Kamnesh Pradhan - Academia.edu (original) (raw)

Papers by Kamnesh Pradhan

Journal of adolescent and young adult oncology, Oct 1, 2022

Purpose: Adolescent and young adult (AYA) survivors of pediatric cancer experience chronic health... more Purpose: Adolescent and young adult (AYA) survivors of pediatric cancer experience chronic health problems following treatment, many of which could be prevented through healthy lifestyle choices. This report describes the development of the AYA Cancer Survivor Attitude (AYA-CSA) Scale, an attitudinal scale that is associated with physical activity in AYA survivors of pediatric cancer. Methods: AYA survivors (n = 100) completed a survey to evaluate their attitudes toward engagement in physical activity. Internal consistency was calculated using Cronbach's alpha. Construct validity was assessed by exploratory factor analysis, correlation with physical activity intention and physical activity behavior, and prediction of physical activity, after adjusting for past physical activity, survivor age, gender, and family income. Results: Data demonstrated a single 6-item scale with excellent internal consistency (α = 0.82). Construct validity was supported by significant correlations with physical activity intention (r = 0.553, p < 0.001) and physical activity behavior (r = 0.489, p < 0.001). After controlling for past physical activity and demographic covariates, survivor age, attitude toward physical activity, and intention were significant predictors of physical activity, and the overall model (F(6, 77) = 7.722, p < 0.001) predicted 39.5% of the variability in physical activity. Conclusion: The AYA-CSA scale demonstrates good reliability and construct validity, most important of which was the ability to predict actual physical activity in AYA survivors of pediatric cancer. This reliable and valid measure is an important tool in the design of behavioral interventions to improve physical activity engagement in AYA survivors.

$Research paper thumbnail of Abstract CT054: A dose escalation and toxicity study using pre-determined target concentration of Ramucirumab, a novel anti-angiogenic agent in children with recurrent / refractory solid tumors: A report from the children's oncology group phase I/ pilot consortium (ADVL1416)$

Ramucirumab (RAM) is a high affinity, humanized, monoclonal antibody that binds to the extra-cell... more Ramucirumab (RAM) is a high affinity, humanized, monoclonal antibody that binds to the extra-cellular domain of the vascular endothelial growth factor receptor (VEGFR). RAM prevents the binding of VEGF ligands with VEGFR-2, the most potent receptor of the VEGF tumor angiogenesis pathway. RAM is FDA approved for adults with NSCLC, as well as for gastric and colorectal adenocarcinoma where higher exposure was associated with better outcomes. Based on population pharmacokinetic (PK) analysis of the adult data, a minimum steady state concentration (Cmin ss) of ≥ 50 µg/ml of RAM was considered the target concentration for pediatrics. The Children's Oncology Group (COG) conducted a phase 1 study using a rolling six design to define the maximum tolerated dose (MTD) and /or a recommended phase 2 dose (RP2D), evaluate toxicities and explore circulating angiogenic cells as a biomarker for RAM monotherapy in children with recurrent/refractory solid tumors. The starting dose of 8 mg/kg IV q2 weeks (DL1) was chosen based on the adult safety profile and effective Cmin ss. Since adult data suggested that lower body weight was associated with lower Cmin ss, dose escalation to 12 mg/kg IV q2 weeks (DL2) was planned provided the MTD was not exceeded in DL1 and up to 16 mg/kg IV q2 weeks (DL3) if Cmin ss was < 50 µg/ml in 1 of 6 subjects on DL2 without exceeding the MTD. An expansion cohort was planned at the lowest dose where at least 5 of 6 subjects exceeded the target in order to generate PK data in at least 6 additional subjects < 12 years of age. In the absence of an MTD, the RP2D was defined as the dose achieving Cmin ss ≥ 50 µg/ml on day 42 ± 2, after 3 doses of RAM administered IV every 2 weeks, in at least 10 of 12 subjects. Sixteen subjects (15 eligible; 7 females), median age of 14 years (3-21 yrs.) have been enrolled. Of the 7 subjects on DL1, two had insufficient PK sampling to establish Cmin ss, including 1 who experienced grade 2 proteinuria (DLT). In the remaining 5, the median (range) Cmin ss was 66 (40-136) µg/ml; 2/5 did not achieve the target of ≥ 50 µg/ml. Of the 8 subjects on DL2, two had insufficient PK sampling, including 1 with grade 2 proteinuria (DLT). In the remaining 6, the median (range) Cmin ss was 64 (51-101) µg/ml, all ≥ 50 µg/ml; thus 12mg/kg IV q2 weeks was identified for the expansion cohort. The most common RAM related non-DLT toxicities were grade 1/2 headache in 6 subjects, grade 1/2 elevation in aspartate aminotransferase in 7 subjects and grade 2/3 hypertension in 2 subjects. Due to low participation, circulating angiogenic cells could not be analyzed. This is the first COG study in which dose escalation and RP2D for a targeted agent incorporated a primary PK endpoint (Cmin ss) based upon efficacy data from adult studies and paves the way for similar study design for future phase-1 studies. Citation Format: Kamnesh Pradhan, Stacey L. Berg, Xiaowei Liu, Charles G. Minard, James Croop, Joel M. Reid, Elizabeth Fox, Brenda J. Weigel. A dose escalation and toxicity study using pre-determined target concentration of Ramucirumab, a novel anti-angiogenic agent in children with recurrent / refractory solid tumors: A report from the children's oncology group phase I/ pilot consortium (ADVL1416) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr CT054.

