Endometrial stromal sarcoma metastasis to the lumbar spine and sphenoid bone

Endometrial stromal sarcoma (ESS) is typically associated with metastasis to the abdomen, pelvis, and lung. We found three case reports of ESS metastasis to the bone (two to the thoracic spine, and one to the parietal bone). Our objective is to review the literature on ESS spinal and intracranial metastases and, report the first case of ESS metastatic to the lumbar paraspinal region and sphenoid bone. A 53-year-old female with ESS status-post radiation, chemotherapy, and pelvic exenteration surgery presented with right hip weakness, back pain, and radicular leg pain that were explained by chemotherapy-induced neuropathy, radiation-induced lumbosacral plexopathy, and femoral nerve and obturator nerve injury during pelvic exenteration surgery. During routine positron emission tomography, we found metastasis to the L3 lumbar spinal region. L3 laminectomy and subtotal resection of the mass was performed with tumor residual in the neuroforamina and pedicles. One month later, magnetic resonance imaging (MRI) performed for persistent headaches revealed a large lesion in the sphenoid bone that was biopsied transsphenoidally with the same diagnosis, but no further surgery was performed. She is intolerant of chemotherapy and currently undergoing whole brain radiation. Delay in the diagnosis and management of lumbar paraspinal and sphenoid bone metastasis of ESS likely occurred because of the uniqueness of the location and aggressiveness of ESS metastasis. Health care providers should be aware of potentially aggressive metastasis of ESS to bone, in particular the unusual locations of the lumbar paraspinal region and sphenoid bone

Sunitinib malate in the treatment of recurrent or persistent uterine leiomyosarcoma: A Gynecologic Oncology Group phase II study

New agents are needed for patients with metastatic uterine leiomyosarcoma who progress after treatment with doxorubicin or gemcitabine-docetaxel. Agents targeting tumor vasculature have potential for activity in leiomyosarcoma. We aimed to assess the activity of sunitinib in patients with recurrent uterine leiomyosarcoma who had received one or two prior therapies by determining the frequency of patients who survived progression-free for at least six months or who achieved objective tumor response. We also aimed to characterize the toxicity of sunitinib and to estimate time-to-progression

Phase I Trial of Carboplatin and Gemcitabine Chemotherapy and Stereotactic Ablative Radiosurgery for the Palliative Treatment of Persistent or Recurrent Gynecologic Cancer.

BackgroundWe conducted a phase I trial to determine the safety of systemic chemotherapy prior to abdominopelvic robotic stereotactic ablative radiotherapy (SABR) in women with persistent or recurrent gynecologic cancers.MethodsPatients were assigned to dose-finding cohorts of day 1 carboplatin (AUC 2 or 4) and gemcitabine (600 or 800 mg/m(2)) followed by day 2 to day 4 Cyberknife SABR (8 Gy × three consecutive daily doses). Toxicities were graded prospectively by common terminology criteria for adverse events, version 4.0. SABR target and best overall treatment responses were recorded according to response evaluation criteria in solid tumors, version 1.1.FindingsThe maximum tolerated dose of chemotherapy preceding SABR was carboplatin AUC 4 and gemcitabine 600 mg/m(2). One patient experienced manageable, dose-limiting grade 4 neutropenia, grade 4 hypokalemia, and grade 3 nausea attributed to study treatment. One patient had a late grade 3 rectovaginal fistula 16 months after trial therapy. Among 28 SABR targets, 22 (79%) showed a partial response and 6 (21%) remained stable.InterpretationSystemic chemotherapy may be given safely prior to abdominopelvic robotic SABR with further investigation warranted

Phase I Trial of Carboplatin and Gemcitabine Chemotherapy and Stereotactic Ablative Radiosurgery for the Palliative Treatment of Persistent or Recurrent Gynecologic Cancer.

