Cisplatin,doxorubicin hydrochloride,and cyclophosphamide followed by radiotherapy in high-risk endometrial carcinoma

OBJECTIVE: Our purpose was to assess the effect of adjuvant platinum-based, multiagent chemotherapy followed by conventional radiotherapy on the recurrence-free interval, patterns of recurrence, and survival of women with completely resected, poor-prognosis endometrial carcinoma. STUDY DESIGN: Surgical stage IC and II endometrial carcinomas involving the outer one third of myometrium and completely resected stage III and IV carcinomas were eligible for six cycles of cisplatin (Platinol), doxorubicin hydrochloride (Adriamycin), and cyclophosphamide (Cytoxan) (50, 50, 500 mg/m²), followed by external beam radiotherapy to pelvis, pelvis and periaortic chain, or whole abdomen, on the basis of documented disease. RESULTS: Forty-seven women were registered between April 1, 1984, and Oct. 10, 1992; 39 were eligible for review. Six were stage I, 28 were stage III, and five were stage IV. Two tumors were grade I, eight were grade 2, and 29 were grade 3. Twenty-three were endometrioid adenocarcinomas, eight papillary serous, six adenosquamous, and two clear cell. Thirty-seven patients (94.9%) completed six courses of chemotherapy, with no deaths ascribed to treatment. Grade 3 or 4 neutropenia was experienced by 17 (44%) and sepsis by three (8%). Current median follow-up is 27.3 months. Fifteen patients (38.5%) have recurrence, and 14 have died after a median interval of 26.9 months. The 2-year progression-free interval is 72.5% for nonpapillary serous histologic types and 22.5% for papillary serous cancers (p = 0.0074). CONCLUSION: Adjuvant chemotherapy with Platinol, Adriamycin, and Cytoxan followed by radiation therapy is well tolerated and seems to confer a survival advantage to women with nonpapillary serous endometrial carcinoma with a poor prognosis compared with historic controls treated by surgery or radiotherapy. (AM J Obstet Gynecol 1994;170:1677-82.)     

High-dose rate brachytherapy for Stage I/II papillary serous or clear cell endometrial cancer

OBJECTIVE: To determine the efficacy of high-dose rate brachytherapy as adjuvant treatment for Stage I/II papillary serous or clear cell endometrial cancer. METHODS: A retrospective study of all patients with Stage I/II papillary serous or clear cell endometrial cancer treated with high-dose rate brachytherapy between 1995 and 2001 was performed. Following surgical staging, which included hysterectomy with pelvic and aortic lymphadenectomy, all patients without extrauterine disease were treated with high-dose rate brachytherapy and followed for recurrence. The locations of recurrences were noted and were classified as local or distant. RESULTS: Three (13%) recurrences occurred among 24 patients with Stage I/II papillary serous or clear cell carcinoma. The risk of recurrence was similar for papillary serous and clear cell cancer (12% vs. 12%). Local control was achieved in 96%. The risk of recurrence for those with no myometrial invasion, less than 1/2, or more than 1/2 myometrial invasion was 0%, 10%, and 50%, respectively (P < 0.04). Two of the three recurrences were distant and all patients with recurrence died despite additional treatment. CONCLUSIONS: High-dose rate brachytherapy (HDR) as the sole adjuvant treatment of Stage I/II papillary serous or clear cell carcinoma is associated with a 13% risk of recurrence. Although local control with HDR is excellent, the risk of distant recurrence is increased with deep myometrial invasion. High-dose rate brachytherapy is adequate for Stage IA cases, but more aggressive treatment combining chemotherapy with HDR should be evaluated for more advanced Stage I/II cases.     