Sigma Theta Tau International's 22nd International Nursing Research Congress, Oct 17, 2011

Cancer Research, Apr 14, 2023

Journal of Clinical Oncology, May 20, 2011

10030 Background: NF1 is a common inherited disorder resulting from mutations in the neurofibromi... more 10030 Background: NF1 is a common inherited disorder resulting from mutations in the neurofibromin gene resulting in a variety of tumors. PN occur in 20-40% of NF1 patients and result from loss of heterozygosity of neurofibromin in Schwann cells. PNs are refractory to conventional chemotherapy and often unresectable. Pre-clinical studies and clinical reports have defined the role of the c-KIT receptor, c-ABL, and PDGFR tyrosine kinases in PN growth and response to the tyrosine kinase inhibitor imatinib. METHODS We conducted a phase II pilot study to examine the response of measurable, clinically significant PNs in NF1 patients to imatinib. The primary 6 month endpoint was PN size by MRI cross sectional area: responsive > 5% reduction; progression > 5% increase; stable < 5% change. Secondary endpoints included symptomatic improvement, expression of 15 plasma cytokines, and safety/toxicity of imatinib. RESULTS 36 pediatric/adult NF1 patients with PNs were enrolled and treated with imatinib; 440 mg/m2/day in children < 19 years old and 800mg/day in adults 19-52 years old. Eleven grade 3/4 toxicities were observed (wt gain, rash, liver functions and blood counts). 12 patients withdrew from study prior to the 6 month endpoint with 3 from toxicity. Of 24 evaluable patients, 9 (38%) responded with tumor reduction; 2 (8%) with stable disease, and 13 (54%) had progression of tumor growth. Out of 87 PNs measured, 17 had a reduction in size (Table) projecting a relative response rate of 20% for tumor reduction (12-29%, 95% CI). There were 23 PN's (26%) that progressed and 47 PNs (54%) were stable. Symptom improvement was reported by 6 of 11 (55%) of patients with non-progressive disease and 1 of 13 (8%) of patients with progression (p = 0.023). A panel of 15 plasma cytokines after 6 months of therapy showed > 2 fold increase in levels in 24% of cytokines measured in patients with progressive disease compared to 2% in patients without progression (p< 0.0001). CONCLUSIONS 1) A subset of NF1 patients with PNs treated with imatinib have reductions in tumor size associated with symptom improvement. 2) cytokine expression correlates with tumor response. [Table: see text].