BackgroundWe conducted a phase I trial to determine the safety of systemic chemotherapy prior to abdominopelvic robotic stereotactic ablative radiotherapy (SABR) in women with persistent or recurrent gynecologic cancers.MethodsPatients were assigned to dose-finding cohorts of day 1 carboplatin (AUC 2 or 4) and gemcitabine (600 or 800 mg/m(2)) followed by day 2 to day 4 Cyberknife SABR (8 Gy × three consecutive daily doses). Toxicities were graded prospectively by common terminology criteria for adverse events, version 4.0. SABR target and best overall treatment responses were recorded according to response evaluation criteria in solid tumors, version 1.1.FindingsThe maximum tolerated dose of chemotherapy preceding SABR was carboplatin AUC 4 and gemcitabine 600 mg/m(2). One patient experienced manageable, dose-limiting grade 4 neutropenia, grade 4 hypokalemia, and grade 3 nausea attributed to study treatment. One patient had a late grade 3 rectovaginal fistula 16 months after trial therapy. Among 28 SABR targets, 22 (79%) showed a partial response and 6 (21%) remained stable.InterpretationSystemic chemotherapy may be given safely prior to abdominopelvic robotic SABR with further investigation warranted

Interferon-α is the primary plasma type-I IFN in HIV-1 infection and correlates with immune activation and disease markers.

Type-I interferon (IFN-I) has been increasingly implicated in HIV-1 pathogenesis. Various studies have shown elevated IFN-I and an IFN-I-induced gene and protein expression signature in HIV-1 infection, yet the elevated IFN-I species has not been conclusively identified, its source remains obscure and its role in driving HIV-1 pathogenesis is controversial. We assessed IFN-I species in plasma by ELISAs and bioassay, and we investigated potential sources of IFN-I in blood and lymph node tissue by qRT-PCR. Furthermore, we measured the effect of therapeutic administration of IFNα in HCV-infected subjects to model the effect of IFNα on chronic immune activation. IFN-I bioactivity was significantly increased in plasma of untreated HIV-1-infected subjects relative to uninfected subjects (p = 0.012), and IFNα was the predominant IFN-I subtype correlating with IFN-I bioactivity (r = 0.658, p<0.001). IFNα was not detectable in plasma of subjects receiving anti-retroviral therapy. Elevated expression of IFNα mRNA was limited to lymph node tissue cells, suggesting that peripheral blood leukocytes are not a major source of IFNα in untreated chronic HIV-1 infection. Plasma IFN-I levels correlated inversely with CD4 T cell count (p = 0.003) and positively with levels of plasma HIV-1 RNA and CD38 expression on CD8 T cells (p = 0.009). In hepatitis C virus-infected subjects, treatment with IFN-I and ribavirin increased expression of CD38 on CD8 T cells (p = 0.003). These studies identify IFNα derived from lymph nodes, rather than blood leukocytes, as a possible source of the IFN-I signature that contributes to immune activation in HIV-1 infection

Effects of the WRITE Symptoms Interventions on Symptoms and Quality of Life Among Patients With Recurrent Ovarian Cancers: An NRG Oncology/GOG Study (GOG-0259)

PurposeGOG-259 was a 3-arm randomized controlled trial of two web-based symptom management interventions for patients with recurrent ovarian cancer. Primary aims were to compare the efficacy of the nurse-guided (Nurse-WRITE) and self-directed (SD-WRITE) interventions to Enhanced Usual Care (EUC) in improving symptoms (burden and controllability) and quality of life (QOL).MethodsPatients with recurrent or persistent ovarian, fallopian, or primary peritoneal cancer with 3+ symptoms were eligible for the study. Participants completed baseline (BL) surveys (symptom burden and controllability and QOL) before random assignment. WRITE interventions lasted 8 weeks to develop symptom management plans for three target symptoms. All women received EUC: monthly online symptom assessment with provider reports; online resources; and every 2-week e-mails. Outcomes were evaluated at 8 and 12 weeks after BL. Repeated-measures modeling with linear contrasts evaluated group by time effects on symptom burden, controllability, and QOL, controlling for key covariates.ResultsParticipants (N = 497) reported mean age of 59.3 ± 9.2 years. At BL, 84% were receiving chemotherapy and reported a mean of 14.2 ± 4.9 concurrent symptoms, most commonly fatigue, constipation, and peripheral neuropathy. Symptom burden and QOL improved significantly over time (P &lt; .001) for all three groups. A group by time interaction (P &lt; .001) for symptom controllability was noted whereby both WRITE intervention groups had similar improvements from BL to 8 and 12 weeks, whereas EUC did not improve over time.ConclusionBoth WRITE Intervention groups showed significantly greater improvements in symptom controllability from BL to 8 and BL to 12 weeks compared with EUC. There were no significant differences between Nurse-WRITE and SD-WRITE. SD-WRITE has potential as a scalable intervention for a future implementation study

