Sentinel lymph node mapping with indocyanine green using SPY-PHI in open radical hysterectomy or trachelectomy.

OBJECTIVE: To evaluate the detection rate of at least one sentinel lymph node (SLN) in patients with early cervical cancer who underwent open radical hysterectomy or trachelectomy using indocyanine green (ICG) with the SPY Portable Handler Imager (SPY-PHI) system. METHODS: We retrospectively reviewed patients with cervical cancer FIGO 2018 stage IA1 with lymphovascular invasion up to stage IIIC1p who underwent SLN mapping and open radical hysterectomy or trachelectomy from March 2018 through August 2022 at The University of Texas MD Anderson Cancer Center. ICG was the only tracer used with the SPY-PHI system. Patient demographics, surgical approach, and tumor factors were analyzed. Overall detection, bilateral detection, and empty lymph node packet rates were determined. RESULTS: A total of 106 patients were included. Ninety-four (88.7%) patients underwent open radical hysterectomy and 12 (11.3%) open radical trachelectomy. Median age was 40 years (range, 23-71). Median body mass index was 28.8 kg/m2 (range, 17.6-48.4). The most common FIGO 2018 stages were IB1 (35%) and IB2 (30%). The most common histologic subtypes were squamous cell carcinoma (45%) and adenocarcinoma (45%). Most patients had grade 2 disease (61%) and no lymphovascular invasion (58%). Median tumor size was 1.8 cm (range, 0.3-4). Median number of detected SLN was 4 (range, 0-12). An SLN was identified during surgery in 104 patients (98%), with bilateral mapping in 94 (89%) and unilateral mapping in 10 (9%). The empty lymph node packet rate was 4 (3.8%). The external iliac (73%) was the most common site of SLN detection. Fourteen patients had positive lymph nodes (13.5%); 3 (21.4%) had macrometastases, 9 (64.3%) had micrometastases, and 2 (14.3%) had isolated tumor cells. CONCLUSION: SLN mapping using ICG with the SPY-PHI system in open radical hysterectomy or trachelectomy is reliable and results in high overall and bilateral detection rates in patients with early cervical cancer.

Accuracy of pre-operative tumor size assessment compared to final pathology and frequency of adjuvant treatment in patients with FIGO 2018 stage IB2 cervical cancer.

OBJECTIVE: The primary aim of our study was to compare tumor size assessment by pre-operative evaluation (physical examination and/or imaging) with tumor size on final pathology. As a secondary outcome, we evaluated the rate of adjuvant treatment in patients who underwent radical hysterectomy whose tumor size was ≥3 cm on final pathology. METHODS: Patient details were collected from three separate databases: the University of Texas MD Anderson Cancer Center Radical Hysterectomy Database, the SUCCOR Study Group Database, and the Multi-institutional Database LATAM (encompassing Latin America and Europe). Patients with International Federation of Gynecology and Obstetrics (FIGO) 2018 stage IB2 cervical cancer on pre-operative evaluation (physical examination or imaging) who underwent radical hysterectomy with a therapeutic intent were included. Any histological subtype, any tumor grade, and pre-operative evaluation with clinical evaluation and/or imaging (ultrasound, MRI, CT, or PET/CT) was considered. RESULTS: A total of 675 patients met eligibility criteria (SUCCOR=350, LATAM=250, MD Anderson=75). The median age was 46 years (range 22-82) and the median body mass index was 25.6 kg/m2 (range 15.1-68). The most common histologic subtype was squamous carcinoma (68%, n=456), and the majority had either grade 2 or 3 disease . Overall pre-operative imaging modalities used were MRI (52%, n=352), ultrasound (21%, n=140), CT (5%, n=32), and PET/CT (1%, n=10). Most patients underwent open surgery (60%, n=404). In total, 113 (17%) patients had lymph node involvement and 58 (9%) patients had parametrial involvement. A total of 343 (51%) patients received adjuvant therapy, with the majority of those receiving chemoradiation (54%, n=186) followed by radiation alone (44%, n=152). The results of the Bland-Altman analysis showed that pre-operative physical examination, MRI, ultrasound, and CT all overestimated tumor size, but only the bias found for physical examination (p<0.0001) and MRI (p=0.0102) were statistically significant. However, in patients who underwent a pre-operative MRI, a total of 293 (83.2%) patients with tumor size 2-4 cm by MRI had concordance with tumor measurement on final pathology. Similarly, when evaluating accuracy of physical examination with tumor size by MRI, we found that there was agreement in 319 (91.1%) patients. Similarly, we found that concordance of physical examination with tumor size on final pathology was 80.6%. There were 340 (50%) patients who had tumor size on pathology ≥3 cm, and 207 (61%) of these received adjuvant therapy. Additionally, there was a significantly higher incidence of positive lymph nodes with increasing tumor size on pathology (2-2.99 cm, 13% (29/222) vs 3-4 cm, 21% (66/316), p=0.022). CONCLUSIONS: Our study showed that there is a high concordance between tumor size assessment by physical examination and MRI, as well as estimates of measurement by MRI and final pathology. In addition, we noted that the majority of patients with FIGO 2018 stage IB2 received adjuvant therapy after radical hysterectomy.

