Publications by authors named "Lara Hathout"

23 Publications

  • Page 1 of 1

PSA outcomes and late toxicity of single-fraction HDR brachytherapy and LDR brachytherapy as monotherapy in localized prostate cancer: A phase 2 randomized pilot study.

Brachytherapy 2021 Jul 5. Epub 2021 Jul 5.

Department of Radiation Oncology, CHU de Québec-Université Laval, Québec, Canada; Research Centre CHU de Québec-Université Laval, Québec, Canada. Electronic address:

Purpose: To evaluate the PSA outcomes and the late patient's reported health related quality of life (HRQOL) and toxicity after single-fraction High-Dose-Rate brachytherapy (HDRB) and Low-Dose-Rate brachytherapy (LDRB) for prostate cancer.

Methods: Men with low and favorable intermediate-risk prostate cancer across 3 centres were randomized between monotherapy brachytherapy with either Iodine-125 LDRB or 19 Gy single-fraction HDRB. Biochemical outcomes were evaluated using the Phoenix definition, PSA nadir and absolute PSA value <0.4 ng/mL. Toxicities and HRQOL were recorded at 24 and 36 months.

Results: A total of 31 patients were randomized, 15 in the LDRB arm and 16 patients in the HDRB arm. After a median follow-up of 45(36-53) months, 3 patients in the HDRB arm experienced biochemical failure (p = 0.092). Nineteen Gy single-fraction HDRB was associated with significantly higher PSA nadir compared to LDRB (1.02 ± 0.66vs 0.25 ± 0.39, p < 0.0001). Moreover, a significantly larger proportion of patients in the LDRB group had a PSA <0.4 ng/mL (13/15 vs 2/16, p < 0.0001). For late Genito-Urinary, Gastro-Intestinal, and sexual toxicities at 24 and 36 months, no significant differences were found between the 2 arms. As for HRQOL, the IPSS and EPIC-26 urinary irritative score were significantly better for patients treated with HDRB over the first 36 months post-treatment (p = 0.001 and p = 0.01, respectively), reflecting superior HRQOL.

Conclusion: HDRB resulted in superior HRQOL in the irritative urinary domain compared to LDRB. PSA nadir was significantly lower in the LDRB group and a higher proportion of patients in the LDRB group reached PSA <0.4 ng/mL.
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http://dx.doi.org/10.1016/j.brachy.2021.05.010DOI Listing
July 2021

Malignancies diagnosed before and after anal squamous cell carcinomas: A SEER registry analysis.

Cancer Med 2021 Jun 7;10(11):3575-3583. Epub 2021 May 7.

Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, Rutgers University, New Brunswick, NJ, USA.

Background: Increased risk of a second primary malignancy (SPM) before or after diagnosis of anal squamous cell carcinoma (ASCC) has been reported in a previous single-institution study. We hypothesize that patients diagnosed with ASCC are at increased risk for developing SPMs before or after the diagnosis of ASCC. The primary objective of this study was to identify the diagnoses of cancer most likely to occur as SPMs before or after ASCC.

Methods: This work employs the Surveillance, Epidemiology, and End Results (SEER) Program registry data to conduct a US-population-based study of patients diagnosed with ASCC between 1975 and 2016. In patients diagnosed with ASCC, we evaluated the risk of SPMs and the risk of developing ASCC as an SPM after another cancer using standardized incidence ratios (SIR) for all SPMs by calculating the ratio of observed events in the ASCC cohort compared to expected (O/E) events in a matched reference cohort of the general population.

Results: A total of 7,594 patients with primary ASCC were included. Patients with ASCC were at increased risk of the diagnosis of an SPM (SIR = 1.45), particularly cancers of the lung, vulva, oropharynx, or colon. Patients with ASCC had an increased rate of previous malignancy (SIR = 1.23), especially Kaposi sarcoma or vulvar cancer. Overall elevated incidence of SPMs was unrelated to prior radiation treatment. Radiation treatment was associated with increased risk for SPMs in the female genital system but appeared protective against prostate cancer as SPMs.

Conclusions: Our findings support increased surveillance and screening for second malignancies in patients with these diagnoses, as patients with ASCC are often either survivors of a prior cancer diagnosis or are at increased risk of developing later malignancies.
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http://dx.doi.org/10.1002/cam4.3909DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8178496PMC
June 2021

A Multi-Institutional Analysis of Adjuvant Chemotherapy and Radiation Sequence in Women With Stage IIIC Endometrial Cancer.

Int J Radiat Oncol Biol Phys 2021 Aug 5;110(5):1423-1431. Epub 2021 Mar 5.

Department of Radiation Oncology, Brigham and Women's Hospital and Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.

Purpose: Our purpose was to evaluate the effect of sequence and type of adjuvant therapy for patients with stage IIIC endometrial carcinoma (EC) on outcomes.

