Pediatric Myeloid Sarcoma, More than Just a Chloroma: A Review of Clinical Presentations, Significance, and Biology.

Myeloid sarcomas (MS), commonly referred to as chloromas, are extramedullary tumors of acute myeloid leukemia (AML) with varying incidence and influence on outcomes. Pediatric MS has both a higher incidence and unique clinical presentation, cytogenetic profile, and set of risk factors compared to adult patients. Optimal treatment remains undefined, yet allogeneic hematopoietic stem cell transplantation (allo-HSCT) and epigenetic reprogramming in children are potential therapies. Importantly, the biology of MS development is poorly understood; however, cell-cell interactions, epigenetic dysregulation, cytokine signaling, and angiogenesis all appear to play key roles. This review describes pediatric-specific MS literature and the current state of knowledge about the biological determinants that drive MS development. While the significance of MS remains controversial, the pediatric experience provides an opportunity to investigate mechanisms of disease development to improve patient outcomes. This brings the hope of better understanding MS as a distinct disease entity deserving directed therapeutic approaches.

Statewide trends and factors associated with genetic testing for hereditary cancer risk in Arkansas 2013-2018.

BACKGROUND: Early identification of hereditary cancer risk would save lives, but genetic testing (GT) has been inadequate. We assessed i) trends for hereditary breast and ovarian cancer (HBOC), Lynch syndrome, and other GT and ii) factors associated with receipt of GT. METHODS: We used data from the Arkansas All-Payer Claims Database from January 2013 through June 2018 (commercial, Medicaid), December 2017 (state employee), or December 2016 (Medicare) and identified enrollees with ≥1 month of enrollment. Using Current Procedural Terminology (CPT-4) codes, rates for GT were calculated per 100,000 person-quarters and time series regressions estimated. Second, GT and covariate information for enrollees with 24 months of continuous enrollment were used to estimate separate logistic regression models for each GT category. RESULTS: Among 2,520,575 unique enrollees, HBOC testing rates were 2.2 (Medicaid), 22.0 (commercial), 40.4 (state employee), and 13.1(Medicare) per 100,000 person-quarters and increased linearly across all plans. Older age (OR=1.24; 95%CI 1.20 - 1.28), female sex (OR=18.91; 95%CI 13.01 - 28.86), higher comorbidity burden (OR=1.08; 95%CI 1.05 - 1.12), mental disorders (OR=1.53; 95%CI 1.15 - 2.00), and state employee coverage (OR=1.65; 95%CI 1.37 - 1.97) were positively associated with HBOC testing. Less than 1 of 10,000 enrollees received Lynch syndrome testing, while < 5 of 10,000 received HBOC testing. CONCLUSION: GT rates for hereditary cancer syndromes have increased in Arkansas but remain low. Receipt of GT was explained with high discrimination by sex and plan type. IMPACT: Expansion of GT for hereditary cancer risk in Arkansas is needed to identify high-risk individuals who could benefit from risk-reduction strategies.

Can Automated Alerts in the Electronic Health Record Encourage Referrals for Genetic Counseling and Testing Among Patients at High Risk for Hereditary Cancer Syndromes?

PURPOSE: Up to 10% of cancers may be associated with an inherited mutation that increases cancer risk. National guidelines emphasize referral for genetic counseling and testing for patients whose personal and/or family history increases their risk of having a hereditary cancer syndrome. METHODS: To increase appropriate referrals for cancer genetic counseling and testing, we piloted an automated alert known as a Best Practice Advisory (BPA) in the electronic health record, Epic, to notify oncology providers when a patient had a personal and/or family history that merited referral to cancer genetics. Epic could not gather the complex clinical data needed for the referral decision automatically, necessitating staff completion of a questionnaire. After educating providers, the BPA was implemented with resources to support its use. RESULTS: Initial interaction with the alert was high but rapidly dwindled, resulting in questionnaire completion in 7.2% of more than 32,000 encounters and 14.9% of patients over 9 months. However, cancer genetics referrals increased 95.9% during the pilot (P < .0001), with 18.5% placed through the BPA and the rest from a non-BPA mechanism. Semistructured interviews with key stakeholders revealed not only general acceptance of the BPA concept but also barriers to completion, such as pressure to room patients quickly in the face of competing BPAs and lack of buy-in from some providers. CONCLUSION: These results suggest that provider engagement and BPA fatigue are significant obstacles to acceptance of a new automated alert. Despite interest in a tool for cancer genetics, the demand on clinical time for this complex BPA was poorly tolerated.

