1.Assessing Patient Risk, Benefit, and Outcomes in Drug Development: A Decade of Abiraterone Clinical Trials
Matthew RASHID ; Eli OLDHAM ; Griffin K. HUGHES ; Andriana M. PEÑA ; Chase LADD ; Brooke GARDNER ; Ryan MCINTIRE ; Bradley JOHNSON ; Jordan TUIA ; Alyson HASLAM ; Vinay PRASAD ; Matt VASSAR
Journal of Urologic Oncology 2024;22(3):211-223
Purpose:
Our study aimed to evaluate the risk and benefit profiles of clinical trials using abiraterone in cancer treatment.
Materials and Methods:
A comprehensive search was conducted on May 24, 2023, using databases such as PubMed, Embase, Cochrane CENTRAL, and ClinicalTrials.gov. We extracted data on adverse events, progression-free survival, overall survival, objective response rate (ORR), and prostate-specific antigen response rate (PSA-RR). The Common Terminology Criteria for Adverse Events were used to assess risks, while ORR and PSA-RR were used to assess benefits. Trials were categorized as positive, negative, or indeterminate based on their safety profiles and efficacy outcomes.
Results:
Nearly all clinical trials testing abiraterone in prostate cancer showed promising outcomes with 89% of studies meeting their endpoint. Our study supports abiraterone’s use in prostate cancer, its only U.S. Food and Drug Administration-approved indication to treat, with a median ORR of 20.0% and a median PSA-RR of 42.0%. However, when looking at the 3 novel indications tested, the risk-to-benefit profile was similar to that of its original approval. Even though most novel indications failed to meet their primary endpoint, the overall toxicity profile was similar to that found in prostate cancer.
Conclusion
Abiraterone showed an overall risk-to-benefit portfolio that supports the use of its treatment in prostate cancer. Although the primary endpoints in ovarian and breast cancer trials were not met, the use was appropriate when assessing how the mechanism of action for abiraterone could be beneficial in patients with these types of cancers.
2.Assessing Patient Risk, Benefit, and Outcomes in Drug Development: A Decade of Abiraterone Clinical Trials
Matthew RASHID ; Eli OLDHAM ; Griffin K. HUGHES ; Andriana M. PEÑA ; Chase LADD ; Brooke GARDNER ; Ryan MCINTIRE ; Bradley JOHNSON ; Jordan TUIA ; Alyson HASLAM ; Vinay PRASAD ; Matt VASSAR
Journal of Urologic Oncology 2024;22(3):211-223
Purpose:
Our study aimed to evaluate the risk and benefit profiles of clinical trials using abiraterone in cancer treatment.
Materials and Methods:
A comprehensive search was conducted on May 24, 2023, using databases such as PubMed, Embase, Cochrane CENTRAL, and ClinicalTrials.gov. We extracted data on adverse events, progression-free survival, overall survival, objective response rate (ORR), and prostate-specific antigen response rate (PSA-RR). The Common Terminology Criteria for Adverse Events were used to assess risks, while ORR and PSA-RR were used to assess benefits. Trials were categorized as positive, negative, or indeterminate based on their safety profiles and efficacy outcomes.
Results:
Nearly all clinical trials testing abiraterone in prostate cancer showed promising outcomes with 89% of studies meeting their endpoint. Our study supports abiraterone’s use in prostate cancer, its only U.S. Food and Drug Administration-approved indication to treat, with a median ORR of 20.0% and a median PSA-RR of 42.0%. However, when looking at the 3 novel indications tested, the risk-to-benefit profile was similar to that of its original approval. Even though most novel indications failed to meet their primary endpoint, the overall toxicity profile was similar to that found in prostate cancer.
Conclusion
Abiraterone showed an overall risk-to-benefit portfolio that supports the use of its treatment in prostate cancer. Although the primary endpoints in ovarian and breast cancer trials were not met, the use was appropriate when assessing how the mechanism of action for abiraterone could be beneficial in patients with these types of cancers.
3.Assessing Patient Risk, Benefit, and Outcomes in Drug Development: A Decade of Abiraterone Clinical Trials
Matthew RASHID ; Eli OLDHAM ; Griffin K. HUGHES ; Andriana M. PEÑA ; Chase LADD ; Brooke GARDNER ; Ryan MCINTIRE ; Bradley JOHNSON ; Jordan TUIA ; Alyson HASLAM ; Vinay PRASAD ; Matt VASSAR
Journal of Urologic Oncology 2024;22(3):211-223
Purpose:
Our study aimed to evaluate the risk and benefit profiles of clinical trials using abiraterone in cancer treatment.