Evaluation of a tiered opioid prescription algorithm in an ERAS pathway: exploring opportunities for further refinement.

BACKGROUND: Opioid over-prescription is wasteful and contributes to the opioid crisis. We implemented a personalized tiered discharge opioid protocol and education on opioid disposal to minimize over-prescription. OBJECTIVE: To evaluate the intervention by investigating opioid use post-discharge for women undergoing abdomino-pelvic surgery, and patient adherence to opioid disposal education. METHODS: We analyzed post-discharge opioid consumption among 558 patients. Eligible patients included those who underwent elective gynecologic surgery, were not taking scheduled opioids pre-operatively, and received discharge opioids according to a tiered prescribing algorithm. A survey assessing discharge opioid consumption and disposal safety knowledge was distributed on post-discharge day 21. Over-prescription was defined as >20% of the original prescription left over. Descriptive statistics were used for analysis. RESULTS: The survey response rate was 61% and 59% in the minimally invasive surgery and open surgery cohorts, respectively. Overall, 42.8% of patients reported using no opioids after hospital discharge, 45.2% in the minimally invasive surgery and 38.6% in the open surgery cohort. Furthermore, 74.9% of respondents were over-prescribed, with median age being statistically significant for this group (p=0.004). Finally, 46.4% of respondents expressed no knowledge regarding safe disposal practices, with no statistically significant difference between groups (p>0.99). CONCLUSION: Despite implementation of the tiered discharge opioid algorithm aimed to personalize opioid prescriptions to estimated need, we still over-prescribed opioids. Additionally, despite targeted education, nearly half of all patients who completed the survey did not know how to dispose of their opioid tablets. Additional efforts are needed to further refine the algorithm to reduce over-prescription of opioids and improve disposal education.

Social media use is associated with higher levels of anxiety and depression in patients with neuroendocrine carcinoma of the cervix: A NeCTuR study.

OBJECTIVE: Neuroendocrine cervical carcinoma (NECC) is rare. Educational resources are limited for NECC patients, leading many to seek information online through patient-led social networks. We sought to characterize the relationships between anxiety and depression levels and social media use among NECC patients. METHODS: Seven surveys assessing social media use, anxiety, and depression were distributed to living NECC patients enrolled in our NECC registry. The primary outcomes were associations between Social Network Time Use Scale (SONTUS) global score and Generalized Anxiety Disorder (GAD-7) and Center for Epidemiologic Studies Depression Scale (CESD) total scores. RESULTS: Eighty-eight patients enrolled; 81 who completed at least 1 survey were included. Ninety-seven percent (70/72) of patients completing SONTUS were low-to-average social media users. Seventy-four percent (53/72) of patients visited a patient-led NECC support-group page on Facebook within the past 4 weeks, and of those, 79% (42/53) reported receiving useful information. Among the patients who did not visit the page, 47% (9/19) reported that the page elicited anxiety and/or sadness. The mean GAD-7 and CES-D scores for the entire cohort were 7.3 and 18.1, respectively. The Spearman correlations between social media use and these scores were significant (GAD-7: 0.23 [p = 0.05]; CESD: 0.25 [p = 0.04]). The estimated odds ratios for moderate/severe anxiety and depression as a function of SONTUS global score were 1.26 (95% CI 1.03-1.55; p = 0.03) and 1.23 (95% CI 1.01-1.49; p = 0.04), respectively. CONCLUSIONS: NECC patients demonstrated low-to-average social media use and relatively high anxiety and depression. Increased social media use was associated with elevated anxiety and depression.

MAGENTA (Making Genetic testing accessible): a prospective randomized controlled trial comparing online genetic education and telephone genetic counseling for hereditary cancer genetic testing.