What's in Between the Lines: Assessing the Readability, Understandability, and Actionability in Breast Cancer Survivorship Print Materials.

Educational print materials for young women breast cancer survivors (YBCS) are supplemental tools used in patient teaching. However, the readability of the text coupled with how well YBCS understand or act upon the material are rarely explored. The purpose of this study was to assess the readability, understandability, and actionability of commonly distributed breast cancer survivorship print materials. We used an environmental scan approach to obtain a sample of breast cancer survivorship print materials available in outpatient oncology clinics in the central region of a largely rural Southern state. The readability analyses were completed using the Flesch-Kincaid (F-K), Fry Graph Readability Formula (Fry), and Simple Measure of Gobbledygook (SMOG). Understandability and actionability were analyzed using Patient Education Materials Assessment Tool for Printable Materials (PEMAT-P). The environmental scan resulted in a final sample of 14 materials. The mean readability of the majority of survivorship materials was "difficult," but the majority scored above the recommended 70% in both understandability and actionability. The importance of understandability and actionability may outweigh readability results in cancer education survivorship material. While reading grade level cannot be dismissed all together, we surmise that patient behavior may hinge more on other factors such as understandability and actionability. Personalized teaching accompanying print material may help YBCS comprehend key messages and promote acting upon specific tasks.

Recurrent gynandroblastoma of the ovary with germline DICER1 mutation: A case report and review of the literature.

Sex cord-stromal tumors (SCSTs) are ovarian tumors that generally present with an adnexal mass and signs/symptoms of hormone excess. Gynandroblastoma is a rare subtype of SCST with a combination of female and male sex cord differentiation. These tumors typically present in premenopausal women and are diagnosed at early stages with benign clinical courses. Here, we present a rare case of recurrent gynandroblastoma in a premenopausal woman with a DICER1 germline mutation. The patient was referred to our clinic for new symptoms of hormonal imbalance with a history of ovarian juvenile granulosa cell tumor (JGCT). Evaluation revealed a 5x5cm complex right adnexal mass and rising inhibin B. Patient underwent total abdominal hysterectomy with right salpingo-oophorectomy, omentectomy and right pelvic and para-aortic lymphadenectomy. Pathology showed a right ovarian gynandroblastoma. Somatic biallelic mutations in the RNase IIIb domain of DICER1 were identified; a 23-gene germline panel confirmed a germline DICER1 pathogenic variant. Cascade testing of her children documented that both daughters inherited the pathogenic variant. Testing for DICER1 mutations has important implications for individual and familial tumor risk assessment given what we know about DICER1 mutation and increased childhood cancer risk.

Phase II study of everolimus and bevacizumab in recurrent ovarian, peritoneal, and fallopian tube cancer.

BACKGROUND: Recurrent ovarian, fallopian tube, and peritoneal cancers have limited potential for cure with traditional therapies. Preliminary results from a phase I study of everolimus and bevacizumab in advanced solid tumors showed it to be a promising combination. The primary objective of this study was to evaluate the 6-month progression-free survival for everolimus and bevacizumab in recurrent ovarian, peritoneal, and fallopian tube cancer. Secondary objectives included evaluation of efficacy and safety. METHODS: In this open-label, single-institution, phase II trial, patients received everolimus 10 mg/day by mouth and bevacizumab 10 mg/kg intravenously every 14 days on a 28-day cycle. Treatment continued until disease progression or adverse event. RESULTS: Fifty patients were enrolled. Median age was 60.5 years (range 28-82). Forty-six (92%) subjects had measurable disease. Thirteen (26%) (24% adjusted) were progression-free at 6 months (95% CI 16.67-42.71%). One patient had a complete response, while six had a partial response and 35 had stable disease as their best response. Patients with both platinum-sensitive and -resistant disease demonstrated responses, as did some prior bevacizumab exposure. There were two grade 4 and 31 grade 3 toxicities noted in 25 distinct patients. The most common reported toxicities included oral mucositis, fatigue, diarrhea, hypertension, pain, nausea and anorexia. Thirty-eight (76%) patients came off study because of disease progression. Unique molecular profiles were identified in long-term responders. CONCLUSIONS: Combining everolimus and bevacizumab does not distinctly improve response compared to bevacizumab alone, but further study of selected patients with alterations in the PI3K/mTOR pathway may document benefit.

