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To develop and validate a comprehensive overall survival (OS) risk-scoring model in women with endometrioid endometrial cancer (EC).Patients with EC diagnosed from 2004 to 2013 were identified through the National Cancer Database (NCDB). Patients with known lymphovascular space invasion (LVSI) status who were treated surgically (with or without adjuvant therapy) were included. Cox proportional hazards analysis was used to identify prognostic factors for OS. This model was used to assign points based on hazard ratios for risk factors and a risk score was obtained. Recursive partitioning analysis (RPA) was used to categorize patients into risk groups. Results were internally validated in a cohort of patients from our institution (CCF cohort). Risk scores were calculated and assessed in a Cox regression model, and Harrell's c-index was calculated to assess model fit.Among 349,404 women with EEC during the study period, 42,107 fulfilled inclusion criteria. Factors associated with worse OS were age ≥ 60, African American race, Charlson-Deyo score 1 or 2+, higher grade, LVSI, tumor size ≥2 cm, and no lymphadenectomy performed. Six risk groups were identified (scores 0-30) and OS estimated for each risk group. Risk score per 1-point increase in HR were comparable between NCDB and CCF cohorts (HR 1.21 (1.20-1.22 p 0.001 vs 1.18 (1.12-1.25), p 0.001), and c-index 0.80 (0.79-0.81) vs. 0.77 (0.68-0.86). Similar analysis was done in stage IA and IB. Adjuvant therapy had a beneficial effect on survival in the majority of stage IB patients, but only one of the six risk groups in stage IA EC.We report a comprehensive validated OS risk-scoring model for patients with.

To evaluate the impact of frailty on postoperative complications following cytoreductive surgery (CRS) with hyperthermic intra-peritoneal chemotherapy (HIPEC) in women with advanced or recurrent gynecologic cancer.An IRB-approved single-institution prospective registry was queried for women who underwent CRS with HIPEC for advanced or recurrent gynecologic cancer from 1/1/2014-12/31/2020. Frailty was defined as a modified Frailty Index (mFI) score of ≥2. Logistic regression was used to assess the impact of mFI upon the rate of moderate or higher (≥ grade 2) Accordion postoperative complications.Of 141 women, 81.6% (n = 115) were non-frail with mFI of 0-1 and 18.4% (n = 26) were frail with mFI ≥2. The incidence of ≥ grade 2 complications was 21.2% (n = 14) for mFI = 0, 26.5% (n = 13) for mFI = 1, 64.7% (n = 11) for mFI = 2 and 100.0% (n = 9) for patients with mFI ≥3. The incidence of re-operation (1.7% vs. 11.5%, p = 0.044), ICU admission (13.2% vs. 34.6%, p = 0.018), acute kidney injury (6.3% vs. 30.8%, p = 0.001), and respiratory failure (0.9% vs. 19.2%, p0.001) were significantly lower amongst non-frail vs. frail women. On multivariable analysis, mFI ≥2 was associated with significantly increased ≥ grade 2 complications versus mFI of 0-1 (OR 9.4, 95% CI 3.3, 26.4, p0.001). Age (OR 1.04, 95% CI 1.00, 1.09, p = 0.07), surgical indication (recurrent vs. primary) (OR 0.71, 95% CI 0.30, 1.7, p = 0.44) and Surgical Complexity Score of Intermediate or High vs. Low (OR 1.5, 95% CI 0.67, 3.5, p = 0.31) were not associated with ≥grade 2 complications.Frailty, defined by the modified frailty index, is predictive of ≥grade 2 postoperative complications following CRS with HIPEC in women with gynecologic cancer. Frailty screening before CRS with HIPEC may assist patient selection and improve postoperative outcomes.

Objective(s) To identify recurrence patterns and outcomes in women with advanced or recurrent epithelial ovarian cancer (EOC) after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Methods This is an IRB-approved single-institution cohort study of women who underwent CRS+HIPEC for advanced or recurrent EOC followed in a prospective registry from 1/12/2014–3/1/2020. Recurrence locations were defined as pelvic, upper abdominal (UA) and/or extra-peritoneal (EP). Univariate analysis assessed associations between recurrence location, progression-free survival (PFS), and overall survival (OS). Results In total, 92 women with EOC underwent interval (56.5%; n=52) or recurrent CRS+HIPEC (43.5%; n=40). For interval CRS+HIPEC, recurrence locations were pelvic in 50.0% (n=15), UA in 23.3% (n=7) and EP in 56.7% (n=17); 40.0% (n=12) were EP alone. Similarly, for recurrent CRS+HIPEC, recurrence locations were pelvic (22.5%, n=9), UA (5.0%, n=2) and EP (60.0%, n=24); 66.7% (n=20) were EP alone. For both interval and recurrent CRS+HIPEC, median PFS was 10.5 vs. 13.0 months for pelvic and UA vs. EP only recurrences (p=0.02). Similarly, median OS was 29.2 months for pelvic and UA and not reached for EP only (p=0.05). For interval CRS+HIPEC, there was no difference in median PFS (10.6 vs. 11.7 months, p=0.68) and OS (27.1 vs. 24.8 months, p=0.96) for pelvic and UA vs EP alone. However, for recurrent CRS+HIPEC, pelvic and UA sites of recurrence were associated with reduced PFS (10.0 vs. 18.1 months, p=0.03) and OS (33.6 months vs. not reached, p=0.02) vs. EP only. Conclusions In women with advanced or recurrent EOC undergoing CRS+HIPEC, one-half of patients experience their first recurrence outside of the peritoneal cavity. Providers must be aware of the risk of EP failure in patients treated with CRS+HIPEC.

