A 47-year-old white man, who had an above-the-knee amputation of his left leg, was treated with single-agent sorafenib 400 mg orally twice daily for metastatic renal cell carcinoma. The patient regularly wore a prosthesis that encases his left stump. After approximately 8 weeks on sorafenib, the patient developed a tingling sensation of bilateral hands, his right sole, and his left stump. These quickly progressed to well-demarcated, tender, erythematous, scaling lesions on his palms, right sole (Fig 1) and left stump (Fig 2). Painless distal subungual splinter hemorrhages were also seen in all of his fingernails. Based on clinical findings and history, a diagnosis of hand-foot and stump syndrome (HFSS) secondary to sorafenib therapy was made.Like hand-foot syndrome, the mechanism by which sorafenib induces the HFSS variant remains only speculative. However, the observed results of this case indicate a possible relationship between the direct toxic effect of the chemotherapeutic drug delivered by the high concentration of eccrine glands in the palms and right sole, and the hyperhidrosis of the encased left stump, which may have contributed to the development of the HFSS on these sites and supporting the notion of anticancer agents in eccrine sweat leading to alterations in skin. 1 Features of the acral skin, such as the temperature gradient, the vascular anatomy, the rapidly dividing epidermis, and the highest number of eccrine sweat glands, favor such a hypothesis. 2,3 In a study looking at 10 patients treated with doxorubicin, a well described culprit for HFS, Jacobi et al 5 measured the fluorescence of the drug qualitatively using a dermatologic laser scanning microscope in one male patient before and after intravenous treatment of doxorubicin on several body surface areas. 4 Doxorubicin fluorescence was detected in the uppermost part of the skin on the palmar-plantar surfaces, deep in sweat ducts, and around their openings in the upper skin layers. 4 This result suggests that the chemotherapeutic agent was delivered by the sweat to the skin surface.Other cutaneous adverse effects that can be caused by sorafenib warrant attention, including a seborrheic dermatitis-like rash, alopecia, stomatitis, splinter hemorrhages, and inflammation of actinic keratoses. 5 The splinter hemorrhages may possibly be explained by the blockade of the vascular endothelial growth factor receptor, which might impair the intrinsic repair mechanisms of delicate injury-prone spiral capillaries. 6 Depigmentation of terminal hairs has also been witnessed in clinical practice, occurring in as few as 8 weeks. In mice, blockade of c-kit signaling leads to complete but reversible hair depigmentation with inhibition of melanocyte proliferation and differentiation. 7 Multitargeted tyrosine kinase inhibitors can induce a variety of dermatologic adverse events, which require early recognition and effective management, 8 in order to ensure continued lifesaving antineoplastic therapy. It is anticipated that observations such as the one described he...

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466 Background: Many pts receiving tyrosine kinase inhibitors for RCC manifest stable disease as their best response by RECIST criteria. We hypothesized that tumor necrosis by DCE and DW-MRI after brief treatment with neoS may correlate with pathologic findings. We investigated in a pilot study whether these MRI changes may serve as an imaging biomarker predictive of clinical outcome. Methods: Pts with locally advanced or metastatic clear cell RCC undergoing nephrectomy or metastastectomy were treated with neoS 400mg PO bid for 28 days prior to surgery. The feasibility and safety of neoS was determined. Tumor necrosis detected by DCE and DW MRI’s pre- and post-neoS were compared and correlated with survival and pathologic findings at surgery. RECIST/WHO criteria were also compared. Results: 9 pts were enrolled, and all underwent surgery after neoS, 4 weeks (n=7) or less for toxicity (n=2). Clear cell/sarcomatoid histology was noted in 8 pts, and papillary in 1. All pts had T3 or T4 disease. 7 had M1 disease. No surgical complications occurred. 7 pts (78%) experienced grade 3 toxicities, including hypertension (n=1), pancreatitis (n=1), hand-foot syndrome (n=1), hyponatremia (n=2), and rash (n=2). No grade 4 or 5 toxicities were observed. 4 of 8 clear cell/sarcomatoid pts (50%) have died, 3 because of progressive disease and 1 of unrelated causes. DCE and DW MRI’s with direct surgical pathological correlation were available in 7 of these pts. The mean ADC DW MRI changes in the renal lesion of 4 longer term survivors (median survival = 43 months) was +.22 vs. –0.07 in the 3 short term survivors (median survival = 13 months). RECIST/WHO criteria did not correlate with response. Evaluation of lack of enhancement on DCE MRI and increase in ADC on DW MRI were seen and correlated with necrosis on pathologic specimens. Conclusions: Four weeks of neoS is associated with significant necrosis that correlates with DCE-MRI and DW-MRI. There may be a trend in survival with greater necrosis, suggesting a role for these imaging biomarkers to assess early benefits of therapy. Clinical trial information: NCT00727532.

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e18523 Background: Lymphomatoid Papulosis (LYP) is a primary cutaneous CD30+ lymphoproliferative disorder and a radiosensitive tumor. Treatment with radiation is typically given in multiple fractions for patients presenting with symptomatic unilesional or multilesional disease. However, a single fraction of radiation is more convenient to the patient. The purpose of this retrospective review was to evaluate the clinical response to a single fraction of radiation for palliation of symptomatic LYP lesions. Methods: The records of 8 (5 female, 3 male) patients with LYP, treated with a single or multi-fractionated palliative radiation therapy between 10/2001 and 9/2011, were reviewed. All patients had received multiple previous treatments such as chemotherapy, PUVA, topical nitrogen mustard, and UVB. A total of 19 sites with disease were given the following single doses: 700 (n=3) and 800 (n=16). In the earlier years, a total of 6 sites with disease were given 250 cGy in 18 fractions for a total dose of 4500 cGy. Radiation therapy was administered with electrons to 20 sites and with photons to 5. A bolus was used in most cases to increase the radiation dosage to the skin. Results: Minimum and median follow-up were 1 and 43 months (range, 1 - 120), respectively. Median age of the patients was 65 (range, 24 - 83). For disease sites receiving a single fraction therapy, a complete response (CR) was seen in 17 of the 19 sites (89.5%), and a partial response (PR) was seen in an additional 2 of the 19 sites (10.5%). Therefore, the overall response rate was 100%. For the disease sites receiving multi-fractionated therapy, a CR was seen in 6 of the 6 sites (100%). Evaluation of patient characteristics and treatment did not reveal any differences between patients achieving a CR or PR. Conclusions: For previously treated, radiation-naıve LYP lesions, palliative radiation therapy with single fractions of 700 - 800 cGy is associated with an excellent CR and is a convenient and cost effective strategy.