Patient-reported outcome changes at the end of life in recurrent platinum-resistant ovarian cancer: An NRG oncology/GOG study.

Objectives: In a prospective study of platinum-resistant ovarian cancer patients, we examined whether the Disease-related Symptoms-Physical (DRS--P) scale of the NCCN/FACT-Ovarian Cancer Symptom Index-18 (NFOSI-18) is responsive to clinical change in patients estimated by their provider to survive at least six months.

Methods: The NFOSI-18, and other FACT measures, was collected at study entry and 3 and 6 months post-enrollment. Measures were compared for those who died or dropped off study prior to 3 months or prior to 6 months (assumed as health deterioration over time), or those who stayed on study through 6 months (presumed as stable disease over time).

Porokeratosis Plantaris, Palmaris et Disseminata Caused by Con- genital Pathogenic Variants in the MVD Gene and Loss of Hetero-zygosity in Affected Skin.

Porokeratoses are a heterogeneous group of keratinization disorders. For linear porokeratosis and disseminated superficial actinic porokeratosis, a heterozygous pathogenic germline variant in a mevalonate pathway gene and a postzygotic second hit mutation present in affected skin have been shown to be the patho-genetic mechanism for the development of the lesions. However, the molecular mechanism leading to development of porokeratosis plantaris, palmaris et disseminata is not known.

Predictive Blood-Based Biomarkers in Patients with Epithelial Ovarian Cancer Treated with Carboplatin and Paclitaxel with or without Bevacizumab: Results from GOG-0218.

Purpose: GOG-0218, a double-blind placebo-controlled phase III trial, compared carboplatin and paclitaxel with placebo, bevacizumab followed by placebo, or bevacizumab followed by bevacizumab in advanced epithelial ovarian cancer (EOC). Results demonstrated significantly improved progression-free survival (PFS), but no overall survival (OS) benefit with bevacizumab. Blood samples were collected for biomarker analyses.

Final Overall Survival of a Randomized Trial of Bevacizumab for Primary Treatment of Ovarian Cancer.

Purpose: We report the final, protocol-specified analysis of overall survival (OS) in GOG-0218, a phase III, randomized trial of bevacizumab in women with newly diagnosed ovarian, fallopian tube, or primary peritoneal carcinoma.

Methods: A total of 1,873 women with incompletely resected stage III to IV disease were randomly assigned 1:1:1 to six 21-day cycles of intravenous carboplatin (area under the concentration time curve 6) and paclitaxel (175 mg/m) versus chemotherapy plus concurrent bevacizumab (15 mg/kg, cycles 2 to 6) versus chemotherapy plus concurrent and maintenance bevacizumab (cycles 2 to 22). Inclusion criteria included a Gynecologic Oncology Group performance status of 0 to 2 and no history of clinically significant vascular events or evidence of intestinal obstruction.

Quality of life, symptoms and care needs in patients with persistent or recurrent platinum-resistant ovarian cancer: An NRG Oncology/Gynecologic Oncology Group study.

Objectives: The goals of treating recurrent platinum-resistant ovarian cancer are palliative, aimed at reducing symptoms and improving progression free survival. A prospective trial was conducted to determine the prevalence and severity of symptoms, and associated care needs.

Methods: Eligible women included those with persistent or recurrent platinum-resistant ovarian cancer with an estimated life expectancy of at least 6 months.

[Generalized eruptive histiocytosis-Juvenile xanthogranuloma: clinical spectrum in a pediatric patient].

Both, generalized eruptive histiocytosis and juvenile xanthogranuloma are dendritic histiocytic disorders (also known as non-Langerhans cells histiocytosis) that share clinicopathological and immunohistiochemical characteristics. We present a 3-year-old female patient with skin lesions that were clinically compatible with generalized eruptive histiocytosis, confirmed by histopathological and immunohistochemical studies. During her development the disorder compromised the central nervous system, and surgical intervention of one symptomatic lesion was needed.

Weekly vs. Every-3-Week Paclitaxel and Carboplatin for Ovarian Cancer.

Background: A dose-dense weekly schedule of paclitaxel (resulting in a greater frequency of drug delivery) plus carboplatin every 3 weeks or the addition of bevacizumab to paclitaxel and carboplatin administered every 3 weeks has shown efficacy in ovarian cancer. We proposed to determine whether dose-dense weekly paclitaxel and carboplatin would prolong progression-free survival as compared with paclitaxel and carboplatin administered every 3 weeks among patients receiving and those not receiving bevacizumab.

