality worldwide. In the United States there are about 220,000 new cases of lung cancer per year, and about 160,000 deaths per year. This is more deaths than colorectal, breast and prostate cancers combined. Indiana has the tenth highest rate of lung cancer within the U.S. The incidence of lung cancer in men dramatically increased and then peaked around 1990, and has since begun to decline, most likely due to a decrease in smoking. The incidence of lung cancer in women seems to have reached a plateau, but lung cancer remains the most common cause of cancer deaths, exceeding breast cancer. In This Issue Lung Cancer: An Overview...1 Lung Cancer Incidence and Mortality: A National, State and County Perspective...2 PET in the Diagnosis of Suspected Lung Cancer...3 Surgical Treatment of Lung Cancer...4 Stereotactic Body Radiotherapy Science Fiction or Reality?...8 Medical Oncology Advances in Lung Cancer Treatment...9 Massage Therapy and Lung Cancer...11 There are a number of risk factors that have been associated with the development of lung cancer, the most common of which is cigarette smoking. Ninety percent of all lung cancers are related to smoking abuse. An individual who smokes one pack of cigarettes a day for 40 years is approximately 20 times more likely to develop lung cancer than a non-smoker. Other risk factors, such as exposure to second hand smoke, asbestos, radon, some metals and radiation, also increase the likelihood of developing lung cancer. About 10 percent of lung cancers have no risk factor association, and they may have some genetic factors associated, which currently have not been specifically identified. Screening patients for lung cancer when they have no pulmonary symptoms has not been proven to be cost effective, or to increase the life expectancy when a cancer is found. Annual chest x-rays or periodic CT scans are not recommended. Thus, the diagnosis of lung cancer is primarily based on evaluation of the patients when symptoms develop. However, there are numerous trials in the U.S. and Europe that are evaluating various strategies in lung cancer screening. Symptoms of lung cancer vary widely for different patients. The most common presenting symptoms include cough, hemoptysis (coughing up blood), chest pain, dyspnea (shortness of breath) and hoarseness. Oftentimes, the presenting symptom may be a sign of a metastatic tumor. Spread beyond the chest includes liver disease, bone pain, seizure or an unexplained blood clot in a vein. Treatment and prognosis of lung cancer depends on the stage of the disease at presentation. There are four stages of lung cancer, with Stage 1 having a small, limited tumor confined to the lung, with no evidence of it spreading to lymph nodes. At Stage 4 the tumor has spread throughout the chest or in other organs beyond the chest. The average survival of patients with Stage 4 disease is only about one year. Treatment may also vary based on cell type. There are four different cell types of lung cancer that are divided into two main groups: small cell and non-small cell lung cancer. Small cell lung cancer has the worst prognosis with the fastest growth rate. It usually presents with widespread metastasis about 70 percent of the time. Squamous cell, adenocarcinoma and large cell are the histologic types of non-small cell lung cancer. Squamous cell cancer often presents with hemoptysis and bronchial obstruction and mass. The incidence of adenocarcinoma has increased dramatically in the last 20 years, which is thought to be due to the introduction of low-tar filter cigarettes. continued on page 2

2 For patients with limited (early) stage lung cancer, the best option for long-term survival and cure is for surgical resection of the cancer (lobectomy or pneumonectomy). Whether a patient is a suitable candidate for surgery depends on the patient s lung function (determining the lung capacity) and evidence of emphysema. Other factors that determine a patient s risk include co-morbidities such as cardiac disease, pulmonary hypertension and age. For patients who cannot have surgical resection, then chemotherapy and/or radiation therapy may be offered, with less likelihood of cure. Currently about 20 percent of adults smoke. The success rate of smoking cessation without any intervention is only about 5 percent abstinence at the end of one year. Current modalities of smoking cessation include counseling, hypnosis, medications and nicotine replacement therapy. With optimal therapy, success rates after one year could be as high as 30 percent. Matthew Koscielski, M.D. is board certified in Pulmonology and Critical Care Medicine in South Bend. Lung Cancer Incidence and Mortality: A National, State and County