S OUTHEAST CANCER C ENTER. Annual Cancer Report 2011

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1 S OUTHEAST CANCER C ENTER Annual Cancer Report 2011

2 Annual Cancer Report 2011 Management of Limited Stage Small Cell Carcinoma of the Lung Medical Director Dr. Steve Stokes ( left), and Dr. Jarrod Adkison lead SAMC s Southeast Cancer Center. Adapted from the National Comprehensive Care Network (NCCN) Guidelines Lung cancer is the most common cancer worldwide and accounts for the most cancer-related deaths. Over 222,000 cases of lung cancer were diagnosed (the second most diagnosed cancer) in the USA in 2010, causing an estimated 157,000 deaths, making it the number one killer of Americans in terms of cancer-related deaths, responsible for 28% of all cancer-related deaths each year (about 160,000 per year, more than all of breast, colorectal, and prostate cancers combined). Small cell lung cancers (SCLC, oat cell cancer ) account for approximately 15% of all lung cancer cases. It is estimated that 33,000 new cases of SCLC will occur in the United States. Nearly all cases of SCLC are attributable to cigarette smoking. Although the incidence of SCLC has been decreasing with the reduction in smoking rates, the incidence in women is increasing (the male-to-female incidence ratio is now 1:1.2). SCLC is a malignant epithelial tumor consisting of small cells with scant cytoplasm, ill-defined cell borders, finely granular nuclear chromatin, absent or inconspicuous nucleoli, and a high mitotic count. The cells are round, oval, or spindle shaped, and nuclear molding is prominent. Dense neurosecretory granules contain neuroendocrine hormones such as adrenocorticotropic hormone (ACTH) and vasopressin. Up to 30% of autopsies in patients with SCLC reveal areas of non-small cell carcinoma differentiation; this finding is more commonly detected in specimens from previously treated patients and suggests that pulmonary carcinogenesis occurs in a pluripotent stem cell capable of differentiation along divergent pathways. Most SCLC stain positively for markers of neuroendocrine differentiation, including chromogranin A, neuron-specific enolase, neural cell adhesion molecule (NCAM; CD56), and synaptophysin. However, these markers alone cannot be used to distinguish SCLC from non-small cell lung carcinoma (NSCLC), because approximately 10% of NSCLC cancers will be immunoreactive for at least one of these neuroendocrine markers. SCLC typically presents as a large hilar mass and bulky mediastinal lymphadenopathy that cause cough and dyspnea. Frequently patients present with symptoms of widespread metastatic disease, such as weight loss, debility, bone pain, and neurologic compromise. It is uncommon for patients to present with a solitary peripheral nodule without central adenopathy; in this situation fine-needle aspiration (FNA) may not adequately differentiate small cell carcinoma from low-grade (typical carcinoid), intermediate-grade (atypical carcinoid), or high-grade (large-cell) neuroendocrine carcinoma. Many neurologic and endocrine paraneoplastic syndromes are associated with SCLC. Patients with the Lambert-Eaton syndrome present with progressive muscular weakness (similar to myasthenia gravis, but starting with the proximal leg muscles) that is caused by antibodies directed against the voltage-gated calcium channels. Paraneoplastic encephalomyelitis and sensory neuropathy are caused by the production of an antibody (anti-hu) that cross reacts with both small cell carcinoma antigens and human neuronal RNA-binding proteins resulting in multiple neurologic deficits. SCLC cells also can produce numerous polypeptide hormones, including adrenocorticotropic hormone (ACTH) which cause Cushing s syndrome (e.g., central obesity, including moon face and buffalo hump, thin skin, hirsutism, striated skin), and vasopressin (ADH) causing hyponatremia of malignancy. When compared with NSCLC, SCLC generally 2