BACKGROUND: Studies have consistently indicated that the majority of individuals meeting the US Prevention Services Task Force guidelines for genetic testing have not had genetic counseling or testing. Despite increased availability and lower costs of multiplex cancer gene panels, there remains a gap in genetics services that has not been addressed by the current care delivery models. Lower cost of DNA sequencing with online patient-initiated ordering could increase test availability, but the ideal quantity and delivery method of patient education is not known. We hypothesized that online genetic education and testing with access to board certified genetic counselors could improve access to genetic testing while maintaining test quality and clinical utility. The MAGENTA (MAking GENetic Testing Accessible) trial is a nationwide randomized study designed to compare the effectiveness of online genetic education with pre- and post-test telephone genetic counseling to three potentially more accessible alternative approaches: online genetic education with optional telephone counseling, online genetic education with required pre-test telephone genetic counseling, and online genetic education with required post-test telephone genetic counseling. METHODS: 3000 women nationwide will undergo genetic testing for 19 hereditary cancer genes. This is a randomized four-arm non-inferiority study with equal randomization. The four study arms were selected to independently assess the delivery of genetic information both before and after genetic testing (pre-test and post-test) by either requiring telephone genetic counseling or providing only online education with optional telephone counseling. Patients have post-test telephone counseling when testing positive for a pathogenic inherited mutation in all four arms. Surveys measuring psychological, behavioral and cognitive state are completed online at baseline, 3 months, 12 months and 24 months post-results disclosure. The primary study outcome is cancer-risk distress at 3 months post-result disclosure. DISCUSSION: This trial will assess the use of a genetic service model using online access and electronic education, while evaluating the need for personal pre- and post-test genetic counseling. Data from this study may lead to increased options for delivery of genetic testing and possibly increase access to genetic testing. Identifying more individuals with inherited cancer susceptibility will allow targeted cancer prevention. TRIAL REGISTRATION: Clinicaltrials.gov: NCT02993068 (registered December 14, 2016).

Nuclear ß-catenin localization and mutation of the CTNNB1 gene: a context-dependent association.

Although the majority of low-grade, early-stage endometrial cancer patients have good survival with surgery alone, patients who recur tend to do poorly. Identification of patients at high risk of recurrence who would benefit from adjuvant treatment or more extensive surgical staging would help optimize individualized care of endometrial cancer patients. CTNNB1 (encodes ß-catenin) mutations identify a subset of low-grade, early-stage endometrial cancer patients at high risk of recurrence. Mutation of CTNNB1 exon 3 is classically associated with translocation of the ß-catenin protein from the membrane to the nucleus and activation of Wnt/ß-catenin signaling. Given the clinical utility of identifying endometrial carcinomas with CTNNB1 mutation, the purpose of this study was to determine if immunohistochemistry could act as a surrogate for CTNNB1 gene sequencing. Next-generation sequencing was performed on 345 endometrial carcinomas. Immunohistochemical localization of ß-catenin was determined for 53/63 CTNNB1 exon 3 mutant tumors for which tissue was available and a subset of wild-type tumors. Nuclear localization of ß-catenin had 100% specificity in distinguishing CTNNB1 mutant from wild type, but sensitivity was lower (84.9%). Nearly half of CTNNB1 mutant cases had only 5-10% of tumor cells with ß-catenin nuclear localization. The concordance between pathologists blinded to mutation status in assessing nuclear localization was 100%. The extent of ß-catenin nuclear localization was not associated with specific CTNNB1 gene mutation, tumor grade, presence of non-endometrioid component, or specific concurrent gene mutations in the tumor. For comparison, nuclear localization of ß-catenin was more diffuse in desmoid fibromatosis, a tumor also associated with CTNNB1 mutation. Thus, nuclear localization of ß-catenin assessed by immunohistochemistry does not detect all endometrial cancers with CTNNB1 gene mutation. The extent of nuclear localization may be tumor type dependent. For endometrial cancer, immunohistochemistry could be an initial screen, with CTNNB1 sequencing employed when nuclear localization of ß-catenin is absent.

Bilateral salpingectomy with delayed oophorectomy for ovarian cancer risk reduction: A pilot study in women with BRCA1/2 mutations.

OBJECTIVE: Risk-reducing salpingo-oophorectomy (RRSO) reduces ovarian cancer risk in BRCA1/2 mutation carriers, but the adverse effects of the associated early-onset surgical menopause are problematic. Despite suggestive evidence, no data demonstrate whether bilateral salpingectomy alone lowers the risk of developing ovarian cancer in BRCA mutation carriers. We conducted a pilot study of bilateral salpingectomy with delayed oophorectomy (BS/DO) in BRCA mutation carriers to determine the safety and acceptability of the procedure. METHODS: In this prospective, multicenter, non-randomized pilot study, pre-menopausal BRCA1/2 mutation carriers aged 30 to 47 years chose screening, RRSO, or BS/DO. For those undergoing BS/DO, the delayed oophorectomy was recommended at age 40 years for BRCA1 and age 45 years for BRCA2 patients. We compared surgical and psychosocial outcomes between time points and between arms. RESULTS: Of the 43 patients enrolled, 19 (44%) chose BS/DO, 12 (28%) chose RRSO, and 12 (28%) chose screening. The cohort was 37% BRCA1 carriers and 63% BRCA2 carriers. One serous tubal intraepithelial carcinoma (STIC) was found in an RRSO patient, and no cases of occult ovarian cancers were found. There were no surgical complications. Twelve months after surgery, responses on the Cancer Worry Scale indicated decreased worry in the BS/DO (P < 0.0001) and RRSO (P = 0.01) arms, while responses on the State Anxiety Inventory indicated decreased anxiety in the BS/DO arm (P = 0.02) compared with preoperative responses. CONCLUSIONS: In this pilot study, BRCA mutation carriers who underwent bilateral salpingectomy had no intraoperative complications, were satisfied with their procedure choice, and had decreased cancer worry and anxiety after the procedure.

