Examining gemcitabine and docetaxel for recurrent NMIBC.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 322-322
Author(s):  
Niv Milbar ◽  
Max Kates ◽  
Meera Chappidi ◽  
Mark Schoenberg ◽  
Trinity J. Bivalacqua

322 Background: BCG relapsing/unresponsive patients who are poor surgical candidates or prefer bladder preservation vs. radical cystectomy (RC) may be offered intravesical therapies. Often in the literature, a “recurrence” after these therapies includes low-grade (LG) lesions, though stage progression and RC may be more meaningful outcomes for therapeutic efficacy. Including LG endpoints may make 2nd line therapies appear less efficacious. 2nd line intravesical Gemcitabine (GEM) with Docetaxel (DOCE) has been offered at Johns Hopkins Hospital (JHH). Our objective was to evaluate JHH experience with GEM/DOCE, and to address whether LG vs high-grade (HG) recurrence endpoints influenced outcomes. Methods: 33 patients who received full induction courses of GEM/DOCE since 2011, per the protocol adapted from Michael O’Donnell at U. Iowa, were identified in the IRB-approved JHH NMIBC database. Multivariable logistic regression determined factors associated with recurrence. Cox proportional hazard models evaluated risk factors for all-grade recurrence-free survival (AG-RFS) and HG recurrence-free survival (HG-RFS). Results: Median AG-RFS was 7.6 months with 42% 1-year and 27% 2-year AG-RFS. Median HG-RFS was 17.5 months with 57% 1-year and 44% 2-year HG-RFS. No adverse effects of GEM/DOCE were observed. There were 5 LG recurrences, 11 HG recurrences, and 3 progressions. Of these, 7 patients had RCs. Within initial LGTa presentation, 80% (4/5) had LG and 20% (1/5) had HG recurrence. Within initial HG-NMIBC presentation, 46% (13/28) had HG recurrence. Only in univariable cox models, LGTa presentation showed increased risk of AG-RFS (HR 3.18, 95% CI 1.08-9.40, p=0.036), but comparable HG-RFS (HR 0.32, 95% CI 0.04-2.47, p=0.275). Conclusions: GEM/DOCE is a well-tolerated alternative to immediate RC for highly selected patients with HG-NMIBC. As anticipated, including LG recurrence as an endpoint for RFS made GEM/DOCE appear less efficacious. However, since standard of care for LG recurrence is further intravesical therapy, this endpoint may not be appropriate, as its recurrence often does not result in RC or worse cancer outcomes. Future studies of 2nd line therapies for NMIBC should identify HG endpoints based on clinically meaningful outcomes.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 4546-4546 ◽  
Author(s):  
Niv Milbar ◽  
Max Kates ◽  
Meera R. Chappidi ◽  
Mark P. Schoenberg ◽  
Trinity Bivalacqua

4546 Background: Bacillus Calmette-Guerin (BCG) unresponsive patients with Non-Muscle Invasive Bladder Cancer (NMIBC) who prefer bladder preservation over Radical Cystectomy (RC) or are poor surgical candidates may be offered intravesical therapies. 2nd line intravesical Gemcitabine (GEM) combined with Docetaxel (DOCE) has been offered at Johns Hopkins Hospital (JHH). Our objective was to evaluate JHH experience with GEM/DOCE, and specifically to address appropriate endpoints for 2nd-line therapies in NMIBC. Methods: 33 patients who received full induction courses of GEM/DOCE since 2011, per the protocol adapted from Michael O’Donnell at U. Iowa, were identified in the IRB-approved JHH NMIBC database. Multivariable logistic regression determined factors associated with LG and HG recurrence. Cox proportional hazard models evaluated risk factors for disease free survival (DFS) and HG recurrence-free survival (HG-RFS). Results: Median DFS was 6.5 months with 42% 1-year and 24% 2-year DFS. Median HG-RFS was 17.1 months with 56% 1-year and 42% 2- year HG-RFS. Median HG-RFS among patients who initiated GEM/DOCE with HG pathology was 15.7 months, with 51% 1-year HG-RFS and 34% 2-year HG-RFS. Within initial HG-NMIBC presentation, 46% (13/28) had HG recurrence. 80% (4/5) of patients with initial LgTa had LG recurrence and 20% (1/5) had HG recurrence. There were no significant predictors for HG-RFS or DFS. There were 5 LG recurrences, and 16 HG recurrences, with 6 progressions among these. 7 patients underwent RC at a median of 14.9 months. Conclusions: GEM/DOCE is a well-tolerated alternative to immediate RC for highly selected patients with HG-NMIBC. As anticipated, including LG recurrence as an endpoint made GEM/DOCE appear less efficacious. However, since standard of care for LG recurrence is further intravesical therapy and recurrence does not result in worse cancer outcomes, it may not be an appropriate endpoint. Future studies of 2nd line therapies for NMIBC should identify endpoints based on clinically meaningful outcomes of interest.


