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Objective Uterine papillary serous carcinoma (UPSC) is an aggressive subtype of endometrial cancer. Adjuvant chemotherapy (CT) has become standard care in treatment of women with advanced-stage UPSC, but the role of consolidative radiotherapy (RT) is unclear. This study aims to evaluate survival outcomes of multimodal therapy. Design Retrospective cohort study using a National Cancer Database (NCDB). Setting United States of America. Sample A total of 1816 women diagnosed with UPSC. Methods All women diagnosed with surgically staged FIGO (International Federation of Gynecology and Obstetrics) stage-IIIC UPSC were identified in the NCDB from January 1998 to December 2010. Overall survival (OS) was estimated using the Kaplan–Meier method. Univariate and multivariable analyses were performed to identify and control for prognostic factors. Main outcome measure Overall survival. Results A total of 398 057 cases of uterine cancer were identified, 22 106 of which were UPSC. Of these women, 14 093 underwent lymph-node examination, 2902 (20.6%) were found to have stage-IIIC disease, and 1816 received chemotherapy. Younger age and higher number of total lymph nodes examined were independently predictive of receiving multimodality (CT + RT) therapy, compared with CT only. Median OS was 33.6 and 42.6 months, for the CT and CT + RT groups, respectively (P

Contains fulltext : 155211.pdf (Publisher’s version ) (Closed access) OBJECTIVE: Ovarian cancer is a hormone-related disease with a strong genetic basis. However, none of its high-penetrance susceptibility genes and GWAS-identified variants to date are known to be involved in hormonal pathways. Given the hypothesized etiologic role of gonadotropins, an assessment of how variability in genes involved in the gonadotropin signaling pathway impacts disease risk is warranted. METHODS: Genetic data from 41 ovarian cancer study sites were pooled and unconditional logistic regression was used to evaluate whether any of the 2185 SNPs from 11 gonadotropin signaling pathway genes was associated with ovarian cancer risk. A burden test using the admixture likelihood (AML) method was also used to evaluate gene-level associations. RESULTS: We did not find any genome-wide significant associations between individual SNPs and ovarian cancer risk. However, there was some suggestion of gene-level associations for four gonadotropin signaling pathway genes: INHBB (p=0.045, mucinous), LHCGR (p=0.046, high-grade serous), GNRH (p=0.041, high-grade serous), and FSHB (p=0.036, overall invasive). There was also suggestive evidence for INHA (p=0.060, overall invasive). CONCLUSIONS: Ovarian cancer studies have limited sample numbers, thus fewer genome-wide susceptibility alleles, with only modest associations, have been identified relative to breast and prostate cancers. We have evaluated the majority of ovarian cancer studies with biological samples, to our knowledge, leaving no opportunity for replication. Using both our understanding of biology and powerful gene-level tests, we have identified four putative ovarian cancer loci near INHBB, LHCGR, GNRH, and FSHB that warrant a second look if larger sample sizes and denser genotype chips become available.

For node-positive vulvar cancer, adjuvant radiotherapy has an established benefit, whereas the impact of chemotherapy is unknown. A National Cancer Data Base (NCDB) analysis was conducted to determine patterns of care and evaluate the survival impact of adjuvant chemotherapy.The NCDB was queried for vulvar cancer patients diagnosed from 1998-2011 who underwent extirpative surgery with confirmed inguinal nodal involvement treated with adjuvant radiotherapy. Patients with inadequate follow-up or non-squamous histologies were excluded. Chi-square test, logistic regression analysis, log-rank test and multivariable Cox proportional regression modeling with adjustment using propensity score with inverse probability of treatment weights (IPTW) were conducted to establish factors associated with utilization and survival.A total of 1797 patients were identified: 26.3% received adjuvant chemotherapy and 76.6% had 1-3 involved lymph nodes. Adoption of adjuvant chemotherapy significantly increased over time, from 10.8% in 1998 to 41.0% in 2006 (p0.001). Lower utilization was seen in older patients, Northeast or Southern facilities, and patients with more extensive nodal dissection, whereas greater number of involved nodes, stage IVA disease and positive surgical margins led to a higher probability of receiving chemotherapy. Unadjusted median survival without and with adjuvant chemotherapy was 29.7months and 44.0months (p=0.001). On IPTW-adjusted Cox proportional regression modeling, delivery of adjuvant chemotherapy resulted in a 38% reduction in the risk of death (HR 0.62, 95% CI 0.48-0.79, p0.001).In a large population-based analysis, adjuvant chemotherapy resulted in a significant reduction in mortality risk for node-positive vulvar cancer patients who received adjuvant radiotherapy.