The DISINFECT Initiative: Decreasing the Incidence of Surgical INFECTions in Gynecologic Oncology.

BACKGROUND: Surgical site infections (SSIs) lead to increased patient morbidity and healthcare costs. Our objective was to decrease the SSI rate following gynecologic surgery. METHODS: Adult patients undergoing abdominal surgery for gynecologic malignancy or benign disease received the following: patient education; preoperative antibacterial soap; appropriate antibiotic prophylaxis; change of gloves and use of clean instruments at surgical closure; surgical dressing for 48 h; and a post-discharge phone call. The baseline SSI rate was determined retrospectively (1 April 2014-30 June 2014), while the post-intervention SSI rate was determined prospectively (16 February 2015-15 October 2015). The main outcome was the overall SSI rate with secondary outcomes, including the rate of superficial, deep, incisional and organ space infection, as well as the cost effectiveness of the bundle. RESULTS: A total of 232 baseline and 555 post-intervention patients were included in the study. No differences were observed between the baseline and post-intervention groups with regard to median body mass index (BMI), surgical approach, receipt of preoperative chemotherapy and/or radiation therapy, and cases including bowel surgery. Overall, the SSI rate decreased significantly from baseline [12.5 %] to post-intervention [7.4 %] (odds ratio [OR] 0.56, 90 % confidence interval [CI] 0.37-0.85; p = 0.01). A 40 % decrease was noted in the rate of superficial and deep infections (9.5 vs. 5.9 %; OR 0.60, 90 % CI 0.38-0.97; p = 0.04) and SSIs after open surgery (21.4 vs. 13.2 %; OR 0.56, 90 % CI 0.34-0.92; p = 0.03). The estimated cost of the intervention was $19.26/case and the net total amount saved during the post-intervention period was $65,625 month. CONCLUSIONS: This bundled intervention led to a significant decrease in the overall SSI rate and was cost effective. The largest decreases in SSIs were in incisional infections and following open surgery.

Sensitivity and negative predictive value for sentinel lymph node biopsy in women with early-stage cervical cancer.

OBJECTIVE: The role of sentinel lymph node (SLN) biopsy alone for staging of early-stage cervical cancer remains controversial. We aimed to determine the validity of this technique in women with early-stage cervical cancer. METHODS: We retrospectively reviewed women with early-stage cervical cancer who underwent SLN mapping followed by complete pelvic lymphadenectomy as part of initial surgical management from August 1997 through October 2015. All modes of surgical approach were included. Lymphatic mapping was performed using blue dye, technetium-99m sulfur colloid (Tc-99), and/or indocyanine green (ICG). We determined SLN detection rates, sensitivity and negative predictive value. RESULTS: One hundred eighty-eight patients were included, and 35 (19%) had lymph node metastases. At least one SLN was identified in 170 patients (90%), and bilateral SLNs were identified in 117 patients (62%). The majority of SLNs (83%) were found in the pelvis. There was no difference in detection rates between mapping agents, surgical approach, patients with and without prior conization or between patients with tumors <2cm and ≥2cm. The detection rate for bilateral SLNs was significantly lower in women with body mass index (BMI)>30kg/m2 than in women with lower BMI (p=0.03). Metastatic disease in sentinel nodes was detected by H&E staining in 78% of cases and required ultrastaging/immunohistochemistry in 22% of cases. Only one patient had a false-negative result, yielding a sensitivity of 96.4% (95% CI 79.8%-99.8%) and negative predictive value of 99.3% (95% CI 95.6%-100%). The false-negative rate was 3.6%. CONCLUSIONS: In these women with early-stage cervical cancer, SLN biopsy had very high sensitivity and negative predictive value. We believe it is time to change the standard of care for women with early-stage cervical cancer to SLN biopsy only.

Phase II trial of bevacizumab with dose-dense paclitaxel as first-line treatment in patients with advanced ovarian cancer.

