The TNT protocol: A phase II study using talimogene laherparepvec (TVEC), nivolumab (N) and trabectedin (T) as first, second/third line therapy for advanced sarcoma, including desmoid tumor and chordoma.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. TPS11572-TPS11572 ◽  
Author(s):  
Sant P. Chawla ◽  
Victoria S. Chua ◽  
Katherine Kim ◽  
Paul Stendahl Dy ◽  
Micaela Kristina Paz ◽  
...  
Keyword(s):  
Survival Rate ◽  
Adverse Events ◽  
Desmoid Tumor ◽  
Locally Advanced ◽  
Categorical Variables ◽  
System Organ Class ◽  
Continuous Variables ◽  
Talimogene Laherparepvec ◽  
Combination Methods ◽  
Advanced Sarcoma

TPS11572 Background: Talimogene laherparepvec (TVEC), an oncolytic HSV expressing huGMCSF, may be synergistic with trabectedin (T) and nivolumab (N) in treating advanced sarcoma. Objectives: (1) To evaluate the best overall response by RECIST v1.1, progression-free survival rate (PFS), and overall survival rate, (2) To determine the incidence of conversion of an unresectable tumor to a resectable one, and (3) To evaluate the incidence of adverse events related to the drug combination. Methods: This is an open label phase 2 study. A total of 40 patients will receive T (1.2 mg/m2 CIV over 24 hours q3 weeks), N (240 mg IV over 30 min q 2 weeks) and TVEC (intratumorally q 2 weeks according to tumor size). Eligible patients are those with histopathologically confirmed diagnosis of locally advanced, unresectable or metastatic sarcoma including desmoid tumor and chordoma, previously untreated or treated, with measurable disease by RECIST v1.1, and at least, one accessible tumor for intratumoral injection of TVEC. Currently, 31 of the 40 patients have been enrolled. Statistical Considerations: Continuous variables will be summarized by the sample size (n), mean, standard deviation, first and third quartiles, minimum and maximum. Categorical variables will be summarized by the n and percent in each category. Point estimates for efficacy endpoint incidences will be accompanied by a 2-sided 95% exact binomial CI. Time to event endpoints will be summarized descriptively using the KM method. Safety (incidence and severity of adverse events and significant laboratory abnormalities) will be performed on all patients (ITT population). Patient incidence of all treatment emergent AEs will be tabulated by system organ class and preferred term. Clinical trial information: 03886311 .

Predictors of immune-related adverse events associated with checkpoint inhibitors.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e15159-e15159
Author(s):  
Alhareth Alsayed ◽  
Ashish Manne ◽  
Daisy E Escobar ◽  
Gaurav Sharma ◽  
Pranitha Prodduturvar ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Adverse Events ◽  
Lymphocyte Count ◽  
Checkpoint Inhibitors ◽  
Hematological Parameters ◽  
White Blood Count ◽  
Categorical Variables ◽  
Fisher Exact Test ◽  
Continuous Variables ◽  
Grade 3

e15159 Background: Immune-related adverse events (irAE) remain a significant challenge with the expansion of checkpoint inhibitors (ICI) indications. Unlike previous studies published, we investigated risk factors for irAE development, including lymphocytes and neutrophils counts in lung cancer and melanoma treated with all available ICIs in current clinical practice. Methods: This is a retrospective study conducted at the University of South Alabama Mitchell Cancer Institute. Between 2015-2019. A total of 160 patients with a diagnosis of melanoma (N = 54) or lung cancer (N = 106) who received at least two doses of ICI including ipilimumab (15%), nivolumab (32%), pembrolizumab (35%), dual nivolumab/ipilimumab (5%), durvalumab (9%) and atezolizumab (4%). The patient's baseline characteristics were extracted with irAE (grade 3/4) details and survival outcomes. Descriptive statistics were used, Fisher exact test to compare categorical variables, and Wilcoxon rank sum test for continuous variables using JMP software. Results: The median age at diagnosis was 64 years (range 17-93), with 51% females. Race distribution with 76% Caucasians and 26% African Americans. Around 30% of the cohort was treated for recurrence, and 39% did receive prior systemic chemotherapy. Median overall survival (OS) was 13.5 months (m) for melanoma and 16 m for lung cancer with CI 95% [16-24] and [15-23], respectively. Twenty-nine (29%) percent of the cohort (N = 46) had grade 3/4 irAEs. Median of baseline hematological parameters including total white blood count (WBC), absolute neutrophil count (ANC), absolute lymphocyte count (ALC), ANC to ALC ratio, and platelet to ALC ratio of these patients were not statistically different from the cohort without grade 3/4 irAEs. Interestingly, if a patient has baseline ALC < 1K/μL, the risk of irAE recurrence is low when ICI is re-initiated, p = .0143 (after symptomatic recovery from irAEs). Conclusions: Irrespective of ICI used, baseline lymphocyte count, and its relation to other blood counts have no clear impact on irAE. Larger cohorts or prospective studies are needed to make stronger conclusions about the relationship between the immune system and the occurrence of irAEs