Clear Cell Carcinoma of the Ovary: A Distinct Histologic Type with Poor Prognosis and Resistance to Platinum-Based Chemotherapy in Stage III Disease

Between 1982 and 1992, 24 women with Stage III clear cell ovarian cancer were identified from the tumor registry. Thirty-four women with Stage III papillary serous tumors treated between 1987 and 1989 were used as a comparison. All patients underwent cytoreductive surgery followed by conventional platinum-based chemotherapy. In the women with clear cell histology, nine (37.5%) had endometriosis in the surgical specimen compared with one (3%) in the papillary serous group (P= 0.002). Ten women (42%) with clear cell histology experienced a thromboembolic event during the course of treatment, compared to six (18%) in the papillary serous group (P= 0.05). In the group with clear cell histology, overall, 70% of women had progressive disease. Fifty-two percent experienced clinical progression while receiving platinum-based chemotherapy. In addition, four patients were found to have progressive disease at second-look laparotomy. Only two patients had a pathologic complete response. In the group with papillary serous histology, 29% overall had progressive disease while on chemotherapy (P= 0.005). The median survival for the women with clear cell histology was 12 months compared to 22 months for those with papillary serous (P= 0.02). For women with clear cell histology, univariate analysis was used to evaluate prognostic factors. Age less than 50 was a poor prognostic factor (P= 0.045). The presence of endometriosis, thromboembolic event, or optimal cytoreduction were not prognostic factors (P= 0.67,P= 0.34,P= 0.39). Patients with advanced clear cell ovarian cancer have a poor response to conventional platinum-based chemotherapy and overall prognosis is poor.     

A retrospective assessment of outcomes of chemotherapy-based versus radiation-only adjuvant treatment for completely resected stage I-IV uterine carcinosarcoma

PurposeTo determine the progression-free survival (PFS) and overall survival (OS) in a cohort of patients who received either platinum-based chemotherapy with or without radiation therapy (pelvic or WAI), or RT alone.MethodsMemorial Sloan-Kettering Cancer Center (MSKCC) electronic medical records from 8/1/1995 to 10/3/2007 were reviewed for patient age, diagnosis date, type of primary surgery, residual disease at the completion of primary surgery, FIGO stage, treatment details, dates of progression and death, and site(s) of first recurrence. PFS and OS by stage (I/II v III/IV) and by treatment type (chemotherapy with or without RT v RT alone) were determined using landmark analyses 8 weeks after surgery. Patients who received chemotherapy with or without RT (pelvic or abdominal) or RT alone (pelvic or abdominal) were included in the analysis. Both groups were allowed to have received intravaginal radiation therapy (IVRT).ResultsForty-nine patients met study criteria. Thirty-eight/49 patients received chemotherapy: 23/38 (60.5%) received paclitaxel-carboplatin; 7/38 (18.4%) received ifosfamide-platinum; 8/38 (21.0%) received other chemotherapy. FIGO stage was: I = 15 (31%); II = 5 (10%); III = 21 (43%); IV = 8 (16%). Three-year PFS for the entire cohort was 24%. Three-year OS for the entire cohort was 60%. Three-year median PFS time for the entire cohort was 15 months (95% CI: 11–25 months). Three-year median OS time for the entire cohort was 67 months (95% CI: 23–89 months). Three-year PFS for stages I–II was 43% v 14% for stages III–IV (HR = 1.98 [0.9–4.33]); P = 0.082. Three-year OS for stages I–II was 68% v 55% for stages III–IV (HR = 1.26 [0.47–3.41]); P = 0.648. Three-year PFS for chemotherapy with or without RT was 35% v 9% for RT alone (HR = 1.74 [0.79–3.85]); P = 0.164. Three-year OS for chemotherapy with or without RT was 66% v 34% for RT alone (HR = 2.02 [0.77–5.33]); P = 0.146.ConclusionsOur study corroborates GOG 150 results, and shows that paclitaxel-carboplatin appears to be an efficacious adjuvant chemotherapy regimen for completely resected uterine carcinosarcoma. The role of adjuvant RT in addition to chemotherapy warrants further investigation.     