Methods And Materials: In a multi-institutional retrospective cohort study, patients with stage IIIC EC who had surgical staging and received both adjuvant chemotherapy and radiation therapy (RT) were included. Adjuvant treatment regimens were classified as adjuvant chemotherapy followed by sequential RT (upfront chemo), which was predominant sequence; RT with concurrent chemotherapy followed by chemotherapy (concurrent); systemic chemotherapy before and after RT (sandwich); adjuvant RT followed by chemotherapy (upfront RT); or chemotherapy concurrent with vaginal cuff brachytherapy alone (chemo-brachy). Overall survival (OS) and recurrence-free survival (RFS) rates were estimated by the Kaplan-Meier method.

Results: A total of 686 eligible patients were included with a median follow-up of 45.3 months. The estimated 5-year OS and RFS rates were 74% and 66%, respectively. The sequence and type of adjuvant therapy were not correlated with OS or RFS (adjusted P = .68 and .84, respectively). On multivariate analysis, black race, nonendometrioid histology, grade 3 tumor, stage IIIC2, and presence of adnexal and cervical involvement were associated with worse OS and RFS (all P < .05). Regardless of the sequence of treatment, the most common site of first recurrence was distant metastasis (20.1%). Vaginal only, pelvic only, and paraortic lymph node (PALN) recurrences occurred in 11 (1.6%),15 (2.2 %), and 43 (6.3 %) patients, respectively. Brachytherapy alone was associated with a higher rate of PALN recurrence (15%) compared with external beam radiation therapy (5%) P < .0001.

Conclusions: The sequence and type of combined adjuvant therapy did not affect OS or RFS rates. Brachytherapy alone was associated with a higher rate of PALN recurrence, emphasizing the role of nodal radiation for stage IIIC EC. The vast proportion of recurrences were distant despite systemic chemotherapy, highlighting the need for novel regimens.
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http://dx.doi.org/10.1016/j.ijrobp.2021.02.055DOI Listing
August 2021

The combined use of 2D scout and 3D axial CT images to accurately determine the catheter tips for high-dose-rate brachytherapy plans.

J Appl Clin Med Phys 2021 Mar 27;22(3):273-278. Epub 2021 Feb 27.

Department of Radiation Oncology, Cancer Institute of New Jersey, Rutgers University, New Brunswick, NJ, 08901, USA.

Purpose: To develop a method combining CT scout images with axial images to improve the localization accuracy of catheter tips in high-dose-rate (HDR) brachytherapy treatments.

Materials And Methods: CT scout images were utilized along with conventionally reconstructed axial images to aid the localization of catheter tips used during HDR treatment planning. A method was developed to take advantage of the finer image resolution of the scout images to more precisely identify the tip coordinates. The accuracies of this method were compared with the conventional method based on the axial CT images alone, for various slice thicknesses, in a computed tomography dose index (CTDI) head phantom. A clinical case which involved multiple interstitial catheters was also selected for the evaluation of this method. Locations of the catheter tips were reconstructed with the conventional CT-based method and this newly developed method, respectively. Location coordinates obtained via both methods were quantitatively compared.

Results: Combination of the scout and axial CT images improved the accuracy of identification and reconstruction of catheter tips along the longitudinal direction (i.e., head-to-foot direction, more or less parallel to the catheter tracks), compared to relying on the axial CT images alone. The degree of improvement was dependent on CT slice thickness. For the clinical patient case, the coordinate differences of the reconstructed catheter tips were 2.6 mm ± 0.9 mm in the head-to-foot direction, 0.4 mm ± 0.2 mm in the left-to-right direction, and 0.6 mm ± 0.2 mm in the anterior-to-posterior direction, respectively.

Conclusion: Combining CT scout and axial images demonstrates the ability to provide a more accurate identification and reconstruction of the interstitial catheter tips for HDR brachytherapy treatment, especially in the longitudinal direction. The method developed in this work has the potential to be implemented clinically together with automatic segmentation in modern brachytherapy treatment planning systems, in order to improve the reconstruction accuracy of HDR catheters.
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http://dx.doi.org/10.1002/acm2.13184DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7984491PMC
March 2021

The clinical impact of removing rectal gas on high-dose-rate brachytherapy dose distributions for gynecologic cancers.

J Appl Clin Med Phys 2021 Feb 13;22(2):35-41. Epub 2021 Jan 13.

Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Rutgers University, New Brunswick, NJ, USA.

Purpose: To evaluate the impact of gas removal on bladder and rectal doses during intracavitary and interstitial high-dose-rate brachytherapy (HDRB) for gynecologic cancers.