scholarly journals Influence of Indications on Perinatal Outcomes After Radio frequency Ablation in Complicated Monochorionic Pregnancies: A Retrospective Cohort Study

2020 ◽  
Author(s):  
Hongmei Wang ◽  
Qian Zhou ◽  
Xietong Wang ◽  
Jia Song ◽  
Pengzheng Chen ◽  
...  
Keyword(s):  
Cohort Study ◽  
Survival Rate ◽  
Retrospective Cohort Study ◽  
Retrospective Cohort ◽  
Abdominal Wall Defect ◽  
Perinatal Outcomes ◽  
Neurological Injury ◽  
Categorical Variables ◽  
Continuous Variables ◽  
Arterial Perfusion

Abstract Background:Radiofrequency ablation (RFA) is recommended to prevent potential neurological injury or intrauterine foetal death (IUFD) of the co-twin(s) in complicated monochorionic (MC) pregnancies. However, the impacts of various indications on the pregnancy outcome following RFA remain unclear. This study aimed to determine how the indications influence the perinatal outcomes in complicated MC pregnancies undergoing radiofrequency ablation.Methods:This was a retrospective cohort study performed in a single centre. All consecutive MC pregnancies treated with RFA between July 2011 and July 2019 were included. The adverse perinatal outcomes and the survival rate were analysed based on various indications. The continuous variables with and without normal distribution were compared between the groups using Student’s t-test and Mann–Whitney U test, respectively, and for categorical variables, Chi-square and Fisher’s exact tests were used. P < 0.05 indicated a significant difference.Results:We performed 272 RFA procedures in 268 complicated MC pregnancies, including 60 selective intrauterine growth restriction (sIUGR), 64 twin–twin transfusion syndrome (TTTS), 12 twin reversed arterial perfusion sequence (TRAPs), 66 foetal anomaly and 66 elective foetal reduction (EFR) cases. The overall survival rate of the co-twin was 201/272 (73.9%). The overall technical successful rate was determined at 201/263 (76.7%). The IUFD rate in the co-twin was 20/272 (7.4%). The TTTS group had recorded the lowest survival rate (37/64, 57. 8%), and the survival rate significantly correlated with Quintero stages (P = 0.029). Moreover, the sIUGR III subgroup had a lower survival rate compared with sIUGR II (55.6%, versus 84.3%). The subgroup of foetal anomaly of gastroschisis or exomphalos had the highest IUFD rate (4/10, 40%), followed by sIUGR III (2/9, 22.2%) and dichorionic triamniotic (DCTA) subgroup (8/46, 17.9%). In EFR group, eight IUFD cases were all coming from the DCTA subgroup and received RFA before 17 weeks.Conclusions:The perinatal outcome of RFA was correlated with the indications, with the lowest survival rate in TTTS IV and the highest IUFD incidence in abdominal wall defect followed by sIUGR III. Elective RFA after 17 weeks may prevent IUFD in DCTA pregnancies.