Background Ovarian cancer is the most fatal gynecologic malignancy in the United States. While chemotherapy is effective in the vast majority of ovarian cancer patients, recurrence and resistance to standard systemic therapy is nearly inevitable. We discovered that activation of the non-receptor tyrosine kinase Lymphocyte Cell-Specific Protein-Tyrosine Kinase (LCK) promoted cisplatin resistance. Here, we hypothesized that treating high grade, platinum resistant endometrioid cancer cells with an LCK inhibitor (LCKi) followed by co-treatment with cisplatin would lead to increased cisplatin efficacy. Our objective was to assess clinical outcomes associated with increased LCK expression, test our hypothesis of utilizing LCKi as pre-treatment followed by co-treatment with cisplatin in platinum resistant ovarian cancer in vitro, and evaluate our findings in vivo to assess LCKi applicability as a therapeutic agent. Results Kaplan-Meier (KM) plotter data indicated LCK expression is associated with significantly worse median progression-free survival (HR 3.19, p = 0.02), and a trend toward decreased overall survival in endometrioid ovarian tumors with elevated LCK expression (HR 2.45, p = 0.41). In vitro, cisplatin resistant ovarian endometrioid cells treated first with LCKi followed by combination LCKi-cisplatin treatment showed decreased cell viability and increased apoptosis. Immunoblot studies revealed LCKi led to increased expression of phosphorylated H2A histone family X ($$\gamma$$ γ -H2AX), a marker for DNA damage. In vivo results demonstrate treatment with LCKi followed by LCKi-cisplatin led to significantly slowed tumor growth. Conclusions We identified a strategy to therapeutically target cisplatin resistant endometrioid ovarian cancer leading to chemosensitization to platinum chemotherapy via treatment with LCKi followed by co-treatment with LCKi-cisplatin.

To determine whether antibiotic treatment (ABX) during platinum chemotherapy (PC) for epithelial ovarian cancer (EOC) impacts progression-free survival (PFS) and overall survival (OS).Retrospective single institution cohort study in women with newly diagnosed stage III/IV EOC (n = 424) who underwent cytoreductive surgery (CRS) and PC from 2009 to 2015. ABX for48 h, including ABX against gram-positive (anti-G + ABX) bacteria were recorded. The impact of ABX on PFS and OS was assessed using univariate and multivariable Cox regression models.Of 424 eligible women, 34.7% (n = 147) received ABX, with 11.3% (n = 48) treated with anti-G + ABX. ABX decreased PFS (17.4 vs. 23.1 months, HR 1.50, 95% CI 1.20-1.88, p 0.001) and OS (45.6 vs. 62.4 months, HR 1.63, 95% CI 1.27-2.08, p 0.001) compared to no ABX. Similarly, anti-G + ABX worsened PFS (16.5 vs. 23.1 months; HR 1.85, 95% CI 1.33-2.55) and OS (35.0 vs. 62.4 months; HR 2.12, 95% CI 1.50-3.0, p 0.001). On multivariable analysis, all ABX and anti-G + ABX significantly worsened PFS (HR 1.31, 95% CI 1.04-1.65, p = 0.02), (HR 1.50, 95% CI 1.07-2.10, p = 0.02) and OS (HR 1.52, 95% CI 1.18-1.96, p = 0.001), (HR 1.83, 95% CI 1.27-2.62, p = 0.001) respectively. Increased Clavien Dindo score was associated with worsened PFS (1-2 - HR 1.52, 95% CI 1.14-2.03, p = 0.004; 3-4 - HR 1.86, 95% CI 1.27-2.72, p = 0.001) but not OS (1/2 - HR 1.35, 95% CI 0.97-1.88, p = 0.08; 3/4 - HR 1.53, 95% CI 1.00-2.34, p = 0.05); residual disease (p 0.05) and neoadjuvant chemotherapy (p 0.001) were associated with worse PFS and OS.In this retrospective cohort study of women with advanced EOC undergoing PC, ABX treatment was associated with decreased PFS and OS. Mechanistic studies are needed to investigate the negative impact of ABX upon PC response in EOC.

Objective To evaluate the efficacy and toxicity of extended duration pegylated liposomal doxorubicin (PLD) in women with recurrent epithelial ovarian carcinoma (rEOC). Methods Women with rEOC who received >7 cycles of PLD were retrospectively identified. Response was determined by RECIST 1.1. Progression free survival (PFS) and overall survival (OS) were calculated from PLD initiation. Toxicity was assessed by CTCAE v5.0. Kaplan Meier estimates and Cox proportional hazards were used to evaluate differences in time to recurrence or survival. Results 69 patients with rEOC received a median of 11.0 cycles (range, 7–115) at a median cumulative dose of 400 mg/m2 (range, 210–4600 mg/m2); 29.0% (n = 20) had platinum sensitive and 71.0% (n = 49) had platinum resistant disease. Of the observed grade ¾ toxicities (31.9%; n = 22), dermatologic were most frequent (n = 13; 18.8%). 41 women (59.4%) experienced clinical benefit; complete response in 17.4% (n = 12), partial response in 13.0% (n = 9) and stable disease in 29.0% (n = 20). Median PFS for all patients was 13.0 months (95% CI, 10.7, 15.2); there were no significant differences between platinum sensitive versus resistant disease (15.9 months vs. 12.3 months; HR 1.15, 95% CI, 0.66, 2.00; p = .61). With extended duration PLD, median OS was 40.2 months (95% CI 30.0, 49.0); no significant differences were noted for platinum sensitive versus resistant disease (44.7 months vs. 33.3 months; HR 1.85, 95% CI, 0.91, 3.78; p = .07). Four cases (5.8%) of oral squamous cell carcinoma occurred during treatment. Conclusions Among women with both platinum sensitive and resistant rEOC who received >7 cycles of PLD, approximately one-half experienced sustained clinical benefit with acceptable toxicity. PLD may be considered for extended usage and maintenance in initially responding women with rEOC at least stable disease.

To assess incidence and oncologic outcomes in women with advanced epithelial ovarian cancer (EOC) with inguinal lymph node metastasis (ILNM) at diagnosis.An IRB-approved, retrospective single-institution cohort study was performed in women with stage III/IV EOC from 2009 to 2017. Patients with inguinal lymphadenopathy (defined as1 cm in short axis) clinically or radiographically were identified. The impact of ILNM on progression-free survival (PFS) and overall survival (OS) were assessed.Of the 562 women with advanced EOC, 18 (3.2%) had ILNM at diagnosis, accounting for 25.7% of all patients with stage IVB disease (n = 70). Five patients (27.7%) had a known genetic predisposition for EOC, including BRCA1 (11.1%, n = 2), BRCA2 (11.1%, n = 2) and BRIP1 (5.6%, n = 1). The majority of patients underwent optimal primary cytoreductive surgery (CRS), including debulking of inguinal nodal metastasis (83.3%, n = 15), with 50% (n = 9) having no gross residual disease after surgery. There was no difference in PFS (19.9 vs. 19.9 vs. 17.2 months, p = 0.84) or OS (137.2 vs. 52.9 vs. 67.6 months, p = 0.29) in women with stage III/IV with ILNM, stage III/IV without ILNM, and stage IVB disease without ILNM, respectively. Progression-free survival was improved in women with ILNM who underwent an optimal resection to no macroscopic disease vs. non-optimal resection (27.4 vs. 14.3 months, p = 0.019). Median overall survival at the time of analysis did not reach statistical significance (137.2 vs. 57.3 months, p = 0.24).In this retrospective cohort study, 3.2% of women with advanced EOC presented with ILNM at diagnosis. Although ILNM did not portend worse clinical outcomes compared to all Stage III/IV and Stage IVB patients, respectively, resection to no gross residual disease was associated with improved PFS.