Material And Methods: Fifteen patients treated with definitive external beam radiation followed by HDRB for gynecologic cancers for a total of 21 fractions, presented with a significant amount of rectal gas at initial CT imaging (CT ) after implantation. The gas was removed via rectal tubing followed by subsequent scan acquisition (CT ), which was used for planning and treatment delivery. To assess the effect of gas removal on dosimetry, both bladder and rectum volumes were recontoured on CT . In order to evaluate the clinical impact on the total Equivalent-Dose-in-2Gy-fraction (EQD ), each fraction was also replanned to maintain clinically delivered target coverage (HRCTV D90). EQD D2cm for bladder and rectum were compared between plans. The Wilcoxon signed rank test was performed to evaluate statistically significant differences for all comparisons (P < 0.05).

Results: Mean rectum and bladder D , D0.1cm , D1cm , D2cm , and D5cm were significantly different between CT and CT . The mean percent increases on CT for bladder were 12.3, 8.4, 9.9, 10.2, and 9.5% respectively and for rectum were 27.0, 19.6, 18.1, 18.5, and 19.4%, respectively. After replanning with CT to maintain HRCTV D90 EQD , bladder and rectum EQD D2 cm resulted in significantly higher doses. The mean EQD D2 cm difference was 2.4 and 4.1 Gy for bladder and rectum, revealing a higher impact of gas removal on rectal DVH.

Conclusion: Rectal gas removal resulted in statistically significant differences for both bladder and rectum. The resulting larger EQD D2 cm for bladder and rectum demonstrates that if patients were treated without removing gas, target coverage would need to be sacrificed to satisfy the rectum constraints and prevent toxicities. Therefore, this study demonstrates the importance of gas removal for gynecologic HDRB patients.
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http://dx.doi.org/10.1002/acm2.13132DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7882092PMC
February 2021

The Impact of COVID-19 on Brachytherapy During the Pandemic: A Rutgers-Robert Wood Johnson Barnabas Health Multisite Experience.

Adv Radiat Oncol 2021 Jan-Feb;6(1):100600. Epub 2020 Nov 2.

Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey.

Purpose: This study aimed to evaluate whether the coronavirus disease of 2019 (COVID-19) pandemic resulted in treatment delays in patients scheduled for or undergoing brachytherapy.

Methods And Materials: A retrospective cohort study was conducted across 4 affiliated sites after local institutional review board approval. The eligibility criteria were defined as all patients with cancer whose treatment plan included brachytherapy during the COVID-19 pandemic from February 24, 2020 to June 30, 2020. Treatment delays, cancellations, alterations of fractionation regimens, and treatment paradigm changes were evaluated.

Results: A total of 47 patients were eligible for the analysis. Median patient age at the time of treatment was 62 years (interquartile range, 56-70 years). Endometrial, cervical, and prostate cancers were the most common sites included in this analysis. Three patients (6.4%) with cervical cancer were diagnosed with COVID-19 during the course of their treatment. Interruptions of external beam radiation therapy (EBRT), cancellations of EBRT, cancellations of brachytherapy, and treatment delays due to COVID occurred in 5 (10.6%), 3 (6.4%), 8 (17%), and 9 (19%) patients, respectively. The mean and median number of days delayed for patients who experienced treatment interruptions were 16.3 days (standard deviation: 13.9 days) and 14 days (interquartile range, 5.75-23.75 days), respectively. For patients with cervical cancer, the mean and median overall treatment times defined as the time from the start of EBRT to the end of brachytherapy were 56 and 49 days, respectively.

Conclusions: Despite the challenges the health care system faced during the pandemic, most patients with cancer were safely treated with minor treatment delays and interruptions. Long-term follow up is needed to assess the impact of COVID-19 and treatment interruptions on oncologic outcomes.
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http://dx.doi.org/10.1016/j.adro.2020.10.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7605726PMC
November 2020

Dose to the bladder neck is not correlated with urinary toxicity in patients with prostate cancer treated with HDR brachytherapy boost.

Brachytherapy 2020 Sep - Oct;19(5):584-588

CHU de Québec, Université Laval, Service de Radio-Oncologie, Québec, Québec, Canada; Centre de Recherche Sur Le Cancer, Université Laval, Québec, Québec, Canada. Electronic address:

Purpose: The purpose of this study was to evaluate whether the dose to bladder neck (BN) is a predictor of acute and late urinary toxicity after high-dose-rate brachytherapy (HDRB) boost for prostate cancer.

Methods And Materials: Between 2014 and 2016, patients with prostate cancer treated at our institution with external beam radiation therapy and 15 Gy single-fraction HDRB boost for intermediate- and high-risk disease according to D'Amico definition were reviewed. Intraoperative CT scan-based inverse planning and ultrasound-based inverse planning were performed in 173 and 136 patients, respectively. The following structures were prospectively contoured: prostate, urethra, rectum, bladder, and the BN defined as 5 mm around the urethra between the catheter balloon and the prostatic urethra. Dose to the BN was reported only, no constraint was applied. Acute and late urinary toxicity were assessed using the International Prostate Symptom Score (IPSS) and the Common Terminology Criteria for Adverse Events v.4.0. Clinical and dosimetry factors associated with urinary toxicity were analyzed using generalized linear models.