Contains fulltext : 153959.pdf (Publisher’s version ) (Closed access) Epidemiological studies have demonstrated associations between endometriosis and certain histotypes of ovarian cancer, including clear cell, low-grade serous and endometrioid carcinomas. We aimed to determine whether the observed associations might be due to shared genetic aetiology. To address this, we used two endometriosis datasets genotyped on common arrays with full-genome coverage (3194 cases and 7060 controls) and a large ovarian cancer dataset genotyped on the customized Illumina Infinium iSelect (iCOGS) arrays (10 065 cases and 21 663 controls). Previous work has suggested that a large number of genetic variants contribute to endometriosis and ovarian cancer (all histotypes combined) susceptibility. Here, using the iCOGS data, we confirmed polygenic architecture for most histotypes of ovarian cancer. This led us to evaluate if the polygenic effects are shared across diseases. We found evidence for shared genetic risks between endometriosis and all histotypes of ovarian cancer, except for the intestinal mucinous type. Clear cell carcinoma showed the strongest genetic correlation with endometriosis (0.51, 95% CI = 0.18-0.84). Endometrioid and low-grade serous carcinomas had similar correlation coefficients (0.48, 95% CI = 0.07-0.89 and 0.40, 95% CI = 0.05-0.75, respectively). High-grade serous carcinoma, which often arises from the fallopian tubes, showed a weaker genetic correlation with endometriosis (0.25, 95% CI = 0.11-0.39), despite the absence of a known epidemiological association. These results suggest that the epidemiological association between endometriosis and ovarian adenocarcinoma may be attributable to shared genetic susceptibility loci.

Purpose The study aimed to assess the outcome of locally advanced cervical and vaginal cancer treated with high-dose-rate interstitial brachytherapy (HDRB). Methods and materials Between 1998 and 2004, 16 previously unirradiated patients with locally advanced cervical and vaginal cancer not suitable for intracavitary brachytherapy because of distorted anatomy or extensive vaginal disease were treated with HDRB in combination with external beam radiotherapy. All patients received whole pelvis external beam radiation therapy (EBRT) followed by interstitial implantation. The median whole pelvis external beam dose was 45 Gy (range, 39.6–50.4 Gy) with 11 patients receiving parametrial boost to a median dose of 9 Gy. Twelve (75%) of these patients received chemotherapy concurrent with external beam. All patients received a single HDRB procedure using a modified Syed–Neblett template. A CT scan was performed postimplant for needle placement verification and treatment planning purpose. Dose was prescribed to the tumor volume based on the radiographic and clinical examination. All patients received 18.75 Gy in five fractions delivered twice daily. The median followup was 25 months (6–69 months). Results Median cumulative biologic effective dose (EBRT + HDRB) to tumor volume was 78.9 Gy 10 with the range of 72.5–85.2 Gy 10. Median cumulative biologic effective dose for the rectum and bladder were 99.4 Gy 3 (range, 79.6–107.8 Gy 3 ) and 96.4 Gy 3 (range, 78.3–105.3 Gy 3 ), respectively. Complete response was achieved in 13 (81%) patients with 3 patients having persistent disease. Five of these 13 patients developed recurrence at a median time of 14 months (distant in 4 and local and distant in 1). The 5-year actuarial local control and cause-specific survival were 75% and 64%, respectively. In subset analysis, 5-year actuarial local control was 63% for cervical cancer patients and 100% for vaginal cancer patients. No patient had acute Grade 3 or 4 morbidity. Grade 3 or 4 delayed morbidity resulting from treatment occurred in 1 patient with 5-year actuarial rate of 7%. Three patients had late Grade 2 rectal morbidity and 1 patient had Grade 2 small bowel morbidity. Conclusions Our series suggests that single interstitial implantation procedure with five fractions of 3.75 Gy each to target volume is an effective and safe fractionation schedule. The integration of imaging modality helps in decreasing dose to the critical organs. Additional patients and followup are ongoing to determine the long-term efficacy of this approach.

ABSTRACT Aim: As the incidence of endometrial cancer (EC) increased considerably since 2007, this study aimed to project the burden of EC to the year 2030. Methods: Multivariate linear regression was used to project EC incidence by modeling trends in EC incidence from 1990 to 2013, while accounting for temporal changes in obesity, hysterectomy and smoking. Results: The best-fitting model predicting EC rates included a time effect plus effects for hysterectomy (12-year lag), severe obesity (3-year lag) and smoking (9-year lag). The best-fitting model projected an increase to 42.13 EC cases per 100,000 by the year 2030, a 55% increase over 2010 EC rates. Conclusion: The projected increase of EC over next 16 years indicates the need for close monitoring of EC trends.

Cervical cancer during pregnancy is rare, occurring in approximately 3% of cervical cancer cases. Considerable controversy exists as to the long-term prognosis of patients diagnosed during pregnancy. A 32-year-old female presented with vaginal spotting in April 1998. A prenatal smear in December 1996 revealed atypical glandular cells of undetermined significance. A sterile speculum exam in April 1997 at 31-week gestational age revealed a polyp on the anterior lip of the cervix, pathology consistent with a well-differentiated villoglandular adenocarcinoma. In August 1997, the patient underwent a radical hysterectomy with pelvic/para-aortic lymphadenectomy. In April 2001, she represented with nodular perineal mass in the episiotomy incision. She received preoperative radiotherapy with a near-complete response and remained without disease for >10 months. It appears that a less radical procedure can offer significant therapeutic value. Preoperative radiotherapy proved effective at achieving a near-complete response. The patient underwent a wide local excision of the perineal area with resultant negative margins

