Chandana A Reddy

Moncrief Cancer Institute, Fort Worth, Texas, United States

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Publications (278)1028.24 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Despite revisions in 2005 and 2014, the Gleason prostate cancer (PCa) grading system still has major deficiencies. Combining of Gleason scores into a three-tiered grouping (6, 7, 8-10) is used most frequently for prognostic and therapeutic purposes. The lowest score, assigned 6, may be misunderstood as a cancer in the middle of the grading scale, and 3+4=7 and 4+3=7 are often considered the same prognostic group. To verify that a new grading system accurately produces a smaller number of grades with the most significant prognostic differences, using multi-institutional and multimodal therapy data. Between 2005 and 2014, 20 845 consecutive men were treated by radical prostatectomy at five academic institutions; 5501 men were treated with radiotherapy at two academic institutions. Outcome was based on biochemical recurrence (BCR). The log-rank test assessed univariable differences in BCR by Gleason score. Separate univariable and multivariable Cox proportional hazards used four possible categorizations of Gleason scores. In the surgery cohort, we found large differences in recurrence rates between both Gleason 3+4 versus 4+3 and Gleason 8 versus 9. The hazard ratios relative to Gleason score 6 were 1.9, 5.1, 8.0, and 11.7 for Gleason scores 3+4, 4+3, 8, and 9-10, respectively. These differences were attenuated in the radiotherapy cohort as a whole due to increased adjuvant or neoadjuvant hormones for patients with high-grade disease but were clearly seen in patients undergoing radiotherapy only. A five-grade group system had the highest prognostic discrimination for all cohorts on both univariable and multivariable analysis. The major limitation was the unavoidable use of prostate-specific antigen BCR as an end point as opposed to cancer-related death. The new PCa grading system has these benefits: more accurate grade stratification than current systems, simplified grading system of five grades, and lowest grade is 1, as opposed to 6, with the potential to reduce overtreatment of PCa. We looked at outcomes for prostate cancer (PCa) treated with radical prostatectomy or radiation therapy and validated a new grading system with more accurate grade stratification than current systems, including a simplified grading system of five grades and a lowest grade is 1, as opposed to 6, with the potential to reduce overtreatment of PCa. Copyright © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.
    European Urology 07/2015; DOI:10.1016/j.eururo.2015.06.046 · 12.48 Impact Factor
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    ABSTRACT: The patterns of intracranial failure in patients with brain metastasis from pulmonary neuroendocrine carcinoma (PNEC) remain unknown. From 1998 to 2013, 29 patients with the diagnosis of PNEC were treated for brain metastasis: 16 patients (55%) underwent whole-brain radiation therapy (WBRT), 5 (17%) patients underwent WBRT with a stereotactic radiosurgery (SRS) boost, and 8 (28%) patients underwent primary SRS alone. The median age at treatment was 61 years (range: 44-84 years) and the median follow-up was 9.6 months (0-157.4 months). Of the patients treated with SRS alone, 1 patient had radiographic local progression of disease and 1 patient had a distant intracranial failure. Of the patients treated with WBRT with or without an SRS boost, 9 patients developed intracranial progression, including 1 local failure. No differences in rates of intracranial progression or local failure between the 2 groups (P = .94 and P = .44, respectively) were observed. The actuarial rates of distant intracranial failure at 12 months were 32.9% (95% confidence interval [95% CI] 8.9%-56.8%) and 25% (95% CI 0.0%-67.4%) in patients undergoing primary WBRT or SRS, respectively (P = .31). The median overall survival was 15.8 months in patients treated with WBRT and 20.4 months in patients treated with primary SRS (P = .78). Patients with brain metastasis from PNECs can be effectively treated with either WBRT or SRS alone, with a pattern of failure more consistent with non-small cell lung cancer than small cell lung cancer. In this series, there was not a statistically significant increased risk of distant intracranial failure when patients were treated with primary SRS. © The Author(s) 2015.