Clear cell carcinoma of the ovary: a clinicopathologic analysis of 34 cases

Abstract. The clinical and pathologic aspects of 34 cases of pure clear cell carcinoma of the ovary are discussed. These tumors represented 12.1% (34/280) of all ovarian cancers. The ages of the patients ranged from 34 to 78 years (mean 51.6 years) and 59% were postmenopausal. The clinical stages (FIGO) of these patients were as follows; I 22, II 5, III 6, and IV 1. Thirty-nine percent of the patients were nulligravidas. The diameters of the tumor varied from 6 to 31 cm (mean 16 cm), and 47% of the patients had endometriosis. Thirteen tumors were directly connected with endometriosis and this suggests that some ovarian clear cell carcinoma arose from the epithelium of an endometriotic cyst. Three architectural patterns (solid, papillary, and tubulocystic) were recognized. Forty-seven percent of the tumors were predominantly papillary and 24% contained mixtures of these three patterns. Four cell types such as clear, hobnail, eosinophilic, and flattened were also seen. Thirty-eight percent of the tumors had psammoma bodies. Histological patterns and cell types were not prognostic factors, and the stage at presentation was the most important prognostic factor. The 5-year survival rate was 54% (7/13) which was better than that in patients with serous adenocarcinoma of the ovary. The estimated survivals in patients with clear cell carcinoma however, were worse than those in patients with serous adenocarcinoma when compared stage for stage.     

Comparison of early-stage primary serous fallopian tube carcinomas and equivalent stage serous epithelial ovarian carcinomas

ObjectiveTo investigate the outcome of patients with early-stage primary fallopian tube carcinomas (PFTC) and those of patients with equivalent-stage serous epithelial ovarian carcinomas (SEOC).Materials and methodsA balanced and matched, case–control comparison was conducted in a university-based tertiary hospital database between 1978 and 2007. All PFTC and SEOC patients were treated with complete staging surgery followed by multiagent chemotherapy. One SEOC control was matched for each PFTC patient in a very uniform manner (characteristics and treatment). Disease-free survival (DFS) and overall survival (OS) were then compared using Kaplan-Meier analysis.ResultsTwenty-six paired patients were analyzed. Patients with PFTC were significantly older than the SEOC patients (58 years vs. 51 years, p = 0.001). In terms of recurrence, PFTC patients frequently had an extra-abdominal metastasis (3/4, 75%), in contrast to the SEOC patients, who did not (1/5, 20%). The 5-year DFS rate was similar in both groups (85% vs. 81%, p = 0.05), contributing to a similar OS rate (89% vs. 85%, p = 0.50). The median DFS and OS of patients with PFTC and SEOC were also similar without a statistically significant difference (125 months vs. 109 months, and 125 months vs. 122 months, respectively).ConclusionOur study demonstrated that the survival outcome of International Federation of Gynecology and Obstetrics (FIGO) I/II PFTC patients was similar to that of FIGO I/II SEOC patients, and both groups had a >80% 5-year DFS rate after complete staging surgery, followed by multiagent chemotherapy. This finding is worthy of being investigated.     

Same-Day Discharge Among Patients With Obesity Undergoing Laparoscopic Gynaecologic Oncology Surgery

ObjectivesTo determine the likelihood of same-day discharge (SDD) among patients with obesity undergoing laparoscopic gynaecologic oncology surgery and identify predictors of SDD.MethodsWe conducted a retrospective cohort study of gynaecologic oncology patients who underwent laparoscopic procedures between January 2012 and June 2016. Patients were categorized as non-obese, obese class I/II and obese class III (BMI <30, 30–39.9, and ≥40 kg/m², respectively). We used univariate and multivariable logistic regression to identify variables associated with SDD.ResultsOf 496 patients, 288 were non-obese, 161 were obese class I/II, and 47 were obese class III. Overall, 182 patients (36.7%) were discharged same day; 44% of these were non-obese, 30% class I/II and 15% class III. On multivariable analysis, we found negative predictors for SDD to be obesity (OR 0.54; P = 0.03), procedure length (OR 0.51; P < 0.01), and higher American Society of Anesthesiologists (ASA) score (OR 0.63; P < 0.01), while we found being pre-booked for SDD (OR 9.16; P <0.01) was a positive predictor of SDD. Among all patients with obesity, only procedure length (OR 0.47; P < 0.01) and being pre-booked for SDD (OR 9.67; P < 0.01) were associated with SDD when we controlled for BMI, ASA score, intraoperative complications, type of surgery, and surgical start time. Patients discharged same day were less likely to present to the emergency department within 30 days of surgery (OR 0.48; P = 0.01).ConclusionAmong the study cohort and after controlling for potential confounders, women with class I, II, and III obesity had a much lower likelihood of SDD than non-obese women. The only significant predictors of SDD among patients with obesity were duration of procedure and pre-booking for SDD. Further study is needed to identify strategies to improve SDD rates among patients with obesity.     