Methods: We prospectively stratified patients according to whether they elected to receive bevacizumab and then randomly assigned them to receive either paclitaxel, administered intravenously at a dose of 175 mg per square meter of body-surface area every 3 weeks, plus carboplatin (dose equivalent to an area under the curve [AUC] of 6) for six cycles or paclitaxel, administered weekly at a dose of 80 mg per square meter, plus carboplatin (AUC, 6) for six cycles.

Ascites predicts treatment benefit of bevacizumab in front-line therapy of advanced epithelial ovarian, fallopian tube and peritoneal cancers: an NRG Oncology/GOG study.

Objectives: Predictive factors for efficacy of bevacizumab in advanced ovarian cancer have remained elusive. We investigated ascites both as a prognostic factor and as a predictor of efficacy for bevacizumab.

Methods: Using data from GOG 0218, patients receiving cytotoxic therapy plus concurrent and maintenance bevacizumab were compared to those receiving cytotoxic therapy plus placebo.

Risk factors for GI adverse events in a phase III randomized trial of bevacizumab in first-line therapy of advanced ovarian cancer: A Gynecologic Oncology Group Study.

Purpose: To evaluate risk factors for GI adverse events (AEs) within a phase III trial of bevacizumab in first-line ovarian cancer therapy.

Patients And Methods: Women with previously untreated advanced disease after surgery were randomly allocated to six cycles of platinum-taxane chemotherapy plus placebo cycles (C)2 to C22 (R1); chemotherapy plus bevacizumab C2 to C6 plus placebo C7 to C22 (R2); or chemotherapy plus bevacizumab C2 to C22 (R3). Patients were evaluated for history or on-study development of potential risk factors for GI AEs defined as grade ≥ 2 perforation, fistula, necrosis, or hemorrhage.

RASA1 mutations and associated phenotypes in 68 families with capillary malformation-arteriovenous malformation.

Capillary malformation-arteriovenous malformation (CM-AVM) is an autosomal-dominant disorder, caused by heterozygous RASA1 mutations, and manifesting multifocal CMs and high risk for fast-flow lesions. A limited number of patients have been reported, raising the question of the phenotypic borders. We identified new patients with a clinical diagnosis of CM-AVM, and patients with overlapping phenotypes.

Angora hair nevus. A further case of an unusual epidermal nevus representing a hallmark of angora hair nevus syndrome.

Background: The association of Blaschko lines with genetic mosaicism has lead to the concept that this pattern represents the manifestation of genetically abnormal skin tissue contrasting with the genetically normal skin. Various mosaic defects affecting not only the skin but also extracutaneous tissues have lead to the description of different types of epidermal nevus syndromes. We present a further case of an unusual organoid epidermal nevus characterized by depigmented hypertrichosis.

Patient reported outcomes of a randomized, placebo-controlled trial of bevacizumab in the front-line treatment of ovarian cancer: a Gynecologic Oncology Group Study.

Purpose: To analyze quality of life (QOL) in a randomized, placebo-controlled phase III trial concluding that the addition of concurrent and maintenance bevacizumab (Arm 3) to carboplatin and paclitaxel prolongs progression-free survival in front-line treatment of advanced ovarian cancer compared to chemotherapy alone (Arm 1) or chemotherapy with bevacizumab in cycles 2-6 only (Arm 2).

Patients And Methods: The Trial Outcome Index of the Functional Assessment of Cancer Therapy-Ovary (FACT-O TOI) was used to assess QOL before cycles 1, 4, 7, 13, and 21; and 6months after completing study therapy. Differences in QOL scores were assessed using a linear mixed model, adjusting for baseline score, and age.

A phase 2 trial of flavopiridol (Alvocidib) and cisplatin in platin-resistant ovarian and primary peritoneal carcinoma: MC0261.

Purpose: Based upon promising preclinical and phase 1 trial results, combined flavopiridol and cisplatin therapy was evaluated in patients with ovarian and primary peritoneal cancers.