    Technology in cancer research & treatment 06/2015; DOI:10.1177/1533034615589033 · 1.94 Impact Factor
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    ABSTRACT: Severe late dysphagia (SLD) is common after chemoradiation (CRT) for cancers of the larynx and oropharynx. Options for reduction of SLD are limited for HPV-negative patients. Here the role of feeding tube (FT) choice in SLD is investigated. Patients disease-free after CRT for HPV-negative cancers of the laryngopharynx who received a FT on-treatment were identified. The incidence of SLD after reactive nasogastric (R-NG), proactive or reactive percutaneous gastrostomy (P-PEG and R-PEG) was assessed using log-rank and Cox analyses. 78 patients received a FT on-treatment and remained disease-free. Median follow-up was 64 months. The 5-year incidence of SLD was 30.8% in the R-NG cohort (n=36), 56.4% in the R-PEG (n=17, p=0.193) and 60.9% in the P-PEG (n=25, p=0.016) cohorts. On multivariate analysis, PEG feeding was independently associated with an increased rate of SLD. R-NG use during chemoradiation is associated with less SLD and is preferred over PEG. This article is protected by copyright. All rights reserved. © 2015 Wiley Periodicals, Inc.
    Head & Neck 06/2015; DOI:10.1002/hed.24157 · 3.01 Impact Factor
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    ABSTRACT: Definitive resection of primary rectal cancers is frequently incorporated, with or without preoperative radiotherapy and perioperative chemotherapy, in the management of selected patients with metastatic rectal adenocarcinoma. This study reviews the impact of preoperative radiotherapy and perioperative chemotherapy on locoregional recurrence and overall survival in these patients. This retrospective study with an Institutional Review Board (IRB) waiver included 109 patients with metastatic rectal adenocarcinoma who underwent definitive primary resection between 1998 and 2011. In addition to resection, 64 patients were treated with preoperative radiotherapy and perioperative chemotherapy and 45 patients were treated with perioperative chemotherapy alone. Radiotherapy dose was typically 50.4 Gy. Baseline variables were compared using chi-square and unpaired t tests. Overall survival was calculated using Kaplan-Meier method. Univariate and multivariate analyses were performed using Cox proportional hazards regression. There were no significant baseline differences between the two groups. There was no significant difference in locoregional recurrence (10.9 vs. 11.1 %; p = 0.90) or overall survival (34.5 vs. 34.8 months; p = 0.89) for patients treated with preoperative radiotherapy compared to those treated with perioperative chemotherapy alone, respectively. Patients who underwent radiotherapy were less likely to have a positive margin (10.9 vs. 20.0 %; p = 0.19), lymphovascular invasion (32.8 vs. 53.3 %; p = 0.03), and pathologic stage N2 disease (25.0 vs. 42.2 %; p = 0.02). Grade 2 postoperative complications were more common in the preoperative radiotherapy group (32.8 vs. 15.6 %; p = 0.04). Multivariate analysis demonstrated that patients with poorly differentiated tumors (HR 2.19; p = 0.009) and those that did not undergo liver-directed therapy (HR 2.20; p = 0.005) had inferior survival. Locoregional recurrence is modest in patients with metastatic rectal adenocarcinoma receiving definitive primary resection, irrespective of the use of radiotherapy. Preoperative radiotherapy may enhance pathologic downstaging at the expense of increased grade 2 postoperative complications. Its use should be reserved for patients at high risk for locoregional recurrence.
