Combination therapy with anti-PD-1 or PD-1 antibody alone in pediatric patients with relapsed or refractory cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e22004-e22004
Author(s):  
Yi Que ◽  
Juan Wang ◽  
Jia Zhu ◽  
Na Li ◽  
Junting Huang ◽  
...  

e22004 Background: There is limited experience of PD-1 combined with other therapies in children. We aimed to explore the antitumor activity and safety of PD-1 antibody monotherapy or combination with other regimens in relapsed or refractory pediatric cancer. Methods: This was an observational retrospective study performed at two academic medical centers (Sun Yat-sen University Cancer Center and Nanfang Hospital, Southern Medical University) The primary objective of this study was to describe the overall response rate (ORR) and disease control rate (DCR). Secondary objectives included characterizing toxicities according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 as well as describing progression free survival (PFS) and overall survival (OS). Results: Of the 22 pediatric cancer patients who received PD-1 inhibitors, the median follow-up for all patients after the commencement of PD-1 therapy with or without other regimens was 12.3 months (0-43 months). The objective response rate (ORR) and disease control rate (DCR) of the 6 patients with HL were 83.3% (3CR and 2PR) and 100%, respectively. No objective response was observed in patients with melanoma or Burkitt lymphoma evaluated in this study. For patients treated with PD-1 inhibitor combination therapy, PD-1 antibody combined with decitabine showed potential efficacy in advanced pediatric cancer patients. One of the Three of patients who received PD-1 combined with decitabine achieved CR and another two other patients achieved PR. At the data cutoff, 10 of the 13 (76.9%) patients achieved disease control as the best objective response. The median PFS and OS were 90 days (95%CI: 10.733-169.267) and 158 days (95%CI: 131.514-184.486) respectively. There were no severe treatment-related adverse events (TRAEs) directly attributed to PD-1 monotherapy. The severe TRAEs are due to chemotherapy in the combination regimen. Conclusions: PD-1 monotherapy demonstrated antitumor activity in a population of pediatric patients with HL. The regimen of PD-1 inhibitor combined with decitabine showed potential in treating with pediatric cancer patients.

2021 ◽  
Vol 12 ◽  
Author(s):  
Yi Que ◽  
Juan Wang ◽  
Jia Zhu ◽  
Na Li ◽  
Junting Huang ◽  
...  

There is limited experience of PD-1 antibody combined with other therapies in children. We aimed to explore the antitumor activity and safety of PD-1 antibody monotherapy or combination with other regimens in relapsed or refractory pediatric cancer. This is a retrospective-case study conducted in two Chinese expert centers. The primary objective of this study was to describe the overall response rate (ORR) and disease control rate (DCR). Secondary objectives included characterizing toxicities. Of the 22 pediatric patients with cancer who received PD-1 inhibitors, the median follow-up for all patients after the commencement of PD-1 therapy with or without other regimens was 12.3 months (0 - 43 months). PD-1 antibody monotherapy demonstrated antitumor activity in a population of pediatric patients with Hodgkin lymphoma (HL), with an objective response rate (ORR) and disease control rate (DCR) of 83.3% (3CR and 2PR) and 100%, respectively. However, no objective response was observed in patients with melanoma or Burkitt lymphoma evaluated in this study. We reviewed responses for patients with chemotherapy, decitabine or everolimus combination therapies with PD-1 antibodies, and found that PD-1 antibody combined with decitabine showed potential efficacy in pediatric patients with advanced embryonal rhabdomyosarcoma and lymphoepitheliomatoid-like carcinoma. There were no severe treatment-related adverse events (TRAEs) directly attributed to PD-1 antibody monotherapy in Asian pediatric patients with lower incidence of hematologic toxicity and nonhematologic toxicity. The Grade ≥3 TRAEs were attributed to the combination chemotherapy.


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 10518-10518
Author(s):  
Thomas Patrick Curtin ◽  
Wendy Kohlmann ◽  
Luke Devon Maese ◽  
Zhe Yu ◽  
Karen Curtin ◽  
...  

