Mallika Marar

All Publications

• Developing next generation 3D-printing for cervical cancer hybrid brachytherapy: a guided interstitial technique enabling improved flexibility, dosimetry, and efficiency. International journal of radiation oncology, biology, physics Marar, M., Niedermayr, T., Kidd, E. 2023

  Abstract

  We developed a 3D-printed tandem anchored radially guiding interstitial template (TARGIT) to increase the simplicity of intracavitary/interstitial (IC/IS) technique for tandem-and-ovoid (T&O) procedures in cervical cancer brachytherapy. This study compared dosimetry and procedure logistics between T&O implants using the original TARGIT versus the next-generation TARGIT-Flexible-eXtended (TARGIT-FX) 3D-printed template designed for practice-changing ease-of-use with further simplified needle insertion and increased flexibility in needle placement.This single-institution retrospective cohort study included patients undergoing T&O brachytherapy as part of definitive cervical cancer treatment. Procedures utilized the original TARGIT from November 2019 through February 2022 and the TARGIT-FX from March 2022 through November 2022. The FX design features full extension to the vaginal introitus with 9 needle channels and allows for needle additions or depth adjustments intra-procedure and post-CT/MRI imaging.A total of 148 implants were performed, 68 (46%) with TARGIT and 80 (54%) with TARGIT-FX, across 41 patients. Across implants, the TARGIT-FX achieved higher mean V100% (+2.8%, p = 0.0019), and across patients, the TARGIT-FX achieved higher D90 (+2.0 Gy, p = 0.037) and higher D98 (+2.7 Gy, p = 0.016) compared to the original TARGIT. Doses to organs at risk were overall similar between templates. Procedure times for TARGIT-FX implants were 30% shorter on average than for those using the original TARGIT (p < 0.0001), and 28% shorter on average for the subset of implants with HR-CTV ≥30 cc (p = 0.013). All residents (100%, N = 6) surveyed regarding the TARGIT-FX indicated ease-of-use for needle insertion and interest in applying the technique in future practice.The TARGIT-FX achieved shorter procedure times with increased tumor coverage and similar normal tissue sparing compared to the previously applied TARGIT and illustrates the potential of 3D-printing to enhance efficiency and shorten the learning curve for IC/IS procedure technique in cervical cancer brachytherapy.

  View details for DOI 10.1016/j.ijrobp.2023.04.005

  View details for PubMedID 37059235

• Applying 3D-Printed Templates in High-Dose-Rate Brachytherapy for Cervix Cancer: Simplified Needle Insertion for Optimized Dosimetry. International journal of radiation oncology, biology, physics Marar, M., Simiele, E., Niedermayr, T., Kidd, E. A. 2022

  Abstract

  PURPOSE: In cervical cancer brachytherapy, adding interstitial (IS) needles to intracavitary (IC) applicators can enhance dosimetry by improving target coverage while limiting normal tissue dose. However, its use is limited to a subset of practitioners with appropriate technical skill. We designed Tandem Anchored Radially Guiding Interstitial Templates (TARGITs) with a 3D printing workflow to optimize needle placement and facilitate greater ease-of-use of IC/IS technique. This study compared dosimetry and procedure characteristics between tandem-and-ovoid implants (T&O) using TARGIT technique versus non-TARGIT technique.METHODS AND MATERIALS: This single-institution retrospective cohort study included patients undergoing T&O brachytherapy as part of definitive radiation treatment for cervical cancer between February 2017 and January 2021. TARGIT technique was implemented from November 2019 onwards; all prior procedures involved non-TARGIT technique using a No Needle (NN) or Freehand Needle (FN) approach. Target coverage, dose to organs-at-risk, and procedure times were evaluated and compared between TARGIT technique and non-TARGIT technique.RESULTS: The cohort included 70 patients with cervical cancer who underwent 302 T&O procedures: 68 (23%) with TARGIT technique and 234 (77%) with non-TARGIT technique, which included 133 NN and 101 FN implants. TARGIT implants involved longer average procedure times (+6.3 minutes, p<0.0001). TARGIT implants achieved a higher mean high-risk CTV V100% than non-TARGIT implants (+4.4%, p=0.001) including for large tumors 30 cc or greater (+8.1%, p=0.002). Average D90 was 4.6 Gy higher and average D98 was 3.2 Gy higher for TARGIT technique compared to non-TARGIT technique (p=0.006 and p=0.02). Total treatment doses to rectum, bowel, and bladder were not significantly different for TARGIT versus non-TARGIT technique.CONCLUSION: The 3D-printed TARGIT approach to T&O brachytherapy achieved greater tumor coverage while sparing normal tissues, particularly for large tumor volumes, with only a slight increase in average procedure time. TARGIT represents a creative technological solution for increasing accessibility of advanced IC/IS brachytherapy technique for cervical cancer definitive radiation treatment.

  View details for DOI 10.1016/j.ijrobp.2022.05.027

  View details for PubMedID 35654306

• Outcomes Among African American and Non-Hispanic White Men With Metastatic Castration-Resistant Prostate Cancer With First-Line Abiraterone. JAMA network open Marar, M., Long, Q., Mamtani, R., Narayan, V., Vapiwala, N., Parikh, R. B. 1800; 5 (1): e2142093