    Journal of Gastrointestinal Surgery 05/2015; DOI:10.1007/s11605-015-2861-9 · 2.39 Impact Factor
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    ABSTRACT: To report long-term efficacy and toxicity for a single-institution cohort of patients treated with low-dose-rate prostate brachytherapy permanent implant (PI) monotherapy. From 1996 to 2007, 1989 patients with low-risk (61.3%), intermediate-risk (29.8%), high-intermediate-risk (4.5%), and high-risk prostate cancer (4.4%) were treated with PI and followed up prospectively in a registry. All patients were treated with (125)I monotherapy to 144 Gy. Late toxicity was coded retrospectively according to a modified Common Terminology Criteria for Adverse Events 4.0 scale. The rates of biochemical relapse-free survival (bRFS), distant metastasis-free survival (DMFS), overall survival (OS), and prostate cancer-specific mortality (PCSM) were calculated. We identified factors associated with late grade ≥3 genitourinary (GU) and gastrointestinal (GI) toxicity, bRFS, DMFS, OS, PCSM, and incontinence. The median age of the patients was 67 years, and the median overall and prostate-specific antigen follow-up times were 6.8 years and 5.8 years, respectively. The overall 5-year rates for bRFS, DMFS, OS, and PCSM were 91.9%, 97.8%, 93.7%, and 0.71%, respectively. The 10-year rates were 81.5%, 91.5%, 76.1%, and 2.5%, respectively. The overall rates of late grade ≥3 GU and GI toxicity were 7.6% and 0.8%, respectively. On multivariable analysis, age and prostate length were significantly associated with increased risk of late grade ≥3 GU toxicity. The risk of incontinence was highly correlated with both pre-PI and post-PI transurethral resection of the prostate. Prostate brachytherapy as monotherapy is an effective treatment for low-risk and low-intermediate-risk prostate cancer and appears promising as a treatment for high-intermediate-risk and high-risk prostate cancer. Significant long-term toxicities are rare when brachytherapy is performed as monotherapy. Copyright © 2015 Elsevier Inc. All rights reserved.
    International journal of radiation oncology, biology, physics 05/2015; DOI:10.1016/j.ijrobp.2015.02.047 · 4.18 Impact Factor
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    ABSTRACT: A prognostic model for 5-year overall survival (OS), consisting of recursive partitioning analysis (RPA) and a nomogram, was developed for patients with early-stage non-small cell lung cancer (ES-NSCLC) treated with stereotactic ablative radiation therapy (SABR). A primary dataset of 703 ES-NSCLC SABR patients was randomly divided into a training (67%) and an internal validation (33%) dataset. In the former group, 21 unique parameters consisting of patient, treatment, and tumor factors were entered into an RPA model to predict OS. Univariate and multivariate models were constructed for RPA-selected factors to evaluate their relationship with OS. A nomogram for OS was constructed based on factors significant in multivariate modeling and validated with calibration plots. Both the RPA and the nomogram were externally validated in independent surgical (n=193) and SABR (n=543) datasets. RPA identified 2 distinct risk classes based on tumor diameter, age, World Health Organization performance status (PS) and Charlson comorbidity index. This RPA had moderate discrimination in SABR datasets (c-index range: 0.52-0.60) but was of limited value in the surgical validation cohort. The nomogram predicting OS included smoking history in addition to RPA-identified factors. In contrast to RPA, validation of the nomogram performed well in internal validation (r(2)=0.97) and external SABR (r(2)=0.79) and surgical cohorts (r(2)=0.91). The Amsterdam prognostic model is the first externally validated prognostication tool for OS in ES-NSCLC treated with SABR available to individualize patient decision making. The nomogram retained strong performance across surgical and SABR external validation datasets. RPA performance was poor in surgical patients, suggesting that 2 different distinct patient populations are being treated with these 2 effective modalities. Copyright © 2015 Elsevier Inc. All rights reserved.