3 Annual Cancer Report 2011 has a more rapid doubling time, a higher growth fraction, and earlier development of widespread metastases. SCLC is highly sensitive to initial chemotherapy and radiotherapy; however, most patients eventually die from recurrent disease Although the TNM staging system is applicable to SCLC, the Veteran s Administration Lung Group 2-stage classification scheme has been routinely used to define the extent of disease in patients with SCLC. Only about one-third of patients present with limited disease confined to the chest (defined as disease confined to the ipsilateral hemithorax, which can be safely encompassed within a tolerable radiation field). Contralateral mediastinal and ipsilateral supraclavicular lymphadenopathy are generally classified as limited-stage disease, while the classification of contralateral hilar and supraclavicular lymphadenopathy is more controversial. The remaining two-thirds of patients present with extensive-stage disease (defined as disease beyond the ipsilateral hemithorax, which may include malignant pleural or pericardial effusion or hematogenous metastases). Staging should not be focused only to sites of symptomatic disease or sites suggested by laboratory tests. Bone scans are positive in up to 30% of patients without bone pain or an abnormal alkaline phosphatase level. A brain MRI or CT scan can identify central nervous system (CNS) metastases in 10% to 15% of patients at diagnosis, of which about 30% are asymptomatic. Bone marrow involvement is present in 15-30% of patients, but is a solitary site of extensive stage disease in only 2-5% of cases, so bone marrow biopsy is not routinely obtained. Due to the aggressive nature of SCLC, staging should not delay the onset of treatment more than one week; otherwise, many patients may become more seriously ill in the interval with a significant decline in their performance status. Median survival without treatment of SCLC is typically 2 to 4 months, compared to months (5-year survival of 20%) with limited stage disease, and 6-12 months (with few long-term survivors) for extensive stage disease. For patients present with T1 2 N0 M0 (stage I) SCLC (<5% in total incidences), complete surgical resection with a lobectomy and mediastinal nodal dissection may be considered, based on promising outcomes from numerous surgical series. However, proper staging with mediastinoscopy or endobronchial ultrasound (EBUS) must rule out mediastinal nodal involvement. Postoperative chemotherapy must be considered even if surgical pathology demonstrates no mediastinal nodal involvement. In patients with pathologic mediastinal nodal involvement adjuvant chemotherapy and radiotherapy should be considered. For patients with more advanced non-metastatic diseases (95% of limited stage cases) definitive chemoradiation with cisplatin etoposide is standard of care. In clinical practice carboplatin is frequently substituted for cisplatin in order to reduce the risk of emesis, neuropathy, and nephropathy; however, the use of carboplatin carries a greater risk of myelosuppression. The substitution of carboplatin for cisplatin in patients with limited-stage disease has not been adequately evaluated and should only be done when cisplatin is contraindicated or poorly tolerated. Thirteen randomized studies, included 2,140 patients, have investigated the role of thoracic radiotherapy in limited-stage SCLC. Two meta-analyses 1, 2 of these trials that included more than 2,000 patients show that thoracic radiation for limited-stage disease yields a 25% to 30% reduction in local failure and a corresponding 5% to 7% improvement in 2-year survival when compared with chemotherapy alone. Numerous trials and metaanalyses3,4,5 have demonstrated that early utilization of radiation is better than delayed treatment These benefits of combined chemotherapy and radiation therapy do come with an increased risk of esophagitis, pulmonary toxicity, and hematologic toxicity. The optimal radiotherapy schedule is unknown and is being investigated in cooperative clinical trials. Intracranial metastases occur in more than 50% of patients with SCLC. Due to this high rate of developing brain metastases, and their unsatisfactory long-term control with whole brain radiation therapy once there are clinically apparent, prophylactic cranial irradiation (PCI) was first proposed in A meta-analysis of all randomized PCI trials reported a 25% decrease in the 3-year incidence of brain metastases from 58.6% in the control group to 33.3% in the PCI treated group.6 It appears that PCI prevents and does not simply delay the emergence of brain metastases. This meta-analysis also reported a 5.4% increase in 3-year survival in patients treated with PCI from 15.3% in the control group to 20.7% in the PCI group. A recent retrospective study7 of patients with limited-stage disease also found that PCI increased survival at 2, 5, and 10 years when compared to those who did not receive PCI. A randomized trial from the EORTC assessed PCI versus no PCI in 286 patients with extensive-stage SCLC who had responded to initial chemotherapy. PCI decreased symptomatic