# Radiation Oncology/Kaposi's sarcoma

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## 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) :
| 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 - 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.)
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 viscera |
| Immune System (I) | CD4 count ≥ 200 / µL | CD4 count < 200 |
| Systemic 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 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 — "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 — "Kaposi's sarcoma." Antman K et al. N Engl J Med. 2000 Apr 6;342(14):1027-38.