2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Byung Jun Kim ◽  
Hyeonwoo Kim ◽  
Ung Sik Jin ◽  
Kyung Won Minn ◽  
Hak Chang

Background. Dermatofibrosarcoma protuberans (DFSP), a rare low-grade sarcoma of fibroblast origin, tends to extend in a finger-like fashion beyond macroscopic tumor margins. Therefore, incomplete removal and subsequent recurrence are common. This study aimed to determine the efficacy of wide local excision (WLE) for controlling local recurrence of DFSP.Methods. The medical records of 90 DFSP patients who received WLE at our hospital between June 1992 and January 2015 were retrospectively reviewed. WLE was conducted including a 3 cm (range, 1 to 5 cm) safety margin according to tumor size, location, and recurrence status. Clinical and tumor characteristics and surgical methods were evaluated for risk factor analysis and local recurrence-free survival.Results. DFSP occurred most often in patients in their 30s (30%) and on the trunk (51.1%). Five patients (5.5%) experienced local recurrence during the 43.4-month follow-up period. Recurrence was found at a mean of 10.8 months after WLE. Although no factors were significantly associated with recurrence, recurrences were more frequent in head and neck. Recurrence-free survival was 87% in 6 years and 77% in 7 years.Conclusions. WLE with adequate lateral and deep margins can effectively control local recurrence rate and is a simple and effective method to treat DFSP.


2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 294-294
Author(s):  
Andrew J. Lightfoot ◽  
Benjamin N. Breyer ◽  
Henry M. Rosevear ◽  
Badrinath Konety ◽  
Michael A. O'Donnell

294 Background: Combination chemotherapy is the standard of care for neoadjuvant, adjuvant, and metastatic bladder cancer due to increased efficacy when compared to monotherapy. We report our experience with sequential intravesical combination chemotherapy using gemcitabine and mitomycin C (MMC) for non-muscle invasive bladder cancer (NMIBC). Methods: We performed a multi-institutional retrospective review of 47 consecutive patients who received 6 weekly treatments with sequential gemcitabine (1g) and mitomycin C (40mg) chemotherapy for NMIBC. Thirty patients received treatment at University of Iowa, 14 at UCSF and 3 at University of Minnesota. Results: A total 47 patients (median age 70, range 32-85; 36 males, 11 females) previously failing a median of 2 intravesical treatments were reviewed. The complete response (CR), 1-year recurrence-free survival (1-RFS) and 2-year recurrence-free survival (2-RFS) for all patients was 68%, 48% and 38%, respectively. In all, 14 of 47 patients (30%) remain free of recurrence with a median time to followup of 26 months (range 6-80 months). The median time to recurrence for all patients who recurred was 4 months (range 1-33 months). Ten patients required cystectomy. Conclusions: Sequential intravesical combination chemotherapy using gemcitabine and MMC appears to be a useful treatment for patients with a history of NMIC which has failed BCG or other intravesical therapy, in addition to patients with intermediate and high-risk disease.


2021 ◽  
pp. ijgc-2021-003112
Author(s):  
Brenna E Swift ◽  
Allan Covens ◽  
Victoria Mintsopoulos ◽  
Carlos Parra-Herran ◽  
Marcus Q Bernardini ◽  
...  