Outcome and Management of Serous Tubal Intraepithelial Carcinoma Following Opportunistic Salpingectomy: Systematic Review and Meta-Analysis

ObjectiveSerous ovarian cancer is the most common subtype of epithelial ovarian carcinoma—the most prevalent type of ovarian cancer. High-grade serous ovarian carcinoma (HGSOC) is thought to arise from the distal fallopian tube, with a precursor lesion known as serous tubal intraepithelial carcinoma (STIC). STICs are found in the final pathology of a salpingectomy specimen in 10%–20% of women with a BRCA gene mutation and 1%–7% of women without a mutation. However, there is currently no official guideline and a paucity of data on the management of STICs.Data SourcesWe performed a systematic review following PRISMA guidelines. Five databases were searched for relevant studies on STICs.Study SelectionTwo independent reviewers performed the abstract and full-text screening and data extraction, with conflicts resolved through discussion with the third reviewer. The risk of bias of each study was assessed using the Newcastle-Ottawa scale.Data Extraction and SynthesisFourteen articles were included. Ninety-nine patients who were diagnosed with STIC and subsequently followed for a mean period of 55.5 months were included in this analysis. Eighty-three patients (83.9%) were BRCA mutation carriers. After the diagnosis of isolated STIC, 7 patients (7.3%) received chemotherapy and 25 (26%) underwent surgical staging. Three of the 25 patients were diagnosed with HGSOC based on the staging surgery. Nine patients were later diagnosed with HGSOC during follow-up, with an average duration of follow-up of 58.5 months between the diagnosis of STIC and the diagnosis of HGSOC.ConclusionBased on our review of the literature, there is a 10.7% risk of having concurrent HGSOC at the time of STIC diagnosis, and the risk of developing a subsequent HGSOC is 14.5%. BRCA mutation status should be determined in cases of isolated STIC, as 83.9% of patients included in this study were found to carry BRCA mutations. We believe it is necessary to further investigate the role of surgical staging following the diagnosis of STIC.     

Response to Multi-Line Chemotherapy in Non-Serous Epithelial Ovarian Cancer

ObjectivesTo describe the response rate to chemotherapy, rates of recurrence, and overall survival in patients with non-serous epithelial ovarian cancers.MethodsThis retrospective cohort study used the Manitoba Cancer Registry to identify all women with non-serous epithelial ovarian, fallopian, or peritoneal cancer treated between 1995 and 2010. Chart review entailed extracting information regarding therapy and outcomes. All patients with recurrence were identified and response to chemotherapy was assessed.ResultsWe identified 392 patients with non-serous ovarian cancers, 192 of whom received chemotherapy in the first-line setting. Optimal debulking resulted in improvements in rates of recurrence and overall survival (P < 0.001). Histology did not have an effect on recurrence or overall survival. Forty-eight patients (25%) had a recurrence and received second-line therapy, and 21 (11%) received third-line therapy. Response rates were similar regardless of histology. In the second-line setting, 40.9%–83.3% of patients (other > mucinous > clear cell > endometrioid) and in the third-line setting, 33.3%–75.0% of patients (other > mucinous > clear cell > endometrioid) received >6 lines of chemotherapy. Twenty-three percent of patients experienced a recurrence within 2 years of first-line therapy. Two-year survival was 79.4% after first-line treatment, 27.6% after second-line treatment, and 19.5% after third-line treatment.ConclusionPatients with clear cell ovarian cancer had chemotherapy continuation rates similar to those of previously reported studies. This is one of the first studies reporting response rates for mucinous and endometrioid subtypes. Recurrent disease responds to treatment with second- and third-line therapy, emphasizing the importance of offering patients subsequent lines of chemotherapy for disease management. Further studies are needed to determine the optimal regimen.     