Perspective By Jason M. Critchlow Despite ranking 25 th in the entire nation in terms of overall cancer incidence rates, Indiana has the tenth highest lung cancer incidence in the country,* making lung cancer a momentous issue concerning the health and well-being of the citizens of Indiana. Figure 1 demonstrates the lung cancer incidence rates of the U.S., Indiana and St. Joseph County for the years Figure 1 Incidence Rate (per 100,000) Lung Cancer Incidence Rates National Indiana St. Joseph County Figure 2 Mortality Rate (per 100,000) Figure 2 exhibits the mortality rates for the U.S., Indiana and St. Joseph County. As is seen with the incidence rate, the mortality rate for lung cancer in Indiana is also much higher than the nation, with St. Joseph County exhibiting slightly lower mortality rates than the state. Figure 3 Lung Cancer Mortality Rates National Indiana St. Joseph County 2 As can be seen, Indiana has a significantly higher incidence rate than the rest of the country. Although St. Joseph County does boast a lower rate than the state, the incidence rate of 76.6 continues to be much higher than the national rate of As would be expected, the mortality rate for lung cancer in these three geographic domains follows a similar pattern. Incidence Rate (per 100,000) Lung Cancer Stage at Diagnosis Indiana State vs. St. Joseph County Local Regional Distant Unknown Indiana St. Joseph

3 Figure 3 shows the Stage at Diagnosis rates for Indiana in comparison to St. Joseph County. This figure demonstrates slightly more cases of earlier stage lung cancers are being diagnosed here in St. Joseph County as compared to the state. Also worth noting is the significantly fewer unknown stages identified in St. Joseph County. Unknown stages often occur when an individual s cause of death is determined to be lung cancer, but comprehensive autopsy and staging does not occur. It can then be extrapolated that fewer deaths of previously unknown lung cancers are occurring in St. Joseph County as a result of increased detection efforts. Figures 1 and 2 both demonstrate that St. Joseph County has been successful in lowering both the incidence and mortality rate of Lung Cancer. The suspected cause of this difference would fall into two categories: education and superior medical intervention. Educating the population on the causes and prevention of lung cancer, as well as access to excellent medical intervention, are both resources provided to the county by Memorial Hospital of South Bend. Although the incidence rate has been steadily decreasing, the rate of tobacco users in Indiana is still much higher than the national average, and Indiana ranks sixth among all states in adult smoking prevalence.*** The often repeated link between tobacco use and lung cancer has reached the point of being undeniable. Therefore, it may go without saying that the higher incidence and mortality rates for lung cancer in Indiana are a direct result of the high prevalence of tobacco use in the state. Despite this, St. Joseph County is still faring better than the overall state. This is likely due to the increased awareness and education, as well as the superior medical treatment that St. Joseph County residents are able to access. * Data provided by the Center for Disease Control (CDC). ** Data provided by the National Program of Cancer Registries (NPCR) and the Indiana State Cancer Registry. *** Data provided by Indiana Tobacco Prevention and Cessation ( Jason M. Critchlow is the program coordinator for the Northern Indiana Cancer Research Consortium. PET in the Diagnosis of Suspected Lung Cancer By Jonathan W. Weiss, M.D. Positron emission tomography (PET) is an imaging technology with multiple applications in the management of patients with lung cancer. Specifically, PET has been shown to be useful in the diagnosis of lung cancer in certain clinical situations. Currently, radiolabeled glucose is the most commonly used radiopharmaceutical in oncologic PET imaging. Malignant lesions will typically show increased glucose metabolism as compared to benign disease. Recently, PET has been combined with computed tomography (CT) to improve the specificity of PET and allow for more accurate patient evaluation. This article will discuss the use of PET in patients with suspected lung cancer that is not biopsy proven. Early stage lung cancer typically presents as a single pulmonary nodule, which is defined as a spherical opacity that is less than three cm in size. With the rapid development of CT, pulmonary nodules are being incidentally detected more frequently in examinations performed for other indications. Although the majority of the pulmonary nodules represent benign disease, their evaluation is