To determine the effect of poly-adenosine ribose phosphatase inhibitors (PARPi) on the response to subsequent platinum-based chemotherapy (PBC) in patients with recurrent, platinum-sensitive BRCA-mutated epithelial ovarian, peritoneal, or fallopian cancer (BRCAm EOC). This is a retrospective, single-institution cohort study of patients with BRCAm EOC who received retreatment with PBC. The PFS of patients with BRCAm EOC to 2nd or 3rd PBC with and without a prior PARPi was determined. Additionally, we compared the PFS to subsequent PBC following a prior PARPi for BRCAm and non-BRCAm. One hundred and fifteen patients with BRCAm EOC received a 2nd PBC and 55 received a 3rd PBC. The median PFS was 2.3 and 2.4 times longer, respectively for patients who did not receive a PARPi, (2nd P = 0.005, 3rd P0.001). Among 20 PARPi exposed patients with BRCAm EOC the PFS to a 2nd or 3rd PBC was worse at 8.0 months vs. 19.1 months HR 4.01 [2.25,7.16], P0.001. Following PARPi exposure the PFS for patients with BRCAm EOC was similar for patients with platinum-free intervals of 6-12, 12-24 and24 months. Following PARPi exposure the PFS was similar for patients with BRCAm EOC and non BRCAm EOC. Among patients with BRCAm EOC PARPi exposure significantly reduced PFS following 2nd and 3rd PBC. PARPi exposure nullifies established prognostic factors (i.e. platinum-free interval and BRCA mutational status) in platinum-sensitive recurrent ovarian cancer.

Objective(s) To evaluate the incidence and associated risk factors for anastomotic failure following interval debulking surgery (IDS) with or without hyperthermic intraperitoneal chemotherapy (HIPEC) in women with advanced ovarian cancer. Methods We performed a retrospective cohort study in women with stage III/IV high-grade ovarian cancer treated with neoadjuvant chemotherapy followed by IDS with colorectal resection and HIPEC from 2017 to 2020. These patients were compared to a historical control cohort who underwent IDS with colorectal resection without HIPEC from 2009 to 2016. Data was collected for demographics, surgical variables, and perioperative outcomes. The univariate analysis compared progression-free survival and overall survival. Results 61 women were identified; 21 (34.4%) underwent IDS with HIPEC from 2017 to 2020, and 40 underwent IDS alone from 2009 to 2016. None of the patients who had IDS with HIPEC had protective ileostomy, compared to 10.0% of those who received had IDS alone (n = 4)(p = 0.29). The cumulative incidence of anastomotic leak rate was 8.2% (n = 5). There was no significant difference in anastomotic leak rate for women who underwent IDS with HIPEC (9.5%, n = 2) versus without HIPEC (7.5%, n = 3) (p = 0.99). While there was no difference in PFS (12.2 vs. 13.3 months, log-rank p = 0.31), OS (9.4 vs. 40.6 months, log-rank p = 0.013) was significantly decreased following postoperative anastomotic leak. Conclusions In this retrospective series of women with advanced ovarian cancer, HIPEC was not associated with increased risk for anastomotic leak at the time of IDS with colorectal resection and reanastomosis. While further study is needed, HIPEC alone should not preclude colorectal resection or dictate practices for colonic diversion in IDS.

ObjectiveTo evaluate perioperative outcomes in elderly versus non-elderly women with advanced or recurrent epithelial ovarian cancer undergoing surgery with hyperthermic intraperitoneal chemotherapy (HIPEC).MethodsA single-institution prospective registry was analyzed for women with ovarian cancer who underwent surgery with HIPEC from January 2014 to December 2020. Elderly age was defined as ≥65 years at surgery. Complications were defined according to the Accordion scale. Univariate and multivariable analysis was used to compare progression-free survival and overall survival.ResultsOf 127 women who underwent surgery with HIPEC, 33.1% (n=42) were ≥65 and 17.3% (n=22) were ≥70 years old. The median age for non-elderly and elderly patients were 55.7±8.3 versus 72.0±5.4 years, respectively (pConclusionsIn this prospective registry of women with ovarian cancer, perioperative morbidity is not increased for non-elderly versus elderly patients following surgery with HIPEC. While age should not exclude patients from surgery with HIPEC, additional research is needed regarding oncologic benefits in elderly women.

Objective To determine peri-operative outcomes in women with advanced epithelial ovarian cancer (EOC) undergoing interval debulking surgery (IDS) with hyperthermic intraperitoneal chemotherapy (HIPEC) via minimally invasive interval debulking surgery (MIS) or laparotomy (LAP). Methods A single institution, retrospective cohort study was performed in women with EOC who underwent IDS with HIPEC from 2017 to 2019 via MIS or LAP. Peri-operative outcomes were compared using univariate analysis. Results In total, 50 eligible women were identified; ten (20.0%) underwent MIS + HIPEC and 40 (80.0%) LAP + HIPEC. The median age of patients in the MIS group was 71.1 vs. 64.2 years in LAP (p = 0.031). There was no significant difference in pre-operative complete radiographic response following NACT (p = 0.18). Notably, there was no difference in the rate of R0 resection (70.0% vs. 77.5%; p = 0.39). There was no significant difference in ICU admission, estimated blood loss, operative time, or use of vasopressors between the cohorts. Similarly, there was no difference in 30-day adverse events for MIS vs. LAP, but length of stay was decreased for those who underwent minimally invasive procedures (3 vs. 4 days, p = 0.016). Time to initiation of chemotherapy following surgery was not significantly different between groups (26.2 days vs 32.0 days, p = 0.090). With median follow-up of 15.1 months, there was no difference in recurrence free survival (median 15.0 vs 17.2 months log-rank, p = 0.30) for MIS vs. LAP. Conclusions In this retrospective cohort study, we demonstrate that in women with advanced EOC, HIPEC with MIS at the time of IDS following NACT is feasible. Our institutional experience demonstrates similar rates of R0 cytoreduction, compared to LAP. An MIS approach should not prevent surgeons from utilizing HIPEC where indicated for management of advanced EOC., Highlights • When comparing MIS and LAP at time of HIPEC, no differences are observed in adverse perioperative outcomes. • MIS was associated with shorter hospitalization and with no significant difference in the rate of R0 resections. • Patient candidacy for an MIS IDS should not prevent surgeons from utilizing HIPEC in appropriate candidates.

Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) may be used to treat peritoneal based malignancies, such as epithelial ovarian cancer (EOC). Despite results of clinical trials supporting an increasing indication for HIPEC in EOC, concerns have existed regarding morbidity and challenges with initiating HIPEC at an institutional level. The objective of this review is to describe evidence-based recommendations to guide implementation of a HIPEC program, following our experience at a high-volume tertiary care center. Establishing a HIPEC program requires building a multi-disciplinary team, including gynecologic oncologists, anesthesia, nursing, perfusionists and pharmacists. Team members require education regarding HIPEC protocols, toxic waste and spill management, and personal protective equipment (PPE). Required equipment includes chemotherapy certified PPE and a HIPEC pump which is connected to inflow and outflow catheters placed within the peritoneal cavity. During the procedure, 3–6 L of a hyperthermic perfusate, composed of a isotonic crystalloid vehicle and the chemotherapy of choice, is infused through the peritoneal cavity with goal temperature of 41–43 °C. Prior to HIPEC infusion, surgical teams must communicate with anesthesia and pharmacy. In patients receiving HIPEC with cisplatin, furosemide and mannitol should be administered one hour prior to chemotherapy to ensure adequate diuresis. Sodium thiosulfate may also be considered for renal protection (van Driel et al., n.d. [3]). We utilize a multi-agent pre-medication protocol prior to HIPEC infusion to reduce hypersensitivity reactions, renal toxicity and post-operative nausea and vomiting. Limited data exists to support the optimal regimen for HIPEC at the time of CRS in women with EOC. From our experience, we favor use of cisplatin 100 mg/m2 alone or in combination with paclitaxel 135–175 mg/m2 with 90 min of total perfusion time. Close attention to temperature and glycemic control is essential during the procedure, as electrolyte derangements including hyperglycemia, lactic acidosis and hypokalemia may occur. Continuous patient monitoring and proactive management of abnormalities that arise during HIPEC is imperative to decrease patient morbidity and mortality.

OBJECTIVE: To determine the efficacy of dalantercept, a soluble ALK1 inhibitor receptor fusion protein, in patients with persistent or recurrent ovarian carcinoma and related malignancies METHODS: Eligibility criteria included measurable disease, 1-2 prior cytotoxic regimens and GOG performance status (PS) ≤ 2. Dalantercept was administered subcutaneously at 1.2 mg/kg every 3 weeks until disease progression or development of unacceptable toxicity. The primary null hypothesis was the probability of response ≤0.10 and the probability of 6-month progression-free survival without receipt of non-protocol therapy (event-free survival at 6 months, EFS6) ≤0.15, using RECIST 1.1 criteria. RESULTS: The first stage was closed after enrollment of 30 participants with median age of 56.5 years, high-grade serous histology in 76.7%, 2 prior regimens in 46.7%, and platinum-free interval < 6 months in 73.3%. All participants discontinued dalantercept, 24 (80.0%), 5 (16.7%) and 1 (3.3%) due to progression, toxicity, and other reason, respectively. The median number of treatment cycles per patient was 2 (range 1 – 29). There were six treatment-related grade 3 AEs and no grade ≥ 4 AEs. There were no objective responses. EFS6 was reached in 20% (6 out of 30 participants, 90% CI 9.1% to 35.7%). CONCLUSIONS: Though safe, dalantercept as administered had limited efficacy in this patient population overall.

Introduction Hyperthermic intraperitoneal chemotherapy following cytoreductive surgery (CRS) is a treatment strategy that has been evaluated in recurrent ovarian cancer. The aim of this study was to examine if survival was similar regardless of platinum sensitivity. Methods A retrospective study of women with recurrent platinum sensitive or resisteant epithelial ovarian cancer who were treated with cytoreductive surgery (CRS) and HIPEC between the years 2010–2018 was performed. Recurrence free (RFS) and overall survival (OS) were calculated using the Kaplan-Meier method. Results Thirty-five (72.9 %) were platinum sensitive (PS) and 13 (27.1 %) were platinum resistant (PR). The complete cytoreduction (R0) rate was higher in the PS patients as compared to PR (85.7 % vs 53.8 %; p = 0.017). Median follow-up was 16.9 (range, 11.7–34.5) months. The median recurrence free survival in the patients who had a R0 resection was 22.3 months in PS and 11.1 months in PR patients (p = 0.017), respectively. Median overall survival was 26.9 months in the PR patients, while it had not been reached in the PS patients. In the patients with PS recurrence, the mean treatment free interval (TFI) prior to HIPEC was 1.6 years and following HIPEC, 40 % of those patients were recurrence free at 2 years. In the patients with PR recurrence, the mean TFI prior to HIPEC was 4.6 months and following HIPEC, 61.5 % of those patients had a longer TFI, with a mean increase of 10.1 months. Conclusion Although surgery is not considered standard treatment in PR ovarian cancer, in carefully selected patients, surgery with HIPEC could extend the treatment-free interval.