  Abstract

  Importance: Prospective evidence suggests abiraterone is associated with superior progression-free survival for African American men compared with non-Hispanic White men with metastatic castration-resistant prostate cancer (mCRPC).Objective: To investigate differences in outcomes with first-line abiraterone therapy between African American and non-Hispanic White men with mCRPC in a national real-world cohort.Design, Setting, and Participants: This retrospective cohort study used a nationwide electronic health record-derived database of 3808 men receiving first-line therapy for mCRPC between January 1, 2012, and December 31, 2018. Data analysis was performed between January 1, 2020, and June 1, 2021. Median follow-up was 13 months (IQR, 7-22 months). Propensity score-based inverse probability of treatment weighting was applied to reduce imbalance in measured confounders between patients receiving first-line abiraterone vs other first-line therapies. Deidentified patient data originated from a geographically diverse set of approximately 280 cancer clinics (approximately 800 sites of care) throughout the United States. Participants had newly diagnosed mCRPC and were receiving first-line systemic therapy during the study period.Exposures: Receipt of abiraterone for first-line therapy.Main Outcomes and Measures: Overall survival from start of first-line treatment. Stratified analyses investigated overall survival within each race group, with first-line enzalutamide as the comparator.Results: Among 3808 patients with mCRPC, there were 2615 non-Hispanic White men (68.7%; mean [SD] age at diagnosis, 74 [8] years) and 404 African American men (10.6%; mean [SD] age at diagnosis, 69 [9] years), and 1729 patients (45.4%) in the cohort received first-line abiraterone. Among patients receiving first-line abiraterone, African American men had higher median overall survival than non-Hispanic White men (23 months [IQR, 10-37 months] vs 17 months [IQR, 9-32 months], respectively; inverse probability of treatment weighting hazard ratio, 0.76; 95% CI, 0.60-0.98). A race-by-treatment interaction existed for first-line abiraterone vs first-line enzalutamide (hazard ratio for abiraterone vs enzalutamide: non-Hispanic White men, 1.21 [95% CI, 1.06-1.38]; African American men, 1.05 [95% CI, 0.74-1.50]; interaction P=.02). There was no overall survival difference between first-line abiraterone and first-line enzalutamide among African American patients (24 vs 24 months, respectively; inverse probability of treatment weighting hazard ratio, 1.05; 95% CI, 0.74-1.50). First-line abiraterone was associated with decreased median overall survival relative to first-line enzalutamide among non-Hispanic White patients (17 months [IQR, 9-32 months] vs 20 months [IQR, 10-36 months], respectively; inverse probability of treatment weighting hazard ratio, 1.21; 95% CI, 1.06-1.38).Conclusions and Relevance: In this cohort study of patients who received first-line systemic therapy for mCRPC, African American men who received abiraterone had improved overall survival compared with non-Hispanic White men. Future prospective studies should assess drivers of differential abiraterone outcomes in mCRPC between African American and non-Hispanic White men, including differences in genetic factors and socioeconomic status, to inform treatment strategies.

  View details for DOI 10.1001/jamanetworkopen.2021.42093

  View details for PubMedID 34985518

• Impacts of an Opioid Safety Initiative on United States Veterans Undergoing Cancer Treatment. Journal of the National Cancer Institute Vitzthum, L. K., Nalawade, V., Riviere, P., Marar, M., Furnish, T., Lin, L. A., Thompson, R., Murphy, J. D. 2022

  Abstract

  There is limited research on how the opioid epidemic and consequent risk reduction policies have impacted pain management among cancer patients. The purpose of this study is to analyze how an Opioid Safety Initiative (OSI) implemented at the Veteran's Health Administration (VHA) affected opioid prescribing patterns and opioid-related toxicity.We performed an interrupted time series analysis of 42,064 opioid-naïve patients treated at the VHA for prostate, lung, breast, and colorectal cancer from 2011-2016. Segmented regression was used to evaluate the impact of the OSI on the incidence of any new opioid prescriptions, high-risk prescriptions, persistent use, and pain-related ED visits. We compared the cumulative incidence of adverse opioid events including an opioid related admission or diagnosis of misuse before and after the OSI. All statistical tests were 2-sided.The incidence of new opioid prescriptions was 26.7% (95% CI = 25.0-28.4%) in 2011 and increased to 50.6% (95% CI = 48.3-53.0%) by 2013 prior to OSI implementation (monthly rate of change: +3.3%, 95% CI = 1.3-4.2%, p < .001). After the OSI, there was a decrease in the monthly rate of change for new prescriptions (-3.4%, 95% CI = -3.9 - -2.9%, p < .001). The implementation of the OSI was associated with a decrease in the monthly rate of change of concomitant benzodiazepines and opioid prescriptions (-2.5%, 95% CI = -3.2 - -1.8%, p < .001), no statistically significant change in high-dose opioids (-1.2%, 95% CI = -3.2-0.9%, p = .26), a decrease in persistent opioid use (-5.7%, 95% CI = -6.8 - -4.7%, p < .001), and an increase in pain-related ED visits (+3.0%, 95% CI = 1.0-5.0%, p = .003). The OSI was associated with a decreased incidence of opioid-related admissions (3-year cumulative incidence: 0.9% [95% CI = 0.7-1.0%] vs. 0.5% [95% CI = 0.4-0.6%], p < .001) and no statistically significant change in the incidence of opioid misuse (3-year cumulative incidence: 1.2% [95% CI = 1.0-1.3%] vs. 1.2% [1.1-1.4%], p = .77).The OSI was associated with a relative decline in the rate of new, persistent, and certain high-risk opioid prescribing as well as a slight increase in the rate of pain-related ED visits. Further research on patient-centered outcomes is required to optimize opioid prescribing policies for patients with cancer.

  View details for DOI 10.1093/jnci/djac017

  View details for PubMedID 35078240

• Impact of the VA opioid safety initiative on pain management for cancer patients. Marar, M., Nalawade, V., Panjwani, N., Riviere, P., Furnish, T., Lin, L. A., Thompson, R. F., Murphy, J., Vitzthum, L. K. LIPPINCOTT WILLIAMS & WILKINS. 2021

  View details for DOI 10.1200/JCO.2021.39.15_suppl.102

  View details for Web of Science ID 000708120600004