important because some of them are potentially curable lung cancers. Many factors must be considered in the evaluation of a patient with a single pulmonary nodule: the patient s individual risk for having lung cancer and the morphology of the pulmonary nodule. Patient risk factors for lung cancer include current or past smoking, age and first-degree relative with lung cancer. Morphologic factors that increase the risk a pulmonary nodule is malignant include nodule size, upper lobe location and spiculation of the nodule. Any pulmonary nodule detected on a chest x-ray that does not display benign calcification should undergo CT evaluation for further characterization, unless prior studies show that the nodule has been stable for two years. Despite imaging advancements, many pulmonary nodules remain indeterminate after CT evaluation. Further PET imaging can help triage patients with pulmonary nodules to either observation or 3

4 more invasive testing. PET also has improved specificity and sensitivity in detecting unsuspected metastatic lesions as compared to CT. For patients with a PET positive pulmonary nodule, the examination also serves as a staging study. These results help guide therapy and avoid unnecessary procedures. The results of a PET examination also provide prognostic information for the patient. The radiolabeled glucose uptake within a lung cancer (typically reported as the maximum standardized uptake value, SUV max) is a marker for the aggressiveness of the malignancy. The greater the SUV max, the more aggressive the disease. This has been shown to correlate with decreased survival. PET does have some limitations. Due to the spatial resolution of PET, small pulmonary nodules may be falsely negative on PET. Therefore, pulmonary nodules evaluated by PET should be at least eight to 10 mm in size. False positive PET results also occur and are typically caused by an infectious or inflammatory process. Bronchioloalveolar cell carcinoma, carcinoid tumors and mucinous adenocarcinomas compose a relatively small percentage of malignant lung cancer. These malignancies often display low glucose uptake on PET and can be falsely negative. Bronchioloalveolar cancer often presents as a ground glass pulmonary nodule (a nodule in which the underlying lung septa and vessels can be seen through the nodule). Therefore, PET is often less helpful in these cases due to the increased potential of a false negative PET result. Since PET cannot exclude malignancy within a pulmonary nodule, patients with a negative PET scan should be followed with CT imaging for at least two years to confirm a benign diagnosis. Follow-up CT scans are typically performed at three, six, 12 and 24 months. Alternatively, highrisk patients with a negative PET scan can undergo biopsy. Also, since bronchioloalveolar cancer is a slow growing malignancy, some authors recommend annual CT follow-up of pure ground glass pulmonary nodules beyond two years. PET is a powerful tool in the management of patients with suspected early stage lung cancer. However, PET is not infallible and any positive PET finding that alters patient management should be proven with tissue sampling. The usefulness of PET in the diagnosis of patients with suspected lung cancer has been acknowledged by the American College of Chest Physicians (ACCP). Their 2007 publication, Evaluation of Patients with Pulmonary Nodules: When Is It Cancer?, was used as a reference for this article. They recommend the use of PET imaging in the characterization of pulmonary nodules at least eight to10 mm in size in patients with a low to moderate risk of malignancy (5-60 percent). The ACCP recommends that higher risk patients (>60 percent) with pulmonary nodules at least eight mm in size directly undergo tissue sampling and lower risk patients (< 5 percent) be followed with CT at three, six, 12, and 24 months. Jonathan Weiss, M.D. is board certified in Diagnostic Radiology and Nuclear Medicine and is a radiologist with Radiology, Inc. in South Bend. Surgical Treatment of Lung Cancer By James Kelly, M.D., Thomas Hughes, M.D., Charles J. Lamb, M.D., Walter Halloran, M.D. and Michael Steinberg, M.D. Key Statistics: Lung Cancer (both small cell and non-small cell) is the second most common cause of cancer in both men (after prostate cancer) and women (after breast cancer). It accounts for 15 percent of all new cancers. In 2009, our most recent U.S. cancer statistics show 220,000 new cases of lung cancer. There were 160,000 deaths in 2009 from lung cancer, accounting for 28 percent of all cancer deaths. Lung cancer is by far the leading cause of cancer deaths among men and women. Overall, the chance that a man will develop lung cancer in his