Part A: Module A2 Session 11

1. Diagnosis and Management of HIV-Related Cancers Part A: Module A2 Session 11

2. Objectives • Understand the pathology of Kaposi’s sarcoma • Explain the clinical features, management, treatment and options for KS • Describe the clinical features, management and treatment of NHL and CNS lymphoma • Discuss in-country diagnosis, management and treatment of HIV-related cancers

3. Kaposi’s Sarcoma (KS) • Introduction/pathology • Clinical Features • Management and Treatment • Treatment Options

4. Introduction/Pathology • KS is a spindle-shaped cell tumor thought to be caused by human herpes virus-8 (HHV-8) • May occur at any time regardless of the CD4 cell count, but becomes more common and aggressive as CD4 count drops occur almost equally among men and women • Peak age is from 15-45 years---like that of HIV infection • Is often disseminated and involves many organs of the body—skin, lymph nodes, mouth, lungs, brain, gastrointestinal system, liver and spleen • Usually responds poorly to anti-cancer treatments because of underlying immunosuppression

5. KS: Clinical Features • Painless, non-itching skin lesions which may be macular, papular, nodular or plaque-like • Oral lesions may occur first and are usually present when there are KS lesions elsewhere • Generalized or localized swelling of the face, genital area, or one or more of the lower and upper limbs due to lymphatic infiltration causing lymphedema • Generalized lymphadenopathy due to adenopathic KS • Localized lesions (i.e., eye, foot or hand) • Occasionally a patient may present with abdominal pain, GI bleeding, and distension due to visceral KS which may lead to abdominal obstruction

6. KS: Clinical Features, continued • Cerebral KS may present as a space-occupying lesion, which is difficult to differentiate from other possible causes • Disseminated pulmonary KS presents with progressive shortness of breath and persistent cough with frothy or blood-stained sputum. In some patients, nodular lesions may be present on chest x-ray,and bloody or blood-stained pleural effusion • Diagnosis is confirmed by punch biopsy of a cutaneous lesion • Biopsy of oral lesions may be complicated by excessive bleeding and should be done by an oral surgeon if necessary

7. Management and Treatment

8. KS: Standard Treatment-- Chemotherapy or Radiotherapy • For treatment of systemic KS, alpha interferon alone has been used in patients with severe immunodepression • For rapidly progressive and/or disseminated mucocutaneous disease, or when the tumor compromises the function of vital organs, chemotherapy may effect rapid tumor regression and be life-saving • Among the drugs reported to be effective: liposomal daunorubicin; adriamycin, bleomycin + either vincristine or vinblastine; vincristine/vinblastine; bleomycin/vinca alkaloids • Before considering referral of a patient with KS, the benefits and disadvantages should be weighed and discussed with the patient and caring family

9. KS: Indications for Treatment • Numerous, unattractive, painful, or ulcerating lesions • Bulky lesions of the mouth or tongue which interfere with feeding • Large eye lesions which interfere with vision • Life threatening complications like disseminated pulmonary KS associated with severe shortness of breath, massive oral lesions which interfere with feeding, and GI visceral lesions that obstruct internal functions

10. KS: Indications for Treatment, continued • Severe swelling due to lymphatic obstruction affecting the face, genital organs and limbs • Occasionally patients may request treatment for cosmetic reasons. They should be properly counseled on the available treatment options and their advantages and disadvantages. • Treatment of Kaposi’s and other cancers with chemotherapy has an impact on the immune system. If the patient has only one or two KS lesions, it might be better to postpone chemotherapy because of the potential negative impact

11. KS: Treatment Options • Surgical excision: For isolated lesions or nodules; recurrence may be a problem • Radiation: Effective for localized lesions Most effective for relief of bleeding (80%) and least effective for relief of edema (<30%) Side effects range from mild erythema to moist desquamation of the skin and blistering, painful mucosal reactions in oral lesions Response progressive over few weeks;complete remission (70% cases), but usually temporary; If recurring, further treatment can be given

12. KS: Treatment Options, continued • Chemotherapy: Intralesional cytotoxic chemotherapy can be used for some lesions.Systemic chemotherapy is more often used for widespread KS Good results are obtained with combination therapy even in reduced doses Drugs tend to depress bone marrow and cause pancytopenia so they are best given with a near normal white cell count Neutropenia is a common complication of HIV disease, meaning that many HIV patients cannot be put on chemotherapy Visceral KS responds poorly to chemotherapy

13. Non-Hodgkin’s Lymphoma • Clinical Features • Management and Treatment

14. Clinical Features • Systemic symptoms include fever, night sweats, and unexplained weight loss • Clinical features include lymphadenopathy, splenomegaly, pancytopenia, bowel obstruction, ascites, cranial nerve lesions, spinal cord suppression, and nerve root lesions plus cutaneous, testicular, and lung mass lesions

15. Management and Treatment • Various chemotherapy protocols (as used in seronegative patients) given in several courses over a number of months • Prognosis is often poor, particularly with a CD4 cell count <100/l

16. Central Nervous System Lymphoma • Clinical Features • Management and Treatment

17. CNS Lymphoma: Clinical Features • Occurs at total CD4 counts well under 100 cells and is a typical end-stage complication • Definitive diagnosis is made by brain biopsy or CSF cytology in the presence of a space-occupying lesion (s) on CT or MRI scan • Because brain biopsy may be difficult to obtain, patients who fail a trial therapy for toxoplasmosis are often assumed to have CNS lymphoma

18. Management and Treatment • There is no effective cytotoxic chemotherapy and irradiation is considered palliative • Survival after diagnosis is usually limited to a few months