Materials and Methods:
A comprehensive search was conducted on May 24, 2023, using databases such as PubMed, Embase, Cochrane CENTRAL, and ClinicalTrials.gov. We extracted data on adverse events, progression-free survival, overall survival, objective response rate (ORR), and prostate-specific antigen response rate (PSA-RR). The Common Terminology Criteria for Adverse Events were used to assess risks, while ORR and PSA-RR were used to assess benefits. Trials were categorized as positive, negative, or indeterminate based on their safety profiles and efficacy outcomes.
Results:
Nearly all clinical trials testing abiraterone in prostate cancer showed promising outcomes with 89% of studies meeting their endpoint. Our study supports abiraterone’s use in prostate cancer, its only U.S. Food and Drug Administration-approved indication to treat, with a median ORR of 20.0% and a median PSA-RR of 42.0%. However, when looking at the 3 novel indications tested, the risk-to-benefit profile was similar to that of its original approval. Even though most novel indications failed to meet their primary endpoint, the overall toxicity profile was similar to that found in prostate cancer.
Conclusion
Abiraterone showed an overall risk-to-benefit portfolio that supports the use of its treatment in prostate cancer. Although the primary endpoints in ovarian and breast cancer trials were not met, the use was appropriate when assessing how the mechanism of action for abiraterone could be beneficial in patients with these types of cancers.
4.In Vertebral Hemangiomas with Neurological Deficit, Is a Less Extensive Approach Adequate
Guna Pratheep K. ; Ajoy Prasad SHETTY ; Sri Vijay Anand K. S. ; Rohit KAVISHWAR ; Rishi Mugesh KANNA ; Shanmuganathan RAJASEKARAN
Asian Spine Journal 2023;17(1):37-46
Methods:
Twenty-one patients who underwent surgery for AVH between 2009 and 2018 were analyzed. Demographic and clinical details of patients were retrieved from hospital information system. Imaging information (i.e., radiography, computed tomography, magnetic resonance imaging) of all patients was accessed and analyzed in picture archiving and communication system. Tumor staging was performed using Enneking and Weinstein–Boriani–Biagini classifications and Spinal Instability Neoplastic Score. At followup, neurological and radiological evaluations were performed.
Results:
Twenty-one patients (13 [61.9%] females and 8 [38.1%] males) were included with a mean age of 44.29 years (range, 14–72 years). All patients in the study had neurological deficit. Back pain was present in 80.9% of patients. Mean duration of symptoms was 4.6 months (range, 1 day to 10 months). Most common lesion location was thoracic spine (n=12), followed by thoracolumbar (D11– L2; n=7) and lumbar (n=2) regions. Ten patients had multiple level lesions. All patients underwent preoperative embolization. Nine patients underwent intralesional spondylectomy with reconstruction; another nine patients underwent stabilization, decompression, and vertebroplasty; three patients underwent decompression and stabilization. Neurology improved in all patients, and only one case of recurrence was noted in a mean follow-up of 55.78±25 months (range, 24–96 months).
Conclusions
In AVH, good clinical and neurological outcomes with low recurrence rates can be achieved using less extensive procedures, such as posterior instrumented decompression with vertebroplasty and intralesional tumor resection.
5.Novel Biomarkers of Health and Degeneration in Human Intervertebral Discs: In-depth Proteomic Analysis of Collagen Framework of Fetal, Healthy, Scoliotic, Degenerate, and Herniated Discs
Shanmuganathan RAJASEKARAN ; Dilip Chand Raja SOUNDARARAJAN ; Sharon Miracle NAYAGAM ; Chitraa TANGAVEL ; Muthuraja RAVEENDRAN ; Sri Vijay Anand K S ; Ajoy Prasad SHETTY ; Rishi Mugesh KANNA
Asian Spine Journal 2023;17(1):17-29
Methods:
Forty NP tissues were snap-frozen in liquid nitrogen (–196°C) immediately before being subjected to proteomic and bioinformatic analyses from five different disk phenotypes (eight each).
Results:
Tandem mass spectrometric analysis revealed a total of 1,050 proteins in FDs, 1,809 in ND, 1,487 in SD, 1,859 in DH, and 1,538 in the DD group. Of 28 major collagens reported in the human body, this study identified 24 different collagens with 34 subtypes in NP. Fibril-forming collagens (COL-1, 2, and 11A1) and fibril-associated collagens with interrupted triple helices (COL-9A1, 12A1, and 14A1) were abundantly expressed in FDs, representing their role in the development of NP. Multiplexin (COL-15), a hybrid proteoglycan–collagen molecule, was discovered only in FDs. Degeneration was associated with COL2A1 downregulation and COL-10A1 upregulation.
Conclusions
COL10 was discovered to be a new biomarker for disk degeneration. Besides COL-1 and 2, other important COLs (6, 9, 11, 12, 14, 15) with anabolic potential and abundant expression in the fetal phenotype could be investigated for tissue engineering and novel DDD therapy.
