scholarly journals Complete Clinical Response in Stage IVB Endometrioid Endometrial Carcinoma after First-Line Pembrolizumab Therapy: Report of a Case with Isolated Loss of PMS2 Protein

2020 ◽  
Vol 13 (3) ◽  
pp. 1067-1074
Author(s):  
Jesus Paula Carvalho ◽  
Auro Del Giglio ◽  
Maria Isabel Achatz ◽  
Filomena Marino Carvalho
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Endometrial Carcinoma ◽  
Early Stage ◽  
Gynecological Cancer ◽  
Stage Iv ◽  
Protein Loss ◽  
First Line ◽  
Early Stage Disease ◽  
Endometrioid Endometrial Carcinoma

Endometrial cancer is the only gynecological cancer that is rising in incidence and associated mortality worldwide. Although most cases are diagnosed as early stage disease, with chances of cure after primary surgical treatment, those with advanced or metastatic disease have a poor prognosis because of the quality of treatment options that are currently available. Mismatch repair (MMR)-deficient cancers are susceptible to programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 inhibitors. The US Food and Drug Administration granted accelerated approval to pembrolizumab for MMR-deficient tumors, the first tumor-agnostic approval for a drug. We present a case of stage IV endometrioid endometrial carcinoma with isolated PMS2 protein loss, in which treatment with first-line pembrolizumab therapy achieved a complete clinical and pathological response of tumor.

scholarly journals Immune Checkpoint Inhibition in Oesophago-Gastric Carcinoma

2021 ◽  
Vol 14 (2) ◽  
pp. 151
Author(s):  
Anica Högner ◽  
Peter Thuss-Patience
Keyword(s):  
Cell Death ◽  
Gastric Carcinoma ◽  
Programmed Cell Death ◽  
Immune Checkpoint ◽  
Disease Free Survival ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
The Usa ◽  
First Line Treatment

Immune checkpoint inhibitors enrich the therapeutic landscape in oesophago-gastric carcinoma. With regard to oesophageal squamous cell carcinoma (ESCC), the selective PD-1 (programmed cell death receptor 1)-inhibitor nivolumab improves disease-free survival in the adjuvant therapy setting (CHECKMATE-577). In first-line treatment, ESCC patients (pts) benefit in overall survival (OS) from the PD-1-inhibitor pembrolizumab in combination with chemotherapy (KEYNOTE-590). In the second-line setting, nivolumab (ATTRACTION-03) and pembrolizumab (KEYNOTE-181) demonstrate a benefit in OS compared with chemotherapy. These data resulted in the approval of nivolumab for the second-line treatment of advanced ESCC pts regardless of PD-L1 (programmed cell death ligand 1) status in Europe, Asia, and the USA, and pembrolizumab for pts with PD-L1 CPS (combined positivity score) ≥ 10 in Asia and the USA. Further approvals can be expected. In gastro-oesophageal junction and gastric cancer, the addition of nivolumab to chemotherapy in first-line treatment improves OS in pts with advanced disease with PD-L1 CPS ≥ 5 (CHECKMATE-649). Additionally, pembrolizumab was non-inferior to chemotherapy for OS in PD-L1 CPS ≥ 1 pts (KEYNOTE-062). In third-line treatment, nivolumab shows benefits in OS regardless of PD-L1 expression (ATTRACTION-02) with approval in Asia, and pembrolizumab prolonged the duration of response in PD-L1 positive pts (KEYNOTE-059) with approval in the USA. We discuss the recent results of the completed phase II and III clinical trials.

scholarly journals International Study of Primary Mucinous Ovarian Carcinomas Managed at Tertiary Medical Centers

2018 ◽  
Vol 28 (5) ◽  
pp. 915-924 ◽  
Author(s):  
Jennifer J. Mueller ◽  
Henrik Lajer ◽  
Berit Jul Mosgaard ◽  
Slim Bach Hamba ◽  
Philippe Morice ◽  
...  
Keyword(s):  
Early Stage ◽  
Statistical Tests ◽  
Stage Iv ◽  
Stage I ◽  
Stage Iii ◽  
Oncologic Outcomes ◽  
Disease Stage ◽  
Ovarian Carcinomas ◽  
Early Stage Disease ◽  
Medical Centers