Results: A total of 309 patients with median age of 71 years (range 50-89) were included. Median followup was 25 months (range 0-39 months). Using D'Amico definition, 71% of the patients had intermediate-risk disease, whereas 29% had high-risk disease. The mean pretreatment prostate-specific antigen value was 9.65 ng/mL. The mean pretreatment, after 6 weeks and over 6 months IPSSs were 8.34, 12.14, and 10.02, respectively. Urinary obstruction was reported in 14 cases (4.5%). Pretreatment IPSS (p = 0.003) and prostate volume (p = 0.024) were significantly associated with acute and late urinary toxicity. The dose for the most exposed 2 cc (D) of BN was not correlated with acute (p = 0.798) or late urinary toxicity (p = 0.859). BN D was not correlated with urinary obstruction (p = 0.272), but bladder V was (p = 0.021).

Conclusions: High pretreatment IPSS, large prostate volume and bladder V were the only predictors of acute and late urinary toxicity after HDRB boost in our study. Although BN D was associated with acute and late urinary toxicity after low-dose-rate brachytherapy, no correlation was found after HDRB. A prospective study comparing dose to the BN in HDRB monotherapy would validate the impact of BN dose on acute and late urinary toxicity.
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http://dx.doi.org/10.1016/j.brachy.2020.06.017DOI Listing
May 2021

Stereotactic body radiation therapy for oligometastatic gynecologic malignancies: A systematic review.

Gynecol Oncol 2020 11 9;159(2):573-580. Epub 2020 Sep 9.

Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Rutgers University, New Brunswick, NJ, USA. Electronic address:

Objective: To assess the efficacy and safety of stereotactic body radiation therapy (SBRT) for oligometastatic gynecologic malignancies.

Method: A comprehensive search of the PubMed, Medline, and EMBASE databases was conducted using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. "Oligometastatic" was defined as a limited number of uncontrolled/untreated metastatic lesions (typically ≤ 5), including regional nodal metastases. Primary outcomes were response rate (complete response or partial response), local control of oligometastatic lesions, and toxicity.

Results: Of 716 screened records, 17 studies (13 full length articles, 4 conference abstracts) were selected and analyzed as 16 unique studies. A total of 667 patients were treated with ~1071 metastatic lesions identified. Primary sites included ovarian (57.6%), cervical (27.1%), uterine (11.1%), vaginal (0.4%), vulvar (0.3%), and other/unspecified (3.4%). Most patients (65.4%) presented with a single metastatic lesion. Metastatic lesion sites included the abdomen (44.2%), pelvis (18.8%), thorax (15.5%), neck (4.6%), central nervous system (4.3%), bone (1.6%), and other/unspecified (11%). Of the lesions, 64% were nodal. Response rate (among 8 studies) ranged from 49% to 97%, with 7/8 studies reporting > 75% response rate. Local control ranged from 71% to 100%, with 14/16 studies reporting ≥ 80% local control. No grade ≥ 3 toxicities were observed in 9/16 (56%) studies. Median progression-free survival (PFS) (among 10 studies) ranged from 3.3 months to 21.7 months. Disease progression most commonly occurred outside of the SBRT radiation field (79% to 100% of failures).

Conclusions: SBRT for oligometastatic gynecologic malignancies is associated with favorable response and local control rates but a high rate of out-of-field progression and heterogeneous PFS. Additional study into rational combinations of SBRT and systemic therapy appears warranted to further improve patient outcomes.
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http://dx.doi.org/10.1016/j.ygyno.2020.08.010DOI Listing
November 2020

A Phase 2 Randomized Pilot Study Comparing High-Dose-Rate Brachytherapy and Low-Dose-Rate Brachytherapy as Monotherapy in Localized Prostate Cancer.

Adv Radiat Oncol 2019 Oct-Dec;4(4):631-640. Epub 2019 Apr 18.

Department of Radiation Oncology and Research Centre CHU de Québec-Université Laval, Québec City, QC, Canada.

Purpose: To compare health-related quality of life (HRQOL) of high-dose-rate brachytherapy (HDRB) versus low dose-rate brachytherapy (LDRB) for localized prostate cancer in a multi-institutional phase 2 randomized trial.