The Importance of Surgical Staging in Women With Uterine Serous Carcinoma: Experience in a Single Institution Reveals a Survival Benefit

ObjectiveTo assess the appropriate extent of surgical staging in women with clinically early stage uterine serous carcinoma (USC).MethodsWe conducted a single-institution retrospective cohort study of all women with USC between 2007 and 2012. Treatment practices, outcomes, and factors affecting survival were analyzed using univariate and multivariate analysis.ResultsEighty-four patients were identified, 76 of whom were included in the analysis. Preoperative pathology correctly identified USC in 73.3% of cases. Surgical stage distribution was 44.7% stage I, 7.9% stage II, 31.6% stage III, and 15.8% stage IV. Women thought to have early stage disease preoperatively encompassed 84.2% (64) of the cohort. Fifty-two (81.3%) of these women with clinically early stage disease had complete surgical staging. Thirty-four (53.1%) were determined to have surgical stage I, and the remaining 30 (46.9%) had occult advanced stage disease. Median follow-up was 43.2 months. Univariate analysis found a significant increase in progression-free survival and overall survival for women with clinically early stage disease with positive lymphovascular space invasion (P < 0.001 and P = 0.002, respectively), positive peritoneal cytology (P = 0.022 and P = 0.04, respectively), early stage (P < 0.001 and P = 0.004, respectively), and elevated serum CA125 at diagnosis (P = 0.003 and P = 0.001, respectively). On multivariate analysis, early stage (hazard ratio [HR] 9.87; 95% CI 2.79 to 34.92, P < 0.001) and complete surgical staging (HR 2.96; 95% CI 1.05 to 8.37, P = 0.040) were associated with prolonged progression-free survival, while overall survival was not affected by complete surgical staging (HR 1.92; 95% CI 0.64 to 5.76, P = 0.79).ConclusionComplete surgical staging prolongs the progression-free survival of women with clinical early-stage uterine serous cancer. Although this does not extend to overall survival, this enables patients to have an improved quality of life with a longer interval without the burden of disease.     

An assessment of pathologic features and treatment modalities in ovarian tumors of low malignant potential

Sixty-eight patients with epithelial ovarian tumors of low malignant potential treated at the University of Michigan Medical Center were reviewed for clinical and pathologic features related to recurrence or death. The ovarian tumor of low malignant potential represented 12.6% of all ovarian cancers and 22% of all serous or mucinous tumors. Thirty-four patients were stage I (50%), 13 were stage II (19%), 17 were stage III (25%), two patients could not be staged, and two patients developed ovarian tumor of low malignant potential in a residual ovary. The risk of recurrence was significantly related to stage III disease (P = .023), high nuclear atypia (P = .020), and high grade (P = .017); and was unrelated to capsular status, the presence of psammoma bodies, nucleoli, cribriform pattern, stratification, cystadenofibroma, tumor size, or spillage at surgery. Therapy in all stages included observation, chemotherapy, or radiotherapy. There was one recurrence in 47 patients with stages I-II, and 11 recurrences in 17 patients with stage III disease. The ovarian tumor of low malignant potential carries an extremely favorable prognosis in stage I and II regardless of therapy. Radiotherapy appeared to extend disease-free survival in stage III disease, and future randomized studies should consider this treatment modality.     