brain metastases (14.6% versus 40.4%) and increased the 1-year survival rate (27.1% versus 13.3%) when compared to controls.8 Thus for patients with either limited-stage or extensive-stage disease who attain a complete or partial response to their initial treatment, and who are without clinical evidence of brain metastases on re-staging evaluation, PCI is recommended (NCCN category 1 recommendation, i.e., there is uniform NCCN consensus that the intervention is appropriate). Late neurologic sequelae have been attributed to PCI, particularly in studies using fractions greater than 3 Gy and/or administering PCI concurrent with chemotherapy. Data from randomized PCI trials is not well reported, but the neurotoxicity appears comparable with or without PCI. Ongoing RTOG and EORTC trials will hopefully provide more definitive information about potential neurotoxicity of PCI. 3

4 Annual Cancer Report When given after the completion of chemotherapy and at a low dose per fraction, PCI may cause less neurological toxicity. 25 Gy in 10 fractions is now considered to be standard dosing, based on a randomized trial9 demonstrating no benefit to higher doses. Fatigue, headache, and nausea/vomiting are the most common acute toxic effects after PCI. PCI is not recommended for patients with poor performance status or impaired mental function, or for those patients with NSCLC. For patients with extensive-stage disease, chemotherapy alone is the primary treatment, but for patients with localized symptomatic sites of disease (e.g., painful bony lesions, obstructive atelectasis, or brain metastases), radiotherapy can provide excellent palliation. Smoking cessation should be strongly promoted for those diagnosed with SCLC (as for all patients). Patients who continue to smoke have increased toxicity during treatment and a shorter survival. From 2003 through 2009, 61 patients with limited stage SCLC were treated at the Southeast Alabama Medical Center. Prophylactic cranial irradiation was typically offered following a complete or near-complete response to chemotherapy and thoracic radiation therapy. The most commonly used regimens were 30.6 Gy in 17 fractions and 32.4 Gy in 18 fractions. The comparison of the overall survival of those patients treated with PCI versus those not receiving such treatment (see Figure 1) is Figure 1 RATE LIMITED STAGE SMALL CELL LUNG SURVIVAL MONTHS With PCI Without PCI limited by the retrospective nature of this data, and the inherent patient selection and other biases. Cancer Committee Report The Southeast Alabama Medical Center Cancer Program is accredited by the American College of Surgeons (ACOS) Commission on Cancer, designated as a Community Hospital Comprehensive Program (COMP) and is under the leadership of the Cancer Committee. The Cancer Committee at Southeast Alabama Medical Center is a standing committee meeting quarterly. The Committee is comprised of physicians of varied disciplines, as well as other ancillary departments involved in the treatment and care of cancer patients. Goals are set annually to monitor and improve cancer patient care. Some of the goals set by the Committee are: Participate in Clinical Trials: As a COMP the goal of the Cancer Committee is to ensure that patients are provided information about the availability of cancer-related clinical trials and that two percent of the total analytic caseload is enrolled into clinical trials. To help meet this goal, a full time Clinical Trials and Research Nurse has been hired. The Clinical Trials and Research Nurse will work closely with all hospital departments and physician offices to help reach this goal. Offer Rehab: Southeast Alabama Medical Center offers physical, occupational and speech therapy. This includes 3 lymphedema specialists. Increase cancer awareness and community outreach: The Cancer Committee keeps abreast and assists in programs to educate the community about cancer with emphasis on cancer prevention, early detection and screening. Programs offered to the community in partnership with the ACS are I Can Cope, Look Good-Feel Better, Reach to Recovery, Smoking Cessation and cancer support groups. Various health fairs sponsored by the Medical Center are offered throughout the year at different locations. These functions offer free screening such as Prostatic Specific Antigen (PSA) test for prostate cancer. This year our mobile unit performed a total of 1066 mammograms, number of abnormal mammograms were 63, number of biopsies done were 7 and number that were positive for cancer was 4.

