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Kaposi Sarcoma Treatment (PDQ®): Treatment - Health Professional Information [NCI]
General Information About Kaposi Sarcoma
Stage Information for Kaposi Sarcoma
Classic Kaposi Sarcoma Treatment
Immunosuppressive Therapy-Related Kaposi Sarcoma Treatment
Epidemic Kaposi Sarcoma Treatment
Recurrent Kaposi Sarcoma Treatment
Changes to This Summary (10 / 01 / 2015)
About This PDQ Summary
This information is produced and provided by the National Cancer Institute (NCI). The information in this topic may have changed since it was written. For the most current information, contact the National Cancer Institute via the Internet web site at http://cancer.gov or call 1-800-4-CANCER.
KS was first described in 1872 by the Hungarian dermatologist, Moritz Kaposi. From that time until the current human immunodeficiency virus (HIV) disease epidemic identified with the Acquired Immunodeficiency Syndrome (AIDS), KS remained a rare tumor. While most of the cases seen in Europe and North America have occurred in elderly men of Italian or Eastern European Jewish ancestry, the neoplasm also occurs in several other distinct populations: young black African adult males, prepubescent children, renal allograft recipients, and other patients receiving immunosuppressive therapy. The disseminated, fulminant form of KS associated with HIV disease is referred to as epidemic KS to distinguish it from the classic, African, and transplant-related varieties of the neoplasm. In addition, KS has been identified in homosexual men apart from the HIV disease epidemic.[1 ]
Although the histopathology of the different types of the Kaposi tumor is essentially identical in all of these groups, the clinical manifestations and course of the disease differ dramatically.[2 ] A key piece to the puzzle of KS pathogenesis was the 1994 discovery of a gamma herpes virus, human herpes virus type 8 (HHV-8), also known as Kaposi sarcoma herpes virus.[3 ] HHV-8 was identified in KS tissue biopsies from virtually all patients with classic, African, transplant-related, and AIDS-associated KS but was absent from noninvolved tissue.[4 ,5 ,6 ,7 ]
Classic Kaposi Sarcoma
Considered a rare disease, classic KS occurs more often in males, with a ratio of approximately 10 to 15 males to 1 female. In North Americans and Europeans, the usual age at onset is between 50 and 70 years. Classic KS tumors usually present with one or more asymptomatic red, purple, or brown patches, plaques, or nodular skin lesions. The disease is often limited to single or multiple lesions usually localized to one or both lower extremities, especially involving the ankles and soles.
Classic KS most commonly runs a relatively benign, indolent course for 10 to 15 years or more, with slow enlargement of the original tumors and the gradual development of additional lesions. Venous stasis and lymphedema of the involved lower extremity are frequent complications. In long-standing cases, systemic lesions can develop along the gastrointestinal tract, in lymph nodes, and in other organs. The visceral lesions are generally asymptomatic and are most often discovered only at autopsy, though clinically, gastrointestinal bleeding can occur. As many as 33% of the patients with classic KS develop a second primary malignancy, which is most often non-Hodgkin lymphoma.[8 ,9 ,10 ]
African Kaposi Sarcoma
In the 1950s, KS was recognized as a relatively common neoplasm endemic in native populations in equatorial Africa and comprised approximately 9% of all cancers seen in Ugandan males. African KS is seen as either an indolent neoplasm identical to the classic disease seen in Europe and North America or as an aggressive disease with fungating and exophytic tumors that may invade the subcutaneous and surrounding tissue including the underlying bone. In Africa, both the indolent and locally more aggressive forms of KS occur with a male-to-female ratio comparable to that observed with the classic KS tumor seen in North America and Europe. In general, however, patients in Africa are significantly younger than their European counterparts. A lymphadenopathic form of KS is also seen in Africa, primarily in prepubescent children (male:female ratio, 3:1). In these cases, the generalized lymphadenopathy is frequently associated with visceral organ involvement. The prognosis is very poor with a 100% fatality rate within 3 years.[11 ,12 ]
Immunosuppressive Treatment-Related Kaposi Sarcoma
In 1969, the first case of KS in association with immunosuppression in a renal transplant patient was described. Since that time, a number of renal and other organ allograft recipients who received prednisone and azathioprine developed KS shortly after the onset of immunosuppressive therapy.[13 ] Estimates of the incidence of KS in immunosuppressed renal transplant recipients are between 150 and 200 times the expected incidence of the tumor in the general population. The average time to develop KS after transplantation is 16 months. Although the KS tumor in iatrogenically immunosuppressed patients often remains localized to the skin, widespread dissemination with mucocutaneous or visceral organ involvement is common. In some cases, the KS tumors have regressed as a result of reduction or changes in immunosuppressive therapy. Clinical management of renal transplant patients who develop KS is difficult and requires a balance between the risk of death from generalized KS and the risk of graft rejection and complications of renal failure that may occur if the immunosuppressive therapy is discontinued.
Epidemic Kaposi Sarcoma
In 1981, a fulminant and disseminated form of KS in young homosexual or bisexual men was first reported as part of an epidemic now known as AIDS.[14 ] The etiology of AIDS is a T-cell lymphotropic retrovirus known as HIV. The underlying immunologic deficiency that characterizes HIV disease is an acquired profound disorder of cell-mediated immune functions. This immunologic deficiency and immune dysregulation predisposes the host to a variety of opportunistic infections and unusual neoplasms, especially KS. HIV may play an indirect role in the development of KS.[15 ]
Approximately 95% of all the cases of epidemic KS in the United States have been diagnosed in homosexual or bisexual men. In the past, approximately 26% of all homosexual males with HIV disease presented with, or eventually developed, KS during the course of their illness. By comparison, fewer than 3% of all heterosexual intravenous drug users with HIV disease developed KS. The proportion of HIV disease patients with KS has steadily decreased since the epidemic was first identified in 1981.[16 ] About 48% of AIDS patients in 1981 had KS as their presenting AIDS diagnosis. By August 1987, the cumulative proportion of AIDS patients with KS had diminished to fewer than 20%. The introduction of combined antiretroviral therapy (cART) has delayed or prevented the emergence of drug-resistant HIV strains, profoundly decreased viral load, led to increased survival, and lessened the risk of opportunistic infections.[17 ,18 ,19 ] The use of cART has been associated with a sustained and substantial decline in KS incidence in multiple large cohorts.[20 ,21 ,22 ,23 ,24 ,25 ]
The lesions that develop may involve the skin; oral mucosa; lymph nodes; and visceral organs, such as the gastrointestinal tract, lung, liver, and spleen. Most patients with HIV disease who present with the mucocutaneous lesions of KS feel healthy and are usually free of systemic symptoms, as compared with HIV patients who first develop an opportunistic infection. The sites of disease at presentation of epidemic KS are much more varied than the sites seen in other types of this neoplasm. In an early report on the clinical manifestations of the disease, 49 patients were described.[26 ] Of these patients, 8% had no skin involvement, 27% had localized or fewer than five skin lesions, and 63% had innumerable skin lesions widely distributed over the skin surface area. Of these patients, 61% had generalized lymphadenopathy at the time of the first examination. Four of these patients, who had generalized lymphadenopathy in the absence of skin lesions or detectable visceral organ involvement at the time of presentation, were found to have biopsy-proven KS localized to the lymph nodes. In 45% of the patients studied, KS lesions were found in one or more sites along the gastrointestinal tract. Of these patients, 29% had either unexplained fever or unexplained weight loss when first seen. While most patients present with skin disease, KS involvement of lymph nodes or the gastrointestinal tract may occasionally precede the appearance of the cutaneous lesions.
Eventually, most patients with epidemic KS develop disseminated disease. The disease often progresses in an orderly fashion from a few localized or widespread mucocutaneous lesions to more numerous lesions and generalized skin disease with lymph node, gastrointestinal tract disease, and other organ involvement. Pleuropulmonary KS is an ominous sign usually occurring late in the course of the disease, especially in those patients whose death is directly attributed to KS.[27 ] Most patients with epidemic KS die of one or more complicating opportunistic infections.
Nonepidemic Gay-Related Kaposi Sarcoma
Several reports documented KS in homosexual men who persistently had no evidence of HIV infection. These patients had an indolent and cutaneous form of the disease, which caused new lesions to appear every few years. Lesions occur most commonly on the extremities and genitalia but can occur anywhere on the skin.[1 ] These cases may indicate the presence of causal factors other than HIV that homosexual men may be exposed to because of their lifestyle.
Friedman-Kien AE, Saltzman BR, Cao YZ, et al.: Kaposi's sarcoma in HIV-negative homosexual men. Lancet 335 (8682): 168-9, 1990.
Safai B: Kaposi's sarcoma and acquired immunodeficiency syndrome. In: DeVita VT, Hellman S, Rosenberg S, eds.: AIDS: Etiology, Diagnosis, Treatment and Prevention. 4th ed. Philadelphia, Pa: Lippincott-Raven Publishers, 1997, pp 295-318.
Chang Y, Cesarman E, Pessin MS, et al.: Identification of herpesvirus-like DNA sequences in AIDS-associated Kaposi's sarcoma. Science 266 (5192): 1865-9, 1994.
Moore PS, Chang Y: Detection of herpesvirus-like DNA sequences in Kaposi's sarcoma in patients with and without HIV infection. N Engl J Med 332 (18): 1181-5, 1995.
Su IJ, Hsu YS, Chang YC, et al.: Herpesvirus-like DNA sequence in Kaposi's sarcoma from AIDS and non-AIDS patients in Taiwan. Lancet 345 (8951): 722-3, 1995.
Gao SJ, Kingsley L, Li M, et al.: KSHV antibodies among Americans, Italians and Ugandans with and without Kaposi's sarcoma. Nat Med 2 (8): 925-8, 1996.
Chang Y, Ziegler J, Wabinga H, et al.: Kaposi's sarcoma-associated herpesvirus and Kaposi's sarcoma in Africa. Uganda Kaposi's Sarcoma Study Group. Arch Intern Med 156 (2): 202-4, 1996.
Safai B, Good RA: Kaposi's sarcoma: a review and recent developments. Clin Bull 10 (2): 62-9, 1980.
Reynolds WA, Winkelmann RK, Soule EH: Kaposi's sarcoma: a clinicopathologic study with particular reference to its relationship to the reticuloendothelial system. Medicine (Baltimore) 44 (5): 419-43, 1965.
Safai B, Miké V, Giraldo G, et al.: Association of Kaposi's sarcoma with second primary malignancies: possible etiopathogenic implications. Cancer 45 (6): 1472-9, 1980.
Taylor JF, Templeton AC, Vogel CL, et al.: Kaposi's sarcoma in Uganda: a clinico-pathological study. Int J Cancer 8 (1): 122-35, 1971.
Templeton AC, Bhana D: Prognosis in Kaposi's sarcoma. J Natl Cancer Inst 55 (6): 1301-4, 1975.
Penn I: Kaposi's sarcoma in organ transplant recipients: report of 20 cases. Transplantation 27 (1): 8-11, 1979.
Kaposi's sarcoma and Pneumocystis pneumonia among homosexual men--New York City and California. MMWR Morb Mortal Wkly Rep 30 (25): 305-8, 1981.
Vogel J, Hinrichs SH, Reynolds RK, et al.: The HIV tat gene induces dermal lesions resembling Kaposi's sarcoma in transgenic mice. Nature 335 (6191): 606-11, 1988.