Low BRCA1 and BRCA2 Germline Mutation Rates in a French-Canadian Population with a Diagnosis of Epithelial Tubo-Ovarian Carcinoma

ObjectiveUniversal genetic testing has become increasingly important in the management of epithelial tubo-ovarian and peritoneal carcinoma. Worldwide, reported incidences of deleterious BRCA mutations vary between 12% and 15%. We sought to evaluate the incidence in our population, given its specific genetic background (French-Canadian ancestry).MethodMainstream genetic testing was implemented in our service in May 2017 and offered to all patients with epithelial tubo-ovarian or peritoneal carcinomas, except mucinous and borderline tumours. Data were prospectively collected in a database and retrospectively analyzed.ResultsWe tested 222 patients in our centre, of whom 183 (82.4%) had high-grade serous carcinoma (HGSC). Overall, 139 patients had no identified mutation (62.6%). Deleterious BRCA1 and BRCA2 mutations were found in 12 patients (5.4%): 6 had BRCA1, and 6 BRCA2 mutations; 11 of these patients had HGSC. Other non–BRCA mutations (ATM, RAD51C, RAD51D, BRIP1, CDH1, MRE11, MSH6, MUTYH, PALB2, and PMS2) were observed in an additional 20 patients (9.0%), of whom 18 had HGSC. A total of 63 different variants of unknown significance (VUS) were found, of which 4 were in the BRCA1 and BRCA2 genes. Deleterious mutations were not identified in clear cell carcinomas, and only 1 was found in low-grade serous carcinoma.ConclusionIn our French-Canadian population, the incidence of deleterious germline BRCA mutations was surprisingly low at 5.4%—less than half that reported in the literature. This may affect patient response to poly (ADP-ribose) polymerase (PARP) inhibitor (PARPi) therapy. Mainstream genetic testing was successfully implemented in our service and facilitated access to genetic testing in our patient population.     

Preoperative Anemia as a Prognostic Factor in Endometrioid-Type Endometrial Carcinoma

Objective

This study sought to determine the frequency of preoperative anemia (hemoglobin level <12?g/dL) and its prognostic significance for clinicopathological factors and survival outcomes in Saudi patients with endometrioid-type endometrial carcinoma (EC).

Late relapse of epithelial ovarian cancer: a single institution experience

PURPOSE OF INVESTIGATION: Late relapses are infrequent in ovarian cancer. We present the characteristics and outcome of patients who relapsed at least five years after first-line chemotherapy. METHODS: Six cases were retrieved from 203 patients treated from 1994 to 1998. RESULTS: Time to recurrence ranged from five to nine years. The initial stage was I or II in all cases, while histology was: endometrioid (4 cases), clear cell (1 case) and unspecified adenocarcinoma (1 case). Only two of five assessable patients responded to chemotherapy. Compared to earlier relapses, late relapses were characterized by earlier stages (p < 0.001), non serous histology (p = 0.010) and absence of symptoms (0% vs 46.5%, p = 0.025) at baseline. Five of 16 relapses (31%) among patients with Stage I or II were late relapses. CONCLUSION: Late relapses of ovarian cancer occur in early stages, where they are relatively frequent, while the chemosensitivity of the disease may be less than expected.     

Impact of tubal ligation on routes of dissemination and overall survival in uterine serous carcinoma