Phase I study of intravenous oxaliplatin and intraperitoneal docetaxel in recurrent ovarian cancer.

INTRODUCTION: Intraperitoneal (IP) chemotherapy improves survival in ovarian cancer but its use has been limited by toxicity with cisplatin-based regimens. The primary objective of this study was to define the maximum tolerated dose and dose-limiting toxicity of intravenous (IV) oxaliplatin and IP docetaxel in women with recurrent ovarian, fallopian tube or peritoneal cancer. Secondary objectives were response rate, time to progression, symptom interference with quality of life, and pharmacokinetics. METHODS: Patients received a constant dose of oxaliplatin 75 mg/m2 IV on day 1 and docetaxel escalating from 50 mg/m2 IP on day 2 every 3 weeks using a 3 + 3 design. Treatment continued until disease progression, remission, or intolerable toxicity occurred. Plasma and IP samples were taken to determine drug concentrations. Patients completed the MD Anderson Symptom Inventory weekly. RESULTS: Twelve patients were included. The median number of cycles was 4 (range 2-6) with a median time to progression of 4.5 months. Among eight patients with measurable disease, the best responses were partial response in two patients, stable disease in five, and progressive disease in one. A total of 14 grade 3-4 toxicities were noted, most commonly hematologic. Four patients, all dose level 3, had six dose-limiting toxicities: two with prolonged neutropenia, one with infection, one with hyponatremia, and two with abdominal pain. Dose level 3 was therefore considered intolerable. The mean±SD ratio of docetaxel area under the curve (AUC) in IP fluid to AUC in plasma was 229±111. Symptom interference with life activities steadily decreased from cycle 1 to 5. CONCLUSIONS: Oxaliplatin 75 mg/m2 IV on day 1 and docetaxel 75 mg/m2 IP on day 2 was the maximum tolerated dose. Most patients had partial response or stable disease, even in a heavily pre-treated population. At this dose level, patient-reported outcomes demonstrate temporary but tolerable decrements in quality of life.

Germline pathogenic variants identified in women with ovarian tumors.

OBJECTIVE: The recognition of genes implicated in ovarian cancer risk beyond BRCA1, BRCA2, and the Lynch syndrome genes has increased the variety of testing options available to providers and patients. We report the frequency of pathogenic variants identified among individuals with ovarian cancer undergoing clinical genetic testing via a multi-gene hereditary cancer panel. METHODS: Genetic testing of up to 32 genes using a hereditary cancer panel was performed on 4439 ovarian cancer cases, and results were analyzed for frequency of pathogenic variants. Statistical comparisons were made using t-tests and Fisher's exact tests. RESULTS: The positive yield was 13.2%. While BRCA1/2 pathogenic variants were most frequent, one third (33.7%) of positive findings were in other homologous recombination genes, and accounted for over 40.0% of findings in endometrioid and clear cell cases. Women with a personal history of breast cancer (22.1%), who reported a family history of ovarian cancer (17.7%), and/or serous histology (14.7%) were most likely to harbor a pathogenic variant. Those with very early onset (<30 years) and late onset (≥70 years) ovarian cancer had low positive yields. CONCLUSIONS: Our study highlights the genetic heterogeneity of ovarian cancer, showing that a large proportion of cases are not due to BRCA1/2 and the Lynch syndrome genes, but still have an identifiable hereditary basis. These findings substantiate the utility of multi-gene panel testing in ovarian cancer care regardless of age at diagnosis, family history, or histologic subtype, providing evidence for testing beyond BRCA1/2 and the Lynch syndrome genes.

Challenges in recruiting African-American women for a breast cancer genetics study.