ObjectiveWe sought to describe a large, international cohort of patients diagnosed with primary mucinous ovarian carcinoma (PMOC) across 3 tertiary medical centers to evaluate differences in patient characteristics, surgical/adjuvant treatment strategies, and oncologic outcomes.MethodsThis was a retrospective review spanning 1976–2014. All tumors were centrally reviewed by an expert gynecologic pathologist. Each center used a combination of clinical and histologic criteria to confirm a PMOC diagnosis. Data were abstracted from medical records, and a deidentified dataset was compiled and processed at a single institution. Appropriate statistical tests were performed.ResultsTwo hundred twenty-two patients with PMOC were identified; all had undergone primary surgery. Disease stage distribution was as follows: stage I, 163 patients (74%); stage II, 8 (4%); stage III, 40 (18%); and stage IV, 10 (5%). Ninety-nine (45%) of 219 patients underwent lymphadenectomy; 41 (19%) of 215 underwent fertility-preserving surgery. Of the 145 patients (65%) with available treatment data, 68 (47%) had received chemotherapy—55 (81%) a gynecologic regimen and 13 (19%) a gastrointestinal regimen. The 5-year progression-free survival (PFS) rates were 80% (95% confidence interval [CI], 73%–85%) for patients with stage I to II disease and 17% (95% CI, 8%–29%) for those with stage III to IV disease. The 5-year PFS rate was 73% (95% CI, 50%–86%) for patients who underwent fertility-preserving surgery.ConclusionsMost patients (74%) presented with stage I disease. Nearly 50% were treated with adjuvant chemotherapy using various regimens across institutions. The PFS outcomes were favorable for those with early-stage disease and lower but acceptable for those who underwent fertility preservation.

scholarly journals Durable Tumor Regression and Overall Survival in Patients With Advanced Merkel Cell Carcinoma Receiving Pembrolizumab as First-Line Therapy

2019 ◽  
Vol 37 (9) ◽  
pp. 693-702 ◽  
Author(s):  
Paul Nghiem ◽  
Shailender Bhatia ◽  
Evan J. Lipson ◽  
William H. Sharfman ◽  
Ragini R. Kudchadkar ◽  
...  
Keyword(s):  
Overall Survival ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Cell Carcinoma ◽  
Merkel Cell Carcinoma ◽  
Merkel Cell Polyomavirus ◽  
Merkel Cell ◽  
First Line ◽  
Median Response ◽  
Programmed Cell Death 1

PURPOSE Merkel cell carcinoma (MCC) is an aggressive skin cancer often caused by the Merkel cell polyomavirus. Clinical trials of programmed cell death-1 pathway inhibitors for advanced MCC (aMCC) demonstrate increased progression-free survival (PFS) compared with historical chemotherapy data. However, response durability and overall survival (OS) data are limited. PATIENTS AND METHODS In this multicenter phase II trial (Cancer Immunotherapy Trials Network-09/Keynote-017), 50 adults naïve to systemic therapy for aMCC received pembrolizumab (2 mg/kg every 3 weeks) for up to 2 years. Radiographic responses were assessed centrally per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. RESULTS Among 50 patients, the median age was 70.5 years, and 64% had Merkel cell polyomavirus–positive tumors. The objective response rate (ORR) to pembrolizumab was 56% (complete response [24%] plus partial response [32%]; 95% CI, 41.3% to 70.0%), with ORRs of 59% in virus-positive and 53% in virus-negative tumors. Median follow-up time was 14.9 months (range, 0.4 to 36.4+ months). Among 28 responders, median response duration was not reached (range, 5.9 to 34.5+ months). The 24-month PFS rate was 48.3%, and median PFS time was 16.8 months (95% CI, 4.6 months to not estimable). The 24-month OS rate was 68.7%, and median OS time was not reached. Although tumor viral status did not correlate with ORR, PFS, or OS, there was a trend toward improved PFS and OS in patients with programmed death ligand-1–positive tumors. Grade 3 or greater treatment-related adverse events occurred in 14 (28%) of 50 patients and led to treatment discontinuation in seven (14%) of 50 patients, including one treatment-related death. CONCLUSION Here, we present the longest observation to date of patients with aMCC receiving first-line anti–programmed cell death-1 therapy. Pembrolizumab demonstrated durable tumor control, a generally manageable safety profile, and favorable OS compared with historical data from patients treated with first-line chemotherapy.