    International journal of radiation oncology, biology, physics 05/2015; DOI:10.1016/j.ijrobp.2015.05.003 · 4.18 Impact Factor
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    ABSTRACT: To ascertain the safety and efficacy of permanent prostate brachytherapy (PPB) in early prostate cancer patients who have undergone previous total proctocolectomy and J-pouch anastomosis for inflammatory bowel disease. We identified 10 patients with a previous history of prostate cancer and J-pouch anastomosis from our institutional review board-approved database. Seven patients had PPB and 3 had prostatectomy. Only patients treated with PPB were included. Patient records were reviewed to collect data on treatment-related toxicity and oncological outcomes. All 7 patients who underwent PPB had low- to intermediate-risk prostate cancer. The mean prostatic volume was 24.40 mL and the average number of iodine-125 seeds implanted was 84. Postimplant dosimetric calculations showed a mean prostate volume receiving 100% of the prescribed dose (V100) of 88.76%, V150 of 45.23%, V200 of 16.79%, radiation dose delivered to 90% of the prostate of 147.89 Gy, volume of ileal pouch receiving 100% of the prescribed dose of 0.164 mL, and volume of ileal pouch receiving 50% of the prescribed dose of 1.38 mL. After a mean follow-up of 19 months, none of the patients had evidence of biochemical failure or clinical failure. There were no long-term genitourinary side effects detected. Two patients had Common Terminology Criteria for Adverse Events version 4.0 grade II gastrointestinal side effects, of which symptoms resolved to baseline in 1 patient, whereas the other patient progressed to chronic active enteritis (pouchitis). Low- to intermediate-risk prostate cancer patients with J-pouch anastomosis after total colectomy for inflammatory bowel disease are candidates for definitive treatment with PPB. Caution should be exercised while deploying the most posterior row of seeds to minimize enteral pouch radiation doses. Copyright © 2015 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.
    04/2015; DOI:10.1016/j.prro.2015.03.002
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    ABSTRACT: To examine the influence of zone-specific dosimetry on outcomes during permanent prostate implantation (PI), where the peripheral zone (PZ) and transitional zone (TZ) may receive varying radiation doses. Four hundred and sixteen patients treated with I-125 PI (target dose: 144 Gy) between 1996 and 2003 were included in this Institutional Review Board (IRB) approved, retrospective analysis. Whole prostate (WP), TZ, and PZ were contoured, and zone-specific D90 and V100 were computed. Their influence on biochemical failure (BF) was evaluated using Cox proportional hazards analysis. The median age and initial prostate-specific antigen (PSA) was 68 years and 6.1 ng/ml, respectively, and the median follow-up time was 8.8 years. There were 329 subjects with Gleason score (GS) 6 disease (79.1%), and 82 subjects had GS 7 disease (19.7%). Androgen deprivation therapy (ADT) was used in 20.4% of patients. Median D90 and V100% in the WP, PZ, and TZ were 141.2 Gy, 156.1 Gy, and 134.5 Gy; and 88.8%, 93.3%, and 84.2%, respectively. Ten-year rates for biochemical recurrence-free survival, distant metastasis-free survival, and prostate cancer-specific mortality were 82.4%, 92.4%, and 0.97% respectively. Only initial PSA, GS7+ disease, ADT, and PSA frequency were significant on multivariate analysis. Ten-year rates of grade 3 or higher GU and GI toxicity was 10.9% and 1.8%, respectively. TZ V200 and TZ V300 were significantly associated with late genitourinary toxicity. The TZ received significantly lower doses of radiation compared to the PZ. On multivariate analysis, no dosimetric parameter was associated with efficacy. Higher TZ doses may be associated with higher late GU toxicity without improving efficacy.