Objective Treatment for advanced-stage epithelial ovarian cancer (AEOC) includes primary debulking surgery (PDS) or neoadjuvant chemotherapy (NACT). A randomized controlled trial comparing these treatments resulted in comparable overall survival (OS). Studies report more complications and lower chemotherapy completion rates in patients 65 years old or older receiving PDS. We sought to evaluate the cost implications of NACT relative to PDS in AEOC patients 65 years old or older. Study Design A 5 year Markov model was created. Arm 1 modeled PDS followed by 6 cycles of carboplatin and paclitaxel (CT). Arm 2 modeled 3 cycles of CT, followed by interval debulking surgery and then 3 additional cycles of CT. Parameters included OS, surgical complications, probability of treatment initiation, treatment cost, and quality of life (QOL). OS was assumed to be equal based on the findings of the international randomized control trial. Differences in surgical complexity were accounted for in base surgical cost plus add-on procedure costs weighted by occurrence rates. Hospital cost was a weighted average of diagnosis-related group costs weighted by composite estimates of complication rates. Sensitivity analyses were performed. Results Assuming equal survival, NACT produces a cost savings of $5616. If PDS improved median OS by 1.5 months or longer, PDS would be cost effective (CE) at a $100,000/quality-adjusted life-year threshold. If PDS improved OS by 3.2 months or longer, it would be CE at a $50,000 threshold. The model was robust to variation in costs and complication rates. Moderate decreases in the QOL with NACT would result in PDS being CE. Conclusion A model based on the RCT comparing NACT and PDS showed NACT is a cost-saving treatment compared with PDS for AEOC in patients 65 years old or older. Small increases in OS with PDS or moderate declines in QOL with NACT would result in PDS being CE at the $100,000/quality-adjusted life-year threshold. Our results support further evaluation of the effects of PDS on OS, QOL and complications in AEOC patients 65 years old or older.

Objective The aim of this study is to evaluate the magnitude and time course of change in symptom burden after palliative care (PC) consultation in a cohort of gynecologic oncology inpatients. Methods Women with a gynecologic malignancy and PC consultation for symptom management between 3/1/12 and 2/28/13 were identified. Charts were reviewed for demographic and disease characteristics. Symptom scores on a modified Edmonton Symptom Assessment System (ESAS) scale were abstracted for pain, anorexia, fatigue, depression, anxiety, nausea and dyspnea. Prevalence of moderate-to-severe symptom intensity was compared between the day of PC consultation (D1), the day after PC consultation (D2) and the last recorded symptoms before discharge (DLast). Results PC was consulted for symptom management during 129 admissions of 95 unique patients. Median age was 59, 84% were white and 67% had stage III/IV disease, with ovarian the most common site (52%). Symptom prevalence on D1 for at least mild intensity ranged 14% (dyspnea) to 80% (pain) and for at least moderate intensity from 3% (dyspnea) to 50% (pain). Statistically significant decreases in prevalence of moderate to severe symptom intensity between D1 and DLast occurred for pain, anorexia, fatigue and nausea (magnitude 58–66%) and between D1 and D2 for pain, fatigue and nausea (magnitude 50–55%). The majority of the improvement that occurred between D1 and DLast happened by D2. Conclusions PC consultation is associated with improvement in symptom burden, the majority of which occurs within one day of consultation. PC may be an effective tool for symptom management in patients with moderate to severe symptom intensity even during short hospitalizations and should be considered early in the hospitalization to effect timely symptom relief.

Obesity is a well recognized risk factor for several types of cancers, many of which occur solely or disproportionately in women. Adipose tissue is a rich source of adipose-derived stem cells (ASC), which have received attention for their role in cancer behavior. The purpose of this systematic review is to present the existing literature on the role of ASCs in the growth, development, progression, and metastasis of cancer, with an emphasis on malignancies that primarily affect women. To accomplish this goal, the bibliographic database PubMed was systematically searched for articles published between 2001 and 2014 that address ASCs' relationship to human cancer. Thirty-seven articles on ASCs' role in human cancer were reviewed. Literature suggests that ASCs exhibit cancer-promoting properties, influence/are influenced by the tumor microenvironment, promote angiogenesis, and may be associated with pathogenic processes through a variety of mechanisms, such as playing a role in hypoxic tumor microenvironment. ASCs appear to be important contributors to tumor behavior, but research in areas specific to women's cancers, specifically endometrial cancer, is scarce. Also, because obesity continues to be a major health concern, it is important to continue research in this area to improve understanding of the impact adiposity has on cancer incidence. Cancer Res; 75(7); 1161–8. ©2015 AACR.

