Citations

Abstract Purpose: In the randomized phase III trial, Gynecologic Oncology Group (GOG) protocol 240, the incorporation of bevacizumab with chemotherapy significantly increased overall survival (OS) in women with advanced cervical cancer. A major objective of GOG-240 was to prospectively analyze previously identified pooled clinical prognostic factors known as the Moore criteria. Experimental Design: Potential negative factors included black race, performance status 1, pelvic disease, prior cisplatin, and progression-free interval <365 days. Risk categories included low-risk (0–1 factor), mid-risk (2–3 factors), and high-risk (4–5 factors). Each test of association was conducted at the 5% level of significance. Logistic regression and survival analysis was used to determine whether factors were prognostic or could be used to guide therapy. Results: For the entire population (n = 452), high-risk patients had significantly worse OS (P < 0.0001). The HRs of death for treating with topotecan in low-risk, mid-risk, and high-risk subsets are 1.18 [95% confidence interval (CI), 0.63–2.24], 1.11 (95% CI, 0.82–1.5), and 0.84 (95% CI, 0.50–1.42), respectively. The HRs of death for treating with bevacizumab in low-risk, mid-risk, and high-risk subsets are 0.96 (95% CI, 0.51–1.83; P = 0.9087), 0.673 (95% CI, 0.5–0.91; P = 0.0094), and 0.536 (95% CI, 0.32–0.905; P = 0.0196), respectively. Conclusions: This is the first prospectively validated scoring system in cervical cancer. The Moore criteria have real-world clinical applicability. Toxicity concerns may justify omission of bevacizumab in some low-risk patients where survival benefit is small. The benefit to receiving bevacizumab appears to be greatest in the moderate- and high-risk subgroups (5.8-month increase in median OS). Clin Cancer Res; 21(24); 5480–7. ©2015 AACR.

Background Idiopathic dilated cardiomyopathy ( DCM ) is typically diagnosed in adulthood, yet familial cases exhibit variable age‐dependent penetrance and a subset of patients develop sporadic DCM in childhood. We sought to discover the molecular basis of sporadic DCM in an 11‐year‐old female with severe heart failure necessitating cardiac transplantation. Methods and Results Parental echocardiograms excluded asymptomatic DCM . Whole exome sequencing was performed on the family trio and filtered for rare, deleterious, recessive, and de novo variants. Of the 8 candidate genes identified, only 2 had a role in cardiac physiology. A de novo missense mutation in TNNT 2 was identified, previously reported and functionally validated in familial DCM with markedly variable penetrance. Additionally, recessive compound heterozygous truncating mutations were identified in XIRP 2 , a member of the ancient Xin gene family, which governs intercalated disc ( ICD ) maturation. Histomorphological analysis of explanted heart tissue revealed misregistration, mislocalization, and shortening of ICD s, findings similar to Xirp2 −/− mice. Conclusions The synergistic effects of TNNT 2 and XIRP 2 mutations, resulting in perturbed sarcomeric force generation and transmission, respectively, would account for an early‐onset heart failure phenotype. Whereas the importance of Xin proteins in cardiac development has been well established in animal models, this study implicates XIRP 2 as a novel modifier gene in the pathogenesis of DCM .

Background: Many women have heavy menstrual bleeding during perimenopause that may interfere with overall quality of life and contribute to sexual dysfunction. We aimed to determine whether sexual function in women improves after endometrial ablation for heavy menstrual periods. Methods: Validated surveys (Female Sexual Function Index [FSFI], Female Sexual Distress Scale [FSDS], and Short-Form Health Survey [SF–12]) were administered to 136 women before and after endometrial ablation from August 2008 through June 2013. Scores at baseline and 6 months after surgery were compared using the paired t test. Results: A total of 97 women completed the FSFI and FSDS surveys at baseline and 6 months after ablation. Mean full-scale FSFI score increased from 26.5 to 28.8 ( p < .001), with improvement in 5 of 6 FSFI domains. Mean FSDS score decreased from 13.6 to 9.7 ( p < .001), showing decreased personal distress regarding sexual function. In assessing quality of life, SF–12 scores improved for global physical function ( p < .001) and mental function ( p = .002). Conclusions: Female sexual function improved and personal distress associated with sexual function decreased after endometrial ablation for heavy menstrual cycles.