ObjectivesTo assess the effect of complete surgical staging and adjuvant chemotherapy on survival in stage I, low grade endometrioid ovarian cancer.MethodsThis retrospective study was conducted at two cancer centers from July 2001 to December 2019. Inclusion criteria were all stage I, grade 1 and 2 endometrioid ovarian cancer patients. Patients with mixed histology, concurrent endometrial cancer, neoadjuvant chemotherapy, and patients who did not undergo follow-up at our centers were excluded. Clinical, pathologic, recurrence, and follow-up data were collected. Cox proportional hazard model evaluated predictive factors. Recurrence-free survival and overall survival were calculated using the Kaplan-Meier method.ResultsThere were 131 eligible stage I patients: 83 patients (63.4%) were stage IA, 5 (3.8%) were stage IB, and 43 (32.8%) were stage IC, with 80 patients (61.1%) having grade 1 and 51 (38.9%) patients having grade 2 disease. Complete lymphadenectomy was performed in 34 patients (26.0%), whereas 97 patients (74.0%) had either partial (n=22, 16.8%) or no (n=75, 57.2%) lymphadenectomy. Thirty patients (22.9%) received adjuvant chemotherapy. Median follow-up was 51.5 (95% CI 44.3 to 57.2) months. Five-year recurrence-free survival was 88.0% (95% CI 81.6% to 94.9%) and 5 year overall survival was 95.1% (95% CI 90.5% to 99.9%). In a multivariable analysis, only grade 2 histology had a significantly higher recurrence rate (HR 3.42, 95% CI 1.03 to 11.38; p=0.04). There was no difference in recurrence-free survival (p=0.57) and overall survival (p=0.30) in patients with complete lymphadenectomy. In stage IA/IB, grade 2 there was no benefit of adjuvant chemotherapy (p=0.19), and in stage IA/IB, low grade without complete surgical staging there was no benefit of adjuvant chemotherapy (p=0.16). Twelve patients (9.2%) had recurrence; 3 (25%) were salvageable at recurrence and are alive with no disease.ConclusionsPatients with stage I, low grade endometrioid ovarian cancer have a favorable prognosis, and adjuvant chemotherapy and staging lymphadenectomy did not improve survival.


Stroke ◽  
2020 ◽  
Vol 51 (8) ◽  
pp. 2435-2444 ◽  
Author(s):  
Clare Flach ◽  
Walter Muruet ◽  
Charles D.A. Wolfe ◽  
Ajay Bhalla ◽  
Abdel Douiri

Background and Purpose: With recent advances in secondary prevention management, stroke recurrence rates may have changed substantially. We aim to estimate risks and trends of stroke recurrence over the past 2 decades in a population-based cohort of patients with stroke. Methods: Patients with a first-ever stroke between 1995 and 2018 in South London, United Kingdom (n=6052) were collected and analyzed. Rates of recurrent stroke with 95% CIs were stratified by 5-year period of index stroke and etiologic TOAST (Trial of ORG 10172 in Acute Stroke Treatment) subtype. Cumulative incidences were estimated and multivariate Cox models applied to examine associations of recurrence and recurrence-free survival. Results: The rate of stroke recurrence at 5 years reduced from 18% (95% CI, 15%–21%) in those who had their stroke in 1995 to 1999 to 12% (10%–15%) in 2000 to 2005, and no improvement since. Recurrence-free survival has improved (35%, 1995–1999; 67%, 2010–2015). Risk of recurrence or death is lowest for small-vessel occlusion strokes and other ischemic causes (36% and 27% at 5 years, respectively). For cardioembolic and hemorrhagic index strokes around half of first recurrences are of the same type (54% and 51%, respectively). Over the whole study period a 54% increased risk of recurrence was observed among those who had atrial fibrillation before the index stroke (hazard ratio, 1.54 [1.09–2.17]). Conclusions: The rate of recurrence reduced until mid-2000s but has not changed over the last decade. The majority of cardioembolic or hemorrhagic strokes that have a recurrence are stroke of the same type indicating that the implementation of effective preventive strategies is still suboptimal in these stroke subtypes.