Objectives We sought to characterize gynecologic oncology fellowship directors' perspectives on (1) inclusion of palliative care (PC) topics in current fellowship curricula, (2) relative importance of PC topics and (3) interest in new PC curricular materials. Methods An electronic survey was distributed to fellowship directors, assessing current teaching of 16 PC topics meeting ABOG/ASCO objectives, relative importance of PC topics and interest in new PC curricular materials. Descriptive and correlative statistics were used. Results Response rate was 63% (29/46). 100% of programs had coverage of some PC topic in didactics in the past year and 48% (14/29) have either a required or elective PC rotation. Only 14% (4/29) have a written PC curriculum. Rates of explicit teaching of PC topics ranged from 36% (fatigue) to 93% (nausea). Four of the top five most important PC topics for fellowship education were communication topics. There was no correlation between topics most frequently taught and those considered most important ( r s =0.11, p =0.69). All fellowship directors would consider using new PC curricular materials. Educational modalities of greatest interest include example teaching cases and PowerPoint slides. Conclusions Gynecologic oncology fellowship directors prioritize communication topics as the most important PC topics for fellows to learn. There is no correlation between which PC topics are currently being taught and which are considered most important. Interest in new PC curricular materials is high, representing an opportunity for curricular development and dissemination. Future efforts should address identification of optimal methods for teaching communication to gynecologic oncology fellows.

Purpose Data for salvage radiotherapy for recurrent endometrial cancer are limited especially in the era of modern radiotherapy including IMRT and 3-dimensional image-based HDR brachytherapy. Theoretically, modern radiotherapy reduces the dose to critical organs-at-risk and maximizes dose to the target volume, possibly decreasing morbidity and increasing tumor control. Materials and methods Forty-one patients completing definitive salvage radiotherapy for vaginal recurrence of endometrial cancer from June 2004 to December 2013 were retrospectively reviewed. HDR Brachytherapy was completed using image-based planning with contouring/optimization with each fraction to a median dose of 23.75 Gy in 5 fractions. HDR brachytherapy was preceded by external beam radiotherapy predominately using an IMRT technique (90%) to a median dose of 45 Gy in 25 fractions. Toxicity was reported according to CTCAEv4. Results At a median follow-up of 18 months (range: 3–78), the clinical complete response rate was 95%. The 3-year local control, distant control, recurrence free survival, and overall survival were 95%, 61%, 68%, and 67%. Significant predictors of both distant failure and overall survival were primary prognostic factors of depth of myometrial invasion, FIGO stage, and FIGO grade. There was no grade 3+ acute toxicity; the 3-year rate of grade 3+ late toxicity was 8%. Conclusions Salvage IMRT plus 3-dimensional image-based HDR brachytherapy shows excellent tumor control and minimal morbidity for vaginal recurrence of endometrial cancer. Anticipated salvage rates must be taken in the context of primary risk factors including depth of myometrial invasion, FIGO stage, and FIGO grade.

Objective Hypersensitivity reactions can preclude platinum re-challenge for patients receiving second-line and higher carboplatin/cisplatin salvage therapy. The objective is to report our patient experience with oxaliplatin in recurrent or progressive epithelial ovarian (EOC), primary peritoneal (PPC) or fallopian tube cancer (FTC), including those with prior hypersensitivity reaction. Methods A single institution, retrospective review from 1995 to 2012 of patients receiving oxaliplatin for treatment of recurrent or progressive EOC, PPC, or FTC was performed. Data collected included patient demographics, diagnosis date, prior chemotherapy regimens, platinum-free interval(s), prior hypersensitivity reactions, oxaliplatin toxicity, length of therapy, disease response, and last follow-up. Those who received ≥1cycles were included. A response to therapy was determined after ≥2cycles. Results Forty-four patients were identified. All had prior carboplatin and 38.6% had prior cisplatin therapy. Twenty-three had a prior platinum hypersensitivity reaction. Patients received a median of 2 prior platinum containing regimens and 5 chemotherapy lines prior to oxaliplatin exposure. One patient experienced grade 3 pain. No grade 4 toxicities occurred. No treatment delays for pancytopenia noted. Nausea and dysesthesias were controlled medically and weren't dose-limiting. No nephropathy or neuropathy progressed on oxaliplatin or were dose-limiting. Disease response was observed in 43.2%. Of the responders, 36.8% had a prior platinum hypersensitivity reaction. Median number of 5cycles of an oxaliplatin containing regimen was given. Median follow-up was 15.5months. Conclusions In our experience, oxaliplatin is well tolerated and should be considered for platinum challenge after hypersensitivity even in patients with platinum resistant disease with a reasonable chance of response.

Vaginal cancer is an uncommon malignancy that is usually treated with definitive radiation therapy. Following external beam radiation therapy (EBRT), a brachytherapy boost is delivered to achieve a total dose of 70-85 Gy. We sought to determine the trends of brachytherapy boost utilization in the treatment of vaginal cancer and to identify the factors associated with its utilization.Using the National Cancer Data Base (NCDB), we identified 1530 patients with vaginal cancer from 2004 to 2011 who were treated with radiation therapy and had a recorded boost modality. The following additional variables were identified: age, year of diagnosis, Charlson/Deyo comorbidity score, stage, histology, race, brachytherapy dose rate, brachytherapy applicator technique, treatment facility volume, and utilization of chemotherapy. Multivariable logistic regression analysis was performed to identify factors independently associated with brachytherapy boost.Seventy-seven percent of the 1530 women received brachytherapy boost and 23% received EBRT boost. The rate of brachytherapy boost utilization decreased from 87.7% in 2004 to 68.6% in 2011 (P.001). Of all the nonbrachytherapy boost modalities, intensity modulated radiation therapy (IMRT) demonstrated the greatest increase (4.5% to 23.5%). For those who had brachytherapy boost, the rate of high-dose-rate increased from 76.3% to 90.8% (P = .02). Multivariate analysis revealed that high facility volume was associated with increased odds of brachytherapy boost (odds ratio [OR], 2.3; range, 1.5-3.4). Higher stage and advanced age were associated with decreased odds of brachytherapy boost (OR, 0.2; range, 0.1-0.3 and OR, 0.5; range, 0.3-0.8). Utilization of chemotherapy, histology, race, and comorbidity index were not significantly associated with brachytherapy boost utilization.Using the NCDB, we identified a concerning decline in the utilization of brachytherapy boost for those with vaginal cancer and a corresponding increase in IMRT boost technique. The strongest factor predicting for brachytherapy boost utilization is treatment at a high volume facility.