lifetime is about 1 in 13; for a woman the risk is 1 in 16. Indiana: 25 percent of Indiana adults and 37 percent of Indiana s high school students continue to smoke. Lung cancer is the leading cause of cancer mortality in Indiana, killing an average of 4,000 Hoosiers per year. In any given week, 94 Hoosiers are diagnosed and 75 Hoosiers die from lung cancer. We will shortly comment on stages of diagnosis for lung cancer, but lung cancer in Indiana is diagnosed at a later stage, which negatively impacts the odds of survival. Only 18 percent of lung cancers in Indiana were diagnosed at a local stage as opposed to 40 percent nationally. Population demographics suggest that we should see 200 new cases of lung cancer in St. Joseph County per year (Elkhart County = 135, Marshall County = 35, LaPorte County = 150). Currently, Memorial Hospital sees between new cases of lung cancer per year. 4

5 Surgical Treatment of Lung Cancer Surgery for lung cancer is primarily directed at non-small cell lung cancer (NSCLC) which represents percent of all lung cancers. Surgeons interact with patients on three levels diagnosis, staging and treatment. Diagnosis can take place using a wide variety of methods including direct biopsy, thoracotomy or mediastinoscopy, bronchoscopy (passing a lighted scope into the lung) and needle aspiration. These tests can be initiated by the family physicians or specialists who initially find a suspicious lesion. Staging, however, is oftentimes the first critical process in which the surgeon can interact with the patient. Clinical staging of cancer is based on a physical exam, biopsies and imaging tests, (CT scans, PET scans). As alluded to above, staging is a critical process, especially in Indiana, because patients often present with more regional disease than is seen nationally. Pathologic staging is based on the same factors as the clinical stage, plus what is found at surgery. The system used to describe growth and spread of non-small cell lung cancer (NSCLC) is the American Joint Committee on Cancer (AJCC) TNM staging system. The Staging System provide three key pieces of information: T Indicates size of the main tumor and whether it has grown into nearby structures. N Describes how much cancer has spread into regional lymph nodes. M Indicates whether the primary cancer has spread into other organs. Numbers 0-4 indicate severity of the TNM findings. Once TNM categories have been assigned, this information is combined to assign an overall stage (0, I, II, III, or IV). Figure 1 National Cancer Database Survival Statistics (NCDB) Cumulative Survival Rate Observed Survival For Lung, Bronchus Non-Small Cell Carcinoma Cases Diagnosed in Data from 1316 Programs [National] WARNING: The information within this graphic is not to be used for clinical decision making Years from Diagnosis 0 I II III IV 2008 by James M Banasiak These stages may be subdivided into A or B based on physical location of the tumor and anatomic structures which the tumor may involve. Stages identify tumors that have a similar prognosis and thus are treated the same way. This staging is also used to compare results across institutions and suggest the five-year survival rate for various stages of lung cancer (i.e. Stage I = 48 percent, vs. Stage III = 10 percent) (Figure 1). Once a clinical stage is established, initial treatment decisions can be made by a team of physicians including, but not limited to Pulmonary Medicine, Radiation Oncology, Medical Oncology and Surgery. Decisions can be made for surgery alone, presurgery radiation and/or chemotherapy (neoadjuvant therapy), chemotherapy and/or radiation without surgery, or alternative therapy including other local therapies (radio-frequency ablation, directed radiation) and targeted therapies. Our monthly Lung Cancer Forums are used to discuss particularly complex cases where all specialists are invited to discuss these cases in an open meeting. Depending on the type, stage and quantitative pulmonary functions (measured by special testing) of the patient, surgeons may be able to remove the cancer, with surrounding lung tissue and appropriate lymph node sampling in the chest. If surgery can be done, this provides the best chance to cure NSCLC. Lung cancer is a complex surgery with interactions of all body systems and should be performed by an experienced team (including anesthesia and nursing) who can provide adequate operative and postoperative care. Surgeries can be accomplished with video-assisted cameras (Video assisted thoracic surgery or VATS) or routine thoracotomy. Decisions regarding the extent of the surgery (pneumonectomy entire lung removed; lobectomy lobe of lung; segmentectomy or wedge resection part