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 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)Stage CD4 count (per µL) Tumor Risk Group Median Survival (months) I ≥ 150 (I0) Good (T0): KS confined to skin, lymph nodes, or flat palate lesions; no tumor-associated edema or visceral KS NR II ≥ 150 (I0) Poor (T1): Visceral KS, nodular oral disease, or tumor-associated edema 35 III < 150 (I1) Any 13 Revised ACTG Staging System; 1997 - 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.) +ACTG Staging (1989) Good Risk (All of the following) Poor Risk (Any of the following)Tumor (T) Confined to skin and/or lymph nodes and/or minimal oral disease (non-nodular, confined to palate) Tumor-associated edema or ulceration Extensive oral KS KS of GI tract KS in other non-nodal visceraImmune System (I) CD4 count ≥ 200 / µL CD4 count < 200Systemic Illness (S) No history of opportunistic infection or thrush "B" symptoms absent (include unexplained fever, night sweats, >10% weight loss, or diarrhea persisting > 2 weeks) KPS ≥ 70 History of opportunistic infection and/or thrush "B" symptoms present KPS < 70 Other HIV-related illness (e.g., neurologic disease, lymphoma) AIDS Clinical Trials Group (ACTG); 1989 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 16394668 "Kaposi's sarcoma--radiotherapeutic aspects" (full text at Google books) 7516086 "Radiotherapy in the management of epidemic Kaposi's sarcoma of the oral cavity, the eyelid and the genitals." 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 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 8262827 — "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 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.) 10749966, 2000 — "Kaposi's sarcoma." Antman K et al. N Engl J Med. 2000 Apr 6;342(14):1027-38.