Adding immunotherapy to first-line treatment of advanced and metastatic endometrial cancer.

BACKGROUND: Immunotherapy has transformed the endometrial cancer treatment landscape, particularly for those exhibiting mismatch repair deficiency [MMRd/microsatellite instability-hypermutated (MSI-H)]. A growing body of evidence supports the integration of immunotherapy with chemotherapy as a first-line treatment strategy. Recently, findings from ongoing trials such as RUBY (NCT03981796), NRG-GY018 (NCT03914612), AtTEnd (NCT03603184), and DUO-E (NCT04269200) have been disclosed. MATERIALS AND METHODS: This paper constitutes a review and meta-analysis of phase III trials investigating the role of immunotherapy in the first-line setting for advanced or recurrent endometrial cancer. RESULTS: The pooled data from 2320 patients across these trials substantiate the adoption of chemotherapy alongside immunotherapy, revealing a significant improvement in progression-free survival compared to chemotherapy alone [hazard ratio (HR) 0.70, 95% confidence interval (CI) 0.62-0.79] across all patient groups. Progression-free survival benefits are more pronounced in MMRd/MSI-H tumors (n = 563; HR 0.33, 95% CI 0.23-0.43). This benefit, albeit less robust, persists in the MMR-proficient/microsatellite stable group (n = 1757; HR 0.74, 95% CI 0.60-0.91). Pooled data further indicate that chemotherapy plus immunotherapy enhances overall survival compared to chemotherapy alone in all patients (HR 0.75, 95% CI 0.63-0.89). However, overall survival data maturity remains low. CONCLUSIONS: The incorporation of immunotherapy into the initial treatment for advanced and metastatic endometrial cancer brings about a substantial improvement in oncologic outcomes, especially within the MMRd/MSI-H subset. This specific subgroup is currently a focal point of investigation for evaluating the potential of chemotherapy-free regimens. Ongoing exploratory analyses aim to identify non-responding patients eligible for inclusion in clinical trials.

Characterization of adnexal lesions using photoacoustic imaging to improve sonographic O-RADS risk assessment.

OBJECTIVE: To assess the impact of photoacoustic imaging (PAI) on the assessment of ovarian/adnexal lesion(s) of different risk categories using the sonographic ovarian-adnexal imaging-reporting-data system (O-RADS) in women undergoing planned oophorectomy. METHOD: This prospective study enrolled women with ovarian/adnexal lesion(s) suggestive of malignancy referred for oophorectomy. Participants underwent clinical ultrasound (US) examination followed by coregistered US and PAI prior to oophorectomy. Each ovarian/adnexal lesion was graded by two radiologists using the US O-RADS scale. PAI was used to compute relative total hemoglobin concentration (rHbT) and blood oxygenation saturation (%sO2 ) colormaps in the region of interest. Lesions were categorized by histopathology into malignant ovarian/adnexal lesion, malignant Fallopian tube only and several benign categories, in order to assess the impact of incorporating PAI in the assessment of risk of malignancy with O-RADS. Malignant and benign histologic groups were compared with respect to rHbT and %sO2 and logistic regression models were developed based on tumor marker CA125 alone, US-based O-RADS alone, PAI-based rHbT with %sO2 , and the combination of CA125, O-RADS, rHbT and %sO2. Areas under the receiver-operating-characteristics curve (AUC) were used to compare the diagnostic performance of the models. RESULTS: There were 93 lesions identified on imaging among 68 women (mean age, 52 (range, 21-79) years). Surgical pathology revealed 14 patients with malignant ovarian/adnexal lesion, two with malignant Fallopian tube only and 52 with benign findings. rHbT was significantly higher in malignant compared with benign lesions. %sO2 was lower in malignant lesions, but the difference was not statistically significant for all benign categories. Feature analysis revealed that rHbT, CA125, O-RADS and %sO2 were the most important predictors of malignancy. Logistic regression models revealed an AUC of 0.789 (95% CI, 0.626-0.953) for CA125 alone, AUC of 0.857 (95% CI, 0.733-0.981) for O-RADS only, AUC of 0.883 (95% CI, 0.760-1) for CA125 and O-RADS and an AUC of 0.900 (95% CI, 0.815-0.985) for rHbT and %sO2 in the prediction of malignancy. A model utilizing all four predictors (CA125, O-RADS, rHbT and %sO2 ) achieved superior performance, with an AUC of 0.970 (95% CI, 0.932-1), sensitivity of 100% and specificity of 82%. CONCLUSIONS: Incorporating the additional information provided by PAI-derived rHbT and %sO2 improves significantly the performance of US-based O-RADS in the diagnosis of adnexal lesions. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Radiation therapy for vaginal and perirectal lesions in recurrent ovarian cancer.