Selik RM, Starcher ET, Curran JW: Opportunistic diseases reported in AIDS patients: frequencies, associations, and trends. AIDS 1 (3): 175-82, 1987.
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Lodi S, Guiguet M, Costagliola D, et al.: Kaposi sarcoma incidence and survival among HIV-infected homosexual men after HIV seroconversion. J Natl Cancer Inst 102 (11): 784-92, 2010.
Portsmouth S, Stebbing J, Gill J, et al.: A comparison of regimens based on non-nucleoside reverse transcriptase inhibitors or protease inhibitors in preventing Kaposi's sarcoma. AIDS 17 (11): F17-22, 2003.
International Collaboration on HIV and Cancer: Highly active antiretroviral therapy and incidence of cancer in human immunodeficiency virus-infected adults. J Natl Cancer Inst 92 (22): 1823-30, 2000.
Dupont C, Vasseur E, Beauchet A, et al.: Long-term efficacy on Kaposi's sarcoma of highly active antiretroviral therapy in a cohort of HIV-positive patients. CISIH 92. Centre d'information et de soins de l'immunodéficience humaine. AIDS 14 (8): 987-93, 2000.
Tam HK, Zhang ZF, Jacobson LP, et al.: Effect of highly active antiretroviral therapy on survival among HIV-infected men with Kaposi sarcoma or non-Hodgkin lymphoma. Int J Cancer 98 (6): 916-22, 2002.
Carrieri MP, Pradier C, Piselli P, et al.: Reduced incidence of Kaposi's sarcoma and of systemic non-hodgkin's lymphoma in HIV-infected individuals treated with highly active antiretroviral therapy. Int J Cancer 103 (1): 142-4, 2003.
Grabar S, Abraham B, Mahamat A, et al.: Differential impact of combination antiretroviral therapy in preventing Kaposi's sarcoma with and without visceral involvement. J Clin Oncol 24 (21): 3408-14, 2006.
Krigel RL, Laubenstein LJ, Muggia FM: Kaposi's sarcoma: a new staging classification. Cancer Treat Rep 67 (6): 531-4, 1983.
Gill PS, Akil B, Colletti P, et al.: Pulmonary Kaposi's sarcoma: clinical findings and results of therapy. Am J Med 87 (1): 57-61, 1989.
The staging evaluation of patients with classic Kaposi sarcoma (KS) should be individualized. The advanced age of most of the patients, localized nature of the tumor, rarity of visceral involvement, and usually indolent course of the disease should temper the extent of the evaluation. A careful examination of the skin and lymph nodes is sufficient in most cases. For the rare patient with rapidly progressive tumor or signs or symptoms of visceral involvement, appropriate evaluation is indicated. No universally accepted classification is available for epidemic KS. Staging schemes that incorporate laboratory parameters as well as clinical features have been proposed. Since most patients with epidemic KS do not die from the disease, factors besides tumor burden are apparently involved in survival.
The conventions used to stage KS and the methods used to evaluate the benefits of KS treatment continue to evolve because of changes in the treatment of human immunodeficiency virus (HIV) and in recognition of deficiencies in standard tumor assessment. The clinical course of KS, the selection of treatment, and the response to treatment are heavily influenced by the degree of underlying immune dysfunction and opportunistic infections.
The AIDS Clinical Trials Group (ACTG) Oncology Committee has published criteria for the evaluation of epidemic KS.[1 ] The staging system incorporates measures of extent of disease, severity of immunodeficiency, and presence of systemic symptoms. As shown in Table 1 below, the ACTG criteria categorizes the extent of the tumor as localized or disseminated, the CD4 cell number as high or low, and a systemic illness as absent or present.
A subsequent prospective analysis of 294 patients entered on ACTG trials for KS between 1989 and 1995 showed that each of the tumor, immune system, and systemic illness variables was independently associated with survival.[2 ] Multivariate analysis showed that immune system impairment was the most important single predictor of survival. In patients with relatively high CD4 counts, tumor stage was predictive. A CD4 count of 150 cells/mm³ may be a better discriminator than the published cutoff of 200 cells/mm³. A study is in progress to determine if viral load adds predictive information. None of the prior studies were conducted at a time when combined antiretroviral therapy (cART) was readily available. The impact of cART on survival in KS requires continued assessment.
Table 1. AIDS Clinical Trials Group Staging Classification
Good Risk (0)
Poor Risk (1)
(Any of the following) (Any of the following)
Tumor (T) Confined to skin and/or lymph nodes and/or minimal oral diseaseMinimal oral disease is non-nodular KS confined to the palate. Tumor-associated edema or ulceration
Extensive oral KS
Gastrointestinal KS
KS in other non-nodal viscera
Immune system (I) CD4 cells ≥ = 200/µL CD4 cells <200 per cubic mm
Systemic illness (S) No history of OIs or thrushOIs are opportunistic infections. History of OIs and/or thrush
No "B" symptoms "B" symptoms are unexplained fever, night sweats, >10% involuntary weight loss, or diarrhea persisting >2 weeks. "B" symptoms present
Performance status ≥70 (Karnofsky) Performance status <70
Other HIV-related illness (e.g., neurological disease or lymphoma)
Krown SE, Metroka C, Wernz JC: Kaposi's sarcoma in the acquired immune deficiency syndrome: a proposal for uniform evaluation, response, and staging criteria. AIDS Clinical Trials Group Oncology Committee. J Clin Oncol 7 (9): 1201-7, 1989.
Krown SE, Testa MA, Huang J: AIDS-related Kaposi's sarcoma: prospective validation of the AIDS Clinical Trials Group staging classification. AIDS Clinical Trials Group Oncology Committee. J Clin Oncol 15 (9): 3085-92, 1997.
Classic Kaposi sarcoma (KS) usually is limited to the skin and has an indolent course. Patients with this tumor are predisposed to the development of a second primary malignancy, and the treating physician should consider this factor when arranging a schedule of follow-up treatment for the patient.
Equivalent standard treatment options:
Solitary lesions:
Radiation therapy: For solitary lesions or lesions of limited extent, modest doses of radiation applied to the lesions with a limited margin provide excellent control of disease in the treated area. Usually, superficial radiation beams such as electron beams are used. Some authors believe disease recurrence in adjacent, untreated skin is common if only involved-field radiation therapy is used and claim better cure rates when extended-field radiation therapy is used.[1 ,2 ]
Low-voltage (100 kv) photon radiation: 8 Gy to 10 Gy given as a single dose or 15 Gy to 20 Gy given over 1 week because solitary lesions control nearly 100% of local disease, but recurrence in adjacent areas is common.
Electron-beam radiation therapy (EBRT): 4 Gy given once weekly for 6 to 8 consecutive weeks with a 4-MeV to 6-MeV electron beam. Ports should include the entire skin surface 15 cm above the lesion.
Surgical excision may be of benefit in some patients with small superficial lesions, but local recurrence is likely to be a problem. However, over the years, multiple small excisions can be performed to achieve good disease control.
Widespread skin disease:
Radiation therapy: Modest doses are effective in controlling disease. The type of radiation (i.e., photon vs. electron) and fields used must be tailored to suit the distribution of disease in the individual patient.[2 ]
Extended-field EBRT.
For disease limited to areas distal to the knee, subtotal-skin EBRT directed to skin below the umbilicus.
For disease that extends above the knee, total-skin EBRT.
EBRT used in this manner gave long-term results that were superior to those obtained with radiation therapy administered to successive individual lesions as they appeared.[2 ]
EBRT: 4 Gy given once weekly for 6 to 8 consecutive weeks, and subtotal- or total-skin radiation therapy given for extensive disease.
Chemotherapy: Because classic KS is such a rare disease in the United States and is usually treated initially with radiation therapy, few patients have been treated with chemotherapy, and no randomized prospective trials have compared one agent to another. Several authors have used single-agent vinblastine given as a weekly dose of approximately 0.1 mg/kg.[3 ,4 ,5 ,6 ] Almost all of the patients had good to excellent response. In most cases, patients required prolonged courses of therapy, for several years, to maintain a partial response. Doses of vinblastine were titrated in individual patients to maintain a white blood count of more than 3,000 leukocytes. Follow-up after completion of therapy was not presented. In a multicenter trial of 55 patients who were treated over a decade, a 71% overall response rate was seen using pegylated liposomal doxorubicin.[7 ][Level of evidence: 3iiiDiv] In addition to the positive response rates of pegylated liposomal doxorubicin and the vinca alkaloids, response rates showing a greater than 50% decrease in lesions have also been reported in small, uncontrolled series for etoposide, taxanes, gemcitabine, and interferon alfa.[8 ][Level of evidence: 3iiiDiv]
One patient was treated repeatedly with intralesional injections of 0.25 to 0.50 mg of vincristine, which resulted in complete disappearance of the treated lesion.[9 ] Multiple courses of therapy were required because of the recurrence of disease in untreated areas.
Electroporation of the skin lesions was combined with intravenous bleomycin for 19 patients with classical KS. Most patients responded after one application, the rest after two or three applications, with a median duration of response of 16 months.[10 ][Level of evidence: 3iiiDiv]
Lymph node and gastrointestinal tract involvement:
Chemotherapy: Several patients who had widespread skin disease and were treated with chemotherapy also had lymph node and gastrointestinal tract involvement. The disease in these sites also responded to vinblastine. Trials are required to define therapy. One such trial, MSKCC-04055, has been completed.
Local radiation therapy may be added to chemotherapy if individual lesions require urgent therapy.
Current Clinical Trials
Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.
Hamilton CR, Cummings BJ, Harwood AR: Radiotherapy of Kaposi's sarcoma. Int J Radiat Oncol Biol Phys 12 (11): 1931-5, 1986.
Nisce LZ, Safai B, Poussin-Rosillo H: Once weekly total and subtotal skin electron beam therapy for Kaposi's sarcoma. Cancer 47 (4): 640-4, 1981.
Solan AJ, Greenwald ES, Silvay O: Long-term complete remissions of Kaposi's sarcoma with vinblastine therapy. Cancer 47 (4): 637-9, 1981.
Tucker SB, Winkelmann RK: Treatment of Kaposi sarcoma with vinblastine. Arch Dermatol 112 (7): 958-61, 1976.
Scott WP, Voight JA: Kaposi's sarcoma. Management with vincaleucoblastine. Cancer 19 (4): 557-64, 1966.
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Di Lorenzo G, Kreuter A, Di Trolio R, et al.: Activity and safety of pegylated liposomal doxorubicin as first-line therapy in the treatment of non-visceral classic Kaposi's sarcoma: a multicenter study. J Invest Dermatol 128 (6): 1578-80, 2008.
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Odom RB, Goette DK: Treatment of cutaneous Kaposi's sarcoma with intralesional vincristine. Arch Dermatol 114 (11): 1693-4, 1978.
Di Monta G, Caracò C, Benedetto L, et al.: Electrochemotherapy as "new standard of care" treatment for cutaneous Kaposi's sarcoma. Eur J Surg Oncol 40 (1): 61-6, 2014.
Some patients with Kaposi Sarcoma (KS) have noted spontaneous and lasting remissions following discontinuation of immunosuppressive therapy. In managing these patients, if immunosuppressive therapy is not critical, its discontinuation is a reasonable first step.
Standard treatment options:
Discontinue immunosuppressive therapy (often results in tumor regression). This option is critically important in patients who are receiving immunosuppressive drugs, as in the case of certain transplant patients.