OBJECTIVES: To assess the tolerability and efficacy of bevacizumab with carboplatin and weekly paclitaxel as first-line adjuvant therapy for advanced stage ovarian cancer. METHODS: After IRB approval, this single-institution, phase II study enrolled patients with stage III or IV epithelial ovarian cancer after primary cytoreductive surgery to treatment with carboplatin (AUC 5), weekly paclitaxel (80mg/m2), and bevacizumab (15mg/kg) every 3weeks for at least 6cycles. The primary endpoint was tolerability of at least 4cycles of therapy, with a target treatment success rate of >60%. Secondary endpoints included progression-free survival (PFS) and response rate. Plasma biomarkers were analyzed by the multiplex ELISA assays. RESULTS: Thirty-three patients were enrolled with 30 evaluable patients receiving at least one cycle of combination treatment. Twenty-three patients (77%) were able to complete at least 4cycles of therapy per protocol, and the posterior probability that the treatment success rate is >60% is 0.77. Twenty-one patients (70%) were able to complete ≥6cycles of therapy. Median PFS was 22.4months for patients with optimal (R0) compared to 16.9months for optimal≤1cm (HR 1.71, 95% CI 0.58-4.98, p=0.33), and 16.9months for suboptimal>1cm (HR 3.75, 95% CI 1.05-13.34, p=0.04) disease. Increases in mean Flt-3L was significantly higher in responders versus non-responders (83.4 vs. 28pg/mL, p=0.05). CONCLUSIONS: Adjuvant bevacizumab with dose-dense chemotherapy is associated with acceptable toxicity and a high likelihood of completing 4cycles of therapy. Dynamic changes in Flt-3L may represent a predictive marker to treatment response.

A universal genetic testing initiative for patients with high-grade, non-mucinous epithelial ovarian cancer and the implications for cancer treatment.

OBJECTIVE: Genetic counseling (GC) and germline genetic testing (GT) for BRCA1 and BRCA2 are considered standard of care for patients with high-grade, non-mucinous epithelial ovarian, fallopian tube, and primary peritoneal cancers (HGOC). We describe a universal genetic testing initiative to increase the rates of recommendation and acceptance of GC and GT to >80% for patients with HGOC at our institution. METHODS: Data from a consecutive cohort of patients seen in our gynecologic oncology clinics between 9/1/2012 and 8/31/2015 for evaluation of HGOC were retrospectively analyzed. Data were abstracted from the tumor registry, medical records, and research databases. Descriptive statistics were used to evaluate patient characteristics and GC, GT, and PARP inhibitor use. Various clinic interventions were developed, influenced by the Plan-Do-Study-Act cycle method, which included physician-coordinated GT, integrated GC, and assisted GC referrals. RESULTS: A cohort of 1636 patients presented to the gynecologic oncology clinics for evaluation of HGOC during our study period, and 1423 (87.0%) were recommended to have GC and GT. Of these, 1214 (85.3%) completed GT and 217 (17.9%) were found to have a BRCA1 or BRCA2 mutation. Among BRCA-positive patients, 167 had recurrent or progressive disease, and 56 of those received PARP inhibitor therapy. CONCLUSIONS: The rates of GC and GT recommendation and completion among patients with HGOC at our institution exceeded 80% following the implementation of a universal genetic testing initiative. Universal genetic testing of patients with HGOC is one strategy to identify those who may benefit from PARP inhibitor therapy.

A prospective validation study of sentinel lymph node mapping for high-risk endometrial cancer.

OBJECTIVE: Sentinel lymph node (SLN) mapping continues to evolve in the surgical staging of endometrial cancer (EC). The purpose of this trial was to identify the sensitivity, false negative rate (FNR) and FN predictive value (FNPV) of SLN compared to complete pelvic and para-aortic lymphadenectomy (LAD) in women with high-risk EC. METHODS: Women with high-risk EC (grade 3, serous, clear cell, carcinosarcoma) were enrolled in this prospective surgical trial. All patients underwent preoperative PET/CT and intraoperative SLN biopsy followed by LAD. Patients with peritoneal disease on imaging or at the time of surgery were excluded. Patients were evaluable if SLN was attempted and complete LAD was performed. RESULTS: 123 patients were enrolled between 4/13 and 5/16; 101 were evaluable. At least 1 SLN was identified in 89% (90); bilateral detection 58%, unilateral pelvic 40%, para-aortic only 2%. Indocyanine green was used in 61%, blue dye in 28%, and blue dye and technetium in 11%. Twenty-three pts. (23%) had ≥1 positive node. In 20/23, ≥1 SLN was identified and in 19/20 the SLN was positive. Only 1 patient had bilateral negative SLN and positive non-SLNs on final pathology. Overall, sensitivity of SLN was 95% (19/20), FNR was 5% (1/20) and FNPV was 1.4% (1/71). If side-specific LAD was performed when a SLN was not detected, the FNR decreased to 4.3% (1/23). CONCLUSION: This prospective trial demonstrated that SLN biopsy plus side-specific LAD, when SLN is not detected, is a reasonable alternative to a complete LAD in high-risk endometrial cancer.