IFNα and its signature are increased in plasma of HIV-1-infected subjects not receiving ART.

<p>Plasma IFN-I bioactivity measured by the iLite™ bioassay was increased in plasma of HIV-1-infected subjects in comparison to uninfected subjects (median 1.04 IFNα2 equivalent units for HIV-1-infected subjects, median 0.89 IFNα2 equivalent units for uninfected subjects, p = 0.012) (A). IFNα was increased in plasma of HIV-1-infected subjects in comparison to uninfected subjects (median 4.27 pg/ml for HIV-1-infected subjects, median 3.13 pg/ml for uninfected subjects, p<0.001) (B). IFNβ was not increased in plasma of HIV-1-infected subjects compared to uninfected subjects (median 2.34 pg/ml for HIV-1-infected subjects, median 2.34 pg/ml for uninfected subjects, p = 0.560) (B). IFNω was not increased in plasma of HIV-1-infected subjects compared to uninfected subjects (median 4.69 pg/ml for HIV-1-infected subjects, median 4.69 pg/ml for uninfected subjects, p = 0.837) (B). Plasma IFNα levels were strongly associated with plasma IFN-I bioactivity in HIV-1-infected subjects (r = 0.711, p<0.001) (C). Plasma IP-10 was increased in plasma of HIV-1-infected subjects in comparison to uninfected subjects (median 538.2 pg/ml for HIV-1-infected subjects, median 132.6 pg/ml for uninfected subjects, p = 0.002) (D). Slight variations in sample sizes for different assays occur as results for some subjects were not available.</p

IFNα mRNA expression is elevated in lymph nodes, but not peripheral blood leukocytes, of HIV-1-infected subjects.

<p>There was no significant difference in expression of IFNα mRNA in whole blood leukocytes of HIV-1-infected subjects without ART (median relative expression of 0.10) and uninfected subjects (median relative expression of 0.88) (p = 0.981) (A). Similarly, there was no significant difference in IFNβ mRNA expression in whole blood leukocytes (median relative expression of 0.003 for HIV-1-infected subjects, median relative expression of 0.001 for uninfected subjects; p = 0.298) (A). An IFN-I signature was evident in peripheral blood leukocytes, as expression of the ISG MxA was significantly increased in HIV-1-infected subjects without ART compared to uninfected subjects (median relative expression of 0.85 for HIV-1-infected subjects, median relative expression of 0.26 for uninfected subjects; p = 0.016) (A). In contrast, expression of IFNα mRNA in lymph node tissue was significantly elevated in HIV-1-infected subjects without ART (median relative expression of 0.93) relative to uninfected subjects (median relative expression of 0.12) (p = 0.037) (B). There was no statistically significant difference in IFNβ mRNA expression between the two donor groups (median relative expression of 0.20 for HIV-1-infected subjects, median relative expression of 0.06 for uninfected subjects; p = 0.728) (B). Expression of the ISG MxA was significantly increased in lymph node tissue from HIV-1-infected subjects compared to uninfected subjects (median relative expression of 1.05 for HIV-1-infected subjects vs. 0.45 for uninfected subjects; p = 0.037) (B).</p