Pediatric Blood & Cancer, Aug 11, 2013

Atypical teratoid/rhabdoid tumor (AT/RT) of the central nervous system (CNS) is a rare embryonal ... more Atypical teratoid/rhabdoid tumor (AT/RT) of the central nervous system (CNS) is a rare embryonal neoplasm of early childhood with dismal outcome and no current uniformly accepted treatment. Given its highly aggressive nature and predilection for dissemination at diagnosis, intensive multimodal therapy is required. Nineteen children with newly diagnosed CNS AT/RT were treated on the head start (HS) III protocol. Treatment consisted of surgical resection, 5 cycles of induction chemotherapy, followed by consolidation with myeloablative chemotherapy and autologous hematopoietic progenitor cell rescue (AuHCR). Irradiation was given following recovery from consolidation based on patient age, disease extent at diagnosis, and treatment response to induction. Nineteen children (median age of 14 months) were treated on HS III between 2003 and 2009. Only four finished induction and three proceeded to consolidation. There are presently four survivors at 40, 42, 46, and 79 months from study enrollment. Eleven patients experienced tumor progression at a median time to progression of 4.1 months of whom 10 died with a median time from progression to death of 2.6 months. Five toxic deaths occurred, three of them while on the study. The 3-year event-free survival (EFS) and overall survival (OS) for the whole group was 21 ± 9% and 26 ± 10%, respectively. Five patients received irradiation at progression with only one long-term survivor. A minority of children with CNS AT/RT treated on HS III may be long-term survivors without irradiation. More effective therapies are desperately needed.

The Journal of Clinical Endocrinology and Metabolism, Jul 9, 2019

Context: Childhood cancer survivors experience chronic health conditions that impact healthrelate... more Context: Childhood cancer survivors experience chronic health conditions that impact healthrelated quality of life (HRQOL) and participation in optimal physical activity. Objective: The study aimed to determine independent effects of endocrine and metabolic disorders on HRQOL and physical activity. Design, Setting, and Patients: Retrospective cohort with longitudinal follow-up of survivors of childhood cancer enrolled in the North American Childhood Cancer Survivor Study. Main Outcome Measures: Medical Outcomes Short Form-36 estimated HRQOL, and participation in physical activity was dichotomized as meeting or not meeting recommendations from the Centers for Disease Control and Prevention. Log binomial regression evaluated the association of each endocrine/metabolic disorder with HRQOL scales and physical activity. Results: Of 7287 survivors, with a median age of 32 years (range, 18 to 54 years) at their last followup survey, 4884 (67%) reported one or more endocrine/metabolic disorders. Survivors with either disorder were significantly more likely to be male, older, have received radiation treatment, and have experienced other chronic health conditions. After controlling for covariates, survivors with any endocrine/metabolic disorder were more likely to report poor physical function risk ratio (RR,

Neuro-oncology, Jun 1, 2018

with protons. CONCLUSION: The unintentional WVS dose varies between the different treatment techn... more with protons. CONCLUSION: The unintentional WVS dose varies between the different treatment techniques. Careful pattern of failure studies correlated with radiation dosimetry and clinical-pathological features are needed to define the role of WVS irradiation in NGGCTS.

Description of cancer survivors after exclusion of overweight/obesity and subsequent functional o... more Description of cancer survivors after exclusion of overweight/obesity and subsequent functional outcomes data without these 2 conditions within the endocrine cohor