Contains fulltext : 137688.pdf (Publisher’s version ) (Closed access) SCOPE: We reevaluated previously reported associations between variants in pathways of one-carbon (1-C) (folate) transfer genes and ovarian carcinoma (OC) risk, and in related pathways of purine and pyrimidine metabolism, and assessed interactions with folate intake. METHODS AND RESULTS: Odds ratios (OR) for 446 genetic variants were estimated among 13,410 OC cases and 22,635 controls, and among 2281 cases and 3444 controls with folate information. Following multiple testing correction, the most significant main effect associations were for dihydropyrimidine dehydrogenase (DPYD) variants rs11587873 (OR = 0.92; p = 6 x 10(-5)) and rs828054 (OR = 1.06; p = 1 x 10(-4)). Thirteen variants in the pyrimidine metabolism genes, DPYD, DPYS, PPAT, and TYMS, also interacted significantly with folate in a multivariant analysis (corrected p = 9.9 x 10(-6)) but collectively explained only 0.2% of OC risk. Although no other associations were significant after multiple testing correction, variants in SHMT1 in 1-C transfer, previously reported with OC, suggested lower risk at higher folate (p(interaction) = 0.03-0.006). CONCLUSION: Variation in pyrimidine metabolism genes, particularly DPYD, which was previously reported to be associated with OC, may influence risk; however, stratification by folate intake is unlikely to modify disease risk appreciably in these women. SHMT1 SNP-by-folate interactions are plausible but require further validation. Polymorphisms in selected genes in purine metabolism were not associated with OC.

Objective. The aim of this study was to review the chemotherapy experience at Magee-Womens Hospital for malignant mixed mullerian tumor (MMMT) of the ovary. Patients were treated with either paclitaxel/carboplatin (PC) outpatient chemotherapy or platinum/ifosfamide (PI) inpatient chemotherapy as first- or second-line therapy. Methods. Thirteen patients diagnosed with MMMT of the ovary after complete surgical staging from 1990 to 1999 were studied retrospectively. Six patients received PC combination chemotherapy, of which 3 patients received PC as first-line treatment. The other 3 patients received PC as second-line therapy. Eight patients were treated with PI. Demographic data, pathology, cytoreductive surgery, treatment, and survival rates were reviewed. Complete clinical response (CR) was defined as the disappearance of all measurable disease or normalization of elevated CA 125 level after chemotherapy. Kaplan–Meier analysis was used for survival analysis. Results. The median survival time of patients receiving PC was 19 months. One patient, after receiving PC as first-line treatment, demonstrated a CR and is free of disease beyond 33 months. The median survival time of patients managed with PI was 23 months. Three patients with suboptimal disease demonstrated CR after receiving PI. Conclusions. Optimal chemotherapy regimen for MMMT of ovary remains to be determined. Platinum-based chemotherapy in combination with ifosfamide or paclitaxel may be active against this rare malignancy.

Radiation therapy can provide useful palliation in chemorefractory ovarian cancer patients. The purpose of this study was to prospectively study the palliative effect of a hypofractionated radiation treatment regimen. Change in quality-of-life scores (Functional Assessment of Cancer Therapy [FACT], Karnofsky scale), pain score, and tolerance to therapy were also assessed.A single-institution Phase I/II trial was initiated in patients with chemoresistant recurrent or progressive ovarian cancer. All patients had symptomatic and measurable intra-abdominal disease. Patients were treated with a single radiation fraction (700 cGy) or two fractions (300 cGy twice a day) to the whole abdomen over 1 day. Quality-of-life scale (FACT G version 2) was assessed at baseline and 1 and 3 months following treatment. Karnofsky scale and pain score were also evaluated in the same time frame.Sixteen patients were prospectively entered into this protocol between February 1996 and September 1998. Twelve patients received a single 700 cGy fraction and four 300 cGy twice a day. All were heavily pretreated and 9 (56%) had a poor performance status prior to treatment. Symptoms needing palliation included pain (14), ascites (10), and bleeding (2). Symptomatic improvement occurred in all patients with pain (5 complete response [CR] and 7 partial response [PR], all patients with bleeding (CR 2), and two (20%) with ascites. Five patients (31%) had a reduction in lesion size documented radiologically in three. The mean duration of response was 22 weeks in patients with a Karnofsky score70. Thirteen patients developed transient nausea and vomiting which resolved in 48 hours in all. All patients developed a transient lymphopenia. Thirteen patients completed a follow-up quality-of-life scale. There was an improvement in the physical and functional components of the scale in patients with Karnofsky score of 90-100. There was no improvement in quality of life in patients with Karnofsky score90 despite symptomatic response. Median survival was 3 months from the date of treatment.Hypofractionated radiation therapy is an effective palliative treatment for end-stage ovarian cancer patients. Karnofsky score can help determine the duration of response and survival for this high-risk population.