of lobe) are often made intra-operatively. Surgical sampling of regional lymph node groups is mandatory. We say mandatory because lymph node involvement has prognostic implication regarding the pathologic staging of the cancer (which might be different from the initial clinical stage) and which may direct the team to recommend postoperative chemotherapy and/or radiation (adjuvant therapy). A recent study by the Society for Thoracic Surgery (all of our partners are members) analyzed a database of 19,000 patients from 110 centers undergoing lung cancer surgery from Only six percent of the patients in the database had a pneumonectomy while 66 percent had a lobectomy, with 19 percent having a wedge resection. Using the STS Thoracic Database, we can compare our results with other board certified thoracic surgeons and give patients an accurate assessment of 5

6 risk factors. Furthermore, early results from several studies suggests that surgical results for board certified thoracic surgeons offer better five-year survival for patients with lung cancer undergoing resection (Annals Thoracic Surgery 2009; 87: ). Closer to home, we have looked at Memorial Hospital s results from for non-small cell lung cancer in Stage IIIA & B. The study involved 182 patients (74 female and 108 male) who received all or part of their first course of therapy at Memorial Regional Cancer Center during The ages ranged from years, with the largest group being Pathologically, Stage IIIA represented 51 percent of the cohort for this study. Small cell lung cancers (SCLC) were excluded from our study. Figure 3 Number of Cases Surgery (S) Memorial Regional Cancer Center NSCLC Stage IIIA and IIIB by 1 st Course of Therapy n = Radiation (R) Stage IIIA Stage IIIB Chemo (C) S + R S + C R + C S + R + C No Treatment Treatment Modality Figure 2 shows the histologic distribution of the study group. Of our approximately 150 new cases a year, 25 are stage IIIA or IIIB. Stage IIIA/IIIB are advanced lung cancers, which can be very aggressive locally and can invade the chest wall and other vascular structures in the chest. Our evaluation of these patients, which involved multiple specialists, often took into account the performance status of the patients and their abilities to be involved in multiple sequential therapies. Figure 4 % Surviving 100% 90% 80% 70% 60% 50% 40% Memorial Regional Cancer Center NSCLC Stage IIIA & Stage IIIB 5-Year Observed Survival by Initial Therapy Figure 2 30% 20% Memorial Regional Cancer Center NSCLC Stage IIIA & IIIB by Histology Distribution 10% 0% No Treatment (n = 26) 100.0% 11.5% 3.9% 3.9% 0.0% 0.0% Radiation Only (n = 22) 100.0% 38.1% 14.3% 4.8% 4.8% 4.8% Surgery Only (n = 7) 100.0% 57.1% 42.9% 28.6% 28.6% 28.6% Chemo Only (n = 22) 100.0% 34.8% 17.4% 10.4% 10.4% 10.4% Elapsed Time in Years 9% 19% 8% 32% Adenocarcinoma, NOS Squamous cell carcinoma Non-small cell carcinoma Other non-small cell types Figure 5 Memorial Regional Cancer Center NSCLC Stage IIIA & Stage IIIB 5-Year Observed Survival by Initial Therapy (NCDB data includes no therapy and all treatment regimens) 100% 32% Carcinoma, NOS 90% 80% 70% Figure 3 shows our first course of treatment in all patients in our study. Thirty-eight percent of the patients received radiation plus chemotherapy as destination therapy. Twentythree percent of our patients in this study had surgery alone or with neoadjuvant/adjuvant therapy. This was the subject of our study in these 182 patients. % Surviving 60% 50% 40% 30% 20% 10% NCDB 0% S + R + C (n = 20) 100.0% 75.0% 60.0% 60.0% 60.0% 48.0% S + C (n = 11) 100.0% 91.7% 91.7% 58.3% 58.3% 58.3% S + R (n = 3) 100.0% 100.0% 33.3% 33.3% 33.3% 0.0% R + C (n = 70) 100.0% 57.1% 32.3% 25.1% 18.0% 18.0% NCDB (n = 76962) 100.0% 44.4% 22.9% 14.7% 10.9% 8.6% Elapsed Time in Years 6

7 Figures 4 and 5 show our results. Our data indicate that no therapy offers a zero survival at five years, and that chemotherapy or radiation therapy alone fared poorly. Among the monotherapies, surgery had a 29 percent five-year survival. A closer look at our data at six years suggests that surgery + radiation + chemotherapy and surgery + chemotherapy offered a distinct survival benefit. Figure 6, while quite a busy illustration, compares all the therapeutic strategies, including no treatment and NCDB (National Cancer Data Base) statistics, which blends all forms of treatment for Stage III A & B into one number (approx. 