Methods: A two cohort phase 2 trial of cisplatin (60 mg/m2 IV) immediately followed by flavopiridol (100 mg/m2 IV, 24 h infusion; 21 day cycles) was undertaken in patients with recurrent platin-sensitive or platin-resistant disease (progression>vs. ≤6 months following prior platin-based therapy).

Incorporation of bevacizumab in the primary treatment of ovarian cancer.

Background: Vascular endothelial growth factor is a key promoter of angiogenesis and disease progression in epithelial ovarian cancer. Bevacizumab, a humanized anti-vascular endothelial growth factor monoclonal antibody, has shown single-agent activity in women with recurrent tumors. Thus, we aimed to evaluate the addition of bevacizumab to standard front-line therapy.

Cutis tricolor parvimaculata in two patients with ring chromosome 15 syndrome.

Two unrelated girls presented with multiple disseminated, paired, small café-au-lait spots and hypopigmented macules, suggesting didymosis (twin spotting). The girls also had growth retardation, microcephaly, hypertelorism, triangular facies, and a 46,XY, r(15) karyotype. The term cutis tricolor parvimaculata has been proposed to describe a twin spot phenomenon characterized by small, paired hypochromic and hyperchromic macules on a background of normal intermediate-pigmented skin.

Acanthosis nigricans and hypochondroplasia in a child with a K650Q mutation in FGFR3.

Acanthosis nigricans has been described in several autosomal dominant skeletal dysplasia syndromes due to germline FGFR3 mutations, but rarely specifically in patients with hypochondroplasia. We report a child who presented with extensive acanthosis nigricans, short stature, and radiographic evidence of hypochondroplasia. Genetic analysis revealed a heterozygous K650Q mutation in FGFR3.

A phase II trial of carboplatin and docetaxel followed by radiotherapy given in a "Sandwich" method for stage III, IV, and recurrent endometrial cancer.

Objective: To determine feasibility and efficacy of administering docetaxel and carboplatin chemotherapy followed by pelvic radiotherapy and then consolidation chemotherapy in patients with advanced or recurrent endometrial cancer.

Methods: Patients with surgically staged III-IV (excluding IIIA from positive cytology alone) endometrial cancer or biopsy confirmed recurrent disease were eligible. Treatment consisted of 3 cycles of docetaxel (75 mg/m²) and carboplatin (AUC 6) on a q21 day schedule followed by involved field irradiation (45 Gy)± brachytherapy and three additional cycles of docetaxel and carboplatin.

Homozygous mutations in the 5' region of the JUP gene result in cutaneous disease but normal heart development in children.

Desmosomes are intercellular adhesive junctions and attachment sites for the intermediate filament (IF) cytoskeleton, prominent in tissues subject to high levels of mechanical stress such as the epidermis and heart. The obligate desmosomal constituent, plakoglobin (PG), is involved in coupling transmembrane desmosomal components with IFs. PG also contributes to intercellular adhesion through adherens junctions and has additional signaling roles.

Pronounced linear calcinosis in a boy with mild dermatomyositis. A further possible example of superimposed segmental manifestation of a polygenic disorder.

A pronounced linear eruption with ulcerations and calcium extrusion present in a boy with a mild generalized rash clinically consistent with juvenile dermatomyositis or overlap syndrome is reported. Loss of heterozygosity (LOH) is a postzygotic mechanism by which a heterozygous somatic cell may become homozygous or hemizygous at a given gene locus. Such a mechanism can be suspected when a pronounced segmental manifestation of an acquired skin condition with a polygenic background is found to be superimposed on more or less symmetrically distributed nonsegmental lesions of the same disorder.

IFAP syndrome is caused by deficiency in MBTPS2, an intramembrane zinc metalloprotease essential for cholesterol homeostasis and ER stress response.

Ichthyosis follicularis with atrichia and photophobia (IFAP syndrome) is a rare X-linked, oculocutaneous human disorder. Here, we assign the IFAP locus to the 5.4 Mb region between DXS989 and DXS8019 on Xp22.

PORCN mutations in focal dermal hypoplasia: coping with lethality.

The X-linked dominant trait focal dermal hypoplasia (FDH, Goltz syndrome) is a developmental defect with focal distribution of affected tissues due to a block of Wnt signal transmission from cells carrying a detrimental PORCN mutation on an active X-chromosome. Molecular characterization of 24 unrelated patients from different ethnic backgrounds revealed 23 different mutations of the PORCN gene in Xp11.23.