BACKGROUND: African-American women, especially in the southern United States, are underrepresented in cancer genetics research. A study was designed to address this issue by investigating the germline mutation rate in African-American women in Arkansas with a personal and/or family history of breast cancer. Women were tested for these mutations using a large panel of breast cancer susceptibility genes. In this analysis, we discuss the challenges encountered in recruiting African-American women from an existing biorepository to participate in this study. METHODS: We attempted to contact 965 African-American women with a personal and/or family history of breast cancer who participated in Spit for the Cure (SFTC) between 2007 and 2013 and provided consent to be recontacted. The SFTC participants were invited by telephone and email to participate in the genetic study. Enrollment required completion of a phone interview to obtain a family and medical history and return of a signed consent form. RESULTS: Among eligible SFTC participants, 39.6% (382/965) were able to be contacted with the phone numbers and email addresses they provided. Of these, 174 (45.5%) completed a phone interview and returned a signed consent form. Others were not able to be contacted (n = 583), declined to participate (n = 57), did not keep phone interview appointments (n = 82), completed the phone interview but never returned a signed consent (n = 54), were deceased (n = 13), or were too confused to consent to participate (n = 2). CONCLUSIONS: Recruiting African-American women into our breast cancer genetics study proved challenging primarily due to difficulty establishing contact with potential participants. Given their prior participation in breast cancer research, we anticipated that this would be a highly motivated population. Indeed, when we were able to contact SFTC participants, only 14.9% declined to participate in our study. Innovative communication, retention, and recruitment strategies are needed in future studies to address the recruitment challenges we faced.

The Female Self-Advocacy in Cancer Survivorship Scale: A validation study.

AIM: To develop and psychometrically test the validity of the Female Self-Advocacy in Cancer Survivorship Scale. BACKGROUND: Female cancer survivors need to self-advocate to overcome challenges associated with cancer yet no valid measure of self-advocacy exists. DESIGN: Instrument development. Mixed-mode cross-sectional survey design. PARTICIPANTS: We recruited adult females (18+ years; N = 317) with a history of invasive cancer from local and national tumour registries and advocacy organizations to complete online or paper questionnaires. METHODS: Between July 2014 - March 2015 to evaluate the construct validity based on evidence of the scale's: (1) internal structure consistent with the underlying model of self-advocacy; (2) sensitivity to differences between groups known to differ in self-advocacy skills; (3) relationships between self-advocacy and key potential predictors (openness and conscientiousness; information engagement; social support) and outcomes (symptom burden and healthcare utilization); (4) relationships between self-advocacy and related concepts (patient activation; self-advocacy within another patient population); and (5) relationships between self-advocacy and criterion measures. Analyses included an exploratory factor analysis, t tests, and bivariate correlations using validated, reliable measures for constructs. RESULTS: Evidence from all five hypotheses supported the construct validity of the Female Self-Advocacy in Cancer Survivorship Scale. The factor analysis confirmed the three underlying dimensions of self-advocacy resulting in a 20-item measure with strong internal consistency that explained almost half of response variance. CONCLUSION: The Female Self-Advocacy in Cancer Survivorship Scale is a valid, reliable measure of how well adult female cancer survivors can get their needs met in the face of adversity.

Perspectives on Self-Advocacy: Comparing Perceived Uses, Benefits, and Drawbacks Among Survivors and Providers

Purpose/Objectives: To describe and compare survivors' and providers' views of the uses of and perceived benefits and drawbacks of survivor self-advocacy. Design: A cross-sectional, two-group, mixed-methods survey. Setting: Survivors were recruited from local and national registries and advocacy organizations. Providers were recruited from the University of Pittsburgh Medical Center Cancer Center and a regional Oncology Nursing Society chapter. Sample: 122 female cancer survivors and 39 providers involved in their direct care. Methods: Quantitative survey data were summarized using descriptive statistics, including means and frequencies. Qualitative survey data were collected and analyzed using content analysis techniques, and main themes were counted and summarized. Main Research Variables: Perceptions of the uses, benefits, and drawbacks of female cancer survivor self-advocacy. Findings: Survivors and providers perceived similar but distinct uses of self-advocacy. Survivors and providers generally agreed on the potential benefits of self-advocacy but had different views of the potential drawbacks. Survivors were most concerned with finding and making sense of information, that their questions would not be answered, and having a worse relationship with their provider; providers were concerned with increases in clinic time and difficulties developing treatment plans. Conclusions: Although survivors and providers recognized similar benefits to survivor self-advocacy, they had different views of the uses and drawbacks of female cancer survivor self-advocacy. Implications for Nursing: Attempts to increase self-advocacy among female cancer survivors must address survivors' and providers' views and apprehensions about self-advocacy.

A Critical Analysis of Perioperative Outcomes in Morbidly Obese Patients Following Renal Mass Surgery.