10 percent). Figure 7 is our summary slide which suggests that preoperative chemotherapy and postoperative radiation + chemotherapy offer the best five-year results for this complex set of patients when combined with surgery. Figure 6 Memorial Regional Cancer Center NSCLC Stage IIIA & Stage IIIB 5-Year Observed Survival by Initial Therapy (NCDB data includes no therapy and all treatment regimens) 100% 90% 80% Summary: All the schemata that show improved five-year survival for lung cancer include surgical resection of the tumor. Monotherapy (surgery only) for early stage lung suggests a 48 percent five-year survival (Figure 1). A Memorial Regional Cancer Center study for a much more advanced stage of lung cancer (Stage IIIA & B) suggests an approximate percent five-year survival for patients who were treated with preoperative chemotherapy or postoperative radiation and chemotherapy in conjunction with surgery. This article also cites references from the Society for Thoracic Surgery, that surgical results are best observed at institutions with Boarded Thoracic Surgeons and staff who routinely care for thoracic surgery patients. James Kelly, M.D., Thomas Hughes, M.D., Charles J. Lamb, M.D., Walter Halloran, M.D. and Michael Steinberg, M.D. are partners in Cardiothoracic Surgery of South Bend, Fellows of the American College of Surgeons and Fellows of the American Board of Thoracic Surgery. 70% % Surviving 60% 50% 40% 30% 20% 10% NCDB 0% S + R + C (n = 20) 100.0% 75.0% 60.0% 60.0% 60.0% 48.0% No Treatment (n = 26) 100.0% 11.5% 3.9% 3.9% 0.0% 0.0% Radiation Only (n = 22) 100.0% 38.1% 14.3% 4.8% 4.8% 4.8% S + C (n = 11) 100.0% 91.7% 91.7% 58.3% 58.3% 58.3% S + R (n = 3) 100.0% 100.0% 33.3% 33.3% 33.3% 0.0% Surgery Only (n = 7) 100.0% 57.1% 42.9% 28.6% 28.6% 28.6% Chemo Only (n = 22) 100.0% 34.8% 17.4% 10.4% 10.4% 10.4% R + C (n = 70) 100.0% 57.1% 32.3% 25.1% 18.0% 18.0% NCDB (n = 76962) 100.0% 44.4% 22.9% 14.7% 10.9% 8.6% Elapsed Time in Years Figure 7 100% Memorial Regional Cancer Center NSCLC Stage IIIA & Stage IIIB Neoadjuvant vs. Adjuvant Observed Survival 90% 80% 70% 60% Survivors 50% 40% 30% 20% 10% 0% Elapsed Time in Years S + C Adjuvant Therapy (n = 7) S + R + C Neoadjuvant Therapy (n = 8) S + C Neoadjuvant Therapy (n = 4) S + R Adjuvant Therapy (n = 3) S + R + C Adjuvant Therapy (n = 12) 7

8 Stereotactic Body Radiotherapy Science Fiction or Reality? By David Hornback, M.D. 8 Can you imagine the ability to carve out a tumor without even scratching the skin? An invisible, painless knife that essentially eliminates the cancer without the need of anesthesia or a long hospital stay? Science fiction or reality? Stereotactic radiosurgery (SRS) is a treatment that has become a widely accepted form of therapy for patients with small benign and malignant brain tumors. This treatment, as the name suggests, is an extremely precise method of rendering a tumor inactive by aiming multiple beams of radiation and delivering very high doses while avoiding surrounding normal tissues. We now have the capability to take this technology beyond the limits of the brain to other areas of the body with a technique referred to as Stereotactic Body Radiation Therapy or SBRT. Small tumors in the lung or liver, next to the spinal cord or within areas of previous radiation fields can now be accurately pinpointed and treated, not only safely but with excellent control rates. Patients with small lung tumors are excellent candidates for treatment with SBRT. Unfortunately, lung cancer remains the leading cause of cancer deaths in the United States. While the majority of lung cancer patients present with more advanced stages of disease, approximately percent of all patients with non-small cell lung cancer will be diagnosed with early stage, potentially curable tumors. Surgical resection has traditionally been the standard of care in managing these types of tumors. Removal of a portion of the lung, or in some cases the entire lung has resulted in a percent five-year overall survival rate. However, as you can imagine, the loss of even a portion of the lung can severely compromise a patient s breathing capacity. Patients who have a long history of tobacco use with resulting emphysema or those who have other medical problems such as heart disease or severe diabetes may not be able to tolerate even a limited lung resection. Before SBRT, patients who were felt to be at too high risk to undergo surgery would receive six to seven weeks of daily, Monday through Friday radiation treatments directed at their tumor. While they would generally tolerate the therapy well, the control rates were much lower than surgery in the range of percent at five years. Not only is the course of SBRT much more convenient (usually delivered in 3 4 treatments), the control rates can be as high as 90 percent with minimal side effects. Once patients are determined to be good candidates for SBRT, they go through a simulation process where a mold is made to conform to their body and a vacuum