Immune related adverse events and their treatment in melanoma patients receiving ipilimumab.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e14598-e14598 ◽  
Author(s):  
Gerardo Cabanillas
Keyword(s):  
Clinical Practice ◽  
Adverse Events ◽  
Immune Checkpoint Inhibitor ◽  
Insurance Coverage ◽  
Female Gender ◽  
Gastrointestinal Diseases ◽  
Categorical Variables ◽  
Continuous Variables ◽  
Regular Care ◽  
Melanoma Patients

e14598 Background: Ipilimumab is an immune checkpoint inhibitor approved for the treatment of melanoma. Immune-related adverse events (irAEs) may occur as adverse effects. Most reports on irAEs are from clinical trials, which may not reflect community clinical practice and outcomes. We used a health insurance based database to identify irAEs and their treatment among patients with melanoma that received Ipilimumab, as part of regular care. Methods: We identified all melanoma patients aged 18 and older who received Ipilimumab from the Truven Health Analytics Marketscan database between 2011 and 2014. Patients had continuous insurance coverage from the period of six months prior to Ipilimumab and three months after. We further assessed the treatment for each irAEs. IrAEs were defined base on claims with one or more 228 ICD-9 codes; irAEs had to occur within a 6-month window before treatment. We used summary statistics such as means and standard deviations for continuous variables, frequencies and percentages for categorical variables. Results: The cohort included 1225 patients. Median age was 60 years, 62% were male; 343 (35.44%) patients had one or more irAEs, and 48.6% (211) were treated at least once. Young age and female gender were associated with a higher likelihood of having an irAEs. Endocrinopathies and gastrointestinal diseases were the most common irAEs. The most frequent irAEs was colitis in 27% of patients, followed by hypothyroidism 26%. Six different drugs were used to treat irAEs, and corticosteroids being the most frequently prescribed. Few patients with colitis received Infliximab 14%; and cyclosporine was prescribed in one patient with pancreatitis Conclusions: One third of the patients with melanoma treated with Ipilimumab in the community developed irAEs. Corticosteroids were the most frequent drugs used to treat irAEs. Our results show that toxicity remains high with the use of this agent in clinical practice.

The association between immune-related adverse events and efficacy outcomes with consolidation pembrolizumab after chemoradiation in patients with stage III NSCLC: an analysis from HCRN LUN 14-179.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 9032-9032
Author(s):  
Nikhil Shukla ◽  
Sandra K. Althouse ◽  
Ahad Ali Sadiq ◽  
Shadia Ibrahim Jalal ◽  
Salma K. Jabbour ◽  
...  
Keyword(s):  
Adverse Events ◽  
Stage Iv ◽  
Wilcoxon Test ◽  
Stage Iii ◽  
Categorical Variables ◽  
Rank Test ◽  
Continuous Variables ◽  
Current Standard ◽  
Group A ◽  
Stage Iii Nsclc

9032 Background: Consolidation checkpoint inhibitor therapy (CPI) for up to 1 year following chemoradiation (CRT) is a current standard of care for pts with inoperable stage III NSCLC. However, some pts are not able to complete 1 year of CPI due to immune-related adverse events (irAES). In multiple retrospective studies, pts with stage IV NSCLC treated with CPI who experience irAEs generally receive fewer cycles of CPI without a significant detrimental effect on efficacy. The association between irAEs and outcomes with consolidation CPI after CRT has never been reported. Here we report the association between irAEs and efficacy outcomes from the HCRN LUN 14-179, a single-arm phase II trial of consolidation pembrolizumab following concurrent CRT in pts with unresectable stage III NSCLC. Methods: After completion of CRT eligible pts with stage III NSCLC without PD received pembrolizumab 200 mg IV q 3 wks for up to 1 yr. Demographics, disease characteristics, and number of cycles of pembrolizumab received were reported in pts who had any grade irAEs (except pneumonitis which included grade >2 only) [Group A] and those without irAEs (except grade 1 pneumonitis) [Group B]. Chi-square test (or Fisher's Exact test) were used for comparisons for categorical variables and Wilcoxon test for continuous variables. The Kaplan-Meier method was used to analyze time to metastatic disease (TMDD), PFS, and OS. A log-rank test was used to compare groups. Results: 92 eligible pts for efficacy analysis were enrolled from March 2015 to November 2016. 4 yr OS estimate for all pts is 46.2%. Any grade irAEs (except grade I pneumonitis) (n = 37 pts) included pneumonitis (18.5%), colitis (3.3%), increased creatinine (5.4%), elevated transaminases (3.3%), hyperthyroidism (7.6%), hypothyroidism (13.0%). Grade ≥ 2 irAEs (n = 32 pts) included pneumonitis (18.5%), hypothyroidism (10.8%), and colitis (3.3%). Group A/B: male (21/38), female (16/17), current or former smoker (35/52), stage IIIA (20/35), stage IIIB (17/20), non-squamous (21/30), squamous (16/25). Median number of pembrolizumab cycles received in Group A/B pts were 9 vs 15 (p = 0.0942) respectively. 4 yr efficacy endpoints in Groups A/B were TMDD 35.3% vs 41.3% (p = 0.83), PFS 27.8% vs 28.7% (p = 0.97), OS 43.5% vs 47.9% (p = 0.99), respectively. Conclusions: Despite receiving fewer cycles of consolidation pembrolizumab, pts who experienced any grade irAEs (excluding grade 1 pneumonitis) did not have significantly reduced efficacy outcomes. Clinical trial information: NCT02343952.