Factors prognostic of survival in advanced-stage uterine serous carcinoma.

OBJECTIVES: The study objective was to analyze the impact of prognostic factors, including treatment modality, on outcome in patients with advanced-stage uterine serous carcinoma (USC). METHODS: A retrospective review of patients diagnosed with stage III or IV USC between 1993 and 2012 was performed. Summary statistics were used to describe demographic and clinical characteristics. Overall survival (OS) and recurrence free survival (RFS) were estimated by Kaplan-Meier analysis. Cox proportional hazards regression was used to model the association of potential prognostic factors with OS and RFS. RESULTS: The study included 260 patients with median follow-up of 26.6months (range 1-172.8). Median age was 63years (range 30-88) and 52.3% had stage III disease. In all, 60% were treated with surgery followed by chemotherapy, 18.1% received surgery, chemotherapy, and radiotherapy, 11.5% had surgery and radiotherapy, and 10.4% had neoadjuvant chemotherapy. The overall complete response rate was 68.9%, and the cumulative incidence of recurrence was 82.7%. Treatment that included surgery, chemotherapy, and radiation and stage III disease were associated with improved RFS on multivariate analysis. For OS, therapy with surgery, chemotherapy, and radiation, mixed histology, and stage III disease were associated with better OS on multivariate analysis. CONCLUSIONS: Patients with advanced-stage USC have a poor prognosis, regardless of clinical factors or treatment received. However, combination therapy that includes chemotherapy and radiation appears to be associated with improved survival in these women.

Ewing sarcoma family of tumors in children younger than 10 years of age.

AIM: Few data exist regarding the clinical characteristics and outcome of young children with Ewing sarcoma family of tumors (ESFT). METHODS: We reviewed the records of ESFT patients at our institution younger than 10 years of age at diagnosis. RESULTS: Forty-two patients were identified. Median age was 6.4 years (range 0.6-9.5 years). Most patients had T2 (>5 cm) tumors (n = 31; 74%). Most common primary site was the extremity (n = 17; 41%). Seven patients (17%) had metastasis at diagnosis. For local tumor control, 20 patients had surgery only, 13 had radiation therapy only, and 6 had surgery plus radiation. Surgical margin status was negative in 19 patients (73%). Median follow-up was 4.7 years (range 0.7-29.7 years), and 5-year relapse-free survival (RFS) and overall survival (OS) estimates were 67% (95% CI: 53-84%) and 82% (95% CI: 71-95%), respectively. Metastasis at presentation was the only significant predictor for decreased RFS (P = 0.008) and OS (P = 0.01). A trend was seen for T2 tumors with worse OS (P = 0.09). CONCLUSION: Patients younger than 10 years of age with ESFT may have a better OS than older patients, but further study of a homogeneously treated larger cohort is needed.

Prospective evaluation of the molecular effects of metformin on the endometrium in women with newly diagnosed endometrial cancer: A window of opportunity study.

OBJECTIVE: Metformin reduces cancer incidence and improves overall survival in diabetic patients. In preclinical studies, metformin decreases endometrial cancer (EC) cell growth by activation of AMPK/mTOR inhibition. We sought to determine the effects of metformin on serum/tumor biomarkers in women with EC. METHODS: In this prospective trial, newly diagnosed EC patients underwent pre-treatment blood draw/endometrial biopsy, were administered oral metformin 850mg daily for ≥7days, and underwent post-treatment blood draw/definitive surgery. Pre- and post- serum analyses were performed. Tumor samples were evaluated for changes in AMPK, PI3K/AKT pathway, proliferation, and apoptosis by immunohistochemistry. RESULTS: Twenty patients completed the trial. Median age and BMI were 57years (range: 27-67) and 34.5kg/m2 (range: 21.9-50.0). Median duration of metformin was 9.5days (range: 7-24). A majority of women had endometrioid adenocarcinomas (90%) and were early stage (85%). After metformin, there were significant decreases in serum IGF-1 (p=0.046), omentin (p=0.007), insulin (p=0.012), C-peptide (p=0.018), and leptin (p=0.0035). Compared to baseline, post-treatment tissue showed decreased phospho-AKT in 18/20 patients (90%, p=0.0002), decreased phospho-S6rp in 14/20 patients (70%, p=0.057), and decreased phospho-p44/42MAPK in 15/18 patients (83.3%, p=0.0038). There was no difference in Ki67, phospho-ACC, or caspase 3. Changes did not correlate with BMI, grade, or KRAS mutation. CONCLUSION: In this prospective window of opportunity study, we demonstrated that relevant serum and molecular changes occur in patients with newly diagnosed EC after a short course of metformin. Ongoing clinical trials will help determine the appropriate role for metformin in the treatment of women with EC.