Radiation therapy (for disease limited to skin).[1 ,2 ,3 ,4 ]
Chemotherapy (single or multiple drug): Most systemic chemotherapy trials in KS patients have been carried out in the African and epidemic varieties. See the section on the treatment of Epidemic Kaposi Sarcoma. The applicability of the results of these trials to KS in immunosuppressed patients is unknown.
Cohen L: Dose, time, and volume parameters in irradiation therapy of Kaposi's sarcoma. Br J Radiol 35 (415): 485-488, 1962.
Lo TC, Salzman FA, Smedal MI, et al.: Radiotherapy for Kaposi's sarcoma. Cancer 45 (4): 684-7, 1980.
Treatment may result:
In a disappearance or reduction in size of specific skin lesions, thereby alleviating the discomfort associated with the chronic edema and ulcerations that often accompany multiple skin tumors seen on the lower extremities.
In control of symptoms associated with mucosal or visceral lesions.
No data are available, however, to show that treatment improves survival.[1 ] In addition to antitumor treatment, essential components of an optimal Kaposi sarcoma (KS) treatment strategy include combined antiretroviral treatment (cART), prophylaxis for opportunistic infections, and rapid recognition and treatment of intercurrent infections.
Most good-risk patients, defined by the AIDS Clinical Trials Group as T0, show tumor regression with cART alone.[2 ,3 ,4 ] Poor-risk patients, defined as T1, usually require a combination of cART and chemotherapy with discontinuation of the chemotherapy after disappearance of the skin lesion.[2 ,3 ,4 ] The combination of cART and liposomal doxorubicin resulted in a 5-year overall survival (OS) rate of 85% in 140 patients with T1 disease.[3 ][Level of evidence: 3iiiDiv]
Local modalities
Small localized lesions of KS may be treated by electrodesiccation and curettage, cryotherapy, or by surgical excision. KS tumors are also generally very responsive to local radiation therapy, and excellent palliation has been obtained with doses at 20 Gy or slightly higher.[5 ,6 ,7 ] One report demonstrated a response rate higher than 90%, with a median time to progression of 21 months. Although no difference in response was noted with a variety of fractionation regimens, a single fraction of 8 Gy is indicated for cutaneous lesions and is associated with significantly fewer severe reactions.[8 ] Radiation therapy is generally reserved to treat localized areas of the skin and oral cavity. It is less often used to control pulmonary, gastrointestinal tract, or other sites of KS lesions. Localized KS lesions have also been effectively treated with intralesional injections of vinblastine.[9 ] Alitretinoin 0.1% gel provided local control in a randomized prospective multicenter trial.[10 ][Level of evidence: 1iiDiv]
In epidemic KS, the already profoundly depressed immunologic status of the host limits the therapeutic usefulness of systemic chemotherapy. Systemic chemotherapy studies in epidemic KS have used as single agents or in combinations doxorubicin, bleomycin, vinblastine, vincristine, etoposide, paclitaxel, and docetaxel.[11 ,12 ,13 ,14 ,15 ][Level of evidence: 3iiiDiv] The combination of cART and liposomal doxorubicin resulted in a 5-year OS of 85% in 140 patients with T1 disease.[3 ][Level of evidence: 3iiiDiv]
Randomized multicenter trials showed an improvement in response rate (45%-60% vs. 20%-25%) and a more favorable toxic effects profile for pegylated liposomal doxorubicin or liposomal daunorubicin, compared to the combination of doxorubicin, bleomycin, and vincristine or bleomycin and vincristine.[16 ,17 ,18 ][Level of evidence: 1iiDiv] During cART, both pegylated liposomal doxorubicin and paclitaxel are active single agents with response rates close to 50%.[19 ][Level of evidence: 1iiDiv]
Biologic and targeted therapy
The interferon alphas have also been widely studied and show a 40% objective response rate in patients with epidemic KS.[20 ,21 ] In these reports, the responses differed significantly according to the prognostic factors of extent of disease, prior or coexistent opportunistic infections, prior treatment with chemotherapy, CD4 lymphocyte counts lower than 200 cells/mm³, the presence of circulating acid-labile interferon alpha, and an increase in beta-2-microglobulin. Several treatment studies have combined interferon alpha with other chemotherapeutic agents. Overall, these trials have shown no benefit with the interferon-chemotherapy combinations as compared to the single-agent activities.
Recombinant interferon alpha-2a and interferon alpha-2b were the first agents approved for the treatment of KS. Approval was based on single-agent studies performed in the 1980s before the advent of antiretroviral therapy. The early studies demonstrated improved efficacy at relatively high doses. High-dose monotherapy is rarely used today, and instead, interferon is given in combination with other anti-HIV drugs in doses of 4 to 18 million units. Neutropenia is dose limiting, and trials of doses of 1 to 10 million units combined with less myelosuppressive antiretrovirals are in progress. Response to interferon is slow, and the maximum effect is seen after 6 or more months. Interferon should probably not be used in the treatment of patients with rapidly progressive, symptomatic KS.
Imatinib, a c-kit/PDGF (platelet-derived growth factor) receptor inhibitor, resulted in partial responses in 10 of 30 previously treated patients (cART + chemotherapy).[22 ]
Bevacizumab, the humanized, antivascular, endothelial growth-factor monoclonal antibody, had a response rate in 5 of 16 patients who did not improve after the institution of cART and chemotherapy.[23 ][Level of evidence: 3iiiDiv]
Interleukin-12 had a response rate of 71% (95% confidence interval, 48%-89%) among 24 evaluable patients in a phase I and phase II trial.[24 ][Level of evidence: 3iiiDiv]
Treatment options under clinical evaluation:
Patients with epidemic KS are appropriate candidates for clinical trials evaluating new drugs or biologicals.
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Groopman JE, Gottlieb MS, Goodman J, et al.: Recombinant alpha-2 interferon therapy for Kaposi's sarcoma associated with the acquired immunodeficiency syndrome. Ann Intern Med 100 (5): 671-6, 1984.
Koon HB, Krown SE, Lee JY, et al.: Phase II trial of imatinib in AIDS-associated Kaposi's sarcoma: AIDS Malignancy Consortium Protocol 042. J Clin Oncol 32 (5): 402-8, 2014.
Uldrick TS, Wyvill KM, Kumar P, et al.: Phase II study of bevacizumab in patients with HIV-associated Kaposi's sarcoma receiving antiretroviral therapy. J Clin Oncol 30 (13): 1476-83, 2012.
Little RF, Pluda JM, Wyvill KM, et al.: Activity of subcutaneous interleukin-12 in AIDS-related Kaposi sarcoma. Blood 107 (12): 4650-7, 2006.
The prognosis for any treated Kaposi sarcoma patient with progressing, recurring, or relapsing disease is highly variable. Deciding on further treatment depends on many factors, most importantly the clinical setting (i.e., classic, immunosuppressive treatment, or AIDS) in which the tumor arises as well as individual patient considerations.
Clinical trials are appropriate and should be considered when possible.
The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.
Added text to state that electroporation of the skin lesions was combined with intravenous bleomycin for 19 patients with classical KS. Also added that most patients responded after one application, the rest after two or three applications, with a median duration of response of 16 months (cited Di Monta et al. as reference 10 and level of evidence 3iiiDiv).
Revised text to state that most good-risk patients, defined by the AIDS Clinical Trials Group as T0, show tumor regression with combined antiretroviral therapy (cART) alone. Also revised text to state that poor-risk patients, defined as T1, usually require a combination of cART and chemotherapy with discontinuation of the chemotherapy after disappearance of the skin lesion (cited Krell et al. as reference 4). Added that the combination of cART and liposomal doxorubicin resulted in a 5-year overall survival rate (OS) of 85% in 140 patients with T1 disease (cited Bower et al. as reference 3 and level of evidence 3iiiDiv).
Added text to state that the combination of cART and liposomal doxorubicin resulted in a 5-year OS of 85% in 140 patients with T1 disease (cited level of evidence 3iiiDiv).
Revised subheading to read Biologic and targeted therapy.
Added text to state that imatinib, a c-kit/PDGF (platelet-derived growth factor) receptor inhibitor, resulted in partial responses in 10 of 30 previously treated patients (cited Koon et al. as reference 22).
This summary is written and maintained by the PDQ Adult Treatment Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ® - NCI's Comprehensive Cancer Database pages.
Purpose of This Summary
This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of Kaposi sarcoma. It is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.
Reviewers and Updates
This summary is reviewed regularly and updated as necessary by the PDQ Adult Treatment Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).
Board members review recently published articles each month to determine whether an article should:
be discussed at a meeting,
be cited with text, or
replace or update an existing article that is already cited.
Changes to the summaries are made through a consensus process in which Board members evaluate the strength of the evidence in the published articles and determine how the article should be included in the summary.
The lead reviewers for Kaposi Sarcoma Treatment are:
Eric J. Seifter, MD (Johns Hopkins University)
Minh Tam Truong, MD (Boston University Medical Center)
Any comments or questions about the summary content should be submitted to Cancer.gov through the NCI website's Email Us. Do not contact the individual Board Members with questions or comments about the summaries. Board members will not respond to individual inquiries.
Some of the reference citations in this summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Adult Treatment Editorial Board uses a formal evidence ranking system in developing its level-of-evidence designations.
Permission to Use This Summary
PDQ is a registered trademark. Although the content of PDQ documents can be used freely as text, it cannot be identified as an NCI PDQ cancer information summary unless it is presented in its entirety and is regularly updated. However, an author would be permitted to write a sentence such as "NCI's PDQ cancer information summary about breast cancer prevention states the risks succinctly: [include excerpt from the summary]."
The preferred citation for this PDQ summary is:
PDQ® Adult Treatment Editorial Board. PDQ Kaposi Sarcoma Treatment. Bethesda, MD: National Cancer Institute. Updated <MM/DD/YYYY>. Available at: https://www.cancer.gov/types/soft-tissue-sarcoma/hp/kaposi-treatment-pdq. Accessed <MM/DD/YYYY>. [PMID: 26389335]
Images in this summary are used with permission of the author(s), artist, and/or publisher for use within the PDQ summaries only. Permission to use images outside the context of PDQ information must be obtained from the owner(s) and cannot be granted by the National Cancer Institute. Information about using the illustrations in this summary, along with many other cancer-related images, is available in Visuals Online, a collection of over 2,000 scientific images.
Based on the strength of the available evidence, treatment options may be described as either "standard" or "under clinical evaluation." These classifications should not be used as a basis for insurance reimbursement determinations. More information on insurance coverage is available on Cancer.gov on the Managing Cancer Care page.
More information about contacting us or receiving help with the Cancer.gov website can be found on our Contact Us for Help page. Questions can also be submitted to Cancer.gov through the website's Email Us.
Last Revised: 2015-10-01