5 Annual Cancer Report 2011 Provide patient and family support: A multi-disciplinary team approach is available to cancer patients at the Medical Center. Patients have access to support services either in-house or by referral through discharge planning to include: counseling, hospice, rehabilitation services, support groups, nutritional care, pastoral services, patient education and pain management. Quality Patient Care: Quality improvement issues regarding compliance with the American College of Surgeons Commission on Cancer standards are discussed regularly and treatment standards are kept current, maintaining high standard of care for cancer patients in this area. Cancer Registry data is utilized in reviewing quality of care and performance improvement studies. A study on Limited Stage small cell carcinoma of the lung is presented in this report. Provide multidisciplinary approach to the management of cancer care: Tumor Conferences provide patients with consultative, diagnostic, and treatment planning by a team of highly trained and experienced physicians of different specialties and by allied healthcare professionals. One hour of continuing education is granted for each conference. Physicians can contact the Cancer Conference Coordinator at extension 4446 or 3710 to schedule a case for presentation. Prevention and Early Detection: To improve screening in this area the Southeast Regional Health Screening Program was established to provide underserved residents in the area an opportunity to receive screenings. Services include screening digital mammograms, fecal occult blood testing, PSA (prostate specific antigen) tests, as well as vascular testing which includes: cholesterol, glucose, BMI, blood pressure, height, weight, and a written assessment. The 40-foot mobile unit travels to senior citizen centers, industries, churches, health fairs and other community events. The Southeast Regional Health Screening Program continues to work on diminishing the no show rate for health screenings. We are currently pursuing an automated service that will contact our patients to remind them of their appointments. We are working with each screening site to ensure that we have a working phone number as a point of contact. by the American Cancer Society). Lung and prostate cases were second and third respectively, Colorectal remains the fourth site in incidence for Southeast Alabama Medical Center. The geographic distribution of patients treated during 2010 showed that 23.9% were from Georgia and Florida (see Figure 4). Over half of patients treated in 2010 were between the ages of 60 and 79. Figure 2 shows that patients under the age of 50 totaled 92. The focus of the Registry is to provide quality information to the National Cancer Database, Alabama Statewide Cancer Registry and to healthcare professionals, physicians, and hospital administration. Registry data is also utilized on a local level in patient care and performance improvement studies such as the recent study on Management of Limited Stage small cell lung cancer documented in this report. Lifetime follow-up is provided on all analytic cases since the re-established reference date of The Registry currently maintains a 99.50% follow-up rate, exceeding the American College of Surgeons standard of 90%. DISTRIBUTION BY AGE AT DIAGNOSIS (2010 CASES) Figure 2 AGE % (233) AGE % (117) OTHER 5.1% (53) AGE % (92) AGE % (222) AGE % (328) Cancer Registry Activity and 2010 Data Analysis The goal of the Cancer Registry is to ensure accurate and timely collection of cancer data on patients diagnosed and /or treated at Southeast Alabama Medical Center. The Registry began collecting data in A total of 1,190 cases were added to the database in 2010, which included 551 males and 494 females with 1,045 of these newly diagnosed or analytic cases. The top primary site treated in 2010 was breast cancer which consisted of 19.8% of