The role for localized radiation to treat ovarian cancer (OC) patients with locally recurrent vaginal/perirectal lesions remains unclear, though we hypothesize these patients may be salvaged locally and gain long-term survival benefit. We describe our institutional outcomes using intensity modulated radiation therapy (IMRT) +/- high-dose rate (HDR) brachytherapy to treat this population. Our primary objectives were to evaluate complete response rates of targeted lesions after radiation and calculate our 5-year in-field control (IFC) rate. Secondary objectives were to assess radiation-related toxicities, chemotherapy free-interval (CFI), as well as post-radiation progression-free (PFS) and overall survival (OS). PFS and OS were defined from radiation start to either progression or death/last follow-up, respectively. This was a heavily pre-treated cohort of 17 recurrent OC patients with a median follow-up of 28.4 months (range 4.5-166.4) after radiation completion. 52.9% had high-grade serous histology and 4 (23.5%) had isolated vaginal/perirectal disease. Four (23.5%) patients had in-field failures at 3.7, 11.2, 24.5, and 27.5 months after start of radiation, all treated with definitive dosing of radiation therapy. Patients who were platinum-sensitive prior to radiation had similar median PFS (6.5 vs. 13.4 months, log-rank p = 0.75), but longer OS (71.1 vs 18.8 months, log-rank p = 0.05) than their platinum-resistant counterparts. Excluding patients with low-grade histology or who were treated with palliative radiation, median CFI was 14.2 months (range 4.7 - 33.0). Radiation was well tolerated with 2 (12.0%) experiencing grade 3/4 gastrointestinal/genitourinary toxicities. In conclusion, radiation to treat locally recurrent vaginal/perirectal lesions in heavily pre-treated OC patients is safe and may effectively provide IFC.

COVID-19 lockdown: a rare opportunity to establish baseline pollution level of air pollutants in a megacity, India.

This paper analyses air quality data from megacity Delhi, India, during different periods related to the COVID-19, including pre-lockdown, lockdown and unlocked (post-lockdown) (2018-2020) to determine what baseline levels of air pollutants might be and the level of impact that could be anticipated under the COVID-19 lockdown emission scenario. The results show that air quality improved significantly during the lockdown phases, with the most significant changes occurring in the transportation and industrially dominated areas. A pronounced decline in PM2.5 and PM10 up to 63% and 58%, respectively, was observed during the lockdown compared to the pre-lockdown period in 2020. When compared to 2018 and 2019, they were lower by up to 51% and 61%, respectively, dropping by 56% during unlock. Some pollutants (NOx and CO) dropped significantly during lockdown, while SO2 and O3 declined only slightly. Moreover, when compared between the different phases of lockdown, the maximum decline for most of the pollutants and air quality index occurred during the lockdown phase 1; thus, this period was used to report the COVID-19 baseline threshold values (CBT; threshold value is the upper limit of baseline variation). Of the various statistical methods used median + 2 median absolute deviation (mMAD) was most suitable, indicating CBT values of 143 and 75 ug/m3 for PM10 and PM2.5, respectively. This results although preliminary, but it gives a positive indication that temporary lockdown can be considered as a boon to mitigate the damage we have done to the environment. Also, this baseline levels can be helpful as a first line of information to set future target limits or to develop effiective management policies for achieving better air quality in urban centres like Delhi. Supplementary Information: The online version contains supplementary material available at 10.1007/s13762-021-03142-3.