Methods And Materials: Men with favorable-risk prostate cancer were randomized between monotherapy brachytherapy with either Iodine-125 LDRB to 144 Gy or single-fraction Iridium-192 HDRB to 19 Gy. HRQOL and urinary toxicity were recorded at baseline and at 1, 3, 6, and 12 months using the Expanded Prostate Cancer Index Composite (EPIC)-26 scoring and the International Prostate Symptom Score (IPSS). Independent samples test and mixed effects modeling were performed for continuous variables. Time to IPSS resolution, defined as return to its baseline score ±5 points, was calculated using Kaplan-Meier estimator curves with the log-rank test. A multiple-comparison adjusted value of ≤.05 was considered significant.

Results: LDRB and HDRB were performed in 15 and 16 patients, respectively, for a total of 31 patients. At 3 months, patients treated with LDRB had a higher IPSS score (mean, 15.5 vs 6.0, respectively;  .003) and lower EPIC urinary irritative score (mean, 69.2 vs 85.3, respectively;  .037) compared with those who received HDRB. On repeated measures at 1, 3, 6, and 12 months, the IPSS ( .003) and EPIC urinary irritative scores ( = .019) were significantly better in the HDR arm, translating into a lower urinary toxicity profile. There were no significant differences in the EPIC urinary incontinence, sexual, or bowel habit scores between the 2 groups at any measured time point. Time to IPSS resolution was significantly shorter in the HDRB group (mean, 2.0 months) compared with the LDRB group (mean, 6.0 months;  .028).

Conclusions: HDRB monotherapy is a promising modality associated with a lower urinary toxicity profile and higher HRQOL in the first 12 months compared with LDRB.
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http://dx.doi.org/10.1016/j.adro.2019.04.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6817536PMC
April 2019

Vertebral body irradiation during chemoradiation therapy for esophageal cancer contributes to acute bone marrow toxicity.

J Gastrointest Oncol 2019 Jun;10(3):513-522

Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Robert Wood Johnson Medical School, Rutgers University, New Brunswick, NJ, USA.

Background: Hematologic toxicity (HT) commonly occurs during chemoradiation therapy (CRT) for esophageal cancer. We sought to determine radiation doses that correlate with declines in blood counts due to vertebral body (VB) irradiation during CRT.

Methods: We analyzed 53 esophageal cancer patients who were treated with weekly neoadjuvant carboplatin, paclitaxel and RT with weekly complete blood counts (CBC) available during treatment. HTs were graded according to the Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v4.0). Dose volume histogram (DVH) parameters of Vx, defined as percentage of entire bony vertebra (body, pedicles, laminae, processes) receiving at least x Gy of radiation, were collected for VB V (VBV), VBV-VBV in increments of 10, and mean vertebral dose (MVD). Linear and logistic regressions were performed to identify associations between leukopenia nadirs and DVH parameters. Receiver operator curves identified thresholds to avoid grade ≥3 leukopenia.

Results: A proportion of 32.1% of patients (n=17) developed grade 3 leukopenia and 5.7% (n=3) developed grade 4 leukopenia. VBV, VBV, VBV, VBV, and MVD were significantly associated with worsening leukopenia on univariate and multivariate analysis. Associations with leukopenia were not seen with VBV and VBV DVH values. Thresholds to avoid grade ≥3 leukopenia were VBV <49.1%, VBV <45.6%, and MVD <17.2 Gy.

Conclusions: VBV, VBV, VBV, VBV associate with leukopenia during CRT for esophageal cancer patients. Improved radiation sparing of the VB may decrease HT and may improve tolerability of concurrent chemotherapy and allow for intensification of systemic therapy during RT.
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http://dx.doi.org/10.21037/jgo.2019.01.20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6534715PMC
June 2019

Multiple primary malignancies in patients with anal squamous cell carcinoma.

J Gastrointest Oncol 2018 Oct;9(5):853-857

Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Robert Wood Johnson Medical School, Rutgers University, New Brunswick, NJ, USA.

Prior studies examining the risk of second primary malignancy (SPM) after a first primary cancer generally have used large datasets such as the Surveillance, Epidemiology, and End Results (SEER) registry and excluded survivors of previous primaries and developers of synchronous primaries. The goal of this study was to provide a more complete representation of multiple cancer risk in squamous cell carcinoma of the anus (SCCA) patients. A single-institution retrospective study of 46 patients treated definitively for SCCA between January 2006 and July 2017 was conducted. Of the 46 patients, 18 (39%) had either a primary malignancy before SCCA (n=9) or SPM after an index SCCA (n=9). Six patients had ≥3 total malignancies. In our cohort, patients without SPMs tended to die from SCCA recurrence, while patients with SPMs were more likely to die from their SPM than from SCCA. Our study suggests that patients with SCCA are often either survivors of previous cancers or develop later malignancies. Several risk factors may play a role including HPV infection, HPV-related or treatment-related immunosuppression, somatic mutations due to chemotherapy, and genetic factors. Patients with SCCA require lifelong surveillance given their elevated risk of malignancy. Future work should focus on identifying genomic or immunologic factors that may predispose SCCA patients to develop multiple primary malignancies.
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http://dx.doi.org/10.21037/jgo.2018.06.07DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6219985PMC
October 2018

Management of locally advanced rectal cancer in the elderly: a critical review and algorithm.

