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  • Images in Clinical Medicine

    Metastatic Inguinal Lymphadenopathy

    Figure 1.

    • April 19, 2012
    • Hajdarbegovic E. and Balak D.
    • N Engl J Med 2012; 366:1526
    • Free Full Text

    A 59-year-old man presented with a weeping mole on his back that had been growing for 8 years. On examination, a 10-cm ulcerated lesion was found on his lower back, and multiple subcutaneous areas of swelling were found in both inguinal regions.

  • Original Article

    Brief Report: Immunologic Correlates of the Abscopal Effect in a Patient with Melanoma

    The abscopal effect refers to a rare phenomenon of tumor regression at a site distant from the primary site of radiotherapy. Localized radiotherapy has been shown to induce abscopal effects in several types of cancer, including melanoma, lymphoma, and renal-cell carcinoma.– The biologic…

    • March 8, 2012
    • Postow M.A., Callahan M.K., Barker C.A., et al.
    • N Engl J Med 2012; 366:925-931

      A patient with metastatic melanoma with slowly progressive disease while receiving ipilimumab underwent radiotherapy for a pleural-based metastasis. Tumor lesions in nonirradiated sites began to disappear, and titers of antibody against a tumor-associated antigen increased.

    • Correspondence

      Vemurafenib Sensitivity Skin Reaction after Ipilimumab

      To the Editor: Ipilimumab, and vemurafenib each improve the overall survival of patients with metastatic melanoma. Ipilimumab was approved by the Food and Drug Administration in March 2011; vemurafenib was approved 5 months later. As a result, patients with disease progression during treatment with…

      • March 1, 2012
      • N Engl J Med 2012; 366:866-868
      • Free Full Text

      Patients with melanoma who have received ipilimumab appear to be at an increased risk for a drug-hypersensitivity rash when treated with vemurafenib.

    • Original Article

      Survival in BRAF V600–Mutant Advanced Melanoma Treated with Vemurafenib

      Patients with metastatic melanoma have a median survival of 6 to 10 months.– Few patients have a response to systemic therapies. Ipilimumab, a monoclonal antibody that blocks cytotoxic T-lymphocyte–associated antigen 4 (CTLA4) on lymphocytes, has recently been associated with superior overall…

      • February 23, 2012
      • Sosman J.A., Kim K.B., Schuchter L., et al.
      • N Engl J Med 2012; 366:707-714

        This large, phase 2 study confirms a response rate of more than 50% and a median survival of 16 months among patients with metastatic melanoma treated with vemurafenib. Some patients did not have a response until after 6 or more months of therapy.

      • Original Article

        RAS Mutations in Cutaneous Squamous-Cell Carcinomas in Patients Treated with BRAF Inhibitors

        The T→A transversion at position 1799 of BRAF (BRAF V600E) is present in approximately 50% of patients with metastatic melanoma. BRAF V600E induces constitutive signaling through the mitogen-activated protein kinase (MAPK) pathway, stimulating cancer-cell proliferation and survival. The clinical…

        • January 19, 2012
        • Su F., Viros A., Milagre C., et al.
        • N Engl J Med 2012; 366:207-215

          Patients with melanoma who are treated with a BRAF inhibitor have a high incidence of keratoacanthomas. Most of the tumors have oncogenic mutations in HRAS that probably preceded the use of the BRAF inhibitor. In animal models, second tumors are blocked when a MEK inhibitor is added to the BRAF inhibitor.

        • Editorial

          RAF around the Edges — The Paradox of BRAF Inhibitors

          The recent success of BRAF inhibitors represents a great stride forward for melanoma research. When used to treat patients with melanoma who harbor the BRAF V600E mutation, these inhibitors lead to the remission of even advanced lesions. However, resistance to BRAF inhibitors emerges within months.…

          • January 19, 2012
          • Weeraratna A.T.
          • N Engl J Med 2012; 366:271-273

            The recent success of BRAF inhibitors represents a great stride forward for melanoma research. When used to treat patients with melanoma who harbor the BRAF V600E mutation, these inhibitors lead to the remission of even advanced lesions. However, ...

          • Correspondence

            Vemurafenib for Melanoma Metastases to the Brain

            To the Editor: Vemurafenib is an inhibitor of the BRAF V600E mutation and has recently been approved by the Food and Drug Administration (FDA) for treatment of metastatic melanoma in adults in the absence of brain metastases.– Trials are currently under way involving the use of vemurafenib for…

            • December 22, 2011
            • N Engl J Med 2011; 365:2439-2441
            • Free Full Text

            A 16-year-old girl had melanoma with the BRAF V600E mutation that metastasized to the brain. The response to vemurafenib was dramatic, and the patient continues to improve 6 months after starting therapy.