Objectives List three symptoms that were statistically significantly improved within one day of PC consultation for symptom management in our cohort of gynecologic oncology inpatients. Synthesize the results of this study into one or two sentences that could be used to advocate for greater integration of specialty palliative care consultation into the care of gynecologic oncology inpatients. Original Research Background: The impact of inpatient palliative care (PC) on symptom burden in the gynecologic oncology (GO) population has not been evaluated. Research Objectives: Evaluate the magnitude and time course of change in symptom burden after PC consultation in a cohort of GO inpatients. Methods

Background. The role of adjuvant radiotherapy in the setting of uterine carcinosarcoma has not been clearly established. Methods. A retrospective review of 60 patients receiving definitive therapy for carcinosarcoma of the uterus was undertaken at a single institution. Twenty-nine of 60 patients were treated with adjuvant radiotherapy. Results. The addition of radiotherapy significantly reduced the local recurrence rate from 55% (17 patients) to 3% (1 patient). Adjuvant radiotherapy reduced the risk of distant failure and death in patients with disease confined to the uterus but did not impact distant recurrence or survival in stage III patients. Increasing stage and depth of myometrial tumor invasion were negatively associated with overall survival and disease-free survival but had no impact on local recurrence rates. The nuclear grade of the epithelial component was predictive of local recurrence ( P = 0.0592), but epithelial architectural grade, grade of stromal component, and stromal versus epithelial predominance did not provide prognostic information. The relative risk of local recurrence of unirradiated patients versus irradiated patients was 17.54 ( P = 0.0055) after adjusting for nuclear grade of the epithelial component. Conclusions. Local failure represents a significant site of failure in the absence of adjuvant radiotherapy. The improvement in local failure rates with the addition of radiotherapy translates into an improvement in distant failure rates and survival only for patients with stage I/II disease. Epithelial nuclear grade, in addition to depth of myometrial invasion and stage, provides important prognostic information. Epithelial architectural grade, stromal grade, type of stromal component (homologous versus heterologous), and predominance of either stromal or epithelial component were not found to be significant prognostic factors.

37 Background: Prognosis affects decision making by providers and patients and accurate understanding of prognosis may help avoid futile end-of-life care. Gynecologic oncology (GO) patient and provider perspectives on discussing prognosis have not been described. We sought to analyze patient and provider preferences regarding timing, amount and type of information included in discussions of prognosis. Methods: Semi-structured qualitative interviews regarding palliative care with 19 GO providers (7 physicians, 7 advanced practice providers, 5 nurses) and 29 patients with advanced or recurrent gynecologic cancer at an academic medical center. Communication about prognosis was one interview domain. Two coders independently and iteratively analyzed transcripts using qualitative analysis. Results: Median patient age was 61, the most common cancer was ovary (59%) and 90% had recurrent disease. Providers were 74% female with median 15 years in practice. Themes included patients wanting frank discussions about prognosis, not limited to life expectancy. Further preferences regarding timing and content were individualized. All categories of providers reported having prognosis conversations. Providers saw these conversations as part of their clinical role, though they often found them difficult. Providers commonly equated prognosis purely with life expectancy. Providers recognized variation among patients in preferences regarding these conversations, but did not discuss asking patients directly about their preferences. Conclusions: GO patients want frank discussions about what the future might hold, often including but not limited to life expectancy. Providers see these discussions as being within their scope of practice but often find them difficult. Opportunities exist for provider education regarding communication skills for assessing patient preferences and conducting patient centered prognosis discussions. Education should include GO physicians, advanced practice providers and nurses. Collaboration with specialty palliative care providers could facilitate that education and provide assistance with challenging cases.

Contains fulltext : 172500.pdf (Publisher’s version ) (Closed access) OBJECTIVE: To evaluate whether endometriosis-associated genetic variation affects risk of ovarian cancer. DESIGN: Pooled genetic analysis. SETTING: University hospital. PATIENT(S): Genetic data from 46,176 participants (15,361 ovarian cancer cases and 30,815 controls) from 41 ovarian cancer studies. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Endometriosis-associated genetic variation and ovarian cancer. RESULT(S): There was significant evidence of an association between endometriosis-related genetic variation and ovarian cancer risk, especially for the high-grade serous and clear cell histotypes. Overall we observed 15 significant burden statistics, which was three times more than expected. CONCLUSION(S): By focusing on candidate regions from a phenotype associated with ovarian cancer, we have shown a clear genetic link between endometriosis and ovarian cancer that warrants further follow-up. The functional significance of the identified regions and SNPs is presently uncertain, though future fine mapping and histotype-specific functional analyses may shed light on the etiologies of both gynecologic conditions.

