Radiation Oncology/Kaposi's sarcoma


 * See also: Randomized evidence

Background
Named for Moritz Kaposi, a Hungarian dermatologist, who described the condition in 1872. Caused by infection with HHV-8.

Three types:
 * Classic - affects elderly Mediterranean and Eastern European men
 * Typically begins on the hands and feet and spreads centrally over many years
 * Endemic - in parts of Africa
 * Epidemic (AIDS-associated)
 * Immunosuppression-associated (a.k.a. transplantation-associated)

Presentation

 * Classic KS
 * Violaceous macules, progressing to plaques, then to nodules. Ultimate phase is hyperkeratotic or ulcerative.
 * Classic type is slowly progressive
 * A second primary malignancy (usually lyphoproliferative) may develop in up to 1/3 of patients
 * Endemic KS
 * Has 3 forms:
 * Indolent nodular - behaves similarly to classic KS
 * Locally aggressive
 * Disseminated aggressive

Staging
Multiple staging systems exist.


 * I - locally indolent cutaneous lesions
 * II - locally invasive lesions
 * III - disseminated mucocutaneous form with LN involvement
 * IV - disseminated mucocutaneous form with visceral involvement
 * Each stage is further subdivided into A or B according to presence or absence of systemic symptoms (fever, weight loss > 10%), similar to the Ann Arbor staging system for lymphomas


 * 1983 PMID 6861160 -- "Kaposi's sarcoma: a new staging classification." (Krigel RL, Cancer Treat Rep. 1983 Jun;67(6):531-4.)

HIV-Related

 * Revised ACTG Staging System; 1997 - PMID 9294471 -- "AIDS-related Kaposi's sarcoma: prospective validation of the AIDS Clinical Trials Group staging classification. AIDS Clinical Trials Group Oncology Committee." (Krown SE, J Clin Oncol. 1997 Sep;15(9):3085-92.)


 * AIDS Clinical Trials Group (ACTG); 1989 PMID 2671281 -- "Kaposi's sarcoma in the acquired immune deficiency syndrome: a proposal for uniform evaluation, response, and staging criteria. AIDS Clinical Trials Group Oncology Committee." (Krown SE, J Clin Oncol. 1989 Sep;7(9):1201-7.)

Treatment
Classic or Endemic KS:
 * Excision alone for solitary lesions.
 * For few lesions in a single area - extended field RT (8-12 Gy single dose)
 * Use lower dose for oral mucosa in order to prevent severe mucositis: 15 Gy in 10 fractions
 * PMID 16394668 "Kaposi's sarcoma--radiotherapeutic aspects" (full text at Google books)
 * PMID 7516086 "Radiotherapy in the management of epidemic Kaposi's sarcoma of the oral cavity, the eyelid and the genitals."
 * PMID 9488122 "Radiotherapy in the management of epidemic Kaposi's sarcoma: a retrospective study of 643 cases."
 * Total skin electron therapy - 4 Gy weekly x 6-8 weeks
 * For extensive disease: chemotherapy with vinblastine, bleomycin, doxorubicin, or dacarbazine. Oral etoposide.
 * Intralesional interferon alfa-2b

Immunosuppresion-related KS:
 * Regresses with stopping, modifying, or reducing immunosuppression in most pts.

Epidemic (AIDS related):
 * HAART - highly active anti-retroviral therapy
 * Response to chemotherapy and RT is less durable than in classic KS
 * If widespread mucocutaneous or visceral disease, treat with chemo.

Radiotherapy

 * Johannesburg Hospital (South Africa)(2003-2004) -- RT 24/12 vs. 20/5
 * Randomized. 65 sites of epidemic Kaposi sarcoma (histolocially proven, HIV+, mucosal or cutaneous). Arm 1) RT 24/12 vs. Arm 2) RT 20/5. Tumor + 2cm margin, if oral location then entire oral cavity
 * 2008 PMID 18439694 -- "Hypofractionated radiation therapy in the treatment of epidemic Kaposi sarcoma - A prospective randomized trial." (Singh NB, Radiother Oncol. 2008 Apr 23 [Epub ahead of print])
 * Outcome: CR 24/12 37% vs. 20/5 50% (NS), local control (CR/PR/SD) 66% vs. 90% (NS). Mean time-to-response 3 months
 * Toxicity: No difference, but necrosis/ulceration in 3% vs. 17%
 * Conclusion: The two schedules produced equivalent results


 * University of Washington -- RT 8/1 vs. 20/10 vs. 40/20
 * Randomized, 3 arms. 71 cutaneous lesions. Arm 1) RT 8/1 vs Arm 2) 20/10 vs Arm 3) 40/20
 * 1993 PMID 8262827 &mdash; "A randomized prospective trial of radiation therapy for AIDS-associated Kaposi's sarcoma." (Stelzer KJ, Int J Radiat Oncol Biol Phys. 1993 Dec 1;27(5):1057-61.)
 * Outcome: CR 40/20 83% vs. 20/10 79% vs. 8/1 50% (SS). Median time to failure 9.9 months vs. 6.0 months vs. 3.0 months (SS)
 * Conclusion: Higher doses resulted in improved response and control duration

Reviews

 * PMID 18657433, 2008 -- "Update on classic Kaposi sarcoma therapy: new look at an old disease." (Di Lorenzo G, Crit Rev Oncol Hematol. 2008 Dec;68(3):242-9.)
 * PMID 10749966, 2000 &mdash; "Kaposi's sarcoma." Antman K et al. N Engl J Med. 2000 Apr 6;342(14):1027-38.