10518 Background: Survival rates for childhood cancer patients have improved dramatically, but the growing survivor population suffers from increased treatment-related toxicity including high risk for cardiovascular disease (CVD). While the link between chemotherapy and radiation to cardiotoxicity is well established, few studies seek to determine if an underlying familial risk for cardiovascular disease contributes or predicts this risk. The Utah Population Database (UPDB) is a genealogical resource linked to statewide cancer diagnoses and electronic medical data in which family history is objectively determined. Methods: We calculated the risk of subsequent CVD (ICD-9 401-449) in relatives of 5602 pediatric cancer patients diagnosed at ages 0-19 in Utah from 1966-2013 with no congenital CVD-related anomalies (ICD-9 745-747, 758-759). We identified 964 patients with subsequent CVD diagnoses. Cox models provided recurrence-risk estimates in first-degree relatives of patients compared to relatives of 5:1 matched controls. Results: Pediatric cancer patients were at 5-fold risk of CVD compared to controls ( P< 10-15). In pediatric patients with subsequent CVD, first-degree relatives were at 30% increased CVD risk compared to relatives of cancer-free controls (HR = 1.31, 95%CI 1.16-1.47; P< 10-5). In pediatric patients without CVD, only parents exhibited slight CVD risk (HR = 1.08, 95%CI 1.03-1.14; P= 0.002). In 685,000 individuals with a non-congenital CVD history, pediatric cancers among their first-degree relatives were associated with a similar increased risk of subsequent CVD, compared to pediatric cancers among relatives of controls with no CVD events (HR = 1.39, 95%CI 1.18-1.64, P< 10-4). Conclusions: The UPDB is powerful for investigating comorbidities in cancer patients and their families without recall bias from self-reported family medical history. A family history of CVD may increase risk of CVD-related comorbidities among pediatric cancer patients by 30-40% beyond that observed in patients without a CVD family history. This finding suggests that in addition to a cancer family history, a CVD-related family history should be assessed in children diagnosed with cancer.


2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii378-iii378
Author(s):  
Khin Pyone ◽  
Thwe Tun ◽  
Yin Win ◽  
Aye Thinn ◽  
Khin Win ◽  
...  

Abstract OBJECTIVE Attendance to follow-up after completion of cancer treatment is understudied area. Pediatric cancer patients have sequelae of illness or treatment. Many have no symptom immediately after completion of treatment. Long term follow-up is important to access disease control, early diagnosis of recurrence, second cancer and treatment-related morbidities. Purpose of this study was to evaluate the compliance to follow-up in pediatric patients treated with craniospinal irradiation (CSI). METHODS This was retrospective review of follow-up in pediatric neuro-oncology patients who received (CSI) from January 2017 to June 2018 in the Radiotherapy Department of Yangon General Hospital, Myanmar. RESULT: Twenty-three patients received CSI; majority (43%) were medulloblastoma. Median age was 7.5 years (3–17 years). Only seven patients (30.4%) were attended to follow-up more than 6 months after completion of treatment. More than two-thirds of patients (n=16,69.6%) were lost to follow-up. Patients in active follow-up were diagnosed and treated at earlier age below 10years (n=5,21.7%). Demographically, 5 patients (22%) were living in the region around tertiary hospital. Sixteen patients (69.6%) from rural area had limited transportation and difficulty for accommodation in which they were treated. In socioeconomic points, 18 parents (78.2%) had poor education and financial status, lack of understanding about disease, treatment, long-term effects and follow-up. CONCLUSION Although this was limited data in CSI patients only, loss to follow-up after 6 months was high. We need to evaluate in all pediatric cancer patients and collaborate to provide financial support, childcare centres for lodging, transportation and health education to promote compliance to follow-up.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e22019-e22019
Author(s):  
Terrence C. Lee ◽  
Edmund M. Qiao ◽  
Alexander S. Qian ◽  
Vinit Nalawade ◽  
Rohith S. Voora ◽  
...  