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Neuro-Oncology, 2020

Background “Head Start” III, was a prospective clinical trial using intensive induction followed ... more Background “Head Start” III, was a prospective clinical trial using intensive induction followed by myeloablative chemotherapy and autologous hematopoietic cell rescue (AuHCR) to either avoid or reduce the dose/volume of irradiation in young children with medulloblastoma. Methods Following surgery, patients received 5 cycles of induction followed by myeloablative chemotherapy using carboplatin, thiotepa, and etoposide with AuHCR. Irradiation was reserved for children >6 years old at diagnosis or with residual tumor post-induction. Results Between 2003 and 2009, 92 children <10 years old with medulloblastoma were enrolled. Five-year event-free survival (EFS) and overall survival (OS) rates (±SE) were 46 ± 5% and 62 ± 5% for all patients, 61 ± 8% and 77 ± 7% for localized medulloblastoma, and 35 ± 7% and 52 ± 7% for disseminated patients. Nodular/desmoplastic (ND) medulloblastoma patients had 5-year EFS and OS (±SE) rates of 89 ± 6% and 89 ± 6% compared with 26 ± 6% and 53 ± 7% ...

Neuro-Oncology, 2018

The Journal of Clinical Endocrinology & Metabolism, 2019

Context Childhood cancer survivors experience chronic health conditions that impact health-relate... more Context Childhood cancer survivors experience chronic health conditions that impact health-related quality of life (HRQOL) and participation in optimal physical activity. Objective The study aimed to determine independent effects of endocrine and metabolic disorders on HRQOL and physical activity. Design, Setting, and Patients Retrospective cohort with longitudinal follow-up of survivors of childhood cancer enrolled in the North American Childhood Cancer Survivor Study. Main Outcome Measures Medical Outcomes Short Form-36 estimated HRQOL, and participation in physical activity was dichotomized as meeting or not meeting recommendations from the Centers for Disease Control and Prevention. Log binomial regression evaluated the association of each endocrine/metabolic disorder with HRQOL scales and physical activity. Results Of 7287 survivors, with a median age of 32 years (range, 18 to 54 years) at their last follow-up survey, 4884 (67%) reported one or more endocrine/metabolic disorder...

Cancer Research, 2018

Journal of pediatric oncology nursing : official journal of the Association of Pediatric Oncology Nurses

Providing timely palliative and end-of-life care (PC/EOL) information to parents of children with... more Providing timely palliative and end-of-life care (PC/EOL) information to parents of children with a serious illness is a national health care priority. The goals of this study were to determine feasibility, acceptability, and parent responses related to a PC/EOL communication intervention, titled "Communication Plan: Early through End of Life (COMPLETE)" to parents of children with a brain tumor. The study was a 2-site prospective, single-group pilot study targeting parents' stress and coping outcomes. The sample included 13 parents of 11 children (ie, 11 families). During the first 6 months postdiagnosis, we evaluated parent outcomes at 4 time points (baseline and 3 post-sessions). Our findings included significant decline in decision regret ( P = .0089); strong, significantly increased hope ( P ≤ .0001); and significantly decreased uncertainty ( P = .04). Over time, more than half of the parents (61.5%) preferred to receive information about their child's current...

Journal of Pediatric Hematology/Oncology, 2015

Utilizing a multi-parametric flow cytometry (MPFC) protocol, we assessed various cell-types impli... more Utilizing a multi-parametric flow cytometry (MPFC) protocol, we assessed various cell-types implicated in tumor angiogenesis that were found circulating in the peripheral blood of children with sarcomas (cases) based on their cell surface antigen expression. Circulating endothelial cells (CECs), endothelial colony forming cells (ECFCs) and the ratio of two distinct populations of circulating hematopoietic stem and progenitor cells (CHSPCs), the pro-angiogenic CHSPCs (pCHSPCs) and non-angiogenic CHSPCs (nCHSPCs) were enumerated. MPFC was analyzed in cases at baseline and at 4 additional time-points until the end of treatment and levels compared with each other and with healthy controls. At all time-points, cases had significantly lower levels of CECs, but elevated ECFCs and a pCHSPC:nCHSPC ratio compared to controls (all p values <0.05). There was no significant difference in any of the cell types analyzed based on tumorhistology, stage (localized v/s metastatic) or tumor-size. After treatment, only the CECs among the complete responders were significantly lower at end of therapy (p<0.01) compared to nonresponders, whereas the ECFCs among all cases significantly increased (p<0.05)) compared to baseline. No decline in the pCHSPC:nCHSPC ratio was observed despite tumor response. Based on these results, a validation of CECs as prognostic biomarker is now warranted.