Long-Term Outcomes of Cervical Cancer Patients Treated With Definitive Chemoradiation Following a Complete Metabolic Response.

AIMS: A complete metabolic response (CMR) on early post-treatment 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) is a positive prognostic factor for cervical cancer patients treated with definitive chemoradiation, but long-term outcomes of this group of patients are unknown. Patterns of failure and risk subgroups are identified. MATERIALS AND METHODS: Patients who received curative-intent chemoradiation from 1998 to 2018 for International Federation of Gynecology and Obstetrics (FIGO) stage IB1-IVA cervical cancer and had a CMR on post-treatment FDG-PET within 5 months of treatment completion were included. Cox proportional hazards models determined factors associated with locoregional and distant failure. Kaplan-Meier estimates of freedom from any recurrence (FFR) of patient subgroups were compared with Log-rank tests. RESULTS: There were 402 patients with a CMR after chemoradiation on FDG-PET. Initial T stage was T1 (38%)/T2 (40%)/T3 (20%)/T4 (2%); initial FDG-avid nodal status was no nodes (50%)/pelvic lymph nodes (40%)/pelvic and para-aortic lymph nodes (10%). After a median follow-up of 6 years, 109 (27%) recurred. The pattern of recurrence was locoregional (27%), distant (61%) or both (12%). No factors were associated with locoregional failure. Distant recurrence was more likely in patients with T3-4 lesions (hazard ratio = 2.4, 95% confidence interval 1.5-3.8) and involvement of pelvic (hazard ratio = 1.6, 95% confidence interval 1.0-2.7) or para-aortic lymph nodes (hazard ratio = 2.7, 95% confidence interval 1.4-5.0) at diagnosis. The 5-year FFR rates for T1-2 patients with no nodes, pelvic nodes alone or para-aortic nodes at diagnosis were 85, 76 and 62%, respectively (P = 0.04, none versus para-aortic nodes). The 5-year FFR for T3-4 patients with no nodes, pelvic nodes alone or para-aortic nodes at diagnosis were 68, 56 and 25%, respectively (P = 0.09, none versus para-aortic nodes). CONCLUSIONS: T3-4 tumours and para-aortic nodal involvement at diagnosis are poor prognostic factors, even after a CMR following chemoradiation.

Aortoseptal angle and pressure gradient reduction following balloon valvuloplasty in dogs with severe subaortic stenosis.

INTRODUCTION: To determine the relationship between aortoseptal angle (AoSA) and the short- and long-term systolic pressure gradient (PG) reduction following combined cutting and high-pressure balloon valvuloplasty (CB/HPBV) in dogs with severe subaortic stenosis. ANIMALS: Retrospective study of 22 client-owned dogs of various breeds with severe subaortic stenosis (mean left ventricular to aortic PG = 143 mmHg; range = 80-322 mmHg) that underwent CB/HPBV. MATERIALS AND METHODS: Initial angiographic and left apical and right-sided parasternal long-axis view echocardiographic video loops were used for measuring the angle between the plane of the interventricular septum and the longitudinal axis of the ascending aorta. The PG reduction ratio immediately after CB/HPBV and 6 and 12 months later were compared with AoSA. RESULTS: Weak correlations were observed for all instances of PG reduction ratio and AoSA type. Significantly greater mean differences of PG reduction ratio were observed for angles >160° than for angles <160° at 24 h (>160° mean: 54.45, standard error [SE]: ±3.8; <160° mean: 39.88, SE: ±2.09), 6 months (>160° mean: 57.73, SE: ±10.9; <160° mean: 28.22, SE: ±3.42), and 12 months (>160° mean: 76.11, SE: ±17.5; <160° mean: 27.61, SE: ±6.44; p=0.003). CONCLUSIONS: Dogs with AoSA >160° on right-sided parasternal long-axis view echocardiograms responded with a greater PG reduction following CB/HPBV than did dogs with AoSA <160°. This suggests that AoSA is associated with long-term outcomes of CB/HPBV, and measurement could help in the evaluation of dogs that are candidates for CB/HPBV.