2007 ◽  
Vol 26 (1) ◽  
pp. 64-69 ◽  
Author(s):  
Marjanka K. Schmidt ◽  
Rob A.E.M. Tollenaar ◽  
Sanne R. de Kemp ◽  
Annegien Broeks ◽  
Cees J. Cornelisse ◽  
...  

Purpose Women carrying a CHEK2*1100delC germline mutation have an increased risk of developing breast cancer. This study aims to determine the proportion of CHEK2*1100delC carriers in a premenopausal breast cancer population, unselected for family history of breast cancer, and to investigate tumor characteristics and disease outcome with sufficient follow-up. Patients and Methods We identified a retrospective cohort of 1,479 patients, who received surgery for invasive breast cancer between 1970 and 1994. All patients were diagnosed before age 50. Paraffin-embedded tissue blocks were collected for DNA isolation (normal tissue), subsequent CHEK2*1100delC analysis, and tumor revision. Median follow-up was 10.1 years. Results We detected a CHEK2*1100delC germline mutation in 54 patients (3.7%). Tumor characteristics of CHEK2*1100delC carriers did not differ significantly from those of noncarriers. CHEK2*1100delC carriers had a two-fold increased risk (hazard ratio [HR], 2.1; 95% CI, 1.0 to 4.3; P = .049) of developing a second breast cancer and they had worse recurrence-free survival (HR, 1.7; 95% CI, 1.2 to 2.4; P = .006) and worse breast cancer–specific survival (HR, 1.4; 95% CI, 1.0 to 2.1; P = .072) compared with noncarriers. The poorer disease outcome of CHEK2*1100delC carriers could not be explained by the increased risk of second breast cancer. Conclusion Our study, which is representative for the premenopausal breast cancer population, reveals approximately 4% CHEK2*1100delC carriers have an increased risk of second breast cancer and a worse long-term recurrence-free survival rate. Their identification at time of diagnosis and prolonged intensive follow-up should be considered to optimize clinical management.


Cancers ◽  
2021 ◽  
Vol 13 (19) ◽  
pp. 4772
Author(s):  
Hans-Michael Hau ◽  
Mareen Devantier ◽  
Nora Jahn ◽  
Elisabeth Sucher ◽  
Sebastian Rademacher ◽  
...  

Background: The association of body mass index (BMI) and long-term prognosis and outcome of patients with perihilar cholangiocarcinoma (pCCA) has not been well defined. The aim of this study was to evaluate clinicopathologic and oncologic outcomes with pCCA undergoing resection, according to their BMI. Methods: Patients undergoing liver resection in curative intention for pCCA at a tertiary German hepatobiliary (HPB) center were identified from a prospective database. Patients were classified as normal weight (BMI 18.5–24.9 kg/m2), overweight (BMI 25.0–29.9 kg/m2) and obese (>30 kg/m2) according to their BMI. Impact of clinical and histo-pathological characteristics on recurrence-free survival (RFS) were assessed using Cox proportional hazard regression analysis among patients of all BMI groups. Results: Among a total of 95 patients undergoing liver resection in curative intention for pCCA in the analytic cohort, 48 patients (50.5%) had normal weight, 33 (34.7%) were overweight and 14 patients (14.7%) were obese. After a median follow-up of 4.3 ± 2.9 years, recurrence was observed in totally 53 patients (56%). The cumulative recurrence probability was higher in obese and overweight patients than normal weight patients (5-year recurrence rate: obese: 82% versus overweight: 81% versus normal weight: 58% at 5 years; p = 0.02). Totally, 1-, 3-, 5- and 10-year recurrence-free survival rates were 68.5%, 44.6%, 28.9% and 13%, respectively. On multivariable analysis, increased BMI (HR 1.08, 95% CI: 1.01–1.16; p = 0.021), poor/moderate tumor differentiation (HR 2.49, 95% CI: 1.2–5.2; p = 0.014), positive lymph node status (HR 2.01, 95% CI: 1.11–3.65; p = 0.021), positive resection margins (HR 1.89, 95% CI:1.02–3.4; p = 0.019) and positive perineural invasion (HR 2.92, 95% CI: 1.02–8.3; p = 0.045) were independent prognostic risk factors for inferior RFS. Conclusion: Our study shows that a high BMI is significantly associated with an increased risk of recurrence after liver resection in curative intention for pCCA. This factor should be considered in future studies to better predict patient’s individual prognosis and outcome based on their BMI.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Won Sik Ham ◽  
Jee Soo Park ◽  
Won Sik Jang ◽  
Young Deuk Choi ◽  
Jongchan Kim