Journal of Neuro-Oncology, 2013

This study investigates the outcome of children <10 years old with newly-diagnosed ependymoma tre... more This study investigates the outcome of children <10 years old with newly-diagnosed ependymoma treated on the prospective multinational "Head Start" III clinical trial. Between April 2004 and July 2009, 19 children with newly-diagnosed ependymoma were enrolled. All children were to receive five induction chemotherapy cycles followed by one consolidation cycle of myelo-ablative chemotherapy and autologous hematopoietic cell rescue. Children between 6 and 10 years of age or with residual tumor prior to consolidation were to receive irradiation thereafter. Median age of 19 children (8 female) was 20 months at diagnosis. Median follow up was 44 months. The primary site was infratentorial in 11 and supratentorial in 8 patients. Gross total resection was achieved in 10 patients. After induction chemotherapy, all three supratentorial ependymoma patients with residual disease achieved a complete response (CR), while only one of six infratentorial patients with residual disease achieved CR. Three infratentorial patients developed progressive disease during induction chemotherapy. All four infratentorial patients with residual disease who underwent autologous hematopoietic cell transplant, failed to achieve CR. Four patients received focal irradiation following chemotherapy. The 3-year event free survival (EFS) and overall survival (OS) for supratentorial ependymoma were 86 ± 13 % and 100 % respectively. The 3-year EFS and OS for infratentorial ependymoma were 27 ± 13 % and 73 ± 13 % respectively. The role of intensive induction and consolidation chemotherapy in deferring irradiation should be investigated further in children with supratentorial ependymoma with residual disease following surgery. This approach appears ineffective in children with infratentorial ependymoma in the absence of irradiation. Venkatramani et al.

Pediatric blood & cancer, Jan 22, 2016

To report the final analysis of survival outcomes for children with newly diagnosed high-grade gl... more To report the final analysis of survival outcomes for children with newly diagnosed high-grade glioma (HGG) treated on the "Head Start" (HS) II and III protocols with chemotherapy and intent to avoid irradiation in children <6 years old. Between 1997 and 2009, 32 eligible children were enrolled in HS II and III with anaplastic astrocytoma (AA, n = 19), glioblastoma multiforme (GBM, n = 11), or other HGG (n = 2). Central pathology review was completed on 78% of patients. Patients with predominantly brainstem tumors were excluded. Patients were to be treated with single induction chemotherapy regimen C, comprising four cycles of vincristine, carboplatin, and temozolomide. Following induction, patients underwent marrow-ablative chemotherapy and autologous hematopoietic cell rescue. Irradiation was used for patients with residual tumor after consolidation or >6 years old or at the time of tumor progression. The 5-year event-free survival (EFS) and overall survival (OS) f...

Journal of hematology & thrombosis, 2015

Radiation during childhood cancer treatment increases the propensity to atherosclerotic cardiovas... more Radiation during childhood cancer treatment increases the propensity to atherosclerotic cardiovascular disease among adult survivors of childhood cancer. This is thought to be mediated through the damage to the underlying vascular endothelium. Endothelial progenitor cells (EPCs) involved in vascular endothelial repair after its damage may be affected by radiation therapy but have never been investigated in adult survivors of childhood cancer. In this pilot study, utilizing multi-parametric flowcytometry, endothelial colony forming cells (ECFCs), which are the bonafide EPCs, and circulating endothelial cells (CECs), which are not EPCs, were compared between adult survivors of childhood cancer with or without radiation exposure. In addition, their associations with blood-pressure, physical activity and diet were examined. Survivors who received radiotherapy had lower ECFCs and CECs (p<0.05) compared to those without it. Significant positive correlations included physical activity w...