          • Perspective

            The Emperor of All Maladies — The Beginning of the Beginning

            Richard Feynman, the eminent physicist, once said that "great ideas . . . do not last unless they are passed purposely and clearly from generation to generation." In 1979, Horace Freeland Judson, in his magnificent The Eighth Day of Creation, passed to his generation the great ideas of molecular…

            • December 22, 2011
            • Schwartz R.
            • N Engl J Med 2011; 365:2353-2355
            • Audio

            In his Pulitzer Prize–winning book, Siddhartha Mukherjee explores the great ideas of oncology, up to the development of imatinib. But the research direction set by imatinib has yielded few useful drugs; its model seems to be the wrong roadmap for finding magic bullets.

          • Correspondence

            Hemophilia A Induced by Ipilimumab

            To the Editor: Ipilimumab, a monoclonal antibody against cytotoxic T-lymphocyte–associated antigen 4, has been reported to improve overall survival in patients with metastatic melanoma. Major side effects include immune-related adverse events. We report a rare and severe case of ipilimumab…

            • November 3, 2011
            • N Engl J Med 2011; 365:1747-1748
            • Free Full Text

            A case is reported in which ipilimumab therapy for melanoma was followed by the development of an autoantibody to factor VIII.

          • Images in Clinical Medicine

            Dermatologic Signs of Multiple Myeloma

            Figure 1.

            • July 7, 2011
            • Green W.H. and Schosser R.H.
            • N Engl J Med 2011; 365:71
            • Free Full Text

            An 87-year-old woman presented for evaluation of progressive, nonpruritic, waxy papules and atraumatic ecchymoses in a periorbital (“raccoon eyes”) and perioral distribution. She was otherwise asymptomatic.

          • Editorial

            Been There, Not Done That — Melanoma in the Age of Molecular Therapy

            In 1976, the detection of estrogen-receptor expression in melanomas ushered in the era of targeted therapy in melanoma, although we did not use that term back then. In 1992, Cocconi et al. found that dacarbazine plus tamoxifen provided a higher response rate and longer survival than dacarbazine,…

            • June 30, 2011
            • Ernstoff M.S.
            • N Engl J Med 2011; 364:2547-2548

              In 1976, the detection of estrogen-receptor expression in melanomas ushered in the era of targeted therapy in melanoma, although we did not use that term back then.1 In 1992, Cocconi et al. found that dacarbazine plus tamoxifen provided a higher response ...

            • Original Article

              Improved Survival with Vemurafenib in Melanoma with BRAF V600E Mutation

              Metastatic melanoma has a poor prognosis, with the median survival for patients with stage IV melanoma ranging from 8 to 18 months after diagnosis, depending on the substage. In the United States last year, 8700 deaths from melanoma were projected, with an estimated rate of death of 2.6 in 100,000.…

              • June 30, 2011
              • Chapman P.B., Hauschild A., Robert C., et al.
              • N Engl J Med 2011; 364:2507-2516
              • Free Full Text
              • CME

              In patients with advanced melanomas with the BRAF V600E mutation, vemurafenib produced a response in nearly half the patients; secondary skin tumors, arthralgia, rash, and fatigue were side effects. Dacarbazine produced a response in 6%.

            • Original Article

              Ipilimumab plus Dacarbazine for Previously Untreated Metastatic Melanoma

              The survival rate for patients with metastatic melanoma is low, with an expected 2-year survival rate of 10 to 20%.– Although dacarbazine has never been shown to improve survival in randomized, controlled studies, it has been the drug most frequently compared with new agents or combination…

              • June 30, 2011
              • Robert C., Thomas L., Bondarenko I., et al.
              • N Engl J Med 2011; 364:2517-2526
              • Free Full Text

              Ipilimumab has been shown to improve survival in patients with previously treated metastatic melanoma. In this study, ipilimumab plus dacarbazine improved survival in patients with previously untreated metastatic melanoma.

            • Original Article

              gp100 Peptide Vaccine and Interleukin-2 in Patients with Advanced Melanoma

              Although it is clear that vaccines are important in the prevention of infectious diseases, their benefits with respect to metastatic cancer have been less clear. One of the first studies to show improved survival with vaccines among patients with metastatic cancer was reported recently in a study…

              • June 2, 2011
              • Schwartzentruber D.J., Lawson D.H., Richards J.M., et al.
              • N Engl J Med 2011; 364:2119-2127
              • Free Full Text

              In patients with metastatic melanoma, addition of a gp100 peptide vaccine to high-dose interleukin-2 doubled response rates, delayed disease progression by a few weeks, and extended median overall survival by 6 months. Toxic effects were mainly those associated with high-dose interleukin-2.