J Gastrointest Oncol 2018 Apr;9(2):363-376

Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Rutgers University, New Brunswick, NJ, USA.

Colorectal cancer incidence and death rates have been declining over the past 10 years. However, it remains the second leading cause of death in men ages 60-79 and the third leading cause of death in men over 80 and in women over 60 years old. However, there is little data specific to the treatment of the elder patient, since few of these patients are included in trials. With the advent of improved therapies, there are many alternative options available. Still, no definitive consensus or guidelines have been defined for this particular patient population. The goal of this study is to review the literature on the management of rectal cancer in the elderly and to propose treatment algorithms to help the oncology team in treatment decision-making.
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http://dx.doi.org/10.21037/jgo.2017.10.10DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5934158PMC
April 2018

Decision-Making Strategy for Rectal Cancer Management Using Radiation Therapy for Elderly or Comorbid Patients.

Int J Radiat Oncol Biol Phys 2018 03;100(4):926-944

Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey. Electronic address:

Rectal cancer predominantly affects patients older than 70 years, with peak incidence at age 80 to 85 years. However, the standard treatment paradigm for rectal cancer oftentimes cannot be feasibly applied to these patients owing to frailty or comorbid conditions. There are currently little information and no treatment guidelines to help direct therapy for patients who are elderly and/or have significant comorbidities, because most are not included or specifically studied in clinical trials. More recently various alternative treatment options have been brought to light that may potentially be utilized in this group of patients. This critical review examines the available literature on alternative therapies for rectal cancer and proposes a treatment algorithm to help guide clinicians in treatment decision making for elderly and comorbid patients.
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http://dx.doi.org/10.1016/j.ijrobp.2017.12.261DOI Listing
March 2018

The Impact of Novel Radiation Treatment Techniques on Toxicity and Clinical Outcomes In Rectal Cancer.

Curr Colorectal Cancer Rep 2017 Feb 10;13(1):61-72. Epub 2017 Mar 10.

Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, Rutgers University, New Brunswick, NJ.

Purpose Of Review: Three-dimensional conformal radiation therapy (3DCRT) has been the standard technique in the treatment of rectal cancer. The use of new radiation treatment technologies such as intensity-modulated radiation therapy (IMRT), proton therapy (PT), stereotactic body radiation therapy (SBRT) and brachytherapy (BT) has been increasing over the past 10 years. This review will highlight the advantages and drawbacks of these techniques.

Recent Findings: IMRT, PT, SBRT and BT achieve a higher target coverage conformity, a higher organ at risk sparing and enable dose escalation compared to 3DCRT. Some studies suggested a reduction in gastrointestinal and hematologic toxicities and an increase in the complete pathologic response rate; however, the clinical benefit of these techniques remains controversial.

Summary: The results of these new techniques seem encouraging despite conclusive data. Further trials are required to establish their role in rectal cancer.
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http://dx.doi.org/10.1007/s11888-017-0351-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5808610PMC
February 2017

Adjuvant Chemoradiation Therapy for Cervical Cancer and Effect of Timing and Duration on Treatment Outcome.

Int J Radiat Oncol Biol Phys 2017 08 31;98(5):1132-1141. Epub 2017 Mar 31.

Department of Radiation Oncology, Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick, New Jersey; Department of Radiation Oncology, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, New Jersey. Electronic address:

Purpose: Worse treatment outcomes can be expected with prolongation of the overall treatment time (OTT) during definitive chemoradiation therapy (CRT) for cervical cancer. In the adjuvant setting, data on the relative importance of the OTT and the importance of RT and chemotherapy synchronization are scarce. Using the National Cancer Database, we evaluated the effect of these treatment variables on overall survival in the adjuvant CRT setting.

Methods And Materials: The present analysis included nonmetastatic cervical cancer patients undergoing hysterectomy followed by adjuvant CRT. The proportional hazard model was used to estimate the effect of prognostic factors (age, comorbidity, race, tumor size, tumor grade, tumor histologic type, number of high-risk pathologic factors) and time-related variables (surgery to RT start interval [SR], OTT [RT start to end dates], package time [from diagnosis date to CRT end date] and optimum CRT synchronization [whether chemotherapy and RT start dates coincided]) on survival.

Results: Of 3051 patients, 60% finished RT within 7 weeks and 85% received optimum CRT. Among other factors, univariate analysis identified longer OTT (hazards ratio [HR] 1.33; P<.001), longer SR (HR 1.17; P=.05), and nonoptimum CRT timing (HR 1.21; P=.04) as poor prognosticators. Of these factors, SR (HR 1.20; P=.04) and OTT (HR 1.21; P=.002) retained significance on multivariate analysis. An OTT >7 weeks remained a significant factor even after propensity score matching (P=.04).