Objective To identify factors associated with non-completion of intraperitoneal with intravenous chemotherapy [IP/IV] in women with epithelial ovarian cancer (EOC). Methods This was an Institutional Review Board approved, retrospective cohort study in women with stage III EOC following optimal cytoreductive surgery (CRS) (

Surgical site infection after surgery for gynecologic cancer increases morbidity. Prophylactic closed incision negative pressure therapy has shown promise in reducing infectious wound complications across many surgical disciplines.This study aimed to determine whether closed incision negative pressure therapy is associated with reduced surgical site infections in gynecologic oncology patients undergoing laparotomy compared with standard dressings.This was a retrospective case-control study of patients undergoing laparotomy for known or suspected gynecologic cancer from Jan. 1, 2017, to Feb. 1, 2020. Patients were matched in a 1:3 ratio (closed incision negative pressure therapy to standard dressing) by body mass index, age, diabetes, bowel surgery, smoking, and steroid use. Surgical site infection was defined according to the Centers for Disease Control and Prevention. Multivariable logistic regression using backward selection was performed.Of the 1223 eligible patients undergoing laparotomy, 64 (5.2%) received closed incision negative pressure therapy dressings and were matched to 192 (15.7%) controls. There were no differences in medical comorbidities (P.05), site or stage of malignancy (P.05), duration of surgery (P=.82), or surgical procedures (P.05). Use of closed incision negative pressure therapy was associated with reduction in all adverse wound outcomes (20.3% vs 40.1%; P.001). In particular, closed incision negative pressure therapy was associated with a significant reduction in both superficial incisional surgical site infections (9.4% vs 29.7%; P.001) and deep incisional surgical site infections (0.0% vs 6.8%; P=.04). In multivariable analysis, use of closed incision negative pressure therapy was associated with significant reduction in the incidence of superficial incisional infections alone (odds ratio, 0.29; 95% confidence interval, 0.12-0.73; P=.008) and both superficial and deep incisional infections (odds ratio, 0.29; 95% confidence interval, 0.12-0.71; P=.007).Use of prophylactic closed incision negative pressure therapy after laparotomy in gynecologic oncology patients was found to be associated with reduced superficial incisional and deep incisional infections compared with standard dressings. Furthermore, closed incision negative pressure therapy was associated with reduction in all other adverse wound outcomes. Closed incision negative pressure therapy may be considered for surgical site infection prevention in high-risk gynecologic oncology patients undergoing laparotomy.

Objectives Women with advanced-stage, low-grade serous ovarian carcinoma (LGSC) have low chemotherapy response rates and poor overall survival. Most LGSC tumors overexpress hormone receptors, which represent a potential treatment target. Our study objective was to determine the outcomes of patients with advanced-stage LGSC treated with primary cytoreductive surgery (CRS) and hormone therapy (HT). Methods A retrospective study was performed at two academic cancer centers. Patients with Stage II–IV LGSC underwent either primary or interval CRS followed by adjuvant HT between 2004 and 2016. Gynecologic pathologists reviewed all cases. Two-year progression-free (PFS) and overall survival (OS) were calculated. Results Twenty-seven patients were studied; primary CRS followed by HT were administered in 26, while 1 patient had neoadjuvant chemotherapy followed by CRS and HT. The median patient age was 47.5, and patients had Stage II (n=2), Stage IIIA (n=6), Stage IIIC (n=18), and Stage IV (n=1) disease. Optimal cytoreduction to no gross residual was achieved in 85.2%. Ninety six percent of tumors expressed estrogen receptors, while only 32% expressed progesterone receptors. Letrozole was administered post operatively in 55.5% cases, anastrozole in 37.1% and tamoxifen in 7.4%. After a median follow up of 41months, only 6 patients (22.2%) have developed a tumor recurrence and two patients have died of disease. Median PFS and OS have not yet been reached, but 2-year PFS and OS were 82.8% and 96.3%, respectively, and 3-year PFS and OS were 79.0% and 92.6%, respectively. Conclusions Our series describes the initial experience with cytoreductive surgery and hormonal monotherapy for women with Stage II–IV primary ovarian LGSC. While surgery remains the mainstay of treatment, chemotherapy may not be necessary in patients with advanced-stage disease who receive adjuvant hormonal therapy. A cooperative group, Phase III trial is planned to define the optimal therapy for women with this ovarian carcinoma subtype.

Pegylated liposomal doxorubicin (PLD) is used widely in gynecologic oncology and other oncology disciplines. Native doxorubicin use is associated with the potential for significant toxicity. Cardiac toxicity in particular limits lifetime dose. PLD has not been shown to be associated with clinical cardiac toxicity. We report on the long-term use of PLD in a patient with recurrent high-grade serous ovarian cancer to a lifetime dose of 4600 mg/m. This therapy was associated with long-term stable disease, good performance status, and minimal adverse effects.

To estimate the rate and predictors of surgical site infection (SSI) after hysterectomy performed for benign indications and to identify any association between SSI and other postoperative complications.Retrospective cohort study (Canadian Task Force classification II-2).National Surgical Quality Improvement Program data.Women who underwent abdominal or laparoscopic hysterectomy performed for benign indications from 2005 to 2011.Univariable and multivariable logistic regression analyses were used to identify predictors of SSI and its association with other postoperative complications. Odds ratios were adjusted for patient demographic data, comorbidities, preoperative laboratory values, and operative factors.Of 28 366 patients, 758 (3%) were diagnosed with SSI. SSI occurred more often after abdominal than laparoscopic hysterectomy (4% vs 2%; p.001). Among patients who underwent abdominal hysterectomy, predictors of SSI included diabetes, smoking, respiratory comorbidities, overweight or obesity, American Society of Anesthesiologists class ≥ 3, perioperative blood transfusion, and operative time180 minutes. Among those who underwent laparoscopic hysterectomy, predictors of SSI included perioperative blood transfusion, operative time180 minutes, serum creatinine concentration ≥ 2 mg/dL, and platelet count ≥ 350 000 cells/mL(3). For patients with deep or organ/space SSI, significant predictors included perioperative blood transfusion and American Society of Anesthesiologists class ≥ 3 for abdominal hysterectomy, and non-white race, renal comorbidities, preoperative or perioperative blood transfusion, and operative time180 minutes for laparoscopic hysterectomy. SSI was associated with longer hospital stay and higher rates of repeat operation, sepsis, renal failure, and wound dehiscence. SSI was not associated with increased 30-day mortality.SSI occurred more often after abdominal hysterectomy than laparoscopic hysterectomy performed to treat benign gynecologic disease. SSI was associated with increased postoperative complications but not mortality. Several risk factors for SSI after each abdominal and laparoscopic hysterectomy were identified in this study.

