Durable responses and reversible toxicity of high-dose interleukin-2 treatment of melanoma and renal cancer in a Community Hospital Biotherapy Program.

BACKGROUND: High-dose interleukin-2 (IL-2) has been FDA-approved for over 20 years, but it is offered only at a small number of centers with expertise in its administration. We analyzed the outcomes of patients receiving high-dose IL-2 in relation to the severity of toxicity to ascertain if response or survival were adversely affected. METHODS: A retrospective analysis of the outcomes of 500 patients with metastatic renal cell carcinoma (RCC) (n = 186) or melanoma (n = 314) treated with high-dose IL-2 between 1997 and 2012 at Providence Cancer Center was performed. IL-2 was administered at a dose of 600,000 international units per kg by IV bolus every 8 hours for up to 14 doses. A second cycle was administered 16 days after the first and patients with tumor regression could receive additional cycles. Survival and anti-tumor response were analyzed by diagnosis, severity of toxicity, number of IL-2 cycles and subsequent therapy. RESULTS: The objective response rate in melanoma was 28% (complete 12% and partial 16%), and in RCC was 24% (complete 7% and partial 17%). The 1-, 2- and 3-year survivals were 59%, 41% and 31%, for melanoma and 75%, 56% and 44%, for RCC, respectively. The proportion of patients with complete or partial response in both melanoma and RCC was higher in patients who a) required higher phenylephrine doses to treat hypotension (p < 0.003), b) developed acidosis (bicarbonate < 19 mmol (p < 0.01)), or c) thrombocytopenia (<50, 50-100, >100,000 platelets; p < 0.025). The proportion achieving a complete or partial response was greater in patients with melanoma who received 5 or more compared with 4 or fewer IL-2 cycles (p < 0.0001). The incidence of death from IL-2 was less than 1% and was not higher in patients who required phenylephrine. CONCLUSIONS: High-dose IL-2 can be administered safely; severe toxicity including hypotension is reversible and can be managed in a community hospital. The tumor response and survival reported here are superior to the published literature and support treating patients to their individualized maximum tolerated dose. IL-2 should remain part of the treatment paradigm in selected patients with melanoma and RCC.

Evaluation of suspected local recurrence in head and neck cancer: a comparison between PET and PET/CT for biopsy proven lesions.

BACKGROUND: (18)F-FDG PET has a high accuracy for re-staging of head and neck cancer. The purpose of this study was to determine whether the diagnostic accuracy can be further improved with integrated PET/CT. MATERIALS AND METHODS: Forty-nine patients with a mean age of 59+/-18 years were studied retrospectively. Histo-pathological verification was available either from complete tumor resection with or without lymph node dissection (n=27) or direct endoscopic biopsy (n=16) or ultrasound guided biopsy (n=6). Two reviewers blinded to the pathological findings read all PET images in consensus. An experienced radiologist was added for the interpretation of the PET/CT images. RESULTS: Tissue verification was available for 110 lesions in 49 patients. Sixty-seven lesions (61%) were biopsy positive and 43 (39%) were negative for malignant disease. PET and PET/CT showed an overall accuracy for cancer detection of 84 and 88% (p=0.06), respectively. Sensitivity and specificity for PET were 78 and 93% versus 84 (p=NS) and 95% (p=NS) with PET/CT. A patient-by-patient analysis yielded a sensitivity, specificity and accuracy for PET of 80, 56 and 76%, compared to 88% (p=NS), 78% (p=NS) and 86% (p=0.06) for PET/CT. CONCLUSION: The results of this study indicate that PET/CT does not significantly improve the detection of recurrence of head and neck cancer. However, a trend towards improved accuracy was observed (p=0.06).

Ultrasound-guided laser-induced thermal therapy of malignant cervical adenopathy.