Conclusions: The results of our analysis suggest that prolongation of the adjuvant CRT duration >7 weeks is associated with poor survival and SR of <8 weeks should be attempted whenever clinically feasible.
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http://dx.doi.org/10.1016/j.ijrobp.2017.03.045DOI Listing
August 2017

Revisiting Milan cervical cancer study: Do the original findings hold in the era of chemotherapy?

Gynecol Oncol 2017 Feb 26;144(2):299-304. Epub 2016 Nov 26.

Department of Radiation Oncology, Rutgers, The State University of New Jersey, Cancer Institute of New Jersey, Floor G-2 Level, One Robert Wood Johnson Place, New Brunswick,NJ 08901, United States; Department of Radiation Oncology, Rutgers, The State University of New Jersey, New Jersey Medical School, 150 Bergen St A1122, Newark, NJ 07103-2496, United States. Electronic address:

Background: The primary treatment of early stage cervical carcinoma (IB-IIA) is either surgery or radiation therapy based on the pivotal Milan randomized study published twenty years ago. In the presence of high-risk features, the gold standard treatment is concurrent chemotherapy and radiation therapy (CRT) whether it is the in the postoperative or the definitive setting. Using the National Cancer Data Base (NCDB), the goal of our study is to compare the outcomes of surgery and radiation therapy in the chemotherapy era.

Methods: Between 2004 and 2013, 5478 patients diagnosed with early stage cervical cancer were divided into 2 groups based on their primary treatment: non-surgical (n=1980) and surgical groups (n=3498). The distribution of patient/tumor characteristics and treatment variables with their relation to overall survival and proportional regression models were assessed to investigate the superiority of one approach over the other. Propensity score analysis adjusted for imbalance of covariates to create a well-matched-patient cohort.

Findings: At 46months median follow-up, the 5-year overall survival was similar between both groups (73·8% vs. 75.7%; p=0.619) after applying propensity score analysis. On multivariate analysis, high Charlson comorbidity score, stage IIA disease, larger tumor size, positive lymph nodes and high-grade disease were significant predictors of poor outcome while older age and treatment approach were not.

Interpretation: Our analysis suggests that surgery (followed by adjuvant RT or CRT) and definitive radiotherapy (with or without chemotherapy) result in equivalent survival. Prospective studies are warranted to establish this paradigm in the chemotherapy era.
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http://dx.doi.org/10.1016/j.ygyno.2016.11.034DOI Listing
February 2017

Can chemotherapy boost the survival benefit of adjuvant radiotherapy in early stage cervical cancer with intermediate risk factors? A population based study.

Gynecol Oncol 2016 Dec 18;143(3):539-544. Epub 2016 Oct 18.

Department of Radiation Oncology, Loyola University, Chicago, IL, United States.

Purpose: The Gynecologic Oncology group (GOG) 0263 trial is currently exploring whether adding chemotherapy to adjuvant radiotherapy improves recurrence-free and/or overall survival in stage IB-IIA cervical cancer patients with pathologic intermediate-risk factors. Using the National Cancer Data Base, we evaluated the benefit of adjuvant chemoradiotherapy over adjuvant radiotherapy alone in the community practice setting.

Materials: The analysis included 869 stage IB-IIA cervical cancer patients who underwent radical hysterectomy retrieving intermediate-risk factors justifying adjuvant therapy. Adjuvant chemoradiotherapy and adjuvant radiotherapy were delivered in 440 and 429 patients, respectively. Chi-square test assessed the distribution of variables in each group and the overall survival was estimated using the Kaplan-Meier method. Proportional hazard models were performed to evaluate the impact of the different prognostic factors on survival and propensity score analysis adjusted variables imbalanced distribution.

Results: Adding chemotherapy to ART did not show a survival benefit at 48months median follow-up; the 5-year overall survival was 87% and 81% (p=0.6) in the adjuvant chemoradiotherapy and adjuvant radiotherapy groups, respectively. On univariate analysis, age older than 60, a higher comorbidity score, and stage IIA were significantly associated with worse survival, while none of the other covariates were significant prognosticator on multivariate analysis. The same findings held after propensity score analysis.

Conclusion: Our analysis could not detect a significant survival benefit for adjuvant chemoradiotherapy over adjuvant radiotherapy in women with intermediate-risk factors. Until GOG 0263 results become available, the benefits of adjuvant chemoradiotherapy should be considered on an individual basis within a multidisciplinary approach.
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http://dx.doi.org/10.1016/j.ygyno.2016.10.022DOI Listing
December 2016

Customized high-dose-rate brachytherapy using MRI planning for vaginal rhabdomyosarcoma.