ABSTRACT Aims: The aim of this study was to assess acute and subacacute gastrointestinal toxicity after fractionated stereotactic ablative radiotherapy (SABR) in women having recurrent gynecological cancers in the upper abdomen. Materials & methods: In total, 34 women underwent upper abdominal SABR (24 Gy/three divided 8 Gy consecutive daily doses) using a robotic Cyberknife® (Accuray, CA, USA) platform. Volumes of the duodenum receiving 10% increments of the prescription dose were associated to post-therapy gastrointestinal toxicities using binary logistic regression analyses. Results: Median clinical follow-up was 10 months. In total, 14 (41%) of the 34 women manifested grade 2 or higher post-therapy gastrointestinal adverse events. The duodenal volume, receiving 80% of a 24-Gy dose, was significantly associated with gastrointestinal toxicity (p = 0.03). However, in a multivariate analysis, only patient age at SABR adjusted the odds of experiencing gastrointestinal toxicity (p = 0.02). Conclusion: The duodenal volume receiving 80% of 24 Gy dose may be associated with gastrointestinal toxicity from upper abdominal SABR.

To evaluate hematological toxicity after robotic stereotactic body radiosurgery (SBRT) for treatment of women with metastatic abdominopelvic gynecologic malignancies.A total of 61 women with stage IV gynecologic malignancies treated with abdominopelvic SBRT were analyzed after ablative radiation (2400 cGy/3 divided consecutive daily doses) delivered by a robotic-armed Cyberknife SBRT system. Abdominopelvic bone marrow was identified using computed tomography-guided contouring. Fatigue and hematologic toxicities were graded by retrospective assignment of common toxicity criteria for adverse events (version 4.0). Bone marrow volume receiving 1000 cGy (V10) was tested for association with post-therapy (median 32 days [25%-75% quartile, 28-45 days]) white- or red-cell counts, hemoglobin levels, and platelet counts as marrow toxicity surrogates.In all, 61 women undergoing abdominopelvic SBRT had a median bone marrow V10 of 2% (25%-75% quartile: 0%-8%). Fifty-seven (93%) of 61 women had received at least 1 pre-SBRT marrow-taxing chemotherapy regimen for metastatic disease. Bone marrow V10 did not associate with hematological adverse events. In all, 15 grade 2 (25%) and 2 grade 3 (3%) fatigue symptoms were self-reported among the 61 women within the first 10 days post-therapy, with fatigue resolved spontaneously in all 17 women by 30 days post-therapy. Neutropenia was not observed. Three (5%) women had a grade 1 drop in hemoglobin level to10.0 g/dL. Single grade 1, 2, and 3 thrombocytopenias were documented in 3 women.Abdominopelvic SBRT provided ablative radiation dose to cancer targets without increased bone marrow toxicity. Abdominopelvic SBRT for metastatic gynecologic malignancies warrants further study.

The aim of this study was to determine the dose of weekly oral topotecan that allows safe administration and to evaluate the pharmacokinetics of this dose in patients with recurrent gynecologic malignancies. The first cohort of patients received oral topotecan 6 mg/week administered orally on days 1, 8, and 15 of a 28-day regimen. A standard 3 + 3 dose-escalating phase design was used for dose levels II–V (8, 10, 12 and 14 mg/week). Toxicity was scored according to the Common Terminology Criteria for Adverse Events. Cumulative toxicity was summarized in the 6–12 mg/week combined cohort and 14 mg/week cohort separately. Pharmacokinetic samples were obtained for day 1, cycle 1 only in the expansion cohort (dose level V). Twenty-five patients received a total of 88 cycles of therapy. Hematologic toxicities of grade 3 (6–12 mg dose) were neutropenia (25%) and anemia (8.3%). Gastrointestinal toxicities of grade 3 were diarrhea (16.7%) and obstruction (8.3%, disease-related). Grade 3 or 4 (14 mg/week) hematologic toxicities consisted of neutropenia (38.5%), platelets (15.4%), anemia (15.4%), infection with neutropenia (7.7%), and thrombosis (7.7%). Gastrointestinal toxicities of grade 3 were diarrhea (7.7%), obstruction (7.7%), and vomiting (7.7%). One patient died secondary to neutropenic sepsis. One patient (4%; 95% confidence interval: 2.1, 22.3) showed a partial response and five patients (20%; 95% confidence interval: 7.6, 41.3) had stable disease. An oral topotecan dose of 14 mg/week for 3 consecutive weeks out of 4 is mostly associated with acceptable toxicities and may be considered for use in future single-agent phase II trials.

HypothesisWe hypothesize that adjuvant radiation and chemotherapy improve the clinical benefit from treatment of advanced-stage endometrial adenocarcinoma.MethodsWe conducted a retrospective review of 125 patient with stage III or IVA endometrial adenocarcinoma who received adjuvant chemotherapy (n = 60) or chemoradiation (n = 65). Primary end points were rate of clinical benefit (ie, the percentage of patients who were alive and disease-free for at least 6 months after the last day of adjuvant treatment) and progression-free and overall survival.ResultsThe addition of radiation to chemotherapy improved the rate of clinical benefit from 55% to 77%. Differences in clinical benefit were attributed to a reduction in the number of pelvic relapses after chemoradiation. There were no substantial differences in the rate of extrapelvic relapse events seen between the chemotherapy alone and chemoradiation groups. Patients receiving radiation had prolonged median progression-free survival (36 vs 17 months in chemotherapy alone) and median overall survival (70 vs 64 months in chemotherapy alone).ConclusionsThe addition of radiation to chemotherapy improved the clinical benefit of patients with stage III or IVA endometrial adenocarcinoma. A clinical trial powered to evaluate clinical benefit and survival outcomes of chemotherapy and radiation is under way.