Prognostic factors influencing survival from regionally advanced squamous cell carcinoma of the penis after preoperative chemotherapy.

OBJECTIVE: To describe both clinical and pathological response rates, survival, and predictors of survival when using contemporary perioperative chemotherapy and surgical resection for patients with regionally advanced squamous cell carcinoma (SCC) of the penis. PATIENTS AND METHODS: Retrospective review of all patients diagnosed with SCC of the penis and regional lymph node metastases that were treated with chemotherapy with the intent to undergo lymphadenectomy. Clinical and pathological responses were reported. Recurrence-free and overall survival was estimated using Kaplan-Meier analysis. Cox proportional hazards regression was used to assess factors for survival. RESULTS: In all, 61 patients were identified, of which 54 (90%) received chemotherapy with paclitaxel/ifosfamide/cisplatin. In all, 39 patients (65%) had either a partial (PR) or complete response (CR) to chemotherapy. The 5-year survival varied significantly (P = 0.045-0.001) among patients achieving a CR/PR (50%), stable disease (25%), and progression (7.7%). In all, 10 patients (16.4%) were rendered pN0 with combined therapy and 20 patients (33%) were alive and disease free at a median follow-up of 67 months, while 32 (52%) died from disease. Long-term survival was associated with response to chemotherapy and favourable pathological findings after resection. CONCLUSION: Contemporary chemotherapy resulted in clinically significant responses among patients with regionally advanced penile cancer. About 50% of such patients with an objective response to chemotherapy who undergo consolidative lymphadenectomy will remain alive at 5 years.

Carcinoma of the Bartholin Gland: A Review of 33 Cases.

OBJECTIVE: Primary carcinoma of the Bartholin gland is a rare malignancy that accounts for approximately 5% of vulvar carcinomas. The aim of the study was to compare the outcomes of women with primary Bartholin gland carcinoma (BGC) with those with non-Bartholin gland-related vulvar carcinoma. MATERIALS AND METHODS: A retrospective chart review of 429 patients with invasive vulvar carcinoma evaluated at a single institution between 1993 and 2011 was performed. Medical records were reviewed for demographic data, pathologic information, treatment type, and recurrence/outcome information. These variables were compared between patients with primary BGC and patients with non-Bartholin gland-related vulvar carcinoma. RESULTS: Thirty-three (7.7%) of the 429 patients with invasive vulvar carcinoma had primary carcinoma of the Bartholin gland. Twenty-nine patients (87.9%) had squamous cell histology and 4 patients (12.1%) had adenocarcinoma. When compared with non-Bartholin gland-related vulvar carcinoma, patients with primary BGC had a younger age at diagnosis (median, 57 vs 63 years; P = 0.045), had a higher rate of stage III/IV disease (60.6% vs 35.8%; P = 0.008), and were more likely to receive radiation therapy (78.8% vs 43.9%; P < 0.001). However, there were no significant differences between the 2 groups with regard to histologic subtype, lymphovascular space involvement, perineural invasion, positive margins, recurrence-free survival, or overall survival. CONCLUSIONS: Despite being diagnosed at a more advanced stage, patients with primary carcinoma of the Bartholin gland seem to have similar oncologic outcomes and survival rates to patients with non-Bartholin gland-related vulvar carcinoma.

Stereotactic ablative radiotherapy versus lobectomy for operable stage I non-small-cell lung cancer: a pooled analysis of two randomised trials.