6.Craniospinal irradiation for respiratory failure secondary to central nervous system Erdheim-Chester disease
Rahul N. PRASAD ; Peter J. KOBALKA ; Haley K. PERLOW ; Daniel M. PREVEDELLO ; Dukagjin M. BLAKAJ ; Raju R. RAVAL ; Joshua D. PALMER
Radiation Oncology Journal 2022;40(2):162-168
Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis typically featuring lower extremity osteosclerosis (96%) from Langerin-negative histiocytes with fibrosis. Central nervous system (CNS)-only disease is extremely rare, and particularly difficult to diagnose and manage. Neurologic complaints may be refractory to systemic therapy (ST), and the role of radiation therapy (RT) is undefined. We present a patient with ECD of the medulla complicated by respiratory failure and strength deficits with disseminated leptomeningeal disease (LMD) but not systemic disease, representing the first report of CNS-limited ECD with LMD. He received upfront craniospinal irradiation (CSI), representing a rare account of CSI for ESD, with marked clinical improvement resulting in extubation and improved strength. CSI facilitated excellent preservation of quality of life, and no treatment-related toxicity was observed prior to eventual, unrelated cardiopulmonary arrest. Thus, palliative CSI may augment ST by safely offering improved local control and symptomatic relief for CNS ECD.
7.Impact of Patient Counseling and Socioeconomic Factors on Initiation of Rehabilitation Program in Spinal Cord Injury Patients Presenting to a Tertiary Spine Unit in India
Siddharth Narasimhan AIYER ; Vignesh GUNASEKARAN ; Latha MANI ; Sri Vijay Anand K. S. ; Shanmuganathan RAJASEKARAN ; Ajoy Prasad SHETTY
Asian Spine Journal 2021;15(3):357-364
Prospective case series. This study aimed to investigate the impact of education, financial income, occupation, and patient counseling on the timing of enrolment in a spinal cord injury (SCI) rehabilitation program. A rehabilitation program following SCI is essential to improve functional outcomes. Socioeconomic factors can affect the timing of enrolment to a rehabilitation program. Literature on the effects of socioeconomic factors among patients with SCI in the Indian scenario is limited. A prospective, consecutive analysis of patients with SCI was performed with 1-year follow-up. Assessment of the timing of enrolment to a rehabilitation program was performed using the modified Kuppuswamy socioeconomic scores (MKSS). Patients admitted to the SCI unit (group A), underwent intensive individual, group, and family counseling sessions to encourage early enrolment into a rehabilitation program. Patients presenting directly for rehabilitation (group B) were analyzed for comparison. A total of 153 patients were recruited. Group A was composed of 122 patients who started the rehabilitation program after a mean of 28 days, compared with a mean of 149 days for 31 patients in group B. In group A, 104 patients (85%; mean MKSS, 14.02) and 18 patients (15%; mean MKSS, 15.61) enrolled for rehabilitation <6 weeks and ≥6 weeks, respectively. In group B, 12 patients (39%; mean MKSS, 13.69) and 19 patients (61%; mean MKSS, 12.10) enrolled for rehabilitation <6 weeks and ≥6 weeks, respectively. The total MKSS and scores for education, income, and occupation did not show a significant difference between the two both groups (p>0.05). Early patient counseling in the acute care unit helps in the early enrolment of patients with poor socioeconomic demographic profile to a rehabilitation program.
8.Impact of Patient Counseling and Socioeconomic Factors on Initiation of Rehabilitation Program in Spinal Cord Injury Patients Presenting to a Tertiary Spine Unit in India
Siddharth Narasimhan AIYER ; Vignesh GUNASEKARAN ; Latha MANI ; Sri Vijay Anand K. S. ; Shanmuganathan RAJASEKARAN ; Ajoy Prasad SHETTY
Asian Spine Journal 2021;15(3):357-364
Prospective case series. This study aimed to investigate the impact of education, financial income, occupation, and patient counseling on the timing of enrolment in a spinal cord injury (SCI) rehabilitation program. A rehabilitation program following SCI is essential to improve functional outcomes. Socioeconomic factors can affect the timing of enrolment to a rehabilitation program. Literature on the effects of socioeconomic factors among patients with SCI in the Indian scenario is limited. A prospective, consecutive analysis of patients with SCI was performed with 1-year follow-up. Assessment of the timing of enrolment to a rehabilitation program was performed using the modified Kuppuswamy socioeconomic scores (MKSS). Patients admitted to the SCI unit (group A), underwent intensive individual, group, and family counseling sessions to encourage early enrolment into a rehabilitation program. Patients presenting directly for rehabilitation (group B) were analyzed for comparison. A total of 153 patients were recruited. Group A was composed of 122 patients who started the rehabilitation program after a mean of 28 days, compared with a mean of 149 days for 31 patients in group B. In group A, 104 patients (85%; mean MKSS, 14.02) and 18 patients (15%; mean MKSS, 15.61) enrolled for rehabilitation <6 weeks and ≥6 weeks, respectively. In group B, 12 patients (39%; mean MKSS, 13.69) and 19 patients (61%; mean MKSS, 12.10) enrolled for rehabilitation <6 weeks and ≥6 weeks, respectively. The total MKSS and scores for education, income, and occupation did not show a significant difference between the two both groups (p>0.05). Early patient counseling in the acute care unit helps in the early enrolment of patients with poor socioeconomic demographic profile to a rehabilitation program.