scholarly journals Safety and efficacy evaluation of low-dose trimethoprim-sulfamethoxazole for prophylaxis of Pneumocystis pneumonia in HIV uninfected patients undergoing hemodialysis: a retrospective observational study

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Kanae Yamashita ◽  
Yoshimitsu Shimomura ◽  
Hiroaki Ikesue ◽  
Nobuyuki Muroi ◽  
Akihiro Yoshimoto ◽  
...  
Keyword(s):  
Adverse Events ◽  
Health Care Professionals ◽  
Cumulative Incidence ◽  
Dose Group ◽  
Low Dose ◽  
Standard Dose ◽  
Pneumocystis Pneumonia ◽  
Categorical Variables ◽  
Discontinuation Rate ◽  
Continuous Variables

Abstract Background Pneumocystis pneumonia (PCP) is a potentially life-threatening infection. Trimethoprim-sulfamethoxazole (TMP-SMX) is considered as the first regimen for PCP prophylaxis according to several guidelines. The recommended prophylactic dose of TMP-SMX has been determined based on patients with normal renal function, but the appropriate dosage for patients undergoing hemodialysis is unknown. The aim of this study was to investigate the efficacy and safety of low-dose TMP-SMX in patients undergoing hemodialysis. Methods HIV-uninfected adult patients who were undergoing hemodialysis and administered TMP-SMX for PCP prophylaxis, were included, and divided into standard-dose (≥6 single strength (SS, TMP-SMX 80 mg/400 mg tablets/week) and low-dose groups (< 6 SS tablets/week). The endpoints were cumulative incidence of PCP and cumulative discontinuation rate of TMP-SMX due to adverse events. For comparison of the groups, we employed the chi-squared test for categorical variables and the Mann-Whitney U test for continuous variables. Risk factors for the endpoints were evaluated using the Cox Fine and Gray method. Results The median age of the 81 patients included in the study was 67 years (IQR: 60–76 years), and 52 patients (64.2%) were men. No patients in either group developed PCP during the observation period. The yearly cumulative incidence of discontinuation was 12.1% (95% confidence interval [CI]: 0.027–0.29) in the low-dose group and 35.6% (95% CI: 0.20–0.52) in the standard-dose group (P = 0.019). The adjusted hazard ratio of the low-dose group compared to standard-dose group was 0.18 (95% CI: 0.04–0.86, P = 0.032). Conclusions None of the study patients developed PCP, and the cumulative discontinuation rate of TMP-SMX due to adverse events was significantly lower in the low-dose group compared to that in the standard-dose group (P = 0.032). These results indicate that low-dose TMP-SMX is an appropriate regimen to maintain a balance between PCP prophylaxis and prevention of adverse events due to TMP-SMX administration. These findings can guide health care professionals to determine TMP-SMX dosage when considering PCP prophylaxis for patients undergoing hemodialysis.

A phase 2 study of talimogene laherparepvec, nivolumab, and trabectedin (TNT) in advanced sarcoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 11567-11567
Author(s):  
Neal Shiv Chawla ◽  
Ted Kim ◽  
Travis Sherman ◽  
Jonathan Dang ◽  
Victoria S. Chua ◽  
...  
Keyword(s):  
Immune Response ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Intratumoral Injection ◽  
Spindle Cell Sarcoma ◽  
Talimogene Laherparepvec ◽  
Overall Response ◽  
Intention To Treat ◽  
Grade 3 ◽  
Advanced Sarcoma