total cases (see Figure 3). This was higher than state and national estimates (2010 Cancer Facts and Figures published References 1 Pignon JP, Arriagada R, Ihde DC et al. (1992) A meta-analysis of thoracic radiotherapyfor small-cell lung cancer. N Engl J Med 327: Warde P, Payne D (1992) Does thoracic irradiation improve survival and local control in limited-stage small-cell carcinoma of the lung? A meta-analysis. J Clin Oncol 10: Murray N, Coy P, Pater JL et al. (1993) Importance of timing for thoracic irradiation in the combined modality treatment of limited-stage small-cell lung cancer. The National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol 11: Jeremic B, Shibamoto Y, Acimovic L et al. (1997) Initial versus delayed accelerated hyperfractionated radiation therapy and concurrent chemotherapy in limited small-cell lung cancer: a randomized study. J Clin Oncol 15: Fried DB, Morris DE, Poole C et al. (2004) Systemic review evaluating the timing of thoracic radiation therapy in combined modality therapy for limited-stage small-cell lung cancer. J Clin Oncol 22: Auperin A, Arriagada R, Pignon JP et al. (1999) Prophylactic Cranial irradiation for patients with small-cell lung cancer in complete remission. Prophylactic Cranial Irradiation Overview Collaborative Group. N Eng J Med 341: Patel S, Macdonald OK, Suntharalingam M. (2009) Evaluation of the use of prophylactic cranial irradiation in small cell lung cancer. Cancer 115: Slotman B, Faivre-Finn C, Kramer G et al. (2007) Prophylactic cranial irradiation in extensive small-cell lung cancer. N Engl J Med 16: Le Pechoux C, Dunant A, Senan S et al. (2009) Standard-dose versus higher-dose prophylactic cranial irradiation (PCI) in patients with limited-stage small-cell lung cancer in complete remission after chemotherapy and thoracic radiotherapy (PCI 99-01, EORTC , RTOG 0212, and IFCT 99-01): a randomized clinical trial. Lancet Oncol 10:

6 2010 TOP SITES TREATED A comparison by SAMC, State, and National estimates 19.8% 14.6% 13.7% 17.0% 17.6% 14.5% 16.8% 13.6% 14.2% 9.3% 9.7% 9.3% 4.1% 5.1% 1.3% Breast Lung Prostate Colorectal Melanoma Figure 3 SAMC % State % National % 2010 CASES BY COUNTY DISTRIBUTION County at Diagnosis Report AL Barbour 6.4% (67) AL Coffee 8.7% (90) AL Dale 9.8% (102) GA Outside state/county code unknown 6.8% (71) Other 7.4% (77) AL Geneva 5.7% (59) AL Henry 5.9% (61) FL Outside state/county code unknown 17.1% (178) AL Houston 32.1% (334) 6 Figure 4

7 PRIMARY SITE TABLE, 2010 MALE FEMALE TOTAL ALL SITES COMBINED 551 (52.7%) 494 (47.3%) 1,045 ORAL CAVITY/PHARYNX Tongue Salivary Glands Gum and other mouth Nasopharynx Tonsil Oropharynx Hypopharynx Other Oral Cavity & Pharynx DIGESTIVE SYSTEM Esophagus Stomach Small intestine Colon Rectosigmoid Rectum Anus/Anal Canal Liver/Intrahepatic Bile Duct Gallbaldder Pancreas Retroperitoneum peritoneum, omentum & mesenter RESPIRATORY SYSTEM Larynx Nasal Cavity Bronchus/lung SOFT TISSUE SKIN * BREAST GENITOURINARY Cervix Uteri** Corpus Uteri Ovary Vulva Prostate Testis Penis Bladder Kidney/Renal Pelvis Ureter BRAIN/CNS*** ENDOCRINE SYSTEM LYMPHOMA MYELOMA LEUKEMIA MESOTHELIOMA KAPOSI SARCOMA MISCELLANEOUS * Excludes basal and squamous cell carcinoma ** Excludes carcinoma in-situ of cervix *** Includes benign tumors 7

8 Southeast alabama Medical Center is a 420 bed regional referral center for the Southeast. With a medical staff of 300, 2,600 employees, and 200 volunteers, virtually every facet of medical care is available. The Southeast Cancer Center is an integral part of total patient care at SAMC. The Cancer Center provides a full spectrum of cancer care to a total service population of over 785,000, including all or part of 13 counties in southeast Alabama, six counties in the Florida panhandle and seven counties in southwest Georgia. For more information please call: Southeast Alabama Medical Center Medical Call Center or Visit us online at