e22019 Background: Pediatric cancer patients represent a vulnerable cohort at risk of adverse outcomes after presenting to the emergency department (ED). Given the severity of cancer-related complications and uniqueness of this population, approaches to better risk stratify this cohort could potentially help define future interventions geared towards improving outcomes. We used a high-dimensional machine learning approach to help define the risk of hospitalization after an ED visit among pediatric patients with cancer. Methods: A cohort of cancer patients under 18 was identified from the Nationwide Emergency Department Sample (NEDS) between 2016-2018. We used a lasso regression model to predict inpatient admission after an ED visit. Model covariates included patient demographics, hospital characteristics, and International Classification of Diseases, version 10 (ICD-10) diagnosis codes. The data were split 75%/25% into training/testing data. The model was constructed with training data, and performance assessed on the test data using the area under the curve (AUC), with an AUC of 1.0 indicating perfect prediction. Results: We identified 129,631 pediatric cancer patients who visited the ED, of which 54.5% were subsequently admitted. The final predictive model included 150 variables, including 9 demographic, 6 hospital, and 135 unique ICD-10 codes. The model demonstrated excellent ability to predict hospitalization with an AUC of 0.96. The top 5 most important variables associated with inpatient admission were diagnoses of paralytic ileus/intestinal obstruction, neutropenia, sepsis, aplastic anemia/bone marrow failure, and bacterial infection. Conclusions: Pediatric cancer patients frequently present to the ED with complications of their cancer or their treatment, and over half of these patients are admitted. This study demonstrates the capacity of high-dimensional prediction models to help identify pediatric patients at risk of hospitalization. Additional research is needed to determine how to implement these predictive models in clinical practice.


2019 ◽  
Vol 29 (9) ◽  
pp. 1396-1404 ◽  
Author(s):  
Rebecca S Kristeleit ◽  
Ana Oaknin ◽  
Isabelle Ray-Coquard ◽  
Alexandra Leary ◽  
Judith Balmaña ◽  
...  

ObjectiveTo report results from an integrated efficacy and safety analysis supporting the European Commission's approval of the poly(ADP-ribose) polymerase inhibitor rucaparib as monotherapy treatment for relapsed, platinum-sensitive, BRCA-mutated ovarian cancer.MethodsEfficacy was analyzed in platinum-sensitive patients from Study 10 (NCT01482715) and ARIEL2 (NCT01891344) who had high-grade serous or endometrioid epithelial ovarian, fallopian tube, or primary peritoneal cancer and a deleterious BRCA1 or BRCA2 mutation and received two or more prior chemotherapies (including two or more platinum-based therapies). The primary end point was investigator-assessed, confirmed objective response rate (visit cut-off: April 10, 2017). Safety was analyzed in patients with ovarian cancer, regardless of BRCA mutation status or lines of prior chemotherapies, who received at least one dose of rucaparib 600 mg in either study (visit cut-off: December 31, 2017).ResultsIn the integrated platinum-sensitive efficacy population (n=79), objective response rate was 64.6% (95% CI, 53.0 to 75.0); 10.1% (8/79) of patients had a complete response and 54.4% (43/79) had a partial response. Median duration of response was 294 days (95% CI, 224 to 393). In the integrated safety population (n=565), the most common any-grade treatment-emergent adverse events were nausea (77.7%, 439/565), asthenia/fatigue (74.7%, 422/565), vomiting (45.8%, 259/565), and hemoglobin decreased (44.2%, 250/565). Treatment-emergent adverse events led to treatment interruption, dose reduction, or discontinuation in 60.2% (340/565), 46.0% (260/565), and 16.8% (95/565) of patients.ConclusionsIn patients with platinum-sensitive, BRCA-mutated ovarian cancer, rucaparib demonstrated antitumor activity and is the first and currently the only poly(ADP-ribose) polymerase inhibitor approved by the European Commission as treatment for this population. The safety analysis used a more recent visit cut-off date and larger population than previously published, was consistent with prior reports, and was the basis for the treatment-indication safety population in rucaparib’s recently updated European Union label.