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Skipper Janine van Wyk Seals Deal with Glasgow City FC
by Celine Abrahams | Jul 14, 2020 | Careers, International Championship, Media and Coverage, Newsroom, Professional, Soccer, Update, Women's Sport, Womens Interest | 0 comments
The COVID-19 global pandemic and lack of sporting action has dampened the moods of sport lovers, but true to form, Banyana Banyana players have once again given South Africans something to smile about.
Banyana captain, Janine van Wyk, has become the seventh South African footballer to sign in Europe in 2020. This following news of Amanda Mthandi, Nothando Vilakazi and Jermaine Seoposenwe all making moves internationally in the past couple of days.
The 33-year-old Van Wyk joins Glasgow City FC for a season, according to the media release on the club's website.
As the most capped South African player (170), van Wyk has led the national team to two Olympic Games as well as the 2019 FIFA Women's World Cup in France.
"I am extremely excited to start this new chapter in my football career with a football club that is known to be the best team in the Scottish top league.
"I look forward to playing in the UEFA Women's Champions League, win titles and most importantly continue to learn as much as I can about the insights of the game and hopefully add value to the squad with the experience I carry," van Wyk expressed via her club.
The founder of JVW Girls Football has ample international experience, having turned out for Houston Dash in the National Women's Soccer League in America and Fortuna Hjorring, in Denmark.
Extremely excited for this new chapter in my football career. I can't wait to meet all the members of my new team & be part of a magnificent club such as @GlasgowCityFC.
?⚽? https://t.co/sJvzY4nAoI
— Janine Van Wyk (@Janinevanwyk5) July 14, 2020
Photo 1 Caption: Banyana Banyana captain, Janine van Wyk, signed for Glasgow City FC for the 2020-21 season.