scholarly journals First-line non–anthracycline-based chemotherapy for extranodal nasal-type NK/T-cell lymphoma: a retrospective analysis from the CLCG

2020 ◽  
Vol 4 (13) ◽  
pp. 3141-3153
Author(s):  
Shu-Nan Qi ◽  
Yong Yang ◽  
Yu-Qin Song ◽  
Ying Wang ◽  
Xia He ◽  
...  
Keyword(s):  
T Cell ◽  
Survival Benefit ◽  
Cell Lymphoma ◽  
Early Stage ◽  
T Cell Lymphoma ◽  
Collaborative Group ◽  
First Line ◽  
Early Stage Disease ◽  
Nasal Type ◽  
Nk T Cell

Abstract The present study investigated the survival benefit of non–anthracycline (ANT)-based vs ANT-based regimens in a large-scale, real-world cohort of patients with extranodal natural killer (NK)/T-cell lymphoma, nasal type (ENKTCL). Within the China Lymphoma Collaborative Group (CLCG) database (2000-2015), we identified 2560 newly diagnosed patients who received chemotherapy with or without radiotherapy. Propensity score matching (PSM) and multivariable analyses were used to compare overall survival (OS) and progression-free survival (PFS) between the 2 chemotherapy regimens. We explored the survival benefit of non–ANT-based regimens in patients with different treatments in early-stage disease and in risk-stratified subgroups. Non–ANT-based regimens significantly improved survivals compared with ANT-based regimens. The 5-year OS and PFS were 68.9% and 59.5% for non–ANT-based regimens compared with 57.5% and 44.5% for ANT-based regimens in the entire cohort. The clinical advantage of non–ANT-based regimens was substantial across the subgroups examined, regardless of stage and risk-stratified subgroup, and remained significant in early-stage patients who received radiotherapy. The survival benefits of non–ANT-based regimens were consistent after adjustment using multivariable and PSM analyses. These findings provide additional evidence supporting non–ANT-based regimens as a first-line treatment of patients with ENKTCL.

A metastatic intrahepatic cholangiocarcinoma treated with programmed cell death 1 inhibitor: a case report and literature review

Immunotherapy ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 555-561 ◽  
Author(s):  
Jingjing Zhang ◽  
Lihua Wu ◽  
Jian Liu ◽  
Meihua Lin
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Intrahepatic Cholangiocarcinoma ◽  
Clinical Effectiveness ◽  
First Line ◽  
Mutational Burden ◽  
Programmed Death ◽  
Promising Therapeutic Approach ◽  
Programmed Cell Death 1 ◽  
Tumor Mutational Burden

Intrahepatic cholangiocarcinoma is a disease with grave prognosis due to limited therapeutic regimens. Programmed cell death 1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitor have shown dramatic clinical effectiveness in multiple solid tumors. Here, we report the case that a patient with metastasis intrahepatic cholangiocarcinoma, being failure of first-line chemotherapy, was enrolled into the Phase I study of a PD-1 inhibitor, sintilimab. The patient achieved complete remission after three cycles of treatment with mild adverse reaction. In addition, the tumor mutational burden and the microsatellite instability status were low in the present case. Hence, PD-1 inhibitor might be a promising therapeutic approach for patients with advanced cholangiocarcinoma.

Undifferentiated endometrial carcinoma: a National Cancer Database analysis of prognostic factors and treatment outcomes

2019 ◽  
Vol 29 (7) ◽  
pp. 1126-1133
Author(s):  
Mariam AlHilli ◽  
Paul Elson ◽  
Lisa Rybicki ◽  
Sudha Amarnath ◽  
Bin Yang ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Prognostic Factors ◽  
Adjuvant Therapy ◽  
Endometrial Carcinoma ◽  
Treatment Outcomes ◽  
Survival Data ◽  
Early Stage ◽  
National Cancer Database ◽  
Early Stage Disease ◽  
Prognostic Groups