OBJECTIVE: To evaluate if body mass index (BMI) ≥ 40 is associated with risk of postoperative complications, receipt of perioperative blood transfusion (PBT), length of hospital stay (LOS), perioperative death, or hospital readmission rate following renal mass surgery. MATERIALS AND METHODS: After Institutional Review Board approval, comprehensive information was collected for patients treated with surgery for renal mass from 2000 to 2015 at one institution. Univariable and multivariable analyses were used to evaluate the association of BMI ≥ 40 among other putative risk factors for perioperative outcomes. RESULTS: A total of 1048 patients were treated surgically, including 115 (11%) with BMI > 40. Minimally invasive and open surgical approaches were used for 480 (45.8%) and 568 (54.2%) patients, respectively. Morbid obesity was not associated with risk of major complications, overall complications, receipt of PBT, LOS, hospital readmission rate, or perioperative death. Charlson comorbidity index was the only independent predictor of major complications following renal mass surgery, P = .0006, per point odds ratio 1.2 (95%C.I. 1.08-1.32). Surgical site infections (SSIs) were more common in patients with BMI ≥ 40 vs BMI < 40 (10.5% vs 4.8%, P = .01). Following multivariable analysis, BMI ≥ 40 was the only independent predictor of SSIs, odds ratio 2.6, 95% confidence interval 1.32-5.13; P = .006. CONCLUSION: Morbid obesity (BMI ≥ 40) is an independent predictor of developing SSIs following renal mass surgery. Morbid obesity is not predictive of risk for major complications, receipt of PBT, hospital readmission, perioperative death, or LOS.

Second-line Intraperitoneal Platinum-based Therapy Leads to an Increase in Second-line Progression-free Survival for Epithelial Ovarian Cancer.

OBJECTIVE: Only 3% of patients with epithelial ovarian cancer (EOC) have a longer treatment-free interval (TFI) after second-line intravenous (IV) platinum chemotherapy than with frontline IV therapy. We sought to examine what impact second-line combination IV/intraperitoneal (IV/IP) platinum therapy might have on the ratio of second-line to first-line TFI in patients treated with second-line IP platinum chemotherapy for first recurrence after front-line IV therapy. METHODS: A retrospective analysis of women who received combination platinum-based IV/IP chemotherapy for recurrent EOC between January 2005 and March 2011 was conducted. Patients were identified from the tumor registry, and office records from a large gynecologic oncology practice and patient records were reviewed. The first and second TFIs were defined as the time from the end of previous platinum-based therapy to the start of next therapy. RESULTS: Twenty-five women received IV/IP chemotherapy for their first EOC recurrence after IV chemotherapy. In 10 patients (40%), we observed a longer TFI after IV/IP chemotherapy than after primary IV chemotherapy. For these 10 patients, the median TFI for primary response was 22 months (range, 15-28), whereas median TFI after IV/IP chemotherapy for recurrent disease was 37 months (range, 12-61). CONCLUSIONS: For EOC patients with limited peritoneal recurrence, 40% of patients had a second-line IP-platinum TFI that exceeded their frontline IV-platinum TFI compared to published data. These data support the use of IV/IP chemotherapy as a treatment for recurrence.

Male breast cancer in BRCA1 and BRCA2 mutation carriers: pathology data from the Consortium of Investigators of Modifiers of BRCA1/2.

BACKGROUND: BRCA1 and, more commonly, BRCA2 mutations are associated with increased risk of male breast cancer (MBC). However, only a paucity of data exists on the pathology of breast cancers (BCs) in men with BRCA1/2 mutations. Using the largest available dataset, we determined whether MBCs arising in BRCA1/2 mutation carriers display specific pathologic features and whether these features differ from those of BRCA1/2 female BCs (FBCs). METHODS: We characterised the pathologic features of 419 BRCA1/2 MBCs and, using logistic regression analysis, contrasted those with data from 9675 BRCA1/2 FBCs and with population-based data from 6351 MBCs in the Surveillance, Epidemiology, and End Results (SEER) database. RESULTS: Among BRCA2 MBCs, grade significantly decreased with increasing age at diagnosis (P = 0.005). Compared with BRCA2 FBCs, BRCA2 MBCs were of significantly higher stage (P for trend = 2 × 10(-5)) and higher grade (P for trend = 0.005) and were more likely to be oestrogen receptor-positive [odds ratio (OR) 10.59; 95 % confidence interval (CI) 5.15-21.80] and progesterone receptor-positive (OR 5.04; 95 % CI 3.17-8.04). With the exception of grade, similar patterns of associations emerged when we compared BRCA1 MBCs and FBCs. BRCA2 MBCs also presented with higher grade than MBCs from the SEER database (P for trend = 4 × 10(-12)). CONCLUSIONS: On the basis of the largest series analysed to date, our results show that BRCA1/2 MBCs display distinct pathologic characteristics compared with BRCA1/2 FBCs, and we identified a specific BRCA2-associated MBC phenotype characterised by a variable suggesting greater biological aggressiveness (i.e., high histologic grade). These findings could lead to the development of gender-specific risk prediction models and guide clinical strategies appropriate for MBC management.