11567 Background: Combination trabectidin (T) and nivolumab (N) has been shown to be a safe and effective therapy in soft tissue sarcoma (STS). Intratumoral injection of talimogene laherparepvec (TVEC) has a local oncolytic effect, and increases immune response via enhanced recruitment of antigen presenting cells, and thereby cytotoxic immune response. This study aims to determine if the addition of TVEC to combination trabectedin and nivolumab is effective and safe in advanced sarcoma. Methods: Eligible patients include patients ≥ 18 years of age with locally advanced unresectable or metastatic STS, measurable disease by RECIST v1.1, and at least one accessible tumor for TVEC intratumoral injection. N (3 mg/kg i.v. q 2 weeks), T (1.2 mg/m2 i.v. q 3 weeks) and TVEC (1x10e8 PFU/ml q 2 weeks depending on tumor size) were administered. A test dose of TVEC (1x10e6 PFU/ml) was initially given, followed three weeks later by full dose TVEC. Primary endpoint: Progression-free survival (PFS); Secondary endpoints: (1) Best overall response during treatment period, (2) PFS rate at 6 and 9 months, (3) Overall survival (OS) rate at 6, 9, and 12 months, (4) Incidence of conversion from unresectable to resectable tumor, and (5) Incidence of treatment-related adverse events. Interim. Results: There were 36 evaluable subjects under the Modified Intention-to-Treat (MITT) population, having completed the first cycle of TNT and a CT or MRI scan at the 6-week follow-up period. The most common histological subtypes include leiomyosarcoma (9), liposarcoma (5), spindle cell sarcoma (3), pleomorphic sarcoma (2), Ewing’s sarcoma (2), and other (5). Median number of prior lines of therapy was 4 (range 1-8). Best Overall Response by RECIST v1.1 = 3 PR, 27 SD, 5 PD. One patient, with previously unresectable disease was taken for resection and was found to have 100% necrosis on surgical pathology. Disease control rate (CR+PR+SD) was 86.1%. The median PFS was 5.5 (range: 1-18) months; 6-month PFS rate: 62.1%. Median PFS on therapy immediately preceding this trial was 2.0 months (range = 1-14 months). There were 47 evaluable subjects for OS analysis under the Intention-to-Treat (ITT) population having received at least one dose of T and N. The median OS was 9.0 (range 0-20) months; 6-month OS rate: 73%. Safety analysis: There were 47 evaluable subjects under the ITT population. 28% of these patients experienced ³1 SAE. The most common grade 3/4 TRAEs include anemia (12), increased ALT (8), fatigue (4), thrombocytopenia (4), neutropenia (4). There were no grade 3/4 TVEC injection site reactions. 22% of patients in the MITT cohort remain on study. Conclusions: These results suggest that combination therapy with TNT appears to be as effective as standard therapy, with no new safety signals seen. Furthermore, median PFS exceeded that of the immediately preceding lines of therapy in this heavily pre-treated cohort. As data matures, further data will be reported. Clinical trial information: NCT03886311.

scholarly journals Effectiveness and tolerability of nimotuzumab in unresectable, locally advanced/metastatic esophageal cancer: Indian hospital-based retrospective evidence

2019 ◽  
Vol 08 (02) ◽  
pp. 112-115
Author(s):  
Sundaram Subramanian ◽  
Nithya Sridharan ◽  
V. Balasundaram ◽  
Sameer Chaudhari
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Cancer ◽  
Survival Rate ◽  
Adverse Events ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Tumor Response ◽  
Response Rate ◽  
Locally Advanced ◽  
Tumor Response Rate

Abstract Context: Epidermal growth factor receptor (EGFR) is overly expressed in esophageal squamous cell carcinoma (ESCC) and is important prognostic and predictive biomarker. Nimotuzumab is a humanized anti-EGFR monoclonal antibody and has documented promising clinical outcomes and survival rates in various solid tumors with high EGFR expression. Aims: Attempt to fill gap on paucity of data in India on the efficacy of Nimotuzumab in the treatment of locally advanced/metastatic ESCC. Settings and Design: Hospital records of 15 patients with unresectable, locally advanced/metastatic esophageal cancers, histologically confirmed squamous cell carcinoma being treated with Nimotuzumab along with standard treatments from October 2006 to November 2016 were retrospectively analyzed. Subjects and Methods: The tumor response rate and overall survival (OS) were analyzed. All patients were assessed for toxicity and adverse events (AEs) as per Common Terminology Criteria for Adverse Events (CTCAE) v4. Results: Majority had lower thoracic esophageal cancer. Tumor response rate observed was as follows 33% had a complete response, 67% had a partial response, and objective response rate was 100%. Survival rate at 1-, 3-, and 5-year was 58.33%, 29.17%, and 29.17%, respectively. Median OS was 26.8 months (95% confidence interval, 2.63–not reached). No Grade III or Grade IV AEs were observed. No added toxicity was observed due to nimotuzumab.Conclusions: Nimotuzumab combined with standard treatment in locally advanced/metastatic ESCC improved the survival rate and achieved a better tumor response rate without accumulation of toxicity and was well tolerated.