OBJECTIVES: Laser-induced thermal therapy (LITT) for cancer is a technique whereby a source of energy (laser, radiofrequency, ultrasonic, cryoenergy, and so on) is directly applied into a tumor at various depths. Recent studies have demonstrated the efficiency of ultrasound (UTZ) and magnetic resonance imaging (MRI) for real- or "near" real-time tumor and vessel identification as well as monitoring and quantifying energy-induced tissue damage. The objective of this study is to report UCLA's experience using UTZ monitoring of Nd:YAG laser thermal ablation of malignant cervical adenopathy in a phase II study. STUDY DESIGN: The authors conducted a retrospective study of patients treated at a tertiary medical center. METHODS: Forty-seven patients with a total of 55 neck tumors were treated on an outpatient basis in the operating room using UTZ for image-guided laser interstitial thermal therapy. Laser energy was delivered through an SLT Nd:YAG laser powered at 30 W (power density: 2,200 J/cm). RESULTS: Eleven patients had a complete response ranging from 5.5 to 90 months (mean, 22.1 months). Based on the findings of this study, it was possible to show that proximity to the carotid artery was the most relevant factor in projecting patient survival. Patients' individual treatment analysis and final outcome are further discussed. CONCLUSIONS: LITT ablation of malignant cervical adenopathy was considered safe and feasible. No intraoperative complications occurred. Further development of this technique applying laser energy delivery to mathematical imaging models should lead to more effective tumor palliation as an alternative to surgery.

Incidental paranasal sinus imaging abnormalities and the normal Lund score in children.

OBJECTIVES: Our goal was to determine the incidental Lund score for pediatric patients without chronic rhinosinusitis (CRS). METHODS: Pediatric patients with computed tomography scans of the orbit or brain were identified. Patients with a clinical history of sinonasal disorders or skeletal facial trauma were excluded. The remaining scans were scored according to the Lund-MacKay system. Pneumatization of the frontal and sphenoid sinuses was also recorded. A scaled Lund score was computed, and the mean Lund score for this normal population was determined. RESULTS: One hundred ninety-two computed tomography scans were examined (mean age, 9.0 years). The frontal sinuses and sphenoid sinuses were absent in 40.1% and 1.6% of cases, respectively. The mean scaled Lund score in this pediatric population without CRS was 2.81 (95% confidence interval, 2.40 to 3.22). This result differed statistically from a score of 0 (P < 0.001). Only 37 (19.3%) patients had completely radiographically normal sinuses. CONCLUSIONS: The mean incidental Lund score in the absence of CRS approaches 3, and this should be considered when determining the diagnostic likelihood of CRS in pediatric patients.

Longitudinal progression of subclinical structural brain disease in normal aging.

OBJECTIVE: The authors describe four types of brain structural change in "normal aging:" cortical atrophy, central atrophy, deep white-matter hyperintensities (DWMH), and periventricular hyperintensities (PVH). Cross-sectional investigations have reported that greater volumes of these forms of "subclinical structural brain disease" (SSBD) were found with increasing age. Greater volumes were also associated with poorer cognition, even though subjects performed within the normal range. The natural history of these forms of SSBD and their functional impact are not well established. METHODS: Twenty-nine normal subjects, ages 60-89, were examined longitudinally by volumetric magnetic resonance imagery, with two assessments performed at least 2 years apart; 26 also completed neuropsychological testing to evaluate processing speed, executive functions, language, and other cognitive functions. Associations between structure and function were evaluated with regression models. RESULTS: For most subjects, the volumes for signs of all types of SSBD were found to have increased; for many subjects, increases were small, and a few showed no change or small decreases. PVH and DWMH increases were predicted by baseline cerebrovascular risk factors. Cognitive test performance changed little over time for these normal subjects. CONCLUSIONS: SSBD volumes increased for most subjects over time, with small average increases for most types. Pretreatment cerebrovascular risk factors were associated with greater increases of PVH and DWMH, suggesting that progression of these types of SSBD may be amenable to intervention.

Recurrent pleomorphic adenoma of the parotid gland in pediatric and adult patients: value of multiple lesions as a diagnostic indicator.