    Journal of Contemporary Brachytherapy 02/2015; 7(1):17-22. DOI:10.5114/jcb.2015.48875
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    ABSTRACT: Androgen deprivation therapy (ADT) is typically provided neoadjuvantly and concurrently with radiotherapy (RT) in the management of intermediate and high-risk prostate cancer. Our objective was to compare outcomes between patients who received adjuvant ADT (ADJ), ie, immediately after the completion of RT, to those who received a neoadjuvant and concurrent regimen (NEO). From 1995 to 2002, 515 patients with prostate cancer were definitively treated with RT and ADT. NEO was provided 2 to 3 months before the start of RT (n = 311). ADJ was initiated immediately after the completion of RT (n = 204). Kaplan-Meier analysis was used to calculate biochemical relapse-free survival (bRFS), distant metastasis-free survival (DMFS), and overall survival (OS). Cox proportional hazards regression was used to examine the impact of ADT timing on outcomes. Ten-year bRFS, DMFS, and OS rates were 61%, 80%, and 66%, respectively. Ten-year bRFS rates for ADJ versus NEO were 63% versus 60% (P = .98). Ten-year DMFS rates for ADJ versus NEO were both 80% (P = .60). Ten-year OS rates for ADJ versus NEO were 65% versus 67% (P = .98). There was no significant difference in bRFS, DMFS, or OS between neoadjuvant versus adjuvant ADT in the setting of dose-escalated RT for localized prostate cancer. This suggests that the synergy between RT and androgen deprivation is independent of the sequencing of both modalities and that the initiation of RT does not need to be delayed for a course of neoadjuvant ADT. Copyright © 2015 Elsevier Inc. All rights reserved.
    Clinical Genitourinary Cancer 12/2014; 13(3). DOI:10.1016/j.clgc.2014.12.009 · 1.69 Impact Factor
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    ABSTRACT: Object Traditionally, the treatment of choice for patients with metastases to the calvaria or skull base has been conventional radiation therapy. Because patients with systemic malignancies are also at risk for intracranial metastases, the utility of Gamma Knife surgery (GKS) for these patients has been explored to reduce excess radiation exposure to the perilesional brain parenchyma. The purpose of this study was to report the efficacy of GKS for the treatment of calvarial metastases and skull base lesions. Methods The authors performed a retrospective chart review of 21 patients with at least 1 calvarial or skull base metastatic lesion treated with GKS during 2001-2013. For 7 calvarial lesions, a novel technique, in which a bolus was placed over the treatment site, was used. For determination of local control or disease progression, radiation therapy data were examined and posttreatment MR images and oncology records were reviewed. Survival times from the date of procedure were estimated by using Kaplan-Meier analyses. Results The median patient age at treatment was 57 years (range 29-84 years). A total of 19 (90%) patients received treatment for single lesions, 1 patient received treatment for 3 lesions, and 1 patient received treatment for 4 lesions. The most common primary tumor was breast cancer (24% of patients). Per lesion, the median clinical and radiographic follow-up times were 10.3 months (range 0-71.9 months) and 7.1 months (range 0-61.3 months), respectively. Of the 26 lesions analyzed, 14 (54%) were located in calvarial bones and 12 (46%) were located in the skull base. The median lesion volume was 5.3 cm(3) (range 0.3-55.6 cm(3)), and the median prescription margin dose was 15 Gy (range 13-24 Gy). The median overall survival time for all patients was 35.9 months, and the 1-year local control rate was 88.9% (95% CI 74.4%-100%). Local control rates did not differ between lesions treated with the bolus technique and those treated with traditional methods or between calvarial lesions and skull base lesions (p > 0.05). Of the 3 patients for whom local treatment failed, 1 patient received no further treatment and 2 patients responded to salvage chemotherapy. Subsequent brain parenchymal metastases developed in 2 patients, who then underwent GKS. Conclusions GKS is an effective treatment modality for patients with metastases to the calvarial bones or skull base. For patients with superficial calvarial lesions, a novel approach with bolus application resulted in excellent rates of local control. GKS provides an effective therapeutic alternative to conventional radiation therapy and should be considered for patients at risk for calvarial metastases and brain parenchymal metastases.