BACKGROUND: The standard of care for operable, stage I, non-small-cell lung cancer (NSCLC) is lobectomy with mediastinal lymph node dissection or sampling. Stereotactic ablative radiotherapy (SABR) for inoperable stage I NSCLC has shown promising results, but two independent, randomised, phase 3 trials of SABR in patients with operable stage I NSCLC (STARS and ROSEL) closed early due to slow accrual. We aimed to assess overall survival for SABR versus surgery by pooling data from these trials. METHODS: Eligible patients in the STARS and ROSEL studies were those with clinical T1-2a (<4 cm), N0M0, operable NSCLC. Patients were randomly assigned in a 1:1 ratio to SABR or lobectomy with mediastinal lymph node dissection or sampling. We did a pooled analysis in the intention-to-treat population using overall survival as the primary endpoint. Both trials are registered with ClinicalTrials.gov (STARS: NCT00840749; ROSEL: NCT00687986). FINDINGS: 58 patients were enrolled and randomly assigned (31 to SABR and 27 to surgery). Median follow-up was 40·2 months (IQR 23·0-47·3) for the SABR group and 35·4 months (18·9-40·7) for the surgery group. Six patients in the surgery group died compared with one patient in the SABR group. Estimated overall survival at 3 years was 95% (95% CI 85-100) in the SABR group compared with 79% (64-97) in the surgery group (hazard ratio [HR] 0·14 [95% CI 0·017-1·190], log-rank p=0·037). Recurrence-free survival at 3 years was 86% (95% CI 74-100) in the SABR group and 80% (65-97) in the surgery group (HR 0·69 [95% CI 0·21-2·29], log-rank p=0·54). In the surgery group, one patient had regional nodal recurrence and two had distant metastases; in the SABR group, one patient had local recurrence, four had regional nodal recurrence, and one had distant metastases. Three (10%) patients in the SABR group had grade 3 treatment-related adverse events (three [10%] chest wall pain, two [6%] dyspnoea or cough, and one [3%] fatigue and rib fracture). No patients given SABR had grade 4 events or treatment-related death. In the surgery group, one (4%) patient died of surgical complications and 12 (44%) patients had grade 3-4 treatment-related adverse events. Grade 3 events occurring in more than one patient in the surgery group were dyspnoea (four [15%] patients), chest pain (four [15%] patients), and lung infections (two [7%]). INTERPRETATION: SABR could be an option for treating operable stage I NSCLC. Because of the small patient sample size and short follow-up, additional randomised studies comparing SABR with surgery in operable patients are warranted. FUNDING: Accuray Inc, Netherlands Organisation for Health Research and Development, NCI Cancer Center Support, NCI Clinical and Translational Science Award.

Retrospective review of symptoms and palliative care interventions in women with advanced cervical cancer.

OBJECTIVE: The objective of this study was to delineate and measure the symptom distress experienced by patients with advanced cervical cancer at the time of palliative care (PC) referral. METHODS: A total of 156 patients with advanced cervical cancer were referred to PC from 2010 to 2012. Of these, 88 patients had completed the Edmonton Symptom Assessment System (ESAS) and were included in the analysis. RESULTS: The mean age was 45years (25-76), 47% were white, 18% were African American, and 33% were Hispanic. Fifty-one percent were married, 64% had no advance directives, and 75% had recurrent disease. Clinically significant symptoms recorded by patient reported outcome measurement (defined as ESAS scores ≥4) were pain (81%), anorexia (72%), a poor feeling of well-being (70%), fatigue (69%), and insomnia (54%). The chief complaint recorded for the visit was pain in 94% of patients. According to the PC specialists' assessment, pain (96%), emotional distress (77%), and constipation (50%) were predominant symptoms. Various PC interventions including opioids, laxatives, and expressive supportive counseling were provided. Clinically significant symptoms including nausea, depression, anxiety, and feeling of well-being were significantly improved at follow-up visits. CONCLUSION: More than half of patients with advanced cervical cancer were significantly burdened with pain, anorexia, a poor feeling of well-being, fatigue, insomnia, and constipation at the time of PC referral. This research is an integral step towards developing a standardized tool for assessing symptoms in women diagnosed with cervical cancer and thus maximizing effectiveness of patient centered care.

Perioperative blood transfusion in gynecologic oncology surgery: analysis of the National Surgical Quality Improvement Program Database.

OBJECTIVE: To use a large-scale multi-institutional dataset to quantify the prevalence of packed red blood cell transfusions and examine the associations between transfusion and perioperative outcomes in gynecologic cancer surgery. METHODS: The American College of Surgeons National Surgical Quality Improvement Program (NSQIP) participant use file was queried for all gynecologic cancer cases between 2010 and 2012. Demographic, preoperative and intraoperative variables were compared between transfusion and non-transfusion groups using chi-squared, Fisher's exact and Wilcoxon rank-sum tests. The primary endpoint was 30-day composite morbidity. Secondary endpoints included composite surgical site infections, mortality and length of stay. RESULTS: A total of 8519 patients were analyzed, and 13.8% received a packed red blood cell transfusion. In the multivariate analysis, after adjusting for key clinical and perioperative factors, including preoperative anemia and case magnitude, transfusion was associated with higher composite morbidity (OR = 1.85, 95% CI 1.5-2.24), surgical site infections (OR 1.80, 95% CI 1.39-2.35), mortality (OR 3.38, 95% CI 1.80-6.36) and length of hospital stay (3.02 days v. 7.17 days, P < 0.001). CONCLUSIONS: Blood transfusions are associated with increased surgical wound infections, composite morbidity and mortality. Based on our analysis of the NSQIP database, transfusion practices in gynecologic cancer should be scrutinized. Examination of institutional practices and creation of transfusion guidelines for gynecologic malignancies could potentially result in better utilization of blood bank resources and clinical outcomes among patients.