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Solid Tumors

I. Incidence and Mortality Data

A. Mortality rates

1. Lung is the highest (recent rise in women) followed by breast and colorectal

2. Gastric and uterine (cervix) are falling

3. Mortality decreasing in those under 55 and increasing in those 65 and older

II. Lung Cancer

A. Cell Types and Characteristics

 

Location Hormone Production Relationship to Smoking Miscellaneous
Epidermoid

squamous).

central PTH-Iike +++ often cavitates
Small cell (ost cell) central ACTH, ADH, carcinoid

 

+++ metastatic at times of diagnosis Eaton-Lambert Syndrome
adenocarcinoma peripheral ?HGH ++
May arise in scars:

acanthosis

nigricans:

osteoarthropathy

large cell central HCG ++ 4-gynecomastia


B. Treatment of non-small cell lung cancer

1. Surgery is treatment of choice for States I and II disease (primary tumor with or without involvement of bronchial and/or hilar nodes)

2. Contraindications to surgical resection

a. Co-morbid medical disease

b. Small cell (oat cell) pathology

c. Extrathoracic metastases

d. ? superior sulcus (Pancoast) syndrome

e. Paralyzed vocal cord (ie, laryngeal nerve palsy)

f. Malignant pleural effusion

g. Spread to carina, mediastinum, contralateral lung or nodes

3. Stage Ill disease -mediastinal node involvement (A -- ipsilateral, B = contralateral)

a. Ilia - ? role for initial chemotherapy and/or radiation, then resection.

b. IIIB - unresectable; radiation and/or chemotherapy

4. Stage IV disease - metastatic

a. chemotherapy may be superior to supportive care with respect to both quality of life and cost

C. Small cell (oat cell) carcinoma

1. Usually disseminated at time of diagnosis

2. Complete response may now be achieved in approximately 50% of patients using intensive combination chemotherapy and local radiation therapy; complete response has been associated with an increase in median survival from 3-4 months to 15-20 months with some patients remaining disease-free 24 months after diagnosis

3. ? whether high dose chemotherapy with autologous stem cell support can increase fraction of complete responders who achieve long-term relapse-free survival

D. Approach to the solitary pulmonary nodule

1. Is the nodule new, altered in size, calcified?

2. Is the lesion really solitary? Obtain CT or MRI

3. Pre-biopsy evaluation

a. Cytology, bronchoscopy with brushings

b. Rule out extrapulmonary primary site such as breast, ENT, renal, GI, or gynecologic malignancy with appropriate studies.

4. If studies are negative and the nodule is indeed new and solitary, a biopsy (closed or open) or resection is appropriate

a. Many such lesions are benign or inflammatory

b. Pulmonary adenocarcinomas often present as a solitary nodule-surgery can be curative

c. Never treat with radiation or cytotoxic chemotherapy without tissue confirmation.

III. Colorectal Cancer

A. Anatomic Location

cecum                                                    8.3%

ascending colon and transverse colon      19.2%

descending colon                                    11.4%

rectum                                                   40.7 %

2. More recent experience suggests that rectal tumors are becoming less common and that the disease is becoming more proximal.

B. Presenting symptoms by anatomic location



Rectal bleeding Change in bowel habit Obstruction Anemia
right colon + + 0 - + + +
transverse colon + + + + +
sigmoid colon + + + + + 0 - +
rectum + + + + + + 0- + 0

C. Screening

1. Based on assumption that adenomatous polyps precede development of colon cancer by 5-10 years or more

2. No present screening technique is optimal for sensitivity, specificity and economic feasibility

3. Digital rectal exam and fecal occult blood test (FOBT} is more cost-effective

4. ? role for FOBT and flexible sigmoidoscopy

5. ? role for one-time colonoscopy with immediate removal of polyps if found

6. ? begin at age 50; ? repeat every 5 years

7. Mandatory colonoscopy in high risk patient

8. CEA of no value in screening; newer markers, molecular genetic probes may eventually be important

 

 

Methods for Screening Programs
Screening Program       Frequency of Screening     Method
FOBT     Annual Screening     Rehydrated FOB 

Slides

FS  Baseline Examination; if negative, repeat in 5 yrs 55-cm examination
FS/FOBT        Annual FOBT; FS x 2 over

10 yr

Colonoscopy        One-Time Screening Polypectomy at time of colonoscopy
Barium Enema   Baseline examination; if negative, repeat in 5 yrs    Air Contrast technique

                           Lieberman DA.Gastroenterology 1995; I09:1781-90.




Cost-effectiveness
Test  % deaths prevented Cost/screenee ($) ($) Cost/death prevented
100% Compliance
FOBT

FS alone

FS/FOBT

Colonoscopy

Barium Enema

47

52

66

80 

57

1067

1355

1721

2191

1610 

225,000

258,000

260,000

274,000

280,000

50% Compliance
FOBT

FS alone

FS/FOBT

Colonoscopy

Barium Enema

23

26

33

40

29

783

927

1110

1345 

1027 

331,000

353,000

335,00

337,000

367,000

            Lieberman D A .Gastroenterology 1995:109:1781-90.