  • International journal of radiation oncology, biology, physics 11/2014; 90(5). DOI:10.1016/j.ijrobp.2014.08.155 · 4.18 Impact Factor
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    ABSTRACT: Introduction: To examine regional nodal failure patterns with respect to lesion size in medically inoperable early-stage non-small cell lung cancer (NSCLC) patients treated with definitive lung stereotactic body radiation therapy (SBRT). Methods: Between 2004 and 2012, 342 medically inoperable early-stage NSCLC patients treated with definitive SBRT were identified in our institutional review board-approved prospective registry. All patients were treated on a Novalis/BrainLAB system using ExacTrac for image guidance. Kaplan-Meier analysis was performed with the log-rank test used to detect differences between lesion size and nodal failure patterns. Cox-proportional hazard regression analysis was performed to identify predictors of nodal failure. Results: Median follow-up was 17.6 months (range, 0-84 months). Median tumor size, positron emission tomography maximum standardized uptake value, and dose/fractionation were 2.2 cm (range, 0.8-7.2 cm), 6.7 (range, 1-59), and 50 Gray (Gy)/five fractions, respectively. Of the 342 lesions evaluated, 14.6% (50 of 342) experienced nodal failure. Nodal failure rates were 17.45% (26 of 149), 10.3% (11 of 107), 14.1% (10 of 71), and 20% (3 of 15) for lesions less than or equal to 2 cm, 2.1 to 3 cm, 3.1 to 5 cm, and greater than 5 cm, respectively. Rates of nodal failure were not significantly different between the four different size groups (p = 0.15). On univariate analysis, 2.1 to 3 cm lesions versus less than or equal to 2 cm exhibited less nodal failure after SBRT (hazard ratio = 0.406; 95% confidence interval = 0.189-0.87; p = 0.0205). No other patient, tumor, or treatment factor significantly affected nodal failure. Conclusion: For early-stage NSCLC treated with SBRT, tumor size does not influence the rates of regional nodal failure. This finding warrants further investigation on the possible mechanisms of SBRT by which loco-regional control is improved.
    Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 09/2014; 9(11). DOI:10.1097/JTO.0000000000000313 · 5.80 Impact Factor
  • International journal of radiation oncology, biology, physics 09/2014; 90(1):S542. DOI:10.1016/j.ijrobp.2014.05.1646 · 4.18 Impact Factor
  • International journal of radiation oncology, biology, physics 09/2014; 90(1):S317. DOI:10.1016/j.ijrobp.2014.05.1054 · 4.18 Impact Factor
  • International journal of radiation oncology, biology, physics 09/2014; 90(1):S301. DOI:10.1016/j.ijrobp.2014.05.1011 · 4.18 Impact Factor
  • International journal of radiation oncology, biology, physics 09/2014; 90(1):S659. DOI:10.1016/j.ijrobp.2014.05.1945 · 4.18 Impact Factor
  • International journal of radiation oncology, biology, physics 09/2014; 90(1):S28. DOI:10.1016/j.ijrobp.2014.05.130 · 4.18 Impact Factor
  • International journal of radiation oncology, biology, physics 09/2014; 90(1):S567-S568. DOI:10.1016/j.ijrobp.2014.05.1714 · 4.18 Impact Factor
  • M. Naik · C.A. Reddy · K.L. Stephans · R.D. Tendulkar
    International journal of radiation oncology, biology, physics 09/2014; 90(1):S155-S156. DOI:10.1016/j.ijrobp.2014.05.638 · 4.18 Impact Factor
  • Z. Zheng · E. Onukwugha · C.A. Reddy · J.P. Ciezki
    International journal of radiation oncology, biology, physics 09/2014; 90(1):S444. DOI:10.1016/j.ijrobp.2014.05.1394 · 4.18 Impact Factor

Publication Stats

3k Citations
1,028.24 Total Impact Points

Institutions

  • 2009–2015
    • Moncrief Cancer Institute
      Fort Worth, Texas, United States
  • 2001–2015
    • Cleveland Clinic
      • Department of Radiation Oncology
      Cleveland, Ohio, United States
  • 2011
    • Cleveland State University
      Cleveland, Ohio, United States
  • 2003–2010
    • Kaiser Permanente
      Oakland, California, United States
  • 2003–2006
    • University of Texas MD Anderson Cancer Center
      Houston, Texas, United States
  • 2002
    • Lerner Research Institute
      Cleveland, Ohio, United States