SO U T H E A S T CA N C ER CEN T ER

Annual Cancer Report 2011

2

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 decreas-

ing with the reduction in smoking rates, the inci-

dence 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 neurosecre-

tory 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 differen-

tiation along divergent pathways.

Most SCLC stain positively for markers of neu-

roendocrine 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 carci-

noma (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 neuro-

logic 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 carci-

noid), 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 progres-

sive 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

Medical Director Dr. Steve Stokes ( left),and Dr. Jarrod Adkisonlead SAMC’s SoutheastCancer Center.

Management of Limited Stage Small Cell Carcinoma of the Lung

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 classifica-

tion 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 posi-

tive 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 16-24 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. Postopera-

tive 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 carbo-

platin 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 substi-

tution 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 meta-

analyses3,4,5 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 metas-

tases, and their unsatisfactory long-term control with whole brain

radiation therapy once there are clinically apparent, prophylactic

cranial irradiation (PCI) was first proposed in 1973.

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 ap-

pears 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 metas-

tases on re-staging evaluation, PCI is recommended (NCCN cat-

egory 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

Annual Cancer Report 2011

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, obstruc-

tive 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

limited by the retrospective nature of this data, and the inherent

patient selection and other biases.

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 Commit-

tee 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 infor-

mation 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 commu-

nity 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.

Annual Cancer Report 2011

Cancer Committee Report

LIMITED STAGE SMALL CELL LUNG SURVIVAL

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24

1

0.9

0.8

0.7

0.6

0.5

0.4

0.3

0.2

0.1

0

MONTHS With PCI Without PCI

RAT

E

Figure 1

4

5

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 stan-

dards 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 consulta-

tive, 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 serv-

ice that will contact our patients to remind them of their appoint-

ments. We are working with each screening site to ensure that we

have a working phone number as a point of contact.

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 1988. 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

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 2002. The Registry currently

maintains a 99.50% follow-up rate, exceeding the American

College of Surgeons standard of 90%.

Figure 2

Annual Cancer Report 2011

DISTRIBUTION BY AGE AT DIAGNOSIS (2010 CASES)

Cancer Registry Activity and 2010 Data Analysis

References

1 Pignon JP, Arriagada R, Ihde DC et al. (1992) Ameta-analysis of thoracic radiotherapyfor small-celllung cancer. N Engl J Med 327:1618–16242 Warde P, Payne D (1992) Does thoracic irradiationimprove survival and local control in limited-stagesmall-cell carcinoma of the lung? A meta-analysis. J Clin Oncol 10:890–8953 Murray N, Coy P, Pater JL et al. (1993) Importanceof timing for thoracic irradiation in the combinedmodality treatment of limited-stage small-cell lungcancer. The National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol 11:336–444 Jeremic B, Shibamoto Y, Acimovic L et al. (1997)Initial versus delayed accelerated hyperfractionatedradiation therapy and concurrent chemotherapy inlimited small-cell lung cancer: a randomized study. J Clin Oncol 15:893–9005 Fried DB, Morris DE, Poole C et al. (2004) Systemicreview evaluating the timing of thoracic radiation

therapy in combined modality therapy for limited-stage small-cell lung cancer. J Clin Oncol22:4837–48456 Auperin A, Arriagada R, Pignon JP et al. (1999)Prophylactic Cranial irradiation for patients withsmall-cell lung cancer in complete remission. Prophylactic Cranial Irradiation Overview Collabora-tive Group. N Eng J Med 341:476–4847 Patel S, Macdonald OK, Suntharalingam M. (2009)Evaluation of the use of prophylactic cranial irradia-tion in small cell lung cancer. Cancer 115:842-8508 Slotman B, Faivre-Finn C, Kramer G et al. (2007)Prophylactic cranial irradiation in extensive small-celllung cancer. N Engl J Med 16:664–672 9 Le Pechoux C, Dunant A, Senan S et al. (2009)Standard-dose versus higher-dose prophylactic cranial irradiation (PCI) in patients with limited-stagesmall-cell lung cancer in complete remission afterchemotherapy and thoracic radiotherapy (PCI 99-01,EORTC 22003- 08004, RTOG 0212, and IFCT 99-01):a randomized clinical trial. Lancet Oncol 10:467–474

AGE 60-6931.4% (328)

AGE 50-5921.2% (222)

AGE 40-498.8% (92)

AGE 80-8911.2% (117)

AGE 70-7922.3% (233)

OTHER5.1% (53)