bag restriction system is utilized to immobilize the patient and help ensure that they remain as still as possible during treatment. Next, a CT scan is obtained in all phases of the breathing cycle at full inspiration, partial inspiration and full expiration to determine any tumor motion during respiration. This scan is then fused with a PET CT to help identify the full extent of tumor. Complex treatment planning is utilized to develop optimal beam arrangement and modulation to deliver a highly focused dose of radiation to the tumor with a very small margin. A sample SBRT plan above shows a highly conformal treatment plan that delivers a precise amount of radiation to the tumor seen here in the center of the treatment field. The different colored rings around the tumor indicate amounts of radiation delivered with the highest dose delivered inside the smallest ring. Notice that the majority of the lung is spared these high levels of radiation dose. Once the planning is complete, the patient will return and undergo a series of 3 4 painless treatments over the course of a week or so. Each treatment will require the patient to lie still for approximately 45 minutes. Sedation may be used to help a person tolerate this procedure better. While 3 4 SRBT treatments are considered standard, we are currently enrolling medically inoperable patients with early stage, non-small cell lung cancer in a study (RTOG Protocol 0915) that is comparing four fractions to just a single treatment of SBRT.

9 Stereotactic Body Radiation Therapy may seem like a futuristic, science fiction treatment you might see only in an episode of Star Trek, but it is real and it is available here at Memorial Hospital of South Bend. Memorial has been using this treatment technique since This is just one of a number of tools we have available in the fight against cancer and another reason Memorial remains the leader in cancer care in the Michiana region. For more information, please call (574) David Hornback, M.D. is board certified in Radiation Oncology and is the medical director for the Memorial Regional Cancer Center in South Bend. Medical Oncology Advances in Lung Cancer Treatment By Mohamed Farhat, M.D. More than 95 percent of lung cancers consist of four major histologic types that are divided into two groups: 1) small cell lung cancers (SCLC) and 2) squamous (or epidermoid), adenocarcinoma, and large cell cancers, known collectively as non-small cell lung cancers (NSCLC). Other subtypes, which are rare and therefore less well studied, include carcinoid, large cell cancer with neuroendocrine features and large cell neuroendocrine cancer. In spite of being more sensitive to chemotherpy and radiation, SCLC tend to have a more rapid clinical course than NSCLC, and are more commonly associated with paraneoplastic syndromes and neuroendocrine features on pathologic examination. Patients with stage I, II, or III NSCLC are generally treated with curative intent using surgery, chemotherapy, radiation therapy (RT) or a combined modality approach. Five-year survival is between percent in stage IA. The greatest challenge of this disease has been to increase survival in the metastatic setting. Metastases are seen in up to 50 percent of patients at time of initial presentation in adenocarcinoma and 75 percent in SCLC. Traditionally, metastatic disease is treated with chemotherapy, typically a platinum doublet. This regimen is effective in prolonging survival compared to either best supportive care or less intense single-agent chemotherapy. The side effects differ depending on the regimen used, but typically are fairly tolerable. 9

10 Chemotherapy tolerance has improved dramatically over the last decade, mainly due to the development of better antiemetic and anti-diarrheal medications and greater use of supportive measures. The side effects that were prevalent 20 years ago no longer hold true. Patients who would not have been chemotherapy candidates by old standards are now experiencing the benefit of chemotherapy with well tolerated side effects. Standard of care is four to six cycles of chemotherapy followed by close observation with repeated imaging. More recently published clinical trials showed a greater benefit in decreasing disease progression with the use of single agent (chemotherapy or targeted treatment), following initial treatment as maintenance therapy. Even more clinical studies are ongoing, investigating the role of different maintenance therapies in this very aggressive disease. It is important to keep in mind when contemplating the use of maintenance treatment that we must first weigh the risks and benefits of prolonged use of chemotherapy. At the turn of the new millennium, great