Purpose To examine clinical outcomes and relapse patterns in locally advanced vulvar carcinoma treated using preoperative chemotherapy and intensity modulated radiation therapy (IMRT). Methods and Materials Forty-two patients with stage I-IV A (stage I, n=3; stage II, n=13; stage III, n=23; stage IV A , n=3) vulvar cancer were treated with chemotherapy and IMRT via a modified Gynecological Oncology Group schema using 5-fluorouracil and cisplatin with twice-daily IMRT during the first and last weeks of treatment or weekly cisplatin with daily radiation therapy. Median dose of radiation was 46.4 Gy. Results Thirty-three patients (78.6%) had surgery for resection of vulva; 13 of these patients also had inguinal lymph node dissection. Complete pathologic response was seen in 48.5% (n=16) of these patients. Of these, 15 had no recurrence at a median time of 26.5 months. Of the 17 patients with partial pathological response, 8 (47.1%) developed recurrence in the vulvar surgical site within a median of 8 (range, 5-34) months. No patient had grade ≥3 chronic gastrointestinal/genitourinary toxicity. Of those having surgery, 8 (24.2%) developed wound infections requiring debridement. Conclusions Preoperative chemotherapy/IMRT was well tolerated, with good pathologic response and clinical outcome. The most common pattern of recurrence was local in patients with partial response, and strategies to increase pathologic response rate with increasing dose or adding different chemotherapy need to be explored to help further improve outcomes.

This multi-institutional phase II trial assessed the activity and tolerability of the anti-metastatic A6 peptide that binds CD44 in patients with persistent or recurrent epithelial ovarian, fallopian tube, or primary peritoneal carcinoma (EOC/FTC/PPC).Women with persistent or recurrent EOC/FTC/PPC were eligible for participation if they had measurable disease defined by RECIST criteria, good performance status, and good overall organ function. Patients must have received one prior platinum-based chemotherapeutic regimen and were allowed to have received one additional cytotoxic regimen for the management of recurrent or persistent disease. Women received a 150 mg twice daily subcutaneous dose of A6 and continued on treatment until disease progression or unacceptable toxicity. Primary measures of clinical efficacy were objective tumor response and progression-free survival (PFS) at 6 months. The association of CD44 in archival tissue specimens with clinical outcome was investigated.Thirty-one eligible patients were evaluated. No responses were observed. Two patients (6.5%) were progression free for at least 6 months. The median PFS was 2.0 months, and median overall survival has not yet been reached. One patient died of hemorrhage which was possibly study related. There were no grade 4 toxicities. The most common grade 3 toxicities were constitutional (2/31; 6.5%). Archival specimens were available for 27 patients, and 5 (18.5%) were CD44 positive by immunohistochemistry. CD44 expression was not associated with the 6-month PFS (p=0.342).A6 was well tolerated but had minimal activity in patients with persistent or recurrent EOC/FTC/PPC.

Purpose There is limited published data on high-dose-rate interstitial brachytherapy (HDRBT) for cervical cancer resulting in no consensus on a fractionation schedule. This study reports our experience of CT-based HDRBT for treating locally advanced cervical cancer. Methods and Materials Forty-seven patients diagnosed with Stage IIB–IVA cervical cancer not suitable for intracavitary brachytherapy were treated with HDRBT from March 2005 to November 2010. All patients received external beam radiation therapy with a median dose of 45 Gy and all had one interstitial implantation followed by 3.75–5 Gy × 5 fractions in a twice daily (BID) schedule. Total doses for clinical target volume and organs at risk, including rectum, bladder, and sigmoid, were summated and normalized to a biologically equivalent dose of 2 Gy per fraction. At 3 months posttherapy, early response was assessed with clinical examination and positron emission tomography (PET/CT) imaging. Results Median clinical target volume D 90 (dose delivered to 90% of the clinical target volume) was 76.3 (59.0–86.9) Gy and the 2 cc dose to the bladder, rectum, and sigmoid colon organs were 70.2 (55.9–77.7), 65.8 (54.9–80.6), and 56.5 (45.0–71.2) Gy, respectively. Posttreatment, 12 patients had evidence of persistent disease on PET/CT. Eleven of the 35 patients who had complete response developed recurrences. Two patients developed late Radiation Therapy Oncology Group ≥3 rectal toxicities. Two-year actuarial local control, disease-free survival, overall survival, and Grade ≥3 toxicities were 61%, 43%, 59%, and 10%, respectively. Conclusion Our approach of a single implantation procedure followed by five fractions of HDRBT was well tolerated with early results demonstrating a moderate response and local control rate with acceptable toxicities.