redpajama_set_name: RedPajamaCommonCrawl


SOS was proud to support the Haven at Skanda and their 2018 Little Moe 5k.
The Haven at Skanda provides a loving home to rescued and endangered animals where they can relax, live in their own natural rhythms of life, and emerge into who they really are. They offer programs to kids and adults where they can experience the brilliance of animals, and discover new possibilities. The Haven provides preventive programs and education to the public, so that together we can create networks of support so no animal ever need suffer.


The franchise is to operate a "professional organizing" business that provides organizing products and services to residential clients.
The initial franchise fee paid to us for a Clutterbusters Franchise is $25,000. The estimated initial investment required ranges from $45,650 to $73,500.
1. THE FRANCHISE AGREEMENT PERMITS YOU TO ARBITRATE AGAINST US ONLY WHERE OUR PRINCIPAL BUSINESS ADDRESS THEN IS LOCATED OR THE FEDERAL COURTS IN OUR HOME JUDICIAL DISTRICT WHERE OUR PRINCIPAL BUSINESS ADDRESS THEN IS LOCATED (CURRENTLY MONTGOMERY COUNTY, MARYLAND). OUT OF STATE LITIGATION MIGHT FORCE YOU TO ACCEPT A LESS FAVORABLE SETTLEMENT FOR DISPUTES. IT MIGHT ALSO COST YOU MORE TO SUE US IN MARYLAND THAN IN YOUR HOME STATE. SOME STATE FRANCHISE LAWS PROVIDE THAT CHOICE OF FORUM PROVISIONS ARE VOID OR SUPERSEDED. YOU MIGHT WANT TO INVESTIGATE WHETHER YOU ARE PROTECTED BY A STATE FRANCHISE LAW.
2. THE FRANCHISE AGREEMENT STATES THAT MARYLAND LAW GOVERNS THE AGREEMENT, AND THIS LAW MIGHT NOT PROVIDE THE SAME PROTECTION AND BENEFITS AS LOCAL LAW. YOU MIGHT WANT TO COMPARE THESE LAWS. SOME STATE FRANCHISE LAWS PROVIDE THAT CHOICE OF LAW PROVISIONS ARE VOID OR SUPERSEDED. YOU MIGHT WANT TO INVESTIGATE WHETHER YOU ARE PROTECTED BY A STATE FRANCHISE LAW. YOU SHOULD REVIEW ANY ADDENDA OR RIDERS ATTACHED TO THIS OFFERING CIRCULAR FOR DISCLOSURES REGARDING STATE FRANCHISE LAWS.
THERE MIGHT BE OTHER RISKS CONCERNING THIS FRANCHISE.
Information comparing franchisors is available. Call the state administrators listed in Exhibit A (as applicable) or your public library for sources of information.
Registration of this franchise with the state does not mean that the state recommends it or has verified the information in this Offering Circular. If you learn that anything in this Offering Circular is untrue, contact the Federal Trade Commission and the state administrators listed in Exhibit A.
The franchisor is Clutterbusters Franchising, Inc. ("we," "us", or "our"). "You" means the person to whom we grant a franchise. If you are a corporation, partnership, or other entity, your owners must sign our "Guaranty and Assumption of Obligations," (which is Exhibit C to our Franchise Agreement). If your owners sign the Guaranty, all of the provisions of our Franchise Agreement also will apply to your owners. The Franchise Agreement is attached as Exhibit C.
We were formed in Delaware in July, 2005, and have just begun operations. Our principal business address is 15521 Grinnell Terrace, Derwood, Maryland 20855. We operate under our corporate name and the trademarks described in Item 13 (the "Marks") and no other name.
If we have an agent in your state for service of process, we disclose that agent in Exhibit A.
We have no affiliates. Our predecessor is Choice Placements, Inc., a Maryland corporation, d/b/a "Clutterbusters!!" that was formed in March 2002. Its principal business address is the same as ours. It performs the same services as you will be performing under the "Clutterbusters" name. It operates in the Washington, DC and Greater Atlanta metropolitan areas only.
We grant franchises for businesses under the "Clutterbusters" name and other Marks. (We call these businesses "Clutterbusters". We will call your business Clutterbusters (the "Business"). Clutterbusters offers organizing services for our clients, and we can perform our services either by the hour or by the project, like a garage, bedroom or home office that needs to be organized (the "Services"). Typically, a client of Clutterbusters is considerably disorganized and has a current need that motivates them to pay for professional help. Most jobs are done within the client's residence or at a corporate location. If you acquire a franchise, you must operate your Business according to our business formats, methods, procedures, designs, layouts, standards, and specifications. Your Business must offer the products and services we specify. In certain instances we will offer franchises to individuals who are already in the professional organizing business and may discount our initial franchise fee to them.
We will begin offering franchises for Clutterbusters in September 2005. We do not operate and have not operated any Clutterbusters franchises. However, our predecessor operates Clutterbusters professional organizer businesses in the greater Washington, DC and greater Atlanta areas (See Item 20). It has operated the Washington, DC Business since March, 2002. We have no other business activities and have not offered franchises in other lines of business. Neither we nor our predecessor, has offered franchises in any other line of business.
You will compete with other businesses that offer organizing services to residential home owners and businesses, some of which might be franchise systems. You will offer your products and services to a specific target market, which is described in the Operations Manual. The professional organizing industry, while competitive, is relatively new and growing in most markets.
Most states do not have laws which regulate any aspects of your Business. You must comply with those that apply generally to all businesses. You should investigate these laws.
Mrs. Fein has been President of Clutterbusters Franchising Inc. since inception. From March 2002 to the present she has held the same position with our predecessor, Choice Placements; Previous to that, Ms. Fein was in the HR/Recruitment field for 10 years; six of those years she worked as a Recruiting Director for a Fortune 500 company, hiring over 10,000 employees and directly managing 15 employees.
Mr. Fein, Betsy Fein's husband, has been our CEO since inception. From March 2002 to present he has also served as CEO of our Predecessor. During that time, he was also a practicing real estate attorney in Rockville, Maryland, a Mortgage Banker with a leading home finance company, Director of Government Affairs for the Direct Marketing Association in Washington, DC, and General Counsel and Director of Taxation and Government Affairs with the National Society of Accountants in Alexandria, Virginia.
No litigation is required to be disclosed in this Offering Circular.
No person previously identified in Item 1, and no officer previously identified in Item 2, of this offering circular has been involved as a debtor in proceedings under the U.S. Bankruptcy Code required to be disclosed in this Item.
You must pay to us an initial franchise fee of $25,000 at the time you sign the Franchise Agreement. This amount is not refundable. If you wish to purchase a second franchise, we will discount the initial fee by 2/3's of the then current initial franchise fee, and this too is payable when you sign the Franchise Agreement and is not refundable.
In the State of Rhode Island only, we will defer the payment of the initial franchise fee, development fee and any other initial payment until all of our material pre-opening obligations have been satisfied. The initial franchise fee and development fee are deferred until you open your business and it is operating. However, you must execute the Franchise Agreement prior to looking for a site or beginning training.
If you are an existing organizer who wishes to join our system, and you have generated more than $60,000 in sales over the prior twelve month period, you will pay 50% of the then current initial franchise fee when you sign our Franchise Agreement. This fee is not refundable. In addition, we intend to convert our Atlanta location to a franchise, and will be discounting their initial franchise fee, and we may sell to selected relatives and friends at a substantially discounted fee.
Due every other Friday by automatic debit for the preceding 2 weeks.
Week defined as Monday thru Sunday Royalty due following Friday.
Royalties are payment for the use of the Marks, System, Territory, and Manuals. "Gross Revenues" means all income you derive from the business including all sales and revenue shares (but excluding taxes collected from customers and paid to taxing authorities).
Week defined as Monday thru Sunday National Marketing and Advertising Fund fee due following Friday.
"Gross Revenues" means all income you derive from the business including all sales and revenue shares (but excluding taxes collected from customers and paid to taxing authorities).
A cooperative is formed by multiple franchisees operating in contiguous territories.
No less than 4% of Gross Revenues of the preceding two weeks or $125, whichever is greater.
Must have listings in local white and yellow pages. Must have a dedicated business phone line with a 24 hour answering machine/service.
If more than one franchisee in local area, listing fees can be split between the franchisees equally.
You must reimburse us if we are held liable for claims from your Business's operation.
40% of our then current initial franchise fee.
Due if you understate royalty by 3% or more or if you fail to furnish us on a timely basis reports, records, or other related information we request.
A one time setup fee of $500 and a monthly fee of $75. These fees will go towards proprietary software licensing fees and into a fund to provide all future technology based solutions to operations requirements.
All due on the first day of the month by automatic debit.
Purchase a Dell or other high quality, high speed computer with current Microsoft Office package, including MS Outlook, and Windows XP Pro. Must include Word, Excel and PowerPoint.
may vote to change the required cooperative allocation of expenditures among the media forms but not the total amount of contributions to the Cooperative or the allocation of expenses among the members. Each Business owner will have one vote regardless of the number of businesses that the owner operates within the Cooperative's area.
"CI utter busters" franchise. During you first 12 months in operation you must generate no less than $30,000 in Gross Revenues; $60,000 during the second 12 months; and $120,000 during the third year of operations. (See Item 12). If you fail to achieve one of the required Gross Revenues, we may, at our discretion, either terminate your Business or reduce your territory size.
Liquidated Damages. If we terminate the Franchise Agreement with cause, you must pay us liquidated damages equal to the present value (using the then-current 30-Year Treasury Bond rate) of the Royalty Fees you would have paid us on the product of (a) your Business' average monthly Gross Revenue during its most recent 12 months of operation before the termination multiplied by (b)the number of months remaining in the Franchise Agreement had we not terminated it.
1. We describe the initial franchise fee in Item 5.
2. We strongly recommend that you initially operate your Business from your home, thereby reducing your overhead expenses significantly. However, if you wish to operate the Business from an office location then the premises should be in an office building in a central location in the territory. We suggest that the premises be 500 to 1,000 square feet for most offices. Leasehold improvement costs, including floor covering, painting, window coverings, electrical, carpentry, and similar work, and contractor's fees, depend on the site's condition, location, and size; the demand for the site among prospective lessees; the site's previous use; the build-out required to conform the site for your Business; and any construction or other allowances the landlord grants. The low-end of the range contemplates a situation where the landlord includes the build- out in the regular lease payments, in which case you would not have any initial expense.
3. Whether you operate from your home or not, you will need a computer, a telephone/fax/copier/scanner combo machine, a PDA phone and a vehicle that you will either already own, or that you will lease. If you choose to operate from office space, you will also need desks, chairs and a telephone system. We describe the telephone and computer systems in Item 11.
space for your Business is $10.00 to $20.00 per square foot, depending on your location, plus common area maintenance charges.
5. This covers travel, car rental expenses, hotel and food for you while attending training. This also covers the travel, car rental expenses, hotel and food when our personnel travels to your location for the onsite training as part of the initial training program.
6. This covers miscellaneous opening costs and expenses, including installing telephones; deposits for gas, electricity, and similar items; business licenses; legal and accounting expenses; and insurance premiums.
7. This item estimates your initial start up expenses (other than the items identified separately in the table). These expenses include payroll costs and a reasonable draw or salary for you. These figures are estimates, and we cannot guarantee that you will not have additional expenses starting the business. Your costs depend on how much you follow our methods and procedures; your management skill, experience, and business acumen; local economic conditions; the local market for your products and services; the prevailing wage rate; competition; and the sales level reached during the initial period.
We relied on our Predecessor's experience since 2002 in operating the original Business during that time to compile these estimates. You should review these figures carefully with a business advisor before deciding to acquire the franchise. We do not offer financing directly or indirectly for any part of the initial investment at the present time. The availability and terms of financing depend on many factors, including the availability of financing generally, your creditworthiness and collateral, and lending policies of financial institutions from which you request a loan.
Except where otherwise noted, all fees that you pay to us are nonrefundable. Third-party lessors, contractors, and suppliers will decide if payments to them are refundable.
You must operate the Business according to our System Standards. System Standards may regulate, among other things, the types, models, and brands of fixtures, furnishings, furniture, equipment (including a recommended or approved computer system and telephone system), and signs (collectively, "Operating Assets") required for the Business; required and authorized product and service categories; and designated and approved suppliers of these items and services, which could be limited to us, our affiliates, and other restricted sources, in which case you must acquire certain items for your Business only from such restricted sources at the prices we decide to charge. Except as described in this section, there are no goods, supplies, fixtures, equipment, inventory, or real estate for the Business that you currently must buy or lease from us (or an affiliate) or designated suppliers. As described in Item 11, you must license certain proprietary software from us and from no other entity. Any purchases from us and our affiliates, whether required or voluntary, generally will be at prices exceeding our costs by between 5% to 25%.
To maintain the quality of the goods and services that the Businesses sell and our system's reputation, we may condition your right to buy or lease Operating Assets, (including components of the phone and computer systems) and other items on their meeting our minimum standards and specifications and/or their being acquired from suppliers that we approve. Also, you must purchase from approved suppliers your advertising and marketing materials. We will formulate and modify standards and specifications based on our (and franchisees') experience in the industry and in operating the Businesses.
Our standards and specifications may impose minimum requirements for delivery of services, performance, reputation, prices, quality, design, and appearance. Our Operations Manuals or other communications will identify our standards and specifications and/or names of approved suppliers. We will notify you and, where appropriate, the suppliers. There might be situations where you can obtain items from any supplier who can satisfy our requirements and, therefore, would be an approved supplier. We and our affiliates are approved (but not the only) suppliers of various marketing and promotional items. If you buy or lease any item from us (or an affiliate) because we are a designated or approved supplier (or the only supplier), we (or that affiliate) have the right to charge a price that exceeds our cost and includes a profit margin.
If we institute any type of restrictive sourcing program (which, as noted above, we have the right to do) and you want to use any item or service that we have not yet evaluated or to buy or lease from a supplier that we have not yet approved, you first must send us sufficient information, specifications, and samples so we can determine whether the item or service complies with System Standards or the supplier meets approved supplier criteria. We may charge you or the supplier a reasonable fee for the evaluation (see Item 6) and will, within a reasonable time (typically 30 to 60 days), give you our decision. We periodically will establish procedures for your requests and may limit the number of approved items, services, and/or suppliers as we think best. Supplier approval might depend on product quality, delivery frequency, service standards, financial capability, customer relations, and concentration of purchases with limited suppliers to obtain better prices and service. Approval might be temporary until we evaluate the supplier in more detail. We may inspect a proposed supplier's facilities during and after the approval process to make sure that the supplier meets our standards. If it does not, we may revoke our approval by notifying the supplier and you in writing.