ObjectiveAbdominal peritoneal implants are characteristic of uterine serous carcinoma (USC). The presumed mechanism of dissemination is retrograde transit via the fallopian tube. We assessed the impact of tubal ligation (TL) on the metastatic profile and survival of USC patients.MethodsPatient risk factors, process-of-care variables, and disease-specific parameters were annotated. Categorical variables were compared using the χ² test. Overall survival (OS) was estimated via the Kaplan–Meier method.ResultsAmong 211 USC patients, fallopian tube status was documented in 142 patients; 35 had a history of TL and 107 did not. When comparing patients with and without TL, positive peritoneal cytology was present, respectively, in 18.8% vs 45.0% (P = .01) and stage IV disease in 14.3% vs 34.6% (P = .02). Using Cox models, age was the sole significant determinant of OS in stage I/II USC. By contrast, age, lymphovascular space involvement, positive cytology, and TL independently and adversely affected survival in stage III/IV USC. Adjusting for these factors in a multivariable model, the association between TL and OS among patients with advanced disease yielded a hazard ratio of 8.61 (95% CI, 3.08–24.03; P < .001). The prevalence of lymphatic metastasis and nodal tumor burden was significantly greater in patients who underwent ligation.ConclusionPatients with TL had significantly lower rates of positive cytology and stage IV disease than patients without TL. The lymphatic system appeared to be the dominant mode of spread after TL and was associated with a paradoxic worsening of OS, perhaps reflecting a delay in diagnosis.     

Decreased levels of serum glutathione peroxidase 3 are associated with papillary serous ovarian cancer and disease progression

Background

Glutathione peroxidase 3 (GPX3) is a selenocysteine-containing antioxidant enzyme that reacts with hydrogen peroxide and soluble fatty acid hydroperoxides, thereby helping to maintain redox balance within cells. Serum levels of GPX3 have been found to be reduced in various cancers including prostrate, thyroid, colorectal, breast and gastric cancers. Intriguingly, GPX3 has been reported to be upregulated in clear cell ovarian cancer tissues and thus may have implications in chemotherapeutic resistance. Since clear cell and serous subtypes of ovarian cancer represent two distinct disease entities, the aim of this study was to determine GPX3 levels in serous ovarian cancer patients and establish its potential as a biomarker for detection and/or surveillance of papillary serous ovarian cancer, the most frequent form of ovarian tumors in women.

Patients and Methods

Serum was obtained from 66 patients (median age: 62 years, range: 22-89) prior to surgery and 65 controls with a comparable age-range (median age: 53 years, range: 25-83). ELISA was used to determine the levels of serum GPX3. The Mann Whitney U test was performed to determine statistical significance between the levels of serum GPX3 in patients and controls.

Results

Serum levels of GPX3 were found to be significantly lower in patients than controls (p = 1 × 10^-2). Furthermore, this was found to be dependent on the stage of disease. While levels in early stage (I/II) patients showed no significant difference when compared to controls, there was a significant reduction in late stage (III/IV, p = 9 × 10^-4) and recurrent (p = 1 × 10^-2) patients. There was a statistically significant reduction in levels of GPX3 between early and late stage (p = 5 × 10^-4) as well as early and recurrent (p = 1 × 10^-2) patients. Comparison of women and controls stratified to include only women at or above 50 years of age shows that the same trends were maintained and the differences became more statistically significant.

Conclusions

Serum GPX3 levels are decreased in women with papillary serous ovarian cancer in a stage-dependent manner and also decreased in women with disease recurrence. Whether this decrease represents a general feature in response to the disease or a link to the progression of the cancer is unknown. Understanding this relationship may have clinical and therapeutic consequences for women with papillary serous adenocarcinoma.     

Fractal tumor growth of ovarian cancer: sonographic evaluation

OBJECTIVE: The objective of this study was to determine whether sonographically depicted ovarian tumor growth is fractal, and the mean fractal dimension differs according to stages of the disease and histologic types. METHODS: The fractal dimensions of outlines of sonographically depicted solid components in 160 ovarian tumors were measured using a box-counting method. RESULTS: The mean fractal dimensions of the surface of intracystic solid components in serous, mucinous, endometrioid, and clear cell adenocarcinoma were 1.259, 1.243, 1.238, and 1.182, respectively. These values were significantly greater than the topological dimension of a line (=1). The value was significantly higher in stage I or II (1.381) than stage III or IV (1.205) in serous carcinoma (P = 0.02), but not significantly different in clear cell carcinoma (1.187 and 1.172, respectively). In stage I or II, the value of serous carcinoma (1.381) was significantly higher than that of clear cell carcinoma (1.187) (P = 0.03). The value of mucinous cystadenoma of low malignant potential was 1.337, which was also significantly greater than 1. The mean fractal dimensions of outlines of solid tumors in cases with dysgerminoma and thecoma-fibroma were 1.036 and 1.023, respectively. These values were not significantly different from 1. CONCLUSION: This study shows that the surface of solid components in cystic epithelial ovarian cancers has a fractal structure, and the mean fractal dimension may differ according to stages of the disease and histologic types. Fractal geometry, a vocabulary of irregular shapes, can be useful for describing the pathological architecture of ovarian tumors and for yielding insights into the mechanisms of tumor growth.     