OBJECTIVE: Recurrent pleomorphic adenoma of the parotid gland is a significant problem. Rates have been as high as 40% in some series of patients who have undergone surgery for the primary lesion. In the imaging literature, anecdotal case reports show multiple lesions in recurrent pleomorphic adenoma. Our aim was to analyze the imaging of a series of patients to determine the reliability of multiple lesions as a tool in diagnosing recurrent disease. MATERIALS AND METHODS: Medical records of the patients with recurrent pleomorphic adenoma of the parotid gland referred to our institution were retrospectively reviewed. Before the second surgery, MR imaging had been performed in 15 patients. We retrospectively reevaluated and scored the MR imaging studies with particular attention paid to the location and number of the lesions and the remaining parotid gland tissue. RESULTS: On the basis of imaging findings, eight patients underwent enucleation, superficial parotidectomy had been performed in four patients, and three patients underwent total parotidectomy. For our group, the lesions were multiple in 73.3% of patients. CONCLUSION: To our knowledge, we present the first large series of imaging studies in recurrent pleomorphic adenoma of the parotid gland. Our findings show that recurrent pleomorphic adenomas are most likely to be multiple. Such multiplicity of lesions is a reliable diagnostic indicator of recurrent disease.

MRI-guided access to the retropharynx.

PURPOSE: To describe MR-guided access to the retropharynx for precise fine-needle aspiration cytology (FNAC), and other indications for needle placement. MATERIALS AND METHODS: A retrospective review was made of 15 procedures that had been performed on 14 patients. These patients had a retropharyngeal mass on MRI and had undergone MR-guided minimally invasive access to the retropharynx for either diagnostic or therapeutic intervention in the period of October 1989 to January 2000. RESULTS: All 14 patients underwent MR-guided access to the retropharynx for FNAC without immediate or delayed complications. MRI confirmed that the biopsy needle was within the retropharyngeal mass in all patients. MR-guided FNAC revealed five true-positive, five true-negative, four indeterminate, and no false-positive cases. Ten of the 14 patients (71%) had diagnostic aspirations. In one patient with retropharyngeal extension of carcinoma, an MR-guided approach was used for the experimental interstitial laser therapy (ILT). CONCLUSION: The results suggest that an MR-guided retromandibular approach to biopsy of retropharyngeal mass is minimally invasive and safe.

Isolated inverting papilloma of the sphenoid sinus.

OBJECTIVES/HYPOTHESIS: Primary inverting papilloma of the sphenoid sinus is rare. We present a case of inverting papilloma with isolated involvement of the sphenoid sinus and discuss the incidence, clinical presentation, radiographic features, histological findings, and management of patients with this disease. STUDY DESIGN: Case report. METHODS: The medical records, films, and pathology slides of a patient with isolated inverting papilloma of the sphenoid sinus seen at University of California Los Angeles Medical Center were reviewed. The clinical presentation, radiographic features, histopathological findings, treatment, and outcome of the case were examined. RESULTS: A single case of inverting papilloma with isolated involvement of the sphenoid sinus is presented. Headache and diplopia were the presenting complaints, as is often seen with other isolated sphenoid sinus lesions. Endoscopic intranasal sphenoid sinusotomy was performed, and no evidence of recurrent disease has been seen after 6 months of follow-up. CONCLUSIONS: Isolated inverting papilloma of the sphenoid sinus is a rare phenomenon. In contrast to the vast majority of cases that present with nasal complaints (i.e., unilateral nasal obstruction, epistaxis) because of involvement of the lateral nasal wall, the clinical presentation of inverting papillomas confined to the sphenoid sinus is often nonspecific and insidious, with visual deficits being the predominant feature. Nevertheless, functional endoscopic intranasal sphenoidotomy remains an effective mode of treatment for patients with these lesions.

Cognitive and physiologic correlates of subclinical structural brain disease in elderly healthy control subjects.