Besides these purchases or leases, you must obtain and maintain, at your own expense, the insurance coverage that we periodically require and satisfy other insurance-related obligations. You currently must have comprehensive general liability insurance of $1,000,000 for bodily injury (per person), $1,000,000 per accident, and $1,000,000 for property damage; employer's liability insurance of at least $1,000,000 per occurrence; a surety bond with a minimum limit of $25,000; and workers' compensation insurance required by state law. Premiums depend on the insurance carrier's charges, terms of payment, and your history. A certificate of insurance designating us as an additional insured party is required to be sent to us before operations commence. Clutterbusters suggests you contact Bob Silverman of Silverman Insurance Associates, Rockville, Maryland before deciding upon your insurance provider ((800)364-4249).
Before you use them, you must send us for approval samples of all advertising, promotional, and marketing materials which we have not prepared or have not previously been approved by us. If you do not receive written or verbal approval within 20 days after we receive the materials, they are deemed disapproved. You may not use any advertising, promotional, or marketing materials that we have disapproved or that we have not specifically approved.
You are responsible for developing the Business, If you do not operate from your home office, we will give you mandatory and suggested specifications and layouts for a Business, including requirements for dimensions, design, image, interior layout, decor, operating assets, and color scheme. You must make sure that all required construction plans and specifications for the Business's site comply with applicable ordinances, building codes, permit requirements, and lease requirements and restrictions. We must review and approve all final plans and specifications before you begin constructing the Business. You must submit all revised or "as built" plans and specifications during construction. We may inspect the Business during its development.
(tcNAPO") and, optionally, the International Association of Professional Organizers.
The Business must be at a site that we approve, which may be your home. We have the right to approve the Business's lease or sublease and to require that it include certain provisions (listed in Article 2B of the Franchise Agreement), including our right to the Business's site in certain circumstances. At our request, you must conditionally assign the lease or sublease to us to make sure you comply with the Franchise Agreement and obtain the lessor's consent to the collateral assignment. This means that, if you do not fulfill your obligations, we may take over the premises.
Collectively, the purchases and leases described above are 25% - 50% of your total purchases and leases to establish, and approximately 25% - 50% of your total purchases and leases to operate, the Business. These expenses are limited if the Business is operated from your home environment.
We or our Predecessor will derive revenue on items you must or may buy from us, our affiliates or designated suppliers or national accounts. This revenue could range from 5% to 25% of the cost of the service or item. During our fiscal year ended December 31, 2004, we did not derive any revenue as a result of required purchases or leases of our franchisees. We (and our affiliates) also have the right to receive payments from suppliers on account of their dealings with you and other franchise owners and to use all amounts we receive without restriction (unless the supplier instructs us otherwise) for any purposes we deem appropriate. There currently are no purchasing or distribution cooperatives. We do negotiate purchase arrangements with suppliers (including price terms) for franchisees. We do not provide material benefits to a franchisee for using designated or approved sources.
As the franchise system grows, we expect to facilitate purchasing cooperatives that will create volume discounts for us and for our franchisees.
We do not offer direct or indirect financing. We do not guarantee your note, lease, or other obligation.
5. Train up to five individuals, including your principal owners and key employees (who will be identified in the Franchise Agreement), including spending two days at your Business location. (Franchise Agreement - Article 4A.) We describe this training later in this Item.
National Marketing and Advertising Fund. When created, you agree to contribute toward a "National Marketing and Advertising Fund" an amount equal to 3% of your weekly Gross Revenues every two weeks ending Sunday, and due on the following Friday. Businesses that we or our affiliates own will contribute to the National Marketing and Advertising Fund on the same basis as our franchisees.
of these materials at its direct cost of producing them, plus any related shipping, handling and storage charges, or will arrange for you to purchase these materials directly from the printer or other supplier.
We will account for the National Marketing and Advertising Fund separately from our other funds and will not use the National Marketing and Advertising Fund for any of our general operating expenses, except to compensate the reasonable salaries, administrative costs, travel expenses and overhead we incur in administering the local media placement account and National Marketing and Advertising Fund and their programs, including, without limitation, conducting market research, preparing advertising, promotion and marketing materials, and collecting and accounting for local media placement account funds and National Marketing and Advertising Fund contributions. The National Marketing and Advertising Fund will not be our asset. The National Marketing and Advertising Fund is not a trust, and we do not owe you fiduciary obligations because of our maintaining, directing or administering the National Marketing and Advertising Fund or any other reason. We will not use National Marketing and Advertising Fund contributions for advertising that is principally a solicitation for the sale of franchises except that in certain ads with available space, we may insert a tag line regarding the availability of franchise opportunities. The National Marketing and Advertising Fund may spend in any fiscal year more or less than the total National Marketing and Advertising Fund contributions in that year, borrow from us or others to cover deficits, or invest any surplus for future use. We will use all interest earned on National Marketing and Advertising Fund contributions to pay costs before using the National Marketing and Advertising Fund's other assets. We will prepare, and furnish to you upon written request, an annual, unaudited statement of National Marketing and Advertising Fund collections and expenses and give you the statement upon of the funds collected and costs incurred. We may incorporate the National Marketing and Advertising Fund or operate it through a separate entity whenever we deem appropriate. Currently, our practice is to pass through all National Marketing and Advertising Fund monies we collect to our advertising agency. The National Marketing and Advertising Fund will not place any advertisements. Rather, the National Marketing and Advertising Fund, will create the advertisements that are placed with each franchisee's local media placement account monies. However, in the future, the National Marketing and Advertising Fund may also place advertisements.
We intend the National Marketing and Advertising Fund to maximize recognition of the Marks and patronage of the Businesses. Although we will try to use the National Marketing and Advertising Fund to develop advertising and marketing materials and programs, and to place advertising and marketing, that will benefit all Businesses, we need not ensure that National Marketing and Advertising Fund expenditures in or affecting any geographic area are proportionate or equivalent to the National Marketing and Advertising Fund contributions by Businesses operating in that geographic area or that any Business benefits directly or in proportion to its National Marketing and Advertising Fund contribution from the development or placement of advertising and marketing materials. We have the right, but no obligation, to use collection agents and institute legal proceedings to collect National Marketing and Advertising Fund contributions at the National Marketing and Advertising Fund's expense. We also may forgive, waive, settle and compromise all claims by or against the National Marketing and Advertising Fund. We assume no direct or indirect liability or obligation to you for collecting amounts due to, maintaining, directing or administering the National Marketing and Advertising Fund.
We may at any time defer or reduce the National Marketing and Advertising Fund contributions of a Business and, upon thirty days' prior written notice, reduce or suspend National Marketing and Advertising Fund contributions and operations for one or more periods of any length and terminate (and, if terminated, reinstate) the National Marketing and Advertising Fund. If we terminate the National Marketing and Advertising Fund, we will distribute all unspent monies to all Businesses (whether franchised or operated by us or our affiliates) in proportion to their respective National Marketing and Advertising Fund contributions during the preceding twelve month period.
Advertising By You. You will be required to spend no less than 4% of your Gross Revenues for the preceding two weeks or $125, whichever is greater, on local advertising and marketing. Ad spending requirements may be expended over the period of two weeks preceding, in which the ad spending requirements are calculated, or may be carried over to the next bi-weekly period; however carry-over total ad spending requirements shall not exceed $1,000. If you decide to spend more than the minimum biweekly requirement, your total expenditures may be credited towards future ad spending requirements. The amount will be determined based upon the location of your Business. You will spend each week the dollar amount which will be filled in your Franchise Agreement (See Item 6). You agree to list and advertise the Business in each classified telephone directory (including applicable internet yellow pages) covering the Site (in the business classifications we prescribe from time to time) and, if we require, to use our standard form of classified telephone directory advertisement. If there are other Businesses located within the distribution area of one or more of those directories, we require, and you agree to participate in a collective advertisement with those other Businesses and pay your share of that collective advertisement. The amount you spend on advertising in classified telephone directories will be credited toward the amount you are required to spend on local advertising.
You agree that your advertising promotion and marketing will be completely clear, factual and not misleading and conform to the highest standards of ethical advertising and marketing and the advertising and marketing policies that we prescribe from time to time. Before you use them, you must send us for approval samples of all advertising, promotional and marketing materials which we have not prepared or previously approved. If you do not receive written or verbal approval within twenty days after we receive the materials, they are deemed to be disapproved. You may not use any advertising, promotional or marketing materials that we have disapproved. Advertising promotional or marketing materials which we must approve include any information on a web home page or otherwise on the Internet. You may not operate any web site involving, referring to or in any way related to a competitive business. As described in Item 13, you may not use the Marks as part of any domain name, electronic address or search engine and cannot maintain your own website under any circumstances.
Advertising Cooperatives. Advertising Cooperatives are governed in a form and manner, and begin operating on a date, that we determine in advance. Each Cooperative's purpose is, with our approval, to administer advertising programs and develop advertising, marketing and promotional materials for the area that the Cooperative covers. If, as of the time you sign the Franchise Agreement, we have established a Cooperative for the geographic area in which the Business is located, or if we establish a Cooperative in that area during the Franchise Agreement's term, you agree to sign the documents we require to become a member of the Cooperative and to participate in the Cooperative as those documents require. If we establish a Cooperative, it will operate from written governing documents which will be available for your review. A Cooperative will not be required to produce annual accounting statements.
You agree to contribute to the Cooperative the amounts determined by us and set forth in the governing document for the Cooperative. We shall determine the total amount of contributions to the Cooperative based upon the projected advertising, marketing and promotional expenditures within the Cooperative's area. We will allocate the Cooperative's expenses among the members based on equitable factors we establish. Changes to the allocation of the expenditures among media forms (but not for the amount of contribution to the Cooperative or the allocation of expenses among their members) may be recommended upon a majority vote of all Business owners who are members of that Cooperative, subject to our approval (which will not be unreasonably withheld). Each Business owner (including us, our affiliates and franchisees) will have one vote, regardless of the number of Businesses that the owner operates within the Cooperative's area.
described above. The Cooperative and its members may not use any advertising, marketing or promotional plans or materials without our prior written consent. There currently are no advertising cooperatives. We have the power to form, change, dissolve, or merge Cooperatives.
Once we have between 15 and 20 franchisees we may choose to create a franchisee Advisory Council. We will select 6 franchisees. The first 3 will have an 18 month term, the next 3 will have a 12 month term. Elections will be held in December of each year to elect 6 new members. Members will hold two consecutive terms, then must sit out for 6 months before being reelected.
You agree to use in operating the Business the computer equipment, operating software and telephone equipment we specify- We may require you to obtain specified telephone equipment, computer hardware and software (as described below), and may periodically modify our specifications. If we modify our specifications, it may require you to acquire new or modified phone equipment, computer hardware or software. Although we cannot estimate the future cost of the phone or computer system, you agree to incur the costs of obtaining the phone and computer systems and required service or support. We have no obligation to reimburse you for any costs related to the phone system or computer system. You agree to acquire any components of the phone or computer system within 60 days after you receive notice from us.
No other provider of software outside of the Microsoft and QuickBooks Pro software are permitted to be used in conjunction with your Business. Anti-virus and firewall protection software are required, to prevent potential systemwide problems.
This hardware and Microsoft software can be purchased or leased from suppliers of computer equipment. We reserve the right to require you to download and utilize any proprietary software that we may develop. We estimate that this cost will be a one-time licensing fee of $500 and a monthly maintenance fee of $75. You must also maintain high speed Internet access (such as Tl line, cable modem or DSL) at all times.
All hardware components are the proprietary property of their manufacturers, who need not provide ongoing maintenance, repairs, upgrades, or updates unless you pay for them. Their charges depend on the length and nature of the service contract. We will have independent access to data on your computer system and there are no contractual limits on our rights to access your data.
You must upgrade the computer system, and/or obtain service and support, as we require or as is necessary because of technological developments or events. There are no contractual limitations on the frequency and cost of this obligation. We have no obligation to reimburse you for any of these costs. We will have independent, unlimited access to information on your computer system.
Unless you are operating from a home-based office, you are responsible for selecting the site for your Business, but you must obtain our written approval of any proposed site in accordance with our procedures. You must submit to us a complete site report for the proposed site which shall contain such demographic, commercial and other information and photographs as we require. We will approve or disapprove each site you propose by giving you written notice. We will use reasonable efforts to deliver such a notice to you within 7 days after we receive your complete site report. In evaluating a site, we may consider such factors as we deem material including demographic characteristics, traffic patterns, parking, the predominant character of the neighborhood, competition within the area, rental obligations, and the site's size, appearance and other physical characteristics. If we and you cannot agree on a site in time for you to sign a lease for the site within 30 days after you sign the Franchise Agreement, then we can terminate the Franchise Agreement.
Once we approve a proposed site, you must sign a lease for the site. You must sign a lease for the site within 30 days after signing the Franchise Agreement. Any site lease must be in a form satisfactory to us and must contain certain clauses which we require. You must deliver to us a copy of the lease for the site, and you may not execute a lease without our prior written approval of its terms. If we do not approve a proposed lease within 7 days after we receive it, it shall be deemed disapproved. If you have failed to sign a lease for the site within 30 days after signing the Franchise Agreement, we may, in addition to our termination rights, withdraw approval of the site.