Extreme obesity does not predict poor cancer outcomes after surgery for renal cell cancer.

OBJECTIVE: To assess whether extreme obesity (body mass index [BMI] ≥ 40 kg/m(2) ) is associated with peri-operative outcomes, overall survival (OS), cancer-specific survival (CSS), or recurrence-free survival (RFS) after surgical treatment for renal cell carcinoma (RCC). PATIENTS AND METHODS: After institutional review board approval, we used an institutional database to identify patients treated surgically between January 2000 and December 2014 with a pathological diagnosis of RCC. Comprehensive clinical and pathological data were reviewed. Kaplan-Meier analyses were used to estimate OS, RFS and CSS. Univariate and multivariate Cox proportional hazards analysis was used to evaluate associations with OS, CSS and RFS in patients with extreme obesity, among other known predictive variables. RESULTS: In all, 100 patients (11.9%) with a BMI ≥ 40 kg/m(2) and 743 patients (88.1%) with a BMI < 40 kg/m(2) who were treated surgically for RCC were identified. Morbid obesity was not associated with an increased risk of blood transfusion (odds ratio [OR] 1, 95% confidence interval [CI] 0.587-1.70; P = 1.0). The median (interquartile range) length of hospital stay (LOS) was 4 (3-6) days. Morbid obesity was not associated with longer LOS (P = 0.26) or 30-day hospital readmission rates (P = 1.0). Major complications (Clavien ≥ 3a) were recorded in 67 patients (7.95%). BMI ≥ 40 kg/m(2) was not a predictor of major complications (OR 0.58, 95% CI 0.227-1.47; P = 0.251) or 90-day mortality (P = 0.4067). BMI ≥ 40 kg/m(2) was not associated with worse OS (P = 0.7), CSS (P = 0.2) or RFS (P = 0.5). BMI ≥ 35 kg/m(2) was also not associated with worse OS, CSS or RFS (P = 0.3, 0.1, 0.5, respectively). The 5-year OS rate was 68.9% for the entire cohort, including 69 and 70% for patients with BMI < 40 kg/m(2) and BMI ≥ 40 kg/m(2) , respectively (P = 0.69). The 5-year CSS was 79.5% for the entire cohort, including 78.4 and 87.9% (P = 0.16) for patients with BMI < 40 kg/m(2) and BMI ≥ 40 kg/m(2) , respectively. The 5-year RFS rates for BMI < 40 kg/m(2) and BMI ≥ 40 kg/m(2) were 84.1 and 90.6%, respectively (P = 0.48). CONCLUSIONS: Extreme obesity is not associated with worse peri-operative or cancer outcomes after surgery for RCC. Surgery should remain a standard treatment option in well selected morbidly obese patients.

Use of Metformin in Obese Women With Type I Endometrial Cancer Is Associated With a Reduced Incidence of Cancer Recurrence.

OBJECTIVES: Recent evidence suggests that hyperinsulinemia associated with obesity may be a significant risk factor for the development of endometrial cancer. Metformin is used in type II diabetes to lower circulating insulin levels. We sought to examine our obese patients with endometrial cancer and examine those who were on metformin to determine any impact on their cancer course. METHODS: A retrospective review of all women with the diagnosis of endometrial cancer and a body mass index of 30 kg/m(2) or higher during a 6-year period (2005-2011) at our institution was conducted. Records were reviewed for standard demographic data, use of metformin, cancer characteristics, treatment, and cancer follow-up. RESULTS: A total of 351 women were identified who were obese and diagnosed as having endometrial cancer. Of these, 64 were on metformin (M+) at the time of diagnosis of endometrial cancer. The women on metformin had a significantly higher mean body mass index (44.6 vs 41.6, P < 0.05). Age, grade, stage, and adjuvant therapy did not differ between the 2 groups. Recurrence occurred in 15.3% of the M- women versus 7.8% of the M+ women (not significant). However, for those patients with type I endometrial cancer, only 1 patient (1.9%) who was on metformin recurred versus 10.3% who were not on the drug (P = 0.05). With a minimum of 24 months of follow-up, 89.1% of metformin users were alive and free of disease versus 83.9% of nonusers (not significant). CONCLUSIONS: Obese women who developed endometrial cancer while on metformin did not seem to have pathologic risk factors different from those not on metformin. However, the type I cancer patients on metformin were less likely to recur than those not on the drug. This suggests that a prospective trial of metformin at the time of diagnosis of endometrial cancer in the obese population may be warranted.