scholarly journals Influence of Indications on Perinatal Outcomes After Radio frequency Ablation in Complicated Monochorionic Pregnancies: A Retrospective Cohort Study

2020 ◽  
Author(s):  
Hongmei Wang ◽  
Qian Zhou ◽  
Xietong Wang ◽  
Jia Song ◽  
Pengzheng Chen ◽  
...  
Keyword(s):  
Cohort Study ◽  
Survival Rate ◽  
Retrospective Cohort Study ◽  
Retrospective Cohort ◽  
Abdominal Wall Defect ◽  
Perinatal Outcomes ◽  
Neurological Injury ◽  
Categorical Variables ◽  
Continuous Variables ◽  
Arterial Perfusion

Abstract Background:Radiofrequency ablation (RFA) is recommended to prevent potential neurological injury or intrauterine foetal death (IUFD) of the co-twin(s) in complicated monochorionic (MC) pregnancies. However, the impacts of various indications on the pregnancy outcome following RFA remain unclear. This study aimed to determine how the indications influence the perinatal outcomes in complicated MC pregnancies undergoing radiofrequency ablation.Methods:This was a retrospective cohort study performed in a single centre. All consecutive MC pregnancies treated with RFA between July 2011 and July 2019 were included. The adverse perinatal outcomes and the survival rate were analysed based on various indications. The continuous variables with and without normal distribution were compared between the groups using Student’s t-test and Mann–Whitney U test, respectively, and for categorical variables, Chi-square and Fisher’s exact tests were used. P < 0.05 indicated a significant difference.Results:We performed 272 RFA procedures in 268 complicated MC pregnancies, including 60 selective intrauterine growth restriction (sIUGR), 64 twin–twin transfusion syndrome (TTTS), 12 twin reversed arterial perfusion sequence (TRAPs), 66 foetal anomaly and 66 elective foetal reduction (EFR) cases. The overall survival rate of the co-twin was 201/272 (73.9%). The overall technical successful rate was determined at 201/263 (76.7%). The IUFD rate in the co-twin was 20/272 (7.4%). The TTTS group had recorded the lowest survival rate (37/64, 57. 8%), and the survival rate significantly correlated with Quintero stages (P = 0.029). Moreover, the sIUGR III subgroup had a lower survival rate compared with sIUGR II (55.6%, versus 84.3%). The subgroup of foetal anomaly of gastroschisis or exomphalos had the highest IUFD rate (4/10, 40%), followed by sIUGR III (2/9, 22.2%) and dichorionic triamniotic (DCTA) subgroup (8/46, 17.9%). In EFR group, eight IUFD cases were all coming from the DCTA subgroup and received RFA before 17 weeks.Conclusions:The perinatal outcome of RFA was correlated with the indications, with the lowest survival rate in TTTS IV and the highest IUFD incidence in abdominal wall defect followed by sIUGR III. Elective RFA after 17 weeks may prevent IUFD in DCTA pregnancies.

scholarly journals Laparoscopic Approach in Surgical Staging of Endometrial Cancer

2019 ◽  
Vol 41 (05) ◽  
pp. 306-311
Author(s):  
Mariana Mouraz ◽  
Cátia Sofia Ferreira ◽  
Sónia Gonçalves ◽  
Nuno Nogueira Martins ◽  
Francisco Nogueira Martins
Keyword(s):  
Endometrial Cancer ◽  
Adverse Events ◽  
Intraoperative Complications ◽  
Laparoscopic Approach ◽  
Hospital Length ◽  
Hospital Length Of Stay ◽  
Surgical Staging ◽  
Categorical Variables ◽  
Complication Rates ◽  
Continuous Variables