text:
<?php

namespace Bsharp\Laralytics;

use Illuminate\Http\Request;
use Illuminate\Routing\Controller;

/**
 * Class LaralyticsController
 * @package Bsharp\Laralytics
 */
class LaralyticsController extends Controller
{
    /**
     * @param Laralytics $laralytics
     * @param Request    $request
     *
     * @return $this|\Illuminate\Http\JsonResponse
     */
    public function payload(Laralytics $laralytics, Request $request) {

        $response = response();

        $payload = $request->only('info', 'click', 'custom');
        $pageCookie = $laralytics->checkPageCookie($request);

        if ($pageCookie) {
            $laralytics->payload($request, $response, $payload, $pageCookie);
        }

        return $response->json();
    }
}

redpajama_set_name: RedPajamaGithub


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text:
Q: Nginx - Routing, Capabililties of with Node.js I am running a Node.js server which is now getting more load and I need to start getting this running on multiple cores, as Node.js is single threaded and can only run on one.
This is a simple solution given the Node.js Cluster module and tons of NPM packages for this very thing.
I have a problem in that I need browser sessions to retain the same Node.js worker after the first request. This is because I store authentication data, etc. in a single node worker process and do not want to open the can of worms of messaging between worker processes, etc. etc.
My browsers store a session id cookie once authenticated, and I want a system to re-route requests to their correct worker based on their session cookie.
Nginx looks promising, but I know nothing about it, and while I will put the work into it, I would like to know before I spend hours diving into it, if it is capable of routing to Node.js worker processes based on arbitrary data from the request header, such as a session cookie.
Is this doable? If I know it is, I'll get down and dirty figuring out Nginx, ground up.