Improved clinical trial enrollments for uterine leiomyosarcoma patients after gynecologic oncology partnership with a sarcoma center.

OBJECTIVE: A retrospective chart review was performed to determine patient outcomes before and after partnership by gynecologic oncologists (GYN/ONC) with a sarcoma center (SC) for patients with recurrent unresectable/metastatic (RM) uterine leiomyosarcoma (uLMS). METHODS: 58 RM patients, identified from medical records of uLMS patients cared for by either GYN/ONC service and/or the SC between 1/1/2000-4/1/2014, were audited for patient and tumor characteristics, outcomes, and clinical trials enrollments. RESULTS: Of the 58 patients, 26 patients (48%) were treated by GYN/ONC alone and 32 were treated by a combination of GYN/ONC and SC (52%). Age, race, tumor size, grade, presence of lymphovascular invasion, cervical involvement, and FIGO stage at diagnosis were not statistically different between the two groups. There was a significant difference between the number of clinical trial enrollments (0.07 vs 0.84 trials/patient, p<0.001) and the number of chemotherapy regimens prescribed (2.67 vs 4.29/patient, p=0.03) by GYN/ONC vs SC; the latter was driven by the number of clinical trial enrollments by the SC. Sixty-nine percent of patients referred to the SC were enrolled in at least one clinical trial, while just 8% of patients in the GYN/ONC group were enrolled in at least one clinical trial, a difference that is significant (p<0.0001). CONCLUSIONS: Referral of RM uLMS patients by GYN/ONC to a dedicated clinical trials-based SC resulted in an increase in the number of chemotherapy regimens prescribed and clinical trial enrollments. Partnership between GYN/ONC and a dedicated SC with access to clinical trials should be encouraged for all RM uLMS patients.

Pre-operative assessment of muscle mass to predict surgical complications and prognosis in patients with endometrial cancer.

BACKGROUND: Sarcopenia or loss of skeletal muscle mass is an objective measure of frailty associated with functional impairment and disability. This study aimed to examine the impact of sarcopenia on surgical complications and survival outcomes in patients with endometrial cancer. METHODS: A retrospective review of endometrial cancer patients who underwent surgery between 2005 and 2009 was performed. Sarcopenia was assessed on preoperative computed tomography (CT) scan by measurement of the lumbar psoas muscle cross-sectional area and defined as any value below the median (<4.33 cm(2)). Sarcopenic obesity was defined as sarcopenia plus a body mass index (BMI) of 30 kg/m(2) or higher. Microsatellite instability (MSI) was analyzed using the National Cancer Institute (NCI) consensus markers and tumor from hysterectomy specimens. RESULTS: Of 122 patients, 27 (22%) met the criteria for sarcopenic obesity. Sarcopenic patients were older than patients with normal muscle mass (mean age, 69.7 vs. 62.1 years; p < 0.001), had a lower BMI (31.1 vs. 39.4 kg/m(2); p < 0.001), and had more comorbidities (p = 0.048). Sarcopenia was not associated with tumor MSI, hospital stay, 90-day readmission rate, or early/late complications. Patients with sarcopenia had a shorter recurrence-free survival than nonsarcopenic patients (median 23.5 vs. 32.1 months; log-rank p = 0.02), but did not differ in terms of overall survival (log-rank p = 0.25). After adjustment for race, BMI, lymphocyte count, and tumor histology, sarcopenia was associated with a fourfold shorter recurrence-free survival (adjusted hazard ratio [HRadj], 3.99; 95% confidence interval [CI], 1.42-11.3). CONCLUSIONS: Sarcopenia has an impact on recurrence-free survival, but does not appear to have a negative impact on surgical outcomes or overall survival among endometrial cancer patients who undergo preoperative CT scan.

Evaluation of a chemoresponse assay as a predictive marker in the treatment of recurrent ovarian cancer: further analysis of a prospective study.