Objective To compare laparoscopy with laparotomy for surgical staging of endometrial cancer. Methods A cohort of women with preoperative diagnosis of endometrial cancer who underwent surgical staging was retrospectively evaluated. The main study end points were: morbidity and mortality, hospital length of stay, perioperative adverse events and recurrence rate. Data analysis was performed with the software SPSS v25 (IBM Corp., Armonk, NY, USA), categorical variables using a Chi-square and Fisher test, and continuous variables using the Student t-test. Results A total of 162 patients were analyzed. One-hundred and thirty eight patients met the inclusion criteria, 41 of whom underwent staging by laparoscopy and 97 by laparotomy. Conversions from laparoscopy to laparotomy happened in 2 patients (4.9%) and were secondary to technical difficulties and poor exposure. Laparoscopy had fewer postoperative adverse events when compared with laparotomy (7.3% vs 23.7%, respectively; p = 0.005), but similar rates of intraoperative complications, despite having a significantly longer operative time (median, 175 vs 130 minutes, respectively; p < 0.001). Hospital stay was significantly lower in laparoscopy versus laparotomy patients (median, 3 vs 7 days, respectively; p < 0.001). No difference in recurrence or mortality rates were observed. Conclusion Laparoscopic surgical staging for endometrial cancer is feasible and safe. Patients have lower postoperative complication rates and shorter hospital stays when compared with the approach by laparotomy.

N0321: A phase II study of bortezomib, paclitaxel, carboplatin (CBCDA), and radiotherapy (RT) for locally advanced non-small cell lung cancer (NSCLC).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 7073-7073
Author(s):  
Steven E. Schild ◽  
Nathan R. Foster ◽  
Julian R. Molina ◽  
Grace K. Dy ◽  
Kendrith M. Rowland ◽  
...  
Keyword(s):  
Survival Rate ◽  
Adverse Events ◽  
Phase I ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Locally Advanced ◽  
Hematologic Toxicity ◽  
Tumor Killing ◽  
Grade 3 ◽  
Ecog Ps

7073 Background: In preclinical studies, combinations of bortezomib and RT result in synergistic tumor killing (Cancer Chemother Pharmacol. 2007;59:207-15). Our group reported the results from the phase I portion of this study previously (J Clin Oncol. 200;28 (suppl; abstr 7085)). Based on these data, we undertook a phase II study of bortezomib in combination with paclitaxel/CBCDA and RT. Methods: Based on results from our previously reported phase I trial, systemic therapy included bortezomib (1.2 mg/m² IV days 1,4,8,11), paclitaxel (175 mg/m² IV day 2), and carboplatin (CBCDA; AUC=6 day 2) given every 3 weeks for 2 cycles. Thoracic radiotherapy (RT) included 60Gy/30 daily fractions starting day 1. The primary endpoint was the 12-month survival rate. If 41 or more of these 60 patients (68%) were alive at least 12 months after study entry, the trial would be deemed as positive and further study would be warranted. Results: 27 pts were enrolled to the phase II portion: M/F=17/10; stage IIIA/IIIB=13/14; ECOG PS 0/1=9/18; and median age: 58 (range 43-79). 18 pts (67%) completed therapy per protocol. At a planned interim analysis, 23 of 26 evaluable patients (88.5%, 95% CI: 70-98%) survived for at least 6 months, which exceeded the boundary of 21 or more needed to continue to full accrual. This trial could have continued per protocol, but was closed early due to slow accrual. With a median follow-up of 15.0 months in the 17 patients still alive, the 12-month survival rate was 71% (95% CI: 49 – 85). The median OS was 19 months (95% CI: 11 – no upper). Grade 3 or higher adverse events (regardless of attribution) were reported in 22 (82%) patients. Grade 4/5 adverse events were reported in 15 (56%) patients. There was one grade 5 event (pneumonitis). The most common (5 or more patients) grade 3/4 adverse events were fatigue (22%), leukopenia (63%), neutropenia (67%), and thrombocytopenia (44%). Conclusions: The addition of bortezomib resulted in high levels of severe hematologic toxicity, but also demonstrated evidence of activity with a 12-month survival rate of 71% and a median OS of 19 months. Further testing of this regimen in a larger study appears warranted.

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