A: I assume you are storing your sessions in nodejs memory. You might want to store your sessions in redis instead. This way it is persisted outside of a single server, and can be accessed from multiple processes.
In addition to redis, you might also want to look into Amazon Elastic Beanstalk for managing your load-balancing. You can setup an nginx proxy to route your requests to multiple servers based on their load.
This link might be able to get you started http://docs.aws.amazon.com/elasticbeanstalk/latest/dg/create_deploy_nodejs_express_elasticache.html

redpajama_set_name: RedPajamaStackExchange


text:
Why Hollywood star Benedict Cumberbatch may face slave reparations
Eliza Bavin
·Personal Finance Editor
Benedict Cumberbatch's ancestors have a sordid history. (Source: Getty)
Benedict Cumberbatch has made no secret of his family's sordid past as slave owners - his distant relative Abraham Cumberbatch purchased a sprawling sugar plantation in Barbados in 1728.
That plantation alone enslaved 250 people, and was the main source of the Cumberbatch family's wealth for generations.
After the Slavery Abolition Act in 1833 the Cumberbatch family received £5,388 (AU$9,593) in compensation. According to the Bank of England's (BoE) inflation calculator that would be the equivalent of £478,362.62 (AU$851,780) today.
Also read: Closing the gap: $82,000 payments to Stolen Generations
Also read: Inheritance tax in Australia 'bound to happen'
Also read: Aussie family discovered as rightful recipients of $1.4 million inheritance
Benedict Cumberbatch has not shied away from his family's dark past, having spoken openly about it in an interview back in 2007.
"When I became an actor, Mum wasn't keen on me keeping it [the Cumberbatch surname]. 'They'll be after you for money', she used to say," he said.
"Reparation cases are ongoing in the American courts."
Would Cumberbatch have to pay reparations?
Not as of yet, but organisations devoted to righting the wrongs of slavery are working to seek reparations - even if it does come from the descendants.
"Any descendants of white plantation owners who have benefited from the slave trade should be asked to pay reparations, including the Cumberbatch family," Caribbean Movement for Peace and Integration general secretary David Denny told the UK Telegraph.
However, Barbados politician and activist David Comissiong said reparations would be mostly sought from government entities and companies rather than specific families.
"To date, neither [the Caribbean Community's reparations commission] nor Barbados has officially leveled a Reparations claim against a European family," Comissiong wrote in an op-ed for Barbados Today.
"And, clearly, the reason is that it is much easier to establish a reparations claim against a legal entity such as a national government or a company than it is against a family."
Follow Yahoo Finance on Facebook, LinkedIn, Instagram and Twitter, and subscribe to the free Fully Briefed daily newsletter.


text:
Tue, 07 Dec, 2021 - 16:48
Squatter who trashed refurbished Dublin apartment jailed for six months
The owner told the court she spent months painting and redecorating the apartment, which she owned for 25 years.
Tom Tuite
A squatter who helped ransack a "pristine" and newly refurbished Dublin apartment has been jailed for six months.
Anne Marie Prince (35), of Thomas Bawn Court, Dublin 8, pleaded guilty at Dublin District Court to a burglary on February 21st, 2021.
The owner, Susan Boylan, told the court she spent months painting and redecorating the apartment at Viking Court, Meath Place, Dublin 8, which she owned for 25 years.
At the time, she was considering whether to sell or rent it out and checked the property regularly. It was "pristine" weeks before the burglary.
After gardaí contacted her, she secured the apartment but found that the alarm had been pulled out.
She described it as "unpleasant" – a red light was placed at the bottom of stairs on a wheelie bin, smears on the wall, drug paraphernalia including syringes, and "lingerie thrown around the place".
The bin had been pulled in from the back garden.
The owner said the damage cost about €2,000 and was paid by insurance, resulting in a premium spike.
She told the court it was demeaning.
In a mitigation plea, defence counsel Eimear Delargy told the sentencing hearing that Prince was not the only person on the premises. The barrister said it was used as a squat.
Difficult childhood
The woman accepted responsibility for the alarm and a damaged window.
The court heard the mother of one, with 38 prior convictions, had a difficult childhood. She later worked in a department store and did a pre-nursing course.
Drug addiction started later in life, and she had a relapse at the time of the offence.
Counsel said Prince had become a born-again Christian, was getting counselling and dealing with her drug issue.
The accused apologised in court and told the injured party she was trying to change her life for the better and give back to the community. "I am very grateful for that," the victim replied.
Judge Hughes noted that the apartment owner had left the property in a pristine condition "through the sweat of her own brow," and she has been left at a loss.
He imposed a nine-month sentence but suspended three months with conditions. Prince must keep the peace for two years, pay €500 compensation by next December, complete an education course with the view of finding a job, as well as drug rehabilitation.
He also warned her to stay away from the victim and the apartment.
Daughter of missing Dublin woman makes plea for information
Taoiseach defends Minister for Health and civil servant's trip to Dubai health conference
Gardaí investigating alleged Sligo assault seek to speak with two couples
Man convicted of sexual assault has 23 character references presented to court


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There are a few things to keep in mind while downloading music. It's something that takes a little knowledge to get into, and that's why this article was written. Read on so that you can start downloading your favorite tunes, today.
When you get music off the Internet, make sure you are picky about the sites you use. Protect yourself by visiting only the most credible sites. Other sites leave you vulnerable to spyware, spam, and viruses. If you are dealing with a little-known site, you are smart to protect your personal information.
You must use your antivirus software when you download music. You are wiser to exercise caution than to proceed heedlessly into danger. Always be safe when downloading songs. If you use a P2P client, this is of particular importance. Scan each file prior to opening it. Otherwise, you may end up with something more than music!
Look at the specials on Amazon's music download site. Both albums and singles are frequently available at incredible discounts, which will save you plenty on getting your favorite music. Discounts change every day, so to save the most, you should check in regularly.
Always remember to backup new downloads. It isn't easy to get together a collection that you love. You can lose all of these files if something were to happen. You can't count on a music site allowing you to download those tunes over again. Back up your music on an external storage drive.
Before you open a file, remember to first check its size. You never know what could be hidden in there. The wrong file may hurt your computer. Pay close attention to the file size. If it appears too small or large, you should delete it without opening it.
For the best sound, be sure to download only the highest quality of music. Check out the kb per second playing speed of the music file. The higher this number is, the higher the quality of the song will be on the various devices you're using.
Google's music downloads are the way to go if you are an Android user. Specifically geared for Android devices, Google's Music All Access is a great option. Costing just $10 monthly, it is a great way to build a comprehensive collection.
You may want to purchase an entire album by an artist, as long as you like a number of the songs. In most instances, buying entire albums can prove to be cheaper than purchasing single tracks, regardless of the retailer. It also gives you the opportunity to explore more and listen longer. You might even discover a new favorite song.
When you want the fastest music download possible, make sure you're the only one using your Internet connection. Shutting down every device that uses your network, and then restarting the computer can help you have a better connection.
Always choose music download websites that allow you to preview tracks before buying. This way you will be able to ensure the music's quality before it is downloaded. Bigger websites might guarantee their content quality, but smaller players won't. Previewing will let you avoid getting stuck with low-quality music.
There are daily deals that are offered by some websites that allow you to download different songs very inexpensively. Sites such as iTunes and Amazon offer promotions daily on a wide range of songs. You can get exposure to many different genres of songs at a good price, and this is a very good deal.
Shop around when choosing a subscription service. Downloading songs individually and legally can become expensive. There are a lot of websites that offer music at a price that will be very cost effective. Check out limits on any accounts you are considering.
Only buy your music downloads off a site that lets you get them directly, rather than having to install extra software. Only big sites like iTunes can be trusted with software downloads. If the site is not as well known, use your common sense. If a site is claiming to offer free downloads, it is highly likely that your files will come packaged with harmful software.
Some websites require you to download files prior to downloading any music. iTunes and Rhapsody are sites that require you to download, but they are well known to be safe sites. A free service might have unsafe programs. This will give you a better chance at attaining a virus.
Try to find a site for downloading music that gives you unlimited downloads. These types of sites will have enormous libraries of music, featuring literally millions of titles you can choose from. Often you can get unlimited downloads by simply paying a membership fee. Make sure that you have a large library to choose from.
Do not download music illegally, but support the artists you enjoy most by buying CDs to load into your computer. That ensures that you aren't breaking the law, too. The best thing is that you can begin making a killer collection where you live.
You should be ready to pay for all of your music downloads. Free music sounds great, but the quality is often lousy. In addition, it is illegal and puts your computer at a high risk for getting a virus. Paying for music downloads isn't that expensive when purchasing individual tracks.
Make sure that you take a minute to back up the iTunes library often. Your computer may break down at any time. You can also install the music you have on iTunes easily if by having a backup disk ready.
A great way to get music downloaded while not breaking any laws is to download the program "Rhapsody". This service only charges $10 per month after your free trial, and you can unlimited downloads. For this nominal fee, you can get access to tons of great music legally.
It should now be apparent that downloading music is easy to do. You only need to use the tips above and put in a little time practicing to become adept at downloading music. Use the information contained in this article, and you will get the hang of downloading music in no time.