Abstract Background Pilocytic astrocytoma is a rare tumor in adults. This report is of a prospective clinical trial with long-term follow-up. Methods Between 1986 and 1994, 20 eligible adults with supratentorial pilocytic astrocytomas were enrolled in a prospective intergroup trial of radiotherapy (RT) after biopsy (3 patients) or observation after gross (11 patients) or subtotal (6 patients) resection. Results At the time of analysis (median follow-up, 20.8 years), 2 patients (10%) have died and 18 patients (90%) are alive. Neurologic and cognitive function were stable or improved over time for the majority of patients. No toxic effects of treatment or malignant transformations have been recorded at last follow-up. For the entire cohort the 20-year time to progression and overall survival rates are 95% and 90% respectively. The cause of death (2.2 and 16.1 years after enrollment) in both patients was unrelated to tumor although both were biopsy-only patients. One subtotally resected tumor progressed 1 month after enrollment requiring P32 injection into an enlarging cyst. Because of further progression this patient required RT 18 months later. This patient is alive without evidence of progression 18 years after RT. Conclusion The long-term follow-up results of this prospective trial confirm that adults with pilocytic astrocytomas have a favorable prognosis with regard to survival and neurologic function. Close observation is recommended for adults with pilocytic astrocytomas, reserving RT for salvage, as the majority remain stable after gross or subtotal resection and no adjuvant therapy.

Purpose In order to achieve an oncological margin during limb salvage surgery for tumours around the hip, part or the entire hip joint is frequently sacrificed. Hip arthroplasty restores a functional extremity and achieves limb salvage. Currently there is a paucity of data concerning the late complications, long-term survival, and the risks of re-revision following aseptic revision of a total hip arthroplasty (THA) performed following an oncological resection. Methods We identified 78 patients who underwent aseptic revision of a THA which was performed for an oncological process involving the hip from 1972 to 2006. All patients had a minimum 5 years of follow-up with a mean of 13 years. Outcomes were compared to 1,378 patients undergoing aseptic revision of a THA that was performed for a diagnosis of osteoarthritis. Results The mean 5-, 10-, 15-, and 20-year re-revision-free survival for an oncologic process of the hip was 100%, 85%, 69%, and 57%. Within this cohort, younger patients were at an increased risk of revision surgery. There was no difference in survivorship of the revision implant at any of the aforementioned time points between the oncologic and osteoarthritis cohorts. Patients with an oncologic diagnosis had a higher rate of dislocations, component wear, and loosening compared to the osteoarthritis group. Conclusion Late complications following revision surgery of THA performed for an oncologic resection are common. The results of this study provide information for counselling patients on implant survivorship and complications following aseptic revision THA after index surgery for an oncologic indication.

Partial knee arthroplasty (PKA), either medial or lateral unicompartmental knee artroplasty (UKA) or patellofemoral arthroplasty (PFA) are a good option in suitable patients and have the advantages of reduced operative trauma, preservation of both cruciate ligaments and bone stock, and restoration of normal kinematics within the knee joint. However, questions remain concerning long-term survival. The goal of this review article was to present the long-term results of medial and lateral UKA, PFA and combined compartmental arthroplasty for multicompartmental disease. Medium- and long-term studies suggest reasonable outcomes at ten years with survival greater than 95% in UKA performed for medial osteoarthritis or osteonecrosis, and similarly for lateral UKA, particularly when fixed-bearing implants are used. Disappointing long-term outcomes have been observed with the first generation of patellofemoral implants, as well as early Bi-Uni (ie, combined medial and lateral UKA) or Bicompartmental (combined UKA and PFA) implants due to design and fixation issues. Promising short- and med-term results with the newer generations of PFAs and bicompartmental arthroplasties will require long-term confirmation.Cite this article: Bone Joint J 2015;97-B(10 Suppl A):9–15.