BACKGROUND: The objective of this study was to compare the incidence of hand-foot syndrome (HFS) in patients who received pyridoxine versus placebo during pegylated liposomal doxorubicin (PLD) chemotherapy for recurrent ovarian, breast, or endometrial cancer. METHODS: Patients received PLD 40 mg/m2 for a maximum of 6 cycles. Patients were assigned randomly to receive pyridoxine 100 mg twice daily (Group A) or placebo (Group B) and received standard HFS education. Patients completed the Functional Assessment of Cancer Therapy quality-of-life (QOL) questionnaire. The incidence of HFS as measured by common toxicity criteria was compared between groups. Analyses were conducted according to an intent-to-treat basis. Chi-square tests or Fisher exact tests were used. RESULTS: Thirty-four patients were enrolled (18 in Group A and 16 in Group B), and 5 patients were unevaluable for HFS assessment. Overall, 15 of 29 patients (52%) had HFS (all grades), and 10 of 29 patients (35%) had grade 2/3 events. Eight of 15 patients in Group A (53%) and 7 of 14 patients in Group B (50%) had HFS (P = .857). For grade 2/3 events, there was no difference between groups: Six of 15 events (40%) occurred in Group A, and 4 of 14 events (29%) occurred in Group B (P = .70). There was no difference in QOL scores between patients who had grade 2/3 HFS and patients who had grade 0/1 HFS. QOL analysis revealed that all patients had elevated social well being. CONCLUSIONS: Pyridoxine as administered in the current study did not prevent HFS in patients who received PLD. It is possible that QOL is not compromised in patients with HFS because they may have increased social well being while coping with their disease. Cancer 2010. © 2010 American Cancer Society.

The management of malignant bowel obstruction is a challenging problem because of the poor definition of malignant bowel obstruction compounded by its myriad clinical presentations. Surgeons are called upon to perform invasive procedures designed to alleviate symptoms or correct the underlying obstruction. Unfortunately, interventions may carry a high rate of morbidity and mortality. Balancing these risks and potential benefits is complicated, and there is a paucity of data to help guide these difficult decisions. The surgeon is further handicapped when he or she is not understanding of the patient's disease status, prognosis, or long-term goals. Diligent discussion with the primary team and frank discussions with the patient and his or her family are essential to formulate an appropriate plan. It is also essential that the surgeon have a thorough understanding of the surgical options to relieve or palliate malignant bowel obstruction as well as effective nonsurgical interventions. The best approach may be appropriate surgical intervention coupled with aggressive medical management.

There is growing recognition that HIV-1 infection leads to an activation of the immune system that includes perturbations of cytokine expression, redistribution of lymphocyte subpopulations, cell dysfunction, and cell death. Here, we explored the relationships between HIV-1 infection and immune activation in chronically HIV-1–infected human lymph nodes. In addition to CD4 T-cell depletion, we found increased effector T-cell frequencies associated with profound up-regulation of an activation marker CD38 in naive, central memory, and effector CD4+ and CD8+ T cells. Likewise, Fas death receptor (CD95) was more frequently detectable on T cells from HIV-1 nodes. Dendritic cell (DC) depletion was dramatic, with plasmacytoid DCs (PDCs) 40-fold and myeloid DCs (MDCs) 20-fold less frequent in HIV+ nodes than in control nodes. Cytokine dysregulation was evident, with IL-2 and IL-15 as much as 2 or 3 logs greater in infected nodes than in control nodes. Thus, activated effector cells are inappropriately attracted and/or retained in lymphoid tissue in chronic HIV-1 infection. High-level cytokine expression in turn activates and retains more cells at these sites, leading to lymphadenopathy and massive bystander activation that characterizes HIV-1 infection. Strategies targeting these activation pathways may lead to new therapies.

ObjectivesTo investigate the incidence of pancreatic leak and other postoperative complications after distal pancreatectomy performed during debulking surgery for gynecologic malignancies.MethodsAll patients who underwent distal pancreatectomy during their debulking surgery from 2010 to 2014 were identified. Postoperative complications within 30 days and pancreatic leak within 120 days after surgery were included.ResultsEighteen patients met the inclusion criteria. The median age was 62 years (36–78 years). Four patients (22%) were admitted to the intensive care unit, and the average length of hospital stay was 10 days. Nine patients developed postoperative complications within 30 days after surgery (50%) with no perioperative mortality up to 90 days after surgery. No patients required reexploration. The median time from surgery to initiation of chemotherapy was 39.5 days. Two patients developed pancreatic leak (11%). Among the patients who developed pancreatic leak, the average length of hospital stay was 11.5 days and time to initiation of chemotherapy was 75 days. Conservative management was successful in both cases.ConclusionIn this series, the rate of pancreatic leak was lower than previously reported with no perioperative mortality or surgical reexploration. However, the time to initiation of chemotherapy was delayed in those who developed pancreatic leak. These data are important in patient counseling and decision making at the time of debulking surgery. Gynecologic oncologists considering distal pancreatectomy should be familiar with perioperative management of these patients.

To compare the molecular profile of a large cohort of uterine papillary serous carcinoma (UPSC) and ovarian serous carcinoma (EOC-S).628 UPSC and 5335 EOC-S tumors were evaluated using a commercial multiplatform profiling service (CARIS Life Sciences, Phoenix, AZ). Specific testing performed included a combination of gene sequencing (Sanger, next generation sequencing), protein expression (IHC) and gene amplification (CISH or FISH).TP53 was the most commonly mutated gene in both UPSC and EOC-S (76% vs. 69%, P = 0.03). UPSC were more likely to have mutation in PIK3CA (29% vs. 2%, P 0.001), FBXW7 (12% vs. 1%, P 0.001), KRAS (9% vs. 5%, P 0.001) PTEN (7% vs. 1%, P 0.001), and CTNNB1 (2% vs. 0%, P 0.001) compared to EOC-S. On the other hand, EOC-S were more likely to harbor mutation in BRCA1 (20% vs. 9% P = 0.17) and BRCA2 (18% vs. 6% P = 0.09). HER2 gene amplification (17% vs. 4%, P0.001) and Her2/neu expression (10% vs. 2%, P 0.001) were more frequent in UPSC than EOC-S, respectively.UPSC have a distinct mutation profile indicating higher activity of PI3K/AKT/mTOR, and MAPK pathways and Her2 expression/amplification but a trend toward lower frequency of alteration in homologous recombination pathway compared to EOC-S. Targeted PI3K/AKT/mTOR inhibitors should be evaluated in UPSC.