BACKGROUND: Recently, a prospective study reported improved clinical outcomes for recurrent ovarian cancer patients treated with chemotherapies indicated to be sensitive by a chemoresponse assay, compared with those patients treated with non-sensitive therapies, thereby demonstrating the assay's prognostic properties. Due to cross-drug response over different treatments and possible association of in vitro chemosensitivity of a tumour with its inherent biology, further analysis is required to ascertain whether the assay performs as a predictive marker as well. METHODS: Women with persistent or recurrent epithelial ovarian cancer (n=262) were empirically treated with one of 15 therapies, blinded to assay results. Each patient's tumour was assayed for responsiveness to the 15 therapies. The assay's ability to predict progression-free survival (PFS) was assessed by comparing the association when the assayed therapy matches the administered therapy (match) with the association when the assayed therapy is randomly selected, not necessarily matching the administered therapy (mismatch). RESULTS: Patients treated with assay-sensitive therapies had improved PFS vs patients treated with non-sensitive therapies, with the assay result for match significantly associated with PFS (hazard ratio (HR)=0.67, 95% confidence interval (CI)=0.50-0.91, P=0.009). On the basis of 3000 simulations, the mean HR for mismatch was 0.81 (95% range=0.66-0.99), with 3.4% of HRs less than 0.67, indicating that HR for match is lower than for mismatch. While 47% of tumours were non-sensitive to all assayed therapies and 9% were sensitive to all, 44% displayed heterogeneity in assay results. Improved outcome was associated with the administration of an assay-sensitive therapy, regardless of homogeneous or heterogeneous assay responses across all of the assayed therapies. CONCLUSIONS: These analyses provide supportive evidence that this chemoresponse assay is a predictive marker, demonstrating its ability to discern specific therapies that are likely to be more effective among multiple alternatives.

The prognostic significance of lymphovascular space invasion in laparoscopic versus abdominal hysterectomy for endometrioid endometrial cancer.

INTRODUCTION: Recent reports have suggested that uterine manipulators can induce lymphovascular space involvement (LVSI) by endometrial cancer in laparoscopic hysterectomy specimens. The prognostic significance of this phenomenon known as "vascular pseudo invasion" remains elusive. MATERIALS AND METHODS: The authors conducted a retrospective, single institution study of patients who underwent initial surgery for grade 1 and grade 2 endometrioid endometrial cancers with LVSI. Cases were stratified by surgical approach (laparoscopy vs laparotomy). Clinicopathologic and procedure characteristics as well as outcome data were analyzed. Univariate and multivariate analyses were performed. Disease-free survival (DFS) was analyzed using the Kaplan-Meier product limit method. RESULTS: A total of 104 cases (20 laparoscopic, 84 laparotomy) were analyzed. Mean age (65 vs 64 years, respectively), stage distribution, mean number of lymph nodes sampled (18 vs 21, respectively) and use of adjuvant therapy was similar for both groups (p > 0.05). Mean body mass index (BMI) was 30 vs 35 kg/m2, respectively (p = 0.002). Mean follow up was 24 months (range 0.1-102). Univariate analysis demonstrated that LVSI in the laparoscopic setting was associated with worse DFS (p = 0.002). After adjusting for grade the risk of recurrence remained higher for laparoscopic cases (HR: 15.7, 95% CI 1.7-140.0, p = 0.014). CONCLUSIONS: Adjusted risk of recurrence associated with LVSI is higher in cases approached laparoscopically arguing against the concept of "vascular pseudo invasion" associated with the use of uterine manipulators and balloons. LVSI should be regarded as a serious risk factor and taken into account for triage to adjuvant therapies, even in laparoscopically treated early-stage endometrial cancer.

Pelvic exenteration in gynecologic oncology: a single institution study over 20 years.