BackgroundUndifferentiated endometrioid endometrial carcinoma of the uterus is a rare, highly aggressive, and under-recognized subtype of endometrial cancer.ObjectiveThis study evaluates survival, prognostic factors for survival, and treatment outcomes associated with undifferentiated endometrial cancer.MethodsThe National Cancer Database was queried to identify patients with undifferentiated endometrial cancer who underwent definitive primary surgical treatment. Patients with all other histologic subtypes or incomplete treatment data were excluded. Univariable and multivariable Cox proportional hazards analyses were used to determine independent prognostic factors for survival. Points for each prognostic factor were assigned from regression coefficients in the final multivariable model and summed for a total score. Recursive partitioning analysis was used to determine cut-offs in the score to identify unique prognostic groups.ResultsAmong 349 404 women diagnosed with endometrial cancer from 2004 to 2013, 3994 (1.1%) met the criteria for diagnosis of undifferentiated endometrial cancer and 3486 had survival data. Median age at diagnosis was 65 years (interquartile range (IQR) 57–74) and 58% of patients had early stage disease. Median interval from diagnosis to surgery was 3.7 weeks (IQR 2.0–5.7). Five year overall survival was 57% (standard error (SE) 1%). Stage was the strongest predictor of survival, with a 15–20% decrement in 5 year survival for each advance in stage. Stage, age, race, and presence of comorbidities were independent predictors of survival and were used to categorize patients into five prognostic groups. Adjuvant therapy was associated with improved survival across most disease stages and prognostic groups. Multimodal adjuvant therapy was superior to unimodal treatment particularly in advanced stage unfavorable and very unfavorable groups.ConclusionIn women with undifferentiated endometrial cancer, survival is primarily driven by stage. Despite the poor overall prognosis of undifferentiated endometrial cancer, multimodal adjuvant therapy is a key component of treatment.

scholarly journals Lung Cancer in Homeless People: Clinical Outcomes and Cost Analysis in a Single Institute

2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
Koung Jin Suh ◽  
Ki Hwan Kim ◽  
Jin Lim ◽  
Jin Hyun Park ◽  
Jin-Soo Kim ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Early Stage ◽  
Medical Center ◽  
Homeless People ◽  
Stage Iv ◽  
Disease Stage ◽  
Curative Surgery ◽  
Early Stage Disease ◽  
Outpatient Visits

Introduction. To characterize the demographic and clinical features, outcomes, and treatment costs of lung cancer in homeless people. Methods. Medical records of 22 homeless patients with lung cancer at Seoul National University Boramae Medical Center in Seoul, South Korea, were retrospectively analyzed. Results. All patients were men (median age, 62 years). Most patients (78%) had advanced disease (stage IIIB, n=2; stage IV, n=15). Seven died during initial hospitalization (median survival, 1.5 months). Six were lost to follow-up after initial outpatient visits or discharges from initial admission (median follow-up, 13 days). Only 4 received appropriate treatment for their disease and survived for 1, 15, 19, and 28 months, respectively. Conversely, 4 of 5 patients with early stage disease (stage I, n=4; stage IIA, n=1) received curative surgery (median follow-up 25.5 months). The median treatment cost based on 29 days of hospitalization and 2 outpatient visits was $12,513, constituting 47.3% of the 2013 per capita income. Inpatient treatment accounted for 90% of the total costs. The National Health Insurance Service paid 82% of the costs. Conclusion. Among the homeless, lung cancer seems to be associated with poor prognosis and substantial costs during a relatively short follow-up and survival period.

Predictive factors for metastasis in patients (pts) with gastric cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 15056-15056
Author(s):  
S. Kilickap ◽  
O. Dizdar ◽  
H. Harputluoglu ◽  
S. Aksoy ◽  
S. Yalcin
Keyword(s):  
Risk Factors ◽  
Gastric Cancer ◽  
Early Stage ◽  
Stage Iv ◽  
Stage I ◽  
Early Stage Disease ◽  
Increased Risk ◽  
Metastasis Development ◽  
The Mean