strides were undertaken in the development of new and innovative therapeutic interventions that target the molecular basis responsible for tumor growth and tumor progression. Scientific research brought to the forefront the epidermal growth factor receptor (EGFR), a receptor believed to be in part responsible for tumor survival. Inhibiting this receptor therefore helps to prevent tumor progression. Understanding of this molecular pathway gave rise to agents such as erlotinib (Tarceva TM ) and cetuximab (Erbitux TM ) that have gone beyond cytotoxic chemotherapy and provided better tolerated targeted therapy. Clinical evidence showed benefits in increasing survival in selected patients when used as monotherapy and as maintenance treatment in the case of erlotinib (Tarceva). Ongoing clinical trials are investigating the benefit of adding targeted therapy (cetuximab) in the localized and metastatic setting. Research into targeted treatment has helped to develop additional treatment modalities as well. Tumor angiogenesis is a process of proliferation and migration of endothelial cells to form new blood vessels, thus nourishing the tumor and giving it access for metastasis. This process is regulated primarily by vascular endothelial growth factor (VEGF). Use of anti-vegf targeted therapy with bevacizumab (Avastin TM ) in combination with chemotherapy has prolonged survival and decreased disease progression. Increased emphasis on the biology of the disease and integrating clinical characteristics provides insight into therapeutic decisions which provide the greatest benefit and least possible side effects to our patients. More specifically, we have learned that specific histological tumor types such as adenocarcinoma respond more beneficially to a recently developed agent pemetrexed (Alimta TM ). In combination with another chemotherapeutic agent, pemetrexed has helped maximize the benefits of therapy in our patients with minimal side effects. Lung cancer has been and continues to be the subject of intense study. The Northern Indiana Cancer Research Consortium (NICRC) will continue to provide our community the opportunity to participate in clinical trials to further improve the cure rate in localized disease and improve survival in the metastatic setting. The latest advances in molecular studies have enabled us to further characterize the biology of this disease. We are no longer limited by the old standards of therapy. The advent of targeted agents, as monotherapy or in combination with other treatments, has added another dimension to the treatment of lung cancer, and allowed us to tailor therapy specifically to the individual. Mohamed Farhat, M.D. is board certified in Hematology and Oncology and is a medical oncologist with Michiana Hematology Oncology in South Bend. 10

11 Massage Therapy and Lung Cancer By Jeff Nixa, J.D., M.Div., CMT Particularly in the field of cancer treatment, our best care and state-of-the-art treatments can still leave patients feeling a bit lost, isolated and worn out. Until he received the wholeperson care of a skilled massage, I felt like I was just the carrier for the disease, said one patient. Massage quickly helps our patients transform the collateral symptoms of treatment into physical, emotional and spiritual balance. Surveys of Memorial cancer patients show that massage therapy immediately reduces physical pain on average by 58 percent; reduces muscle tension by 67 percent and nausea by more than 50 percent. Similarly, massage reduces the psychological complaints of stress, anxiety and depression immediately and by more than 50 percent. But perhaps, most importantly for outcomes and well-being, our patients state that after a massage they feel more at peace, happier and more hopeful. As the growing field of mind-body medicine has shown, such spiritual factors as hope/hopefulness play a very large role in the successful treatment of cancer. If a medication were available that treated physical, psychological and spiritual symptoms as quickly and inexpensively as massage, with no side effects, it would be a standard of care and one of the most popular pharmaceuticals on the market. Here at Memorial s Regional Cancer Center, our patients look forward to the pleasant, chemical-free touch of massage and the immediate relief it brings for the symptoms they suffer. Our staff of massage therapists are all nationally certified professionals with years of experience in health care, private practice and the broader community. Jeff Nixa, J.D., M.Div. CMT is a nationally certified massage therapist who has worked in health care and private practice for more than 20 years. 11

12 615 N. Michigan St. South Bend, Indiana 46601