OBJECTIVE: The profile of women with gynecologic malignancies treated with pelvic exenteration has changed since the initial description of this procedure. We sought to evaluate our experience with pelvic exenteration over the last 20 years. METHODS: Patients who underwent anterior, posterior, or total pelvic exenteration for vulvar, vaginal, and cervical cancer at Barnes-Jewish Hospital between January 1, 1990 and August 1, 2009 were identified through hospital databases. Patient characteristics, the indications for the procedure, procedural modifications, and patient outcomes were retrospectively assessed. Categorical variables were analyzed with chi-square method, and survival data was analyzed using the Kaplan-Meier method and log rank test. RESULTS: Fifty-four patients were identified who had pelvic exenteration for cervical, vaginal, or vulvar cancer. Recurrent cervical cancer was the most common procedural indication. One year overall survival from pelvic exenteration for the entire cohort was 64%, with 44% of patients still living at 2 years and 34% at 50 months. Younger age was associated with improved overall survival after exenteration (p = 0.01). Negative margin status was associated with a longer disease-free survival (p=0.014). Nodal status at the time of exenteration was not associated with time to recurrence or progression, site of recurrence, type of post-operative treatment, early or late complications, or survival. CONCLUSIONS: Despite advances in imaging and increased radical techniques, outcomes and complications after total pelvic exenteration in this cohort are similar to those described historically. Pelvic exenteration results in sustained survival in select patients, especially those that are young with recurrent disease and pathologically negative margins.

Fate of lysostaphin in milk from individual cows through pasteurization and cheesemaking.

Transgenic cows secreting over 3 microg of lysostaphin/ mL of milk are protected against mastitis caused by Staphylococcus aureus, but it is unknown if active lysostaphin persists through dairy processing procedures or affects the production of fermented dairy foods. The objective of this study was to determine the fate of lysostaphin as milk was pasteurized and then processed into cheese. Raw milk from transgenic cows was heat treated at 63 degrees C for 30 min, 72 degrees C for 15 s (high temperature, short time), or 140 degrees C for 2 s (UHT). Portions of the high temperature, short-time milk were manufactured into semi-hard cheeses. Aliquots taken at each processing step were assayed to determine the quantity (ELISA) and activity (ability to inhibit S. aureus growth) of lysostaphin. Results indicated that most of the lysostaphin was present in the aqueous portion of the milk and was not affected by pasteurization, although UHT treatment reduced enzyme concentration by 60%. The quantity and activity of the lysostaphin decreased during cheesemaking. Based on the amount of lysostaphin present in the starting cheesemilk, 10 to 15% of the lysostaphin was recovered in the whey, 21 to 55% in the cheese curd at d 1, and 21 to 36% in cheese stored at 4 degrees C for 90 d. Enough of the lysostaphin secreted into milk by transgenic cows survived typical dairy processing conditions to impart potential value as a bioprotective agent against staphylococci in dairy foods.

Prognostic factors associated with response in platinum retreatment of platinum-resistant ovarian cancer.

The goal of this study was to determine the factors associated with response to platinum retreatment in patients with platinum-resistant ovarian cancer. A review of patients with epithelial ovarian cancer retreated with cisplatin or carboplatin between 2002 and 2004 was performed. The platinum-free interval (PFI) and treatment-free interval (TFI) were determined for each patient. Response was based on serial CA125 levels using a modification of the Rustin criteria. Patients with clinical benefit ([CB] those who attained at least stable disease) were compared to patients with disease progression (PD). An analysis was performed to determine factors associated with CB in platinum-resistant patients retreated with platinum. Of 48 patients identified, 37 were evaluable included in this analysis. CB was observed in 27 (73%) while disease progression was noted in 10 (27%) women. The PFI was longer in those women who achieved CB (12.3 vs 6.9 months; P = 0.02). The TFI was 7.1 months for patients benefited from platinum retreatment vs 3.5 months for those with disease progression (P = 0.06). There was no statistically significant difference in the number of cytotoxic agents between the time of platinum retreatment and the prior platinum regimen (2 vs 1.5 months; P = 0.61). A prolonged PFI was associated with an improved chance of achieving CB with platinum retreatment. There was no association between the response to platinum retreatment and the number of intervening cytotoxic agents utilized. Further prospective study is warranted to define the optimal timing of platinum retreatment.

A multi-institutional evaluation of factors predictive of toxicity and efficacy of bevacizumab for recurrent ovarian cancer.