            • Images in Clinical Medicine

              Hutchinson's Nail Sign

              Figure 1.

              • May 5, 2011
              • Yun S.J. and Kim S.-J.
              • N Engl J Med 2011; 364:e38
              • Free Full Text

              A 37-year-old man presented with a brownish-black nail on the great toe of the right foot. A darkly pigmented linear patch had started to form within the toenail 4 years earlier and had widened and darkened over time. Two months before the current ...

            • Clinical Therapeutics

              Sentinel-Lymph-Node Biopsy for Cutaneous Melanoma

              Foreword. This Journal feature begins with a case vignette that includes a therapeutic recommendation. A discussion of the clinical problem and the mechanism of benefit of this form of therapy follows. Major clinical studies, the clinical use of this therapy, and potential adverse effects are…

              • May 5, 2011
              • Gershenwald J.E. and Ross M.I.
              • N Engl J Med 2011; 364:1738-1745
              • CME
              • Video

              In a patient with cutaneous melanoma, a sentinel-lymph-node biopsy is performed with the aid of a handheld gamma scanner and the use of isosulfan blue dye. The nodes are dissected as a group and then separated in preparation for histologic analysis.

            • Images in Clinical Medicine

              Amalgam Tattoo

              Figure 1.

              • April 14, 2011
              • Dubach P. and Caversaccio M.
              • N Engl J Med 2011; 364:e29
              • Free Full Text

              A 64-year-old man was referred for evaluation of an asymptomatic pigmented lesion on the buccal mucosa (Panels A and B). After 15 pack-years of smoking, he had quit smoking more than 30 years earlier and had no other risk factors for oral cancer. A biopsy ...

            • Perspective

              Early Accelerated Approval for Highly Targeted Cancer Drugs

              The striking results of recent phase 1 trials of targeted cancer drugs have provoked serious discussion about shortening the road to drug approval. A typical cancer drug takes 7 years from entry into human trials to approval by the Food and Drug Administration (FDA), which requires proof of…

              • March 24, 2011
              • Chabner B.A.
              • N Engl J Med 2011; 364:1087-1089

                Since we can define subgroups of patients who have high rates of response and disease control in phase 1 trials of targeted cancer drugs, the traditional long pathway to FDA approval of these drugs is increasingly under fire for medical and ethical reasons.

              • Images in Clinical Medicine

                Melanonychia Striata

                Figure 1.

                • March 17, 2011
                • de Almeida Santos M. and Malucelli T.O.
                • N Engl J Med 2011; 364:e22
                • Free Full Text

                An otherwise healthy 23-year-old black man was concerned about a dark line, 1 mm in width, arising from the nail bed of his right thumb (Panels A and B). The finding had been present for approximately 2 years and had not changed. The line originated in ...

              • Clinical Implications of Basic Research

                Resistance to BRAF Inhibition in Melanomas

                Approximately 50% of melanomas contain a mutation in the gene that encodes the RAF family member BRAF, a protein kinase that phosphorylates the MEK protein and activates the ERK signaling pathway. This mutation, which in most cases is a substitution of glutamic acid for valine at position 600 of…

                • February 24, 2011
                • Solit D.B. and Rosen N.
                • N Engl J Med 2011; 364:772-774

                  PLX4032, an inhibitor of activated BRAF, has shown clinical efficacy in treating patients with melanomas carrying an activating mutation in BRAF, but resistance to the drug develops in some patients. Two recent studies show possible mechanisms of such resistance.

                Page

                Medical Meetings Pediatrics Conferences and Meetings

                2012 Certifying Examinations of the American Board of Pediatrics

                The general pediatrics examination will be held in various cities, Oct. 16-18. Registration for first-time applicants is ongoing through May 3. Registration for re-registrants is ongoing through May 24. The following subspecialty examinations will be held in various cities: "Hospice and Palliative Medicine" (Oct. 4); "Pediatric Transplant Hepatology" (Oct. 11); "Pediatric Cardiology" (Nov. 7); "Pediatric Pulmonology" (Nov. 8); "Medical Toxicology" (Nov. 12); and "Pediatric Critical Care Medicine" (Nov. 14). Registration for first-time applicants is ongoing through April 30. Registration for re-registrants is ongoing through June 15.

                Contact the American Board of Pediatrics, 111 Silver Cedar Court, Chapel Hill, NC 27514-1513; or call (919) 929-0461; or fax (919) 918-7114 or (919) 929-9255; or see http://www.abp.org .

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