15056 Background: Determination of patients (pts) with early stage disease who have a high risk for developing metastatic disease is crucial. We investigated the risk factors associated with metastases development in pts with operable gastric cancer. Patients and Methods: In this retrospective study, pts with stage I-III and non-metastatic stage IV gastric cancer diagnosed between 1990 and 2006 were evaluated. The medical records of all pts including patient characteristics, laboratory results, histopathological examinations, were reviewed. Logistic regression methods were used to determine the risk factors for developing metastasis and to calculate odds ratios (OR) with 95% confidence intervals (CI). Results: 184 pts (70% male, 30% female) were analyzed. The mean age ± standard deviation was 56.5±11.9. The mean age of female were higher than male (p=0.014). At the time of diagnosis, 13.6% of the pts had stage I, 19.0% had stage II, 53.3% had stage III, and 14.1% had non-metastatic stage IV disease. The tumors were distally localized in 80% of the cases. Median follow-up period was 35 months. During follow up, 51 pts developed metastases. Median time to metastases development was 14 months. Overall survival was shorter in pts who developed metastasis than those who did not. (20 months vs. not reached, respectively, p=0.002). In univariate analyses, stage (p=0.020), tumor localization (p=0.006), extracapsular lymphatic extension (ELE) (p<0.001), the number of metastatic lymph nodes (p=0.001), CEA level (p<0.001), lymphovascular invasion (LVI) (p=0.001), and perineural invasion (p=0.007) were associated with metastasis development. In multivariate analysis, elevated CEA levels (p=0.009; OR: 2.8; CI 95%: 1.29–6.19), LVI (p=0.041; OR: 2.2; CI 95%: 1.03–4.64) and ELE (p=0.029; OR: 2.3; CI 95%: 1.09–4.78) were associated with increased risk of metastasis development while distal localization (p=0.038; OR: 0.42; CI%: 0.18–0.95) was associated with decreased risk in pts with gastric cancer. Discussion: In pts with early stage or locally advanced gastric cancer, elevated CEA levels, LVI, proximal localization and ELE were associated with increased risk of developing metastasis. Aggressive treatment options and closer follow up should be considered for pts with these risk factors. No significant financial relationships to disclose.

Predictors for survival in hepatocellular carcinoma.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14640-e14640
Author(s):  
Glen I. Misek ◽  
Venkata K Jayanti
Keyword(s):  
Hepatitis C ◽  
Hepatitis B ◽  
Treatment Initiation ◽  
Early Stage ◽  
Survival Rates ◽  
Stage Iv ◽  
First Line ◽  
Kaplan Meier ◽  
History Of ◽  
One Year

e14640 Background: The global incidence of HCC is over 700,000 patients making it the sixth leading cancer and the prognosis is poor with a 5 year survival of 11%. It is important to understand if there are differences in survival based on the presence of Hepatitis B or C or alcohol cirrhosis, ethnicity and/or treatments employed in various stages of the disease. Methods: A robust global retrospective study of HCC patients was conducted with nearly 4,000 patient records from US, Germany, France, Spain, Italy, China and South Korea in 2011. Of these nearly 800 included deceased patients. These records were analyzed to study if any known factors such as ethnicity, presence of Hepatitis B, Hepatitis C or alcohol cirrhosis and/or treatments used at diagnosis could serve as predictors for survival. Kaplan-Meier curves were plotted to understand the differences in survival based on ethnicity, Child-Pugh status and treatments employed at various stages. Results: One year survival is lower in China/ Korea compared to US and EU, however, five year survival rates are comparable across regions. Associated hepatitis or cirrhosis does not convey any differences in one year survival whether patients received sorafenib as first line treatment or not. Statistically significant higher one year survival rates are observed for HCC patients in Europe and USA receiving transarterial chemoembolization (TACE) compared with patients receiving sorafenib first line. However, in China and Korea there is no such difference. Across all three regions: USA, EU and Asia there is no difference in survival in stage IV patients receiving sorafenib or no sorafenib. No significant differences in one year survival are seen in USA, EU and Asia for patients with Hepatitis C or B or cirrhosis compared to those with no history of liver disease. The Child-Pugh C patients had lower survival compared to Child-Pugh A or B patients. Conclusions: Early diagnosis of HCC, early intervention and treatment appear to show survival benefits as opposed to drug treatment with sorafenib initiated in the later stages of the disease. Efforts should increase for screening, early detection and treatment initiation at early stage to improve outcomes in HCC patients.

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