While bevacizumab has shown activity in recurrent ovarian cancer, a higher than expected incidence of bowel perforations has been reported in recent trials. We sought to determine factors associated with toxicity and tumor response in patients with relapsed ovarian cancer treated with bevacizumab. A retrospective review of patients with recurrent ovarian cancer treated with bevacizumab was undertaken. Response was determined radiographically and through CA125 measurements. Statistical analysis to determine factors associated with toxicity and response was performed. Sixty-two eligible patients were identified. The cohort had received a median of 5 prior chemotherapy regimens. Single-agent bevacizumab was administered to 12 (19%), while 50 (81%) received the drug in combination with a cytotoxic agent. Grade 3-5 toxicities occurred in 15 (24%) patients, including grade 3-4 hypertension in 4 (7%), gastrointestinal perforations in 7%, and chylous ascites in 5%. Development of chylous ascites and gastrointestinal perforations appeared to correlate with tumor response. The overall response rate was 36% (4 complete response, 17 partial response), with stable disease in 40%. A higher objective response rate was seen in the bevacizumab combination group compared to single-agent treatment (43% vs 10%) (P = 0.07). However, 29 grade 3-5 toxic episodes were seen in the combination group vs only 1 in the single-agent bevacizumab cohort (P = 0.071). We conclude that bevacizumab demonstrates promising activity in recurrent ovarian cancer. The addition of a cytotoxic agent to bevacizumab improved response rates at the cost of increased toxicity. Gastrointestinal perforations occurred in 7%. The perforations occurred in heavily pretreated patients who were responding to therapy.

Cobalt and nickel uptake by rice and accumulation in soil amended with municipal solid waste compost.

Effect of addition of municipal solid waste compost (MSWC) on cobalt (Co) and nickel (Ni) contents of submerged rice paddies were studied. A sequential extraction method was used to determine the metal (Co and Ni) fractions in MSWC and cow dung manure (CDM). Both metals were significantly bound to the organic matter and Fe and Mn oxides in MSWC and CDM. Metal content in rice straw was higher than in rice grain. Metal bound with Fe and Mn oxides in MSWC and CDM best correlated with straw and grain metal followed by water soluble and exchangeable fractions. Carbonate, organic matter bound and residual fractions in MSWC and CDM did not significantly correlate with rice straw and grain metal. MSWC would be a valuable resource for agriculture, but long-term field experiments with MSWC are needed to assess by regular monitoring of the metal loads and accumulation in soil and plants.

Surgical management and adjuvant therapy for patients with uterine clear cell carcinoma: a multi-institutional review.

OBJECTIVE: To assess the role of surgical staging, adjuvant therapy, and cytoreduction in uterine clear cell carcinoma (UCCC). METHODS: A retrospective review was conducted at 2 major gynecologic cancer centers of all primary UCCC between 1982 and 2004. RESULTS: UCCC was confirmed in 99 patients. The 5-year overall survival (OS) was 79%, 77%, 47%, and 21% for stages I-IV respectively. 69 patients had no gross evidence of extra-uterine disease, but 36 (52%) were upstaged at surgery. For those 22 patients with stages I and II disease who had a systematic lymphadenectomy (LND) (> 20 lymph nodes), no lymphatic (LF), peritoneal (PF), or hematological (HF) failures were noted. Radiation (RT) improved PFS (67 vs. 36%, p=0.02), and reduced pelvic sidewall recurrences (18 vs. 53%, p=0.04) and vaginal failures (VF) (7 vs. 35%, p=0.04) for 45 patients at risk for LF (positive nodes or suboptimal LND). 39 patients with stages IIIC and IV disease were separately analyzed. Patients with no visible residual disease after cytoreduction had a significant improvement in median PFS (17 vs. 7 months, p<0.001), and OS (40 vs. 18 months, p=0.02) compared to patients with any residual disease after surgery. CONCLUSION: Comprehensive surgical staging with a systematic LND is essential to accurately define early stage UCCC. Vaginal brachytherapy may be adequate adjuvant therapy for stages I and II UCCC confirmed by systematic LND. Patients at risk for LF appear to benefit from pelvic RT. An effort at cytoreduction to no visible residual disease should be made in advanced UCCC when feasible.

Frequent activating FGFR2 mutations in endometrial carcinomas parallel germline mutations associated with craniosynostosis and skeletal dysplasia syndromes.