2020 ◽  
Vol 38 (5) ◽  
pp. 395-405 ◽  
Author(s):  
Emmanuel S. Antonarakis ◽  
Josep M. Piulats ◽  
Marine Gross-Goupil ◽  
Jeffrey Goh ◽  
Kristiina Ojamaa ◽  
...  

PURPOSE Pembrolizumab has previously shown antitumor activity against programmed death ligand 1 (PD-L1)–positive metastatic castration-resistant prostate cancer (mCRPC). Here, we assessed the antitumor activity and safety of pembrolizumab in three parallel cohorts of a larger mCRPC population. METHODS The phase II KEYNOTE-199 study included three cohorts of patients with mCRPC treated with docetaxel and one or more targeted endocrine therapies. Cohorts 1 and 2 enrolled patients with RECIST-measurable PD-L1–positive and PD-L1–negative disease, respectively. Cohort 3 enrolled patients with bone-predominant disease, regardless of PD-L1 expression. All patients received pembrolizumab 200 mg every 3 weeks for up to 35 cycles. The primary end point was objective response rate per RECIST v1.1 assessed by central review in cohorts 1 and 2. Secondary end points included disease control rate, duration of response, overall survival (OS), and safety. RESULTS Two hundred fifty-eight patients were enrolled: 133 in cohort 1, 66 in cohort 2, and 59 in cohort 3. Objective response rate was 5% (95% CI, 2% to 11%) in cohort 1 and 3% (95% CI, < 1% to 11%) in cohort 2. Median duration of response was not reached (range, 1.9 to ≥ 21.8 months) and 10.6 months (range, 4.4 to 16.8 months), respectively. Disease control rate was 10% in cohort 1, 9% in cohort 2, and 22% in cohort 3. Median OS was 9.5 months in cohort 1, 7.9 months in cohort 2, and 14.1 months in cohort 3. Treatment-related adverse events occurred in 60% of patients, were of grade 3 to 5 severity in 15%, and led to discontinuation of treatment in 5%. CONCLUSION Pembrolizumab monotherapy shows antitumor activity with an acceptable safety profile in a subset of patients with RECIST-measurable and bone-predominant mCRPC previously treated with docetaxel and targeted endocrine therapy. Observed responses seem to be durable, and OS estimates are encouraging.


2007 ◽  
Vol 31 (4) ◽  
pp. 267-273 ◽  
Author(s):  
Azza El –Housseiny ◽  
Susan Saleh ◽  
Ashraf El –Masry ◽  
Amany Allam

The aim of this study was to assess the early oral complications in pediatric patients receiving chemotherapy. An interview and oral examination was conducted on 150 pediatric cancer patients receiving standard dose chemotherapy. Results showed that oral pain and dry mouth were the most frequent patients' complaints. The prevalences of chemotherapy-induced oral mucositis and oral infections were relatively high. The chemotherapeutic antimetabolites were the most frequently associated with oral complications than other types of chemotherapy. The present results indicate that the oral complications among patients receiving chemotherapy are common


2020 ◽  
Vol 7 (4) ◽  
Author(s):  
Cakra Jati Pranata ◽  
Nur Suryawan ◽  
Delita Prihatni

Background: Transfusion is an essential component of supportive management for cancer patients with anemia and thrombocytopenia. It is generally safe; however, it has several risks and complications including those caused by transfusion reactions. This study aimed to describe transfusion reactions in pediatric cancer patients in a tertiary hospital in Indonesia. Methods: This was a descriptive cross-sectional study with a total sampling method. A prospective analysis was performed on episodes of blood transfusion in pediatric patients aged younger than 18 years old with cancer and were hospitalized at the Department of Child Health of the hospital from July to August 2019. After the consent of the parents, the patients were interviewed for various transfusion reactions. Data collected were presented using tables and charts. Results: Leukemia was the most frequent cancer in children cancer patients who need transfusion. Out of 42 children included, 155 episodes of transfusion were observed with 22 episodes showed transfusion reactions (14.2%). The most frequent manifestations were pruritus (31.8%), followed by combination of pruritus and erythema (27.4%) and fever (13.6%). These reactions appeared mostly in 1 to 2 hours (27.2%), with most were mild reactions (59.1%). Conclusion: Transfusion reactions mostly occurred among pediatric patients with cancer in the acute phase with clinical manifestation of allergic reactions, predominantly mild. Early identification of these reactions would result in better treatment and prevention for recurrence of transfusion reactions.