AbstractThere is evidence that a history of benign prostatic hyperplasia increases the incidence of bladder cancer, and treatment with 5-alpha reductase inhibitor or androgen deprivation therapy reduces recurrence of non-muscle invasive bladder cancer. We aimed to evaluate whether prostate volume affects its prognosis. We reviewed medical records of men who underwent transurethral resection of bladder tumor due to non-muscle invasive bladder cancer from January 2012 to December 2017. Patients were divided into two groups based on prostate volume measured by computed tomography (group 1: 264 patients with ≤ 30 mL, group 2: 124 patients with > 30 mL). Propensity score matching analysis was used for adjust selection bias, and then assessed recurrence-free survival and progression-free survival. With a median follow up duration of 52 months, group 1 showed higher 5-year recurrence-free and progression-free survival (69.3% vs 47.0%, p = 0.001; 96.7% vs 87.7%, p = 0.002). Further, cox-regression analysis showed that tumor size (HR = 1.292 p < 0.001), multifocal tumor (HR = 1.993, p < 0.001), adjuvant intravesical therapy (chemotherapy: HR = 0.580, p = 0.037 and bacillus Calmette–Guérin: HR = 0.542, p = 0.004) and prostate volume (HR = 2.326, p < 0.001) were significant predictors of recurrence-free survival. Prostate volume (HR = 2.886, p = 0.014) was also associated with PFS with age (HR = 1.043, p = 0.044) and tumor grade (HR = 3.822, p = 0.013). We conclude higher prostate volume is associated with worse recurrence and progression-free survival in non-muscle invasive bladder cancer.


Oncology ◽  
2021 ◽  
Author(s):  
Kaoru Okugawa ◽  
Hideaki Yahata ◽  
Kazuhisa Hachisuga ◽  
Hiroshi Tomonobe ◽  
Nobuko Yasutake ◽  
...  

Introduction: The prognostic significance of lymphovascular space invasion (LVSI) in stage IA endometrial cancer remains unclear. The aim of this study was to evaluate the clinical significance of LVSI in stage IA endometrial cancer. Methods: Clinical data of patients with stage IA endometrial cancer who underwent initial surgery at our institution between January 2008 and December 2018 were reviewed retrospectively. Information of patients, surgery, and characteristics of cancer were obtained from medical records and pathological reports. Results: Two hundred ninety-seven patients were enrolled in this study. With a median follow-up of 60 months, 15 patients experienced recurrence (5.1%) and four patients died of endometrial cancer (1.3%). The recurrence and mortality rates did not differ significantly between the LVSI-positive and -negative groups (P=0.07 and P=0.41, respectively). Recurrence-free survival and endometrial cancer-specific survival also did not differ significantly between these groups (P=0.11 and P=0.49, respectively). The 5-year endometrial cancer-specific survival rates for tumors with and without LVSI were 97.0% and 98.9%, respectively. Among patients with low-grade tumors, recurrence-free survival and endometrial cancer-specific survival did not differ significantly between patients with tumors with and without LVSI (P=0.92 and P=0.72, respectively). The 5-year endometrial cancer-specific survival rates for low-grade tumors with and without LVSI were 100% and 99.3%, respectively. Conclusion: LVSI was not a prognostic factor of not only stage IA endometrial cancer, but also stage IA low-grade cancer.


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