Endometrial carcinoma is the most common gynecological malignancy in the United States. Although most women present with early disease confined to the uterus, the majority of persistent or recurrent tumors are refractory to current chemotherapies. We have identified a total of 11 different FGFR2 mutations in 3/10 (30%) of endometrial cell lines and 19/187 (10%) of primary uterine tumors. Mutations were seen primarily in tumors of the endometrioid histologic subtype (18/115 cases investigated, 16%). The majority of the somatic mutations identified were identical to germline activating mutations in FGFR2 and FGFR3 that cause Apert Syndrome, Beare-Stevenson Syndrome, hypochondroplasia, achondroplasia and SADDAN syndrome. The two most common somatic mutations identified were S252W (in eight tumors) and N550K (in five samples). Four novel mutations were identified, three of which are also likely to result in receptor gain-of-function. Extensive functional analyses have already been performed on many of these mutations, demonstrating they result in receptor activation through a variety of mechanisms. The discovery of activating FGFR2 mutations in endometrial carcinoma raises the possibility of employing anti-FGFR molecularly targeted therapies in patients with advanced or recurrent endometrial carcinoma.

Salvage of isolated vaginal recurrences in women with surgical stage I endometrial cancer: a multiinstitutional experience.

The objective of this study was to evaluate the treatment outcomes and risk factors of women with surgical stage I endometrial adenocarcinoma who were initially treated with surgery alone and subsequently developed isolated vaginal recurrences. Patients with surgical stage I endometrial adenocarcinoma diagnosed from 1975 to 2002 were identified from tumor registry databases at seven institutions. All patients were treated with surgery alone including a total hysterectomy, bilateral salpingo-oophorectomy, pelvic (+/- para-aortic) lymph node dissection, and peritoneal cytology and did not receive postoperative radiation therapy. Vaginal recurrences were documented histologically. Metastatic disease in the chest and abdomen was excluded by radiologic studies. Overall survival was calculated by the Kaplan-Meier method. Sixty-nine women with surgical stage I endometrial cancer with isolated vaginal recurrences were identified. Of the 69 patients, 10 (15%) were diagnosed with stage IA disease, 43 (62%) were diagnosed with stage IB disease, and 16 (23%) were diagnosed with stage IC disease. Patients diagnosed with grade 1 disease were 22 (32%), grade 2 disease were 26 (38%), and grade 3 disease were 21 (30%). Among women, 81% with isolated vaginal recurrences were salvaged with radiation therapy. The mean time to recurrence was 24 months, and the mean follow-up was 63 months. Among women, 18% died from subsequent recurrent disease. The 5-year overall survival was 75%. The majority of isolated vaginal recurrences in women with surgical stage I endometrial cancer can be successfully salvaged with radiation therapy, further questioning the role of adjuvant therapy for patients with uterine-confined endometrial cancer at the time of initial diagnosis.

Municipal waste compost as an alternative to cattle manure for supplying potassium to lowland rice.

The importance of the use of potassium in agriculture is increasing in South Asia for making most productive use of the nutrient in terms of economic returns. Nutrient supply traditionally by cattle manure is constrained by its insufficient availability. Municipal waste compost may be an alternative source of nutrient supplements. Field experiments were conducted at the Experimental Farm of Calcutta University, West Bengal, India during the wet seasons of 1997, 1998 and 1999 on flooded lowland rice. Potassium fractions in municipal waste compost and cattle manure were determined by sequential extraction and also the potassium uptake by rice to compare the effectiveness of municipal waste compost with traditional manure. Potassium was significantly bound to the organic matter in municipal waste compost. Potassium uptake by rice grain and straw increased significantly with the combined application of organics and fertilizers and it was higher in grain than in straw. Water-soluble and non-exchangeable potassium contents of municipal waste compost and cattle manure were highly correlated with the uptake of potassium by straw and grain. Exchangeable and residual potassium were also significantly correlated with the uptake of potassium by straw and grain of rice. Much higher uptake of K in rice straw and rain resulted from applying the manures in conjunction with fertilizers than when applied singly.