Objective The purpose of this phase II trial was to evaluate the toxicity and antitumor activity of EGEN-001 in platinum resistant recurrent ovarian cancer. Methods Eligible patients had weekly IP infusion of EGEN-001 at a dose of 24mg/m 2 . Toxicity and antitumor activity were evaluated using CTCAE and RESIST criteria, respectively. Co-primary endpoints were tumor response and survival without progression (PFS) for at least 6months. Survival without progression before going onto a subsequent therapy (EFS) for at least six months was also considered. Results A total of 58 EGEN-001 cycles were administered to 20/22 enrolled patients (median 2cycles, range 1–9). The most frequently associated adverse events related specifically to EGEN-001 treatment were grade 1/2 fatigue, fever, chills, abdominal pain, nausea, vomiting, anemia, thrombocytopenia, and leukopenia. Three of 20 EGEN-001 treated patients evaluable for toxicity elected to withdraw from the study motivated in part by grade 1 treatment related toxicities. There were no patients with partial or complete response (0%; 90% CI 0–10.9%). Seven (35%) of 16 patients evaluable for response had stable disease, and 9 (45%) had progressive disease. Six (30%) patients had a PFS of greater than six months, although three had gone off study and onto other therapies before six months. The estimated six-month EFS was 15%. The median PFS and OS were 2.89 and 9.17months, respectively. Conclusion EGEN-001 at the dose and schedule evaluated was associated with some but limited activity and was seemingly less tolerated in platinum resistant recurrent ovarian cancer patients.

The determinants of HIV-1-associated lymphadenopathy are poorly understood. We hypothesized that lymphocytes could be sequestered in the HIV-1+ lymph node (LN) through impairments in sphingosine-1-phosphate (S1P) responsiveness. To test this hypothesis, we developed novel assays for S1P-induced Akt phosphorylation and actin polymerization. In the HIV-1+ LN, naïve CD4 T cells and central memory CD4 and CD8 T cells had impaired Akt phosphorylation in response to S1P, whereas actin polymerization responses to S1P were impaired dramatically in all LN maturation subsets. These defects were improved with antiretroviral therapy. LN T cells expressing CD69 were unable to respond to S1P in either assay, yet impaired S1P responses were also seen in HIV-1+ LN T cells lacking CD69 expression. Microbial elements, HIV-1, and interferon α - putative drivers of HIV-1 associated immune activation all tended to increase CD69 expression and reduce T-cell responses to S1P in vitro. Impairment in T-cell egress from lymph nodes through decreased S1P responsiveness may contribute to HIV-1-associated LN enlargement and to immune dysregulation in a key organ of immune homeostasis.

Objective Cervical and vaginal cancers have virally-mediated or mutated defects in DNA damage repair responses, making these cancers sensible targets for ribonucleotide reductase inhibition during radiochemotherapy. Methods We conducted a phase II study evaluating 3× weekly 2-hour intravenous 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP, 25mg/m 2 ) co-administered with 1× weekly intravenous cisplatin (40mg/m 2 ) and daily pelvic radiation (45Gy) in women with stage I B2 –IV B cervical (n=22) or stage II–IV vaginal (n=3) cancers. Brachytherapy followed (40Gy). Toxicity was monitored by common terminology criteria for adverse events (version 3.0). The primary end point of response was assessed by 3-month posttherapy 2-[ 18 F] fluoro-2-deoxy-d-glucose positron emission tomography (PET/CT) and clinical examination. Results 3-AP radiochemotherapy achieved clinical responses in 24 (96% [95% confidence interval: 80–99%]) of 25 patients (median follow-up 20months, range 2–35months). 23 (96% [95% confidence interval: 80–99%]) of 24 patients had 3-month posttherapy PET/CT scans that recorded metabolic activity in the cervix or vagina equal or less than that of the cardiac blood pool, suggesting complete metabolic responses. The most frequent 3-AP radiochemotherapy-related adverse events included fatigue, nausea, diarrhea, and reversible hematological and electrolyte abnormalities. Conclusions The addition of 3-AP to cisplatin radiochemotherapy was tolerable and produced high rates of clinical and metabolic responses in women with cervical and vaginal cancers. Future randomized phase II and III clinical trials of 3-AP radiochemotherapy are warranted.

Purpose 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 6 months or who achieved objective tumor response. We also aimed to characterize the toxicity of sunitinib and to estimate time-to-progression. Patients and methods Eligible patients with uterine leiomyosarcoma were treated with sunitinib 50 mg by mouth daily for 4 weeks, with 2 weeks rest. Tumor response and progression-free status were assessed every 6 weeks. Results Twenty-three of 25 patients enrolled were evaluable for efficacy (two wrong histologies). The median number of cycles was one. Two of 23 patients achieved a partial response (8.7%, 90% two-sided, binomial confidence interval (CI) 1.6–24.9%). Four patients remained progression-free at 6 months (17.4%, 90% two-sided, binomial confidence interval 6.2–35.5%). Toxicities included: grade 3 neutropenia (17.4%); grade 3 thrombocytopenia (13%); grade 3 anemia (17.4%); grades 3–4 lymphopenia (8.7%); grades 3–4 fatigue (30%); grade 3 vomiting/diarrhea (21.7%); skin rash/hand–foot syndrome, grade 2 (13%), grade 3 (4.3%); hypertension, grade 2 (39%), grade 3 (4.3%); grade 2 decrease in cardiac ejection fraction (4.3%), and grade 3 thrombosis (4.3%) Median progression-free survival (PFS) was 1.5 months. Conclusion Sunitinib fails to achieve sufficient objective response or sustained disease stabilization as second- or third-line treatment for uterine leiomyosarcoma.

Objective The purpose of this study was to determine the impact of patient weight on the frequency of surgical staging lymphadenectomy and pelvic radiation. Adverse effects, disease relapse, and survival outcomes were investigated. Study Design Records of 766 women who underwent surgery for presumed corpus-confined endometrial cancer were reviewed. Body mass index (BMI) was calculated to categorize women as obese (BMI, ≥30 kg/m 2 ) or nonobese (BMI, 2 ). Radiation-related toxicity was scored retrospectively. Median duration of follow-up period was 38 months. χ 2 , logistic regression, correlation, Kaplan-Meier, and Cox multivariate proportional hazards were used for analysis. Results Lymphadenectomy was completed as often in nonobese as obese women ( P = .24). Adjuvant pelvic radiation treatment was administered more often in nonobese women ( P = .01). Among 681 women with endometrioid histopathologic findings, 4-year cancer-related survival in obese women was 10% higher than all cause deaths, compared with 6% in nonobese women. Conclusion Obesity was not a barrier to lymphadenectomy, but did influence adjuvant pelvic radiation use.

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