9.Effect of dexmedetomidine on dynamic cerebral autoregulation and carbon dioxide reactivity during sevoflurane anesthesia in healthy patients
Sujoy BANIK ; Girija Prasad RATH ; Ritesh LAMSAL ; Parmod K BITHAL
Korean Journal of Anesthesiology 2020;73(4):311-318
Background:
There are conflicting opinions on the effect of dexmedetomidine on cerebral autoregulation. This study assessed its effect on dynamic cerebral autoregulation (dCA) using a transcranial Doppler (TCD).
Methods:
Thirty American Society of Anesthesiologists physical status I and II patients between 18 and 60 years, who underwent lumbar spine surgery, received infusions of dexmedetomidine (Group D) or normal saline (Group C), followed by anesthesia with propofol and fentanyl, and maintenance with oxygen, nitrous oxide and sevoflurane. After five minutes of normocapnic ventilation and stable bispectral index value (BIS) of 40-50, the right middle cerebral artery flow velocity (MCAFV) was recorded with TCD. The transient hyperemic response (THR) test was performed by compressing the right common carotid artery for 5-7 seconds. The lungs were hyperventilated to test carbon dioxide (CO2) reactivity. Hemodynamic parameters, arterial CO2 tension, pulse oximetry (SpO2), MCAFV and BIS were measured before and after hyperventilation. Dexmedetomidine infusion was discontinued ten minutes before skin-closure. Time to recovery and extubation, modified Aldrete score, and emergence agitation were recorded.
Results:
Demographic parameters, durations of surgery and anesthesia, THR ratio (Group D: 1.26 ± 0.11 vs. Group C: 1.23 ± 0.04; P = 0.357), relative CO2 reactivity (Group D: 1.19 ± 0.34 %/mmHg vs. Group C: 1.23 ± 0.25 %/mmHg; P = 0.547), blood pressure, SpO2, BIS, MCAFV, time to recovery, time to extubation and modified Aldrete scores were comparable.
Conclusions
Dexmedetomidine administration does not impair dCA and CO2 reactivity in patients undergoing spine surgery under sevoflurane anesthesia.
10.Patterns of failure and clinical outcomes of post-operative buccal mucosa cancers treated with adjuvant ipsilateral radiotherapy
Satyajeet RATH ; Ajeet K. GANDHI ; Madhup RASTOGI ; Rohini KHURANA ; Rahat HADI ; Harikesh B. SINGH ; Sambit S. NANDA ; Mohammad AZAM ; Anoop SRIVASTAVA ; Avinav BHARATI ; Surendra Prasad MISHRA
Radiation Oncology Journal 2020;38(3):189-197
Purpose:
Adjuvant radiotherapy (RT) in buccal mucosa cancers is guided by histopathological factors. The decision to treat ipsilateral or bilateral draining lymph node is on physician discretion and guidelines do not have a defined indication regarding this. We aimed to analyze the failure patterns and survival in buccal mucosa cancers treated with adjuvant ipsilateral RT.
Materials and Methods:
One hundred sixteen cases of post-operative buccal mucosa cancers—pT3 or more, node positive, close margins (1–5 mm), lymphovascular invasion positive, perineural invasion positive, depth of invasion >4 mm—treated with RT to primary and ipsilateral nodes from May 2013 to May 2019 were retrospectively analyzed. Patients were treated to a dose of 60–66 Gy (44 Gy in the first phase and a coned down boost of 16–22 Gy in the second phase) with three-dimensional conformal radiotherapy on a linear accelerator. Primary end point was to assess control rates and secondary end point was to evaluate the overall survival (OS) and disease-free survival (DFS) outcomes.
Results:
Median age was 46 years with male; female ratio of 110:6. The edition of the American Joint Committee on Cancer stage distributions were I (3.4%), II (34.4%), III (24.1%), and IV (37.9%). At a median follow-up of 22 months, crude rates of local failure, regional failure, and contralateral neck failure were 9.4%, 10.3%, and 3.4%, respectively. The 2-year contralateral neck control rate was 94.9%. Pathological positive node portended poorer OS (86.6% vs. 68.6%; p = 0.015) and DFS (86.5% vs. 74.9%; p = 0.01).
Conclusion
Incidence of contralateral recurrence with ipsilateral irradiation in buccal mucosa cancers is low with descent survival outcomes, particularly in node negative cases.

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