Phase I study of intravenous (IV) docetaxel and intraperitoneal (IP) oxaliplatin in recurrent ovarian and fallopian tube cancer.

OBJECTIVE: The primary objective was to define the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of IV docetaxel and IP oxaliplatin in women with recurrent ovarian (OV), fallopian tube (FT) or peritoneal (PP) cancer. Secondary objectives included response rate, time to progression, pharmacokinetics (PK) and quality of life (QoL). METHODS: Patients received docetaxel 75mg/m(2) IV day (d) 1 and oxaliplatin escalating from 50mg/m(2) IP d2 every 3weeks using a 3+3 design. Treatment continued until disease progression, remission, or intolerable toxicity. Plasma and IP samples were taken to determine drug concentrations. MD Anderson Symptom Inventory and symptom interference scale were completed weekly. RESULTS: Thirteen patients were included. Median number of cycles was 6 (range 1-10). Ten patients had measureable disease. Best response was partial response (PR-2), stable disease (SD-7), and progressive disease (PD-1). Twenty-one Grades 3-4 toxicities were noted, commonly hematologic. Two patients had DLTs: prolonged neutropenia (1) and abdominal pain (1). MTD was d1 docetaxel 75mg/m(2) IV and d2 oxaliplatin 50mg/m(2) IP. Symptom burden peaked week one and returned to baseline by week two of each cycle on dose level 1. Dose level 2 had persistently high symptom burden and interference. At IP oxaliplatin doses of 50mg/m(2), total unbound drug exposure (AUC) averaged 8 times larger and Cmax reached concentrations 50-fold greater in IP fluid compared to plasma. CONCLUSIONS: Docetaxel 75mg/m(2) IV d1 and oxaliplatin 50mg/m(2) IP d2 is the MTD. Most patients had PR or SD. Patient-reported outcomes demonstrate temporary but tolerable decrements in QoL. IP oxaliplatin provides PK advantages over IV administration.

Outcomes analysis of an alternative formulation of PEGylated liposomal doxorubicin in recurrent epithelial ovarian carcinoma during the drug shortage era.

BACKGROUND: In response to the critical shortage of Doxil(®), the US Food and Drug Administration (FDA) allowed temporary importation of non-FDA-approved second-generation liposomal doxorubicin, Lipo-Dox(®). Lipo-Dox utilizes a different liposomal particle than Doxil and demonstrates different pharmacokinetic properties. Its use has never been evaluated in a North American population. The objective of this study was to evaluate the efficacy and tolerability of Lipo-Dox at Magee-Womens Hospital, University of Pittsburgh Medical Center, for patients with recurrent epithelial ovarian cancer who were treated during the Doxil shortage. METHODS: Patients treated with Lipo-Dox from January 2012 to December 2012 were identified retrospectively. Disease response was defined radiographically by RECIST (Response Evaluation Criteria in Solid Tumors) or biochemically by CA-125 level if measurable disease was not present. Survival was defined from the start date of Lipo-Dox until the date of progression or death. Toxicity was assessed by the Gynecologic Oncology Group common toxicity criteria. RESULTS: Eighteen patients with recurrent epithelial ovarian cancer who received Lipo-Dox were identified. These patients had a median of three prior treatment regimens. The median number of Lipo-Dox cycles given was 3.5 (range 1-8). No patients had a complete or partial response. Two patients had stable disease over a mean follow-up of 144.5 days. Fourteen patients had progressive disease, with a median time to progression of 82 days. Progression was based on CA-125 in four patients and RECIST in the remainder. Nine patients died from the disease. CONCLUSION: Although this represents a small, pretreated population, there were no clinical responses to Lipo-Dox, raising the question as to whether it is an equivalent substitute for Doxil. Further evaluation is needed, but if confirmed, these findings raise concerns regarding the use of current stocks of Lipo-Dox, as well as the prudence of managing future drug shortages with pharmacologically similar, but clinically untested drugs.