6

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

SAMC % State % National %

Lung Prostate Colorectal Melanoma

2010 TOP SITES TREATED A comparison by SAMC, State, and National estimates

Figure 3

2010 CASES BY COUNTY DISTRIBUTION County at Diagnosis Report

GA—Outside state/county code unknown6.8% (71)

Other7.4% (77)

AL —Coffee8.7% (90)

AL —Dale9.8% (102)

AL —Geneva5.7% (59)

AL—Barbour6.4% (67)

AL —Henry5.9% (61)

AL —Houston32.1% (334)

FL— Outside state/countycode unknown17.1% (178)

Figure 4

ORAL CAVITY/PHARYNX .......................................23....................................7 ................................30Tongue ..................................................................................8 ............................................2.........................................10Salivary Glands ...................................................................2 ............................................1 ...........................................3Gum and other mouth .....................................................3 ............................................1 ...........................................4Nasopharynx.......................................................................3 ............................................3 ...........................................6Tonsil .....................................................................................4 ............................................0 ...........................................4Oropharynx .........................................................................1 ............................................0 ...........................................1Hypopharynx ......................................................................1 ............................................0 ...........................................1Other Oral Cavity & Pharynx ..........................................1 ............................................0 ...........................................1

DIGESTIVE SYSTEM .............................................112 .................................63 ..............................175Esophagus .........................................................................10 ............................................3.........................................13Stomach ...............................................................................7 ............................................4.........................................11Small intestine....................................................................3 ............................................1 ...........................................4Colon...................................................................................51 ..........................................29.........................................80Rectosigmoid ....................................................................4 ............................................2 ...........................................6Rectum ...............................................................................10 ............................................8.........................................18Anus/Anal Canal ................................................................2 ............................................2 ...........................................4Liver/Intrahepatic Bile Duct ...........................................6 ............................................4.........................................10Gallbaldder ..........................................................................0 ............................................2 ...........................................2Pancreas .............................................................................12 ..........................................11.........................................23Retroperitoneum ...............................................................0 ............................................1 ...........................................1peritoneum, omentum & mesenter .............................0 ............................................1 ...........................................1

RESPIRATORY SYSTEM ........................................121 .................................72 ..............................193Larynx .................................................................................12 ............................................2.........................................14Nasal Cavity .........................................................................0 ............................................2 ...........................................2Bronchus/lung ...............................................................120 ..........................................58 ......................................178

SOFT TISSUE ............................................................3....................................0...................................3SKIN *.....................................................................24 .................................19 ................................43BREAST ....................................................................3 ...............................204 ..............................207GENITOURINARY .................................................217 .................................54 ..............................271

Cervix Uteri** ......................................................................0 ..........................................12.........................................12Corpus Uteri ........................................................................0 ............................................9 ...........................................9Ovary .....................................................................................0 ............................................7 ...........................................7Vulva......................................................................................0 ............................................2 ...........................................2Prostate............................................................................176 ............................................0 ......................................176Testis......................................................................................6 ............................................0 ...........................................6Penis ......................................................................................2 ............................................0 ...........................................2Bladder ...............................................................................26 ..........................................11.........................................37Kidney/Renal Pelvis...........................................................6 ..........................................13.........................................19Ureter ....................................................................................1 ............................................0 ...........................................1

BRAIN/CNS*** .......................................................11 .................................11 ................................22ENDOCRINE SYSTEM ...............................................2....................................9 ................................11LYMPHOMA ...........................................................15 .................................24 ................................39MYELOMA................................................................3....................................4...................................7LEUKEMIA..............................................................10....................................4 ................................14MESOTHELIOMA......................................................0....................................1...................................1KAPOSI SARCOMA...................................................2....................................1...................................3MISCELLANEOUS...................................................15 .................................18 ................................33

* Excludes basal and squamous cell carcinoma** Excludes carcinoma in-situ of cervix

*** Includes benign tumors

7

PRIMARY SITE TABLE, 2010 MALE FEMALE TOTAL

ALL SITES COMBINED 551 (52.7%) 494 (47.3%) 1,045

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 isan integral part of total patient care at SAMC. The Cancer Center provides a full spectrum of cancer care to a totalservice population of over 785,000, including all or part of 13 counties in southeast Alabama, six counties in theFlorida panhandle and seven counties in southwest Georgia.

For more information please call:Southeast Alabama Medical CenterMedical Call Center 334-712-3336 or 1-800-735-4998Visit us online at www.samc.org