Radial scar (RS) is characterized by a fibroelastic core with entrapped ducts and lobules. Association with carcinoma is not uncommon. There is some dilemma as to the need for excisional biopsy or follow-up after RS diagnosis on core biopsy.To determine the necessity of excisional biopsy after the diagnosis of benign RS by core biopsy.A total of 67 RS specimens associated with benign findings on core biopsy obtained between 2003 and 2008 were reviewed. They were grouped by their accompanying histopathologic features found upon subsequent surgical excision: benign, high-risk lesion (HRL), or carcinoma. Demographic features, radiologic findings, and needle gauge were compared within subgroups.After surgical excision, 15 (22.4%) patients in the benign group were upgraded to a HRL, 4 (5.9%) patients were upgraded to carcinoma, and 48 (71.6%) remained benign. We found that malignancy is associated with RS more frequently if the patient is older and postmenopausal. Other variables such as symptoms at presentation, presence and type of abnormality on mammography (Breast Imaging Reporting and Data System score), breast density, size of biopsy needle used, and number of core samples retrieved did not help to predict the presence of carcinoma.The HRL and cancer upgrade rate of RS, requiring further intervention such as surgery or chemoprevention, is 28% in this study. However, we found that age and menopausal status may be taken into consideration when making the decision to follow up or excise the RS diagnosed on core biopsy. There is insufficient data to support the predictive value of any variables. Therefore, RS associated with benign findings on core biopsy should be excised.

Purpose To evaluate dosimetric and clinical outcomes of three-dimensional (3D) image–based high-dose-rate (HDR) interstitial brachytherapy (HDRB) in patients with vaginal cancers. Methods and Materials Thirty patients with vaginal cancers were treated with HDRB using Syed-Neblett template. CT scan was done after placement of needles for confirmation of placement and treatment planning. The target volume and organs at risk, including clinical target volume (CTV), rectum, bladder, and sigmoid colon, were contoured on CT scans. Twenty-eight (93.3%) patients received external beam radiation therapy at a median 45 (24.0–50.4) Gy in 12–28 fractions, followed by HDRB at 3.75–5.0 Gy per fraction in five fractions. Total doses for CTV and organs at risk from external beam radiation therapy and HDRB were summated and normalized to a biologically equivalent dose of 2 Gy per fraction. Results Seventeen patients (56.7%) with primary vaginal cancer and 13 patients (43.3%) with recurrent vaginal cancers were treated with 3D HDRB. The mean CTV was 39.3 ± 25.7 cm 3 , and the median tumor diameter was 3.3 (1.3–8.0) cm. The median biologically equivalent dose of 2 Gy per fraction for 2 cc of bladder, rectum, and sigmoid was 55.0, 56.3, 50.0 Gy, respectively. The median D 90 for high-risk CTV was 74.3 (36.3–81.1) Gy. The mean volume receiving 100%, 150%, and 200% of prescribed dose was 90.7 ± 10.0%, 41.3 ± 14.6%, and 17.7 ± 8.3%, respectively. With a median followup of 16.7 months, the respective 1-/2-year locoregional and overall survival rates were 84.4%/78.8% and 82.1%/70.2%, respectively. There were no Grade ≥3 gastrointestinal complications. Late complications of Grade 3 vaginal ulceration and Grade 4 vaginal necrosis were seen in two cases. Conclusions Initial results of 3D HDRB using our fractionation schedule in the treatment of vaginal cancers showed good local response with acceptable morbidities.

Benign breast diseases are common and encompass a spectrum of disorders. The majority of diagnoses will stem from a patient presenting with symptoms such as a mass or discomfort, or as a result of breast imaging which shows abnormalities leading to percutaneous biopsy. When mammographic and pathologic findings are disconcordant or when a high-risk lesion that can be associated with a preinvasive or invasive malignancy is found, formal excisional biopsy is recommended.

Objective Determine predictors of inpatient palliative care (PC) consultation and characterize PC referral patterns with respect to recommendations from the American Society of Clinical Oncology (ASCO). Methods Women with a gynecologic malignancy admitted to the gynecologic oncology service 3/2012–8/2012 were identified. Demographic information, disease and treatment details and date of death were abstracted from medical records. Student's t -test, Fischer's exact test or χ 2 -test was used for univariate analysis. Binomial logistic regression was used for multivariate analysis. Results Of 340 patients analyzed, 82 (24%) had PC consultation. Univariate predictors of PC consultation included race, cancer type and stage, recurrent disease, admission frequency, admission for symptom management or malignant bowel obstruction (MBO), discharge to skilled nursing facility (SNF) and number of lines of chemotherapy. On multivariate analysis, significant predictors of PC consultation were recurrent disease (OR 2.4, 95% CI 1.1–5.3), number of admissions (≥3, OR 10.9, 95% CI 3.4–34.9), admission for symptom management (OR 19.4, 95% CI 7.5–50.1), discharge to SNF (OR 5, 95% CI 1.9–13.5) and death within 6months (OR 16.5, 95% CI 6.9–39.5). Of patients considered to meet ASCO guidelines, 53% (63/118) had PC referral. Of patients referred to PC, 51.2% (42/82) died within 6months of last admission. Conclusions Patients referred to inpatient PC have high disease and symptom burden and poor prognosis. High-risk patients, including those meeting ASCO recommendations, are not captured comprehensively. We continue to use PC referrals primarily for patients near the end of life, rather than utilizing early integration as recommended by ASCO.