2017 ◽  
Vol 10 (2) ◽  
pp. 166-171 ◽  
Author(s):  
Geetika Datta ◽  
Tanvi Saxena ◽  
Ankush G Datta

ABSTRACT Multiagent chemotherapy, radiotherapy, or a combination of both are the contemporary methods of cancer treatment. With medical advancements, though cure rates have increased considerably, focus is now shifted to the potential early and late complications of the same. The aim of this study was to assess the early oral complications in pediatric patients receiving chemotherapy. Sixty-two children with cancer undergoing chemotherapy with the mean age of 7.42 ± 3.6 years were included in the study. The various types of malignancies and oral problems during chemotherapy were recorded in the subjects. The most commonly encountered malignancy was acute lymphoblastic leukemia at 35.5%. Various oral and associated complications like mucosal inflammation with ulcerations, oral pain, xerostomia, and secondary infections were commonly seen, with mucositis being the most commonly observed complication in 58.1% of the subjects undergoing chemotherapy. Clinical importance of timely medical and dental interventions by a multidisciplinary team involving a pediatric dentist at different stages of anticancer treatment is also emphasized to minimize discomfort, increase treatment compliance, and improve the quality of life of pediatric patients. How to cite this article: Gandhi K, Datta G, Ahuja S, Saxena T, Datta AG. Prevalence of Oral Complications occurring in a Population of Pediatric Cancer Patients receiving Chemotherapy. Int Int J Clin Pediatr Dent 2017;10(2):166-171.


2013 ◽  
Vol 31 (31_suppl) ◽  
pp. 49-49
Author(s):  
Jason Lawrence Freedman ◽  
Anne F. Reilly ◽  
L. Charles Bailey

49 Background: Pediatric patients with cancer are at increased risk of influenza, with high mortality, morbidity, and delay of cancer therapy. CDC guidelines support yearly vaccination in these patients. In prior years at our center, only 53-56% of pediatric cancer patients received at least one dose of the vaccine. Our objective was to increase the rates of influenza vaccination in pediatric cancer patients through a multi-faceted QI initiative. Methods: Five interventions were instituted concomitantly, in eligible patients (>6 months old, >100 days from BMT if applicable, and within 1 year of chemotherapy) over a 6-month period (9/1/12 to 3/31/13). 1) Family education: provision of influenza/vaccine handouts to families in clinic waiting rooms; 2) Health informatics intervention: via electronic health records, generation of daily lists of patients due for doses with automated email lists to triage and nurses; 3) Clinical process interventions: standardization of triage process to identify patients needing vaccination and provision of colored wristbands to such patients alerting providers to order the vaccine, or document refusals, during the encounter; 4) Inpatient orders: influenza vaccine order built into computerized physician admission order set to trigger vaccination upon discharge; and 5) Provider education: printed materials and tutorials for staff at conferences on proper screening of patients, vaccine ordering/dose, and correct documenting of refusals/contraindications. These processes were iteratively refined over the 6-month timeframe. Results: Influenza immunization rates increased by 20% after the changes were implemented; this was seen across all tumor subgroups. Overall, 74% of patients received at least one dose as compared with 52% in the prior year. 61% of patients were fully immunized (vs. 42% in 2011-12). Immunizations were deferred due to allergy/refusal in 8% of patients (vs. 7% in 2011-12). Consequently, only 18% of eligible patients were unimmunized as compared to 41% in the prior year. Conclusions: Technology, education, and clinical process changes led to a successful increase in influenza vaccination rates. Ongoing efforts will target subgroups with lowest overall rates of immunization.


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