Factors Affecting Overall Survival in Premenopausal Women With Uterine Leiomyosarcoma: A Retrospective Analysis With Long-Term Follow-Up

ObjectivePremenopausal women with uterine leiomyosarcoma experience different issues than menopausal women with this malignancy. This study evaluated the clinical profile and factors affecting survival outcomes in premenopausal women with uterine leiomyosarcoma.MethodsWe conducted a retrospective analysis of patients with uterine leiomyosarcoma, diagnosed between January 2008 and December 2016. Data were collected from the Alberta Cancer Registry, which reflects all patients in the province. Thirty-eight patients were included in the study, of whom 21 were alive on the last date of review (31 December, 2019).ResultsThe median follow-up period was 86 months. Mean patient age was 44.6 ± 5.7 years. The 5-year survival rate was 34.2%; 45% of patients presented with stage I or II disease and 55%, with stage III or IV. There was no clinical suspicion of malignancy prior to surgery in about 60% of cases. Ovarian preservation was performed in about 34% of cases. Forty-five percent of patients had received chemotherapy and 26%, radiotherapy. Almost 90% had unspecified leiomyosarcoma. Univariate analysis of factors likely to affect overall survival showed that older age at diagnosis (HR 1.19; 95% CI 1.05–1.34, P = 0.005), lymphovascular invasion (HR 9.81; 95% CI 2.88–33.51, P = 0.00), and no radiation therapy (HR 2.60; 95% CI 0.99–6.87, P = 0.05) were associated with worse overall survival. A multivariate analysis of these risk factors showed only lymphovascular invasion of the tumour to be a significant risk factor affecting overall survival. (HR 18.07; 95% CI 4.23–77.15, P =0.00).ConclusionMultivariate analysis showed lymphovascular invasion of tumour to be a significant risk factor affecting overall survival in premenopausal women with uterine leiomyosarcoma. Ovarian preservation, lymph node positivity, age, treatment strategy, hormone receptor status, and grade of tumour were not found out to be significant prognostic variables.     

Endometriumkarzinom

Endometrial cancer (EC) is the 4th most common malignant disease in women in Germany. Most cases of EC become symptomatic at an early stage and have a good prognosis. Five-year overall survival (all stages) amounts to 82%. EC has been traditionally treated with total abdominal hysterectomy plus bilateral salpingo-oophorectomy. For early-stage, low-grade cases (endometrioid, pT1a, pT1b; G1, G2) this is an adequate therapy. For higher stages and grades, especially for type II EC (serous, clear cell), this therapy is insufficient. The efficacy of systematic pelvic and paraaortic lymphadenectomy for high-risk EC, however, remains to be evaluated. In advanced stages, all tumor manifestations should be surgically removed. External pelvic radiotherapy has been shown to improve local control in stages I and II EC, but it has no positive effect on survival. A comparable improvement of local control can be achieved by vaginal brachytherapy with significantly less toxicity. Adjuvant chemotherapy is probably efficacious in EC. Its usefulness as exclusive adjuvant therapy or in combination with brachytherapy and/or external beam radiotherapy remains to be evaluated by prospective trials. In the palliative situation, patients with estrogen-receptor-positive and/or progesterone-receptor-positive tumors that are not life-threatening should receive endocrine therapy. In all other cases or for primary progression under endocrine therapy, palliative chemotherapy is indicated.