CONTEXT: Healthy elderly persons commonly show 4 types of change in brain structure-cortical atrophy, central atrophy, deep white-matter hyperintensities, and periventricular hyperintensities-as forms of subclinical structural brain disease (SSBD). OBJECTIVES: To characterize the volumes of SSBD present with aging and to determine the associations of SSBD, physiology, and cognitive function. DESIGN: Cross-sectional study. SETTING: University of California, Los Angeles, Neuropsychiatric Institute. SUBJECTS: Forty-three community-dwelling healthy control subjects, aged 60 through 93 years. MAIN OUTCOME MEASURES: Volumetric magnetic resonance imaging, neuropsychological testing, and quantitative electroencephalographic coherence (functional connectivity) between brain regions. RESULTS: Regression models demonstrated significant relationships between SSBD volumes, age, cognitive performance, and connectivity. Cortical and central atrophy and periventricular hyperintensities had significant associations with age while deep white-matter hyperintensities did not. Posterior atrophy showed stronger associations with age than did anterior atrophy. Only a subset of subjects at older ages showed large SSBD volumes; older subjects primarily showed increasing variance of SSBD. Although all subjects scored within the normal range on cognitive testing, SSBD volume was inversely related to performance, most notably on the Trail-Making Test part B and the Shipley-Hartford Abstract Reasoning test. Coherence had significant associations with SSBD. Path analysis supported mediation of the effects of deep white-matter hyperintensities and periventricular hyperintensities on cognition by altered connectivity. For several measures, cognitive performance was best explained by coherence, and only secondarily by SSBD. CONCLUSIONS: Modest volumes of SSBD were associated with decrements in cognitive performance within the normal range in healthy subjects. Lower coherence was associated with greater volumes of SSBD and increasing age. Path analysis models suggest that brain functional connectivity mediates some effects of SSBD on cognition.

Congenital implantation cholesteatomas of the occipitoparietotemporal junction.

Two cases of cranial cholesteatomas centered at the occipitoparietotemporal junction are presented, and 12 similar cases reported as diploic cholesteatomas involving the temporal bone are reviewed. Among the reported diploic cholesteatomas, 3 involved the occipitoparietotemporal junction and had the same clinical characteristics as the ones presented here. These 5 lesions did not produce expansion of the cranial tables, they had a predominantly intracranial growth, and their matrix was bonded to the dura, so that their complete excision was prevented. It is proposed that cranial cholesteatomas involving the occipitoparietotemporal junction arise, not from within the tables of the skull, but from squamous cells trapped during closure of the mastoid fontanelle and formation of the suture. Hence, they should be recognized as having an origin different from that of diploic lesions, and termed congenital implantation cholesteatomas.

Fungal mucoceles of the sphenoid sinus.

OBJECTIVE: The purpose of this study was to demonstrate that fungal mucoceles of the sphenoid sinus do not necessarily require an external approach for eradication of disease. We report 6 cases of fungal mucoceles of the sphenoid sinus seen at UCLA Medical Center from 1980-1999, 4 of which were successfully treated with endoscopic intranasal sphenoidotomy and the other 2 through either a transseptal or transantral approach. STUDY DESIGN AND METHODS: Case series. The medical records of 6 patients with fungal mucoceles of the sphenoid sinus treated at UCLA Medical Center over a 20-year period (1980-1999) were retrospectively reviewed. RESULTS: Six patients diagnosed with fungal mucoceles of the sphenoid sinus were seen at UCLA Medical Center from 1980-1999. Endoscopic intranasal sphenoid sinusotomy was performed on 4 patients and a transseptal or transantral approach to the sphenoid sinus was used on the remaining 2 patients. No evidence of recurrent disease has been seen after up to 15 years of follow-up. CONCLUSIONS: When diagnosed early, functional endoscopic intranasal sphenoidotomy represents an effective mode of treatment for patients with fungal mucoceles of the sphenoid sinus, obviating the need for more aggressive surgical approaches.

Estrogen replacement therapy is associated with less progression of subclinical structural brain disease in normal elderly women: a pilot study.

BACKGROUND: Cortical atrophy, central atrophy, deep white-matter hyperintensities, and periventricular hyperintensities are reported in normal aging. OBJECTIVES: We examined the effects of estrogen replacement therapy (ERT) on these forms of 'subclinical structural brain disease' (SSBD) in normal, postmenopausal women in a pilot, naturalistic, longitudinal study of 15 subjects. METHODS: Two assessments were performed at least two years apart, with volumetric magnetic resonance imaging (MRI) and neuropsychological testing. RESULTS: Women receiving open-label ERT showed significantly less progression of SSBD than those who did not. CONCLUSIONS: The association between reduced SSBD progression and ERT suggests this intervention could help preserve normal brain structure in healthy elderly women.