D. Treatment

1. Surgery is primary Rx

2. Post-operative therapy

a. Adjuvant chemotherapy with 5-FU and levamisole or leucovorin improves survival in stage C (positive nodes) colon cancer

b. Adjuvant radiation combined with chemotherapy reduces the recurrence rate and prolongs survival in patients with rectal cancer

3. Metastatic disease

a. 5-FU plus leucovorin is treatment of choice

b. CPT-1 I has efficacy as second line therapy

IV. Ovarian Cancer

A. Epidemiology and screening

1. Over 20,000 new cases per year and 2/3 are fatal

2. Only 25% of patients present with localized (Stage I) disease

3. Screening with CA-125, transvaginal ultrasound not of proven benefit; sensitivity of CA-125 appears too low

4. Incidence higher in women with family history of the disease-lifetime risk may be 50% for a woman if 2 or more first-degree relatives have the disease

a. ? role for prophylactic oophorectomy in this setting

B. Prognosis

1. Stage, histologic grade, bulk important

C. Treatment

1. Surgical TAH -I- BSO for State I - 85% cured

2. More advanced stage usually present at diagnosis - 2/3 are Stage Iil (intraperitoneal spread)

a. Surgically debulk to minimal or no residual disease if possible

b. Post-surgical chemotherapy -Taxol + cis-platinum or carboplatin is current treatment of choice

c. Some long-term disease-free survival in Stage Ill patients (10-20%)

V. Testicular Cancer

A. Natural history and evolution

1. Associated with cryptorchism and inguinal hernia

2. Histologic types: seminoma, embryonal cell carcinoma, teratocarcinoma, choriocarcinoma; tumors are often of mixed histology

3. Prognosis based on histologic type, extent of spread, and bulk

4. Alpha fetoprotein (embryonal cell carcinoma, teratocarcinoma) and chorionic gonadotropin (choriocarcinoma, seminoma) may be elevated

5. Staging -tumor markers, abdominal CT scan, ?retroperitoneal node dissection in stage I disease

B. Treatment

1. Primary therapy - inguinal orchiectomy

2. Metastatic disease

a. pure seminoma - usually curable with radiotherapy

b. other histologies - chemotherapy

i. VP-16- bleomycin -platinum combination affords 80 % complete responses

ii. Adriamycin, ifosfamide, actinomycin, also active

iii. some salvage or relapsing patients with intensive chemotherapy and autologous stem cell transplant

VI. Oncologic Emergencies

A. Acute renal failure

1. Setting - obstruction, uric acid nephropathy, drug toxicity (methotrexate, streptozotocin, cis-platinum, mitomycin-C)

2. Obstruction - usually ureteral

a. Common in pelvic and rectal malignancies

b. Diagnose by ultrasonography, cytoscopy with retrograde pyelography

c. Treat with radiation and/or urinary diversion when appropriate

3. Uric acid nephropathy - best therapy is prevention

a. Vigorous hydration, allopurinol, Urine alkalinization

b. Most common in acute leukemia, myeloproliferative syndromes, and non-Hodgkin's lymphoma

c. Treatment-hemodialysis

B. Fever

1. The single most important factor in evaluation the febrile cancer patient (>101 degrees F.) is the number of circulating granulocytes

2.If the granulocyte count is markedly reduced (500/mm3 or less):

a. Obtain blood, urine, and other cultures

b. Remember that an abscess will lack puss or induration in the absence of granulocytes

c. Hospitalize and empirically begin treatment with broad spectrum antibiotics

d. Search for a microbial source but assume the patient to have an infection

3. If the granulocyte count is normal:

a. Evaluate as any other patient in an emergency room setting

b. Remember that many cancer patients:

i. take various drugs and may have a drug-induced fever

ii. may have received blood products and are prone to hepatitis

4. Tumors that are associated with non-infectious fever

a. Lymphoma

b. Hypernephroma

c. Liver metastases

C. Hypercalcemia

1. Setting

a. Osseous metastases

i. breast and lung carcinomas (commonly), prostate and pancreatic carcinomas (occasionally)

ii. accentuated by bedrest

b. Hematologic cancers

i. multiple myeloma, non-Hodgkin's lymphomas

ii. mediated by osteoclast-activating factor (a lymphokine)

c. "Ectopic parathyroid-like" activity

i. renal cell cancer, hepatocellular carcinoma, islet cell tumors, squamous cell carcinomas (lung, head and neck, cervix)

ii. probably mediated by a "transforming growth factor" released by epithelial cells

2. Therapy

a. Hydration, diuretics, calcitonin, mithramycin (25 ug/kg IV), steroids, disphosphonates, gallium nitrate

b. Treat the underlying malignancy

c. Bisphosphonates may provide chronic control of hypercalcemia and may reduce morbidity (pain, fractures) from osseous metastases as well

D. Spinal cord compression

1. Setting - lymphoma, melanoma, breast, prostate, renal, and lung cancers

2. Symptoms - back pain, radicular pain, sensory "level," rectal and urinary incontinence, paresis

3. Diagnosis

a. MRI replaces myelography as the gold standard

b. If question of cerebral mass, head CT scan or MRI should also be performed

4. Treatment

a. Lymphomas - radiation, chemotherapy

b. Carcinomas and sarcomas - radiation therapy +/- decompressive laminectomy

c. No prior diagnosis - decompressive laminectomy with biopsy/resection followed by radiation or chemotherapy as appropriate

E. Superior Vena Cava Syndrome

1. Setting - lymphoma, breast, lung and thymoma

2. Symptoms -nightmares, confusion, headaches, periobital edema, swelling of upper extremities

3. Therapy - steroids, radiation, chemotherapy for lymphomas

a. Avoid unnecessary upper airway instrumentation such as bronchoscopy or mediastinoscopy

 

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