Brachytherapy 2015 Jan-Feb;14(1):46-50. Epub 2014 Oct 16.

Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY. Electronic address:

Purpose: To report the technical aspects of customized high-dose-rate brachytherapy for vaginal rhabdomyosarcoma using MRI- and CT-based planning in a 20-month-old girl.

Methods And Materials: An impression of the vaginal cavity at the resection site was taken after adequate lubrication of the vagina with lidocaine jelly. The impression was processed in the dental laboratory to obtain an MRI-compatible device with three imbedded catheters 0.4 mm apart, assuring tumor coverage. An MRI- and CT-based simulation under anesthesia with the applicator in place were performed, and the images were registered for contouring and planning to deliver 40 Gy in 10 fractions daily. Dose to the ovaries was limited to a mean dose less than 4 Gy. Treatment was delivered daily under anesthesia with no acute complications.

Results: Brachytherapy using a customized applicator has many advantages over prefabricated vaginal cylinders for young girls. It allows greater dose distribution conformality with the possibility of contralateral vaginal wall sparing and more reproducible daily positioning. MRI-based planning is mainly performed to facilitate delineation of the target volume and the ovaries, which are easily identified on MRI.

Conclusions: The customized applicator offers many advantages of which treatment reproducibility, inherent MRI compatibility, and excellent dose distribution conformality. Our brachytherapy technique using MRI and CT scan planning allows precise tumor and normal tissues delineation resulting in excellent tumor coverage and normal tissues sparing.
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http://dx.doi.org/10.1016/j.brachy.2014.09.005DOI Listing
June 2015

Dose to the bladder neck is the most important predictor for acute and late toxicity after low-dose-rate prostate brachytherapy: implications for establishing new dose constraints for treatment planning.

Int J Radiat Oncol Biol Phys 2014 Oct;90(2):312-9

Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York. Electronic address:

Purpose: To identify an anatomic structure predictive for acute (AUT) and late (LUT) urinary toxicity in patients with prostate cancer treated with low-dose-rate brachytherapy (LDR) with or without external beam radiation therapy (EBRT).

Methods And Materials: From July 2002 to January 2013, 927 patients with prostate cancer (median age, 66 years) underwent LDR brachytherapy with Iodine 125 (n=753) or Palladium 103 (n=174) as definitive treatment (n=478) and as a boost (n=449) followed by supplemental EBRT (median dose, 50.4 Gy). Structures contoured on the computed tomographic (CT) scan on day 0 after implantation included prostate, urethra, bladder, and the bladder neck, defined as 5 mm around the urethra between the catheter balloon and the prostatic urethra. AUT and LUT were assessed with the Common Terminology Criteria for Adverse Events, version4. Clinical and dosimetric factors associated with AUT and LUT were analyzed with Cox regression and receiver operating characteristic analysis to calculate area under the receiver operator curve (ROC) (AUC).

Results: Grade ≥2 AUT and grade ≥2 LUT occurred in 520 patients (56%) and 154 patients (20%), respectively. No grade 4 toxicities were observed. Bladder neck D2cc retained a significant association with AUT (hazard ratio [HR], 1.03; 95% confidence interval [CI], 1.03-1.04; P<.0001) and LUT (HR, 1.01; 95% CI, 1.00-1.03; P=.014) on multivariable analysis. In a comparison of bladder neck with the standard dosimetric variables by use of ROC analysis (prostate V100 >90%, D90 >100%, V150 >60%, urethra D20 >130%), bladder neck D2cc >50% was shown to have the strongest prognostic power for AUT (AUC, 0.697; P<.0001) and LUT (AUC, 0.620; P<.001).

Conclusions: Bladder neck D2cc >50% was the strongest predictor for grade ≥2 AUT and LUT in patients treated with LDR brachytherapy. These data support inclusion of bladder neck constraints into brachytherapy planning to decrease urinary toxicity.
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http://dx.doi.org/10.1016/j.ijrobp.2014.06.031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5705020PMC
October 2014

High-dose-rate brachytherapy for vaginal rhabdomyosarcoma using a personalized mold in a 20-month old patient.

Pediatr Blood Cancer 2015 Mar 4;62(3):531-2. Epub 2014 Oct 4.

Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York.

Treatment of vaginal rhabdomyosarcoma (RMS) with conservative approaches is presently the standard of care. Intravaginal high-dose rate brachytherapy is a very effective treatment while sparing the normal tissue to preserve growth, fertility and prevent organ dysfunction. In this report, we describe the management of an infant with Stage I vaginal RMS, treated with chemotherapy, maximal safe resection and intravaginal brachytherapy using a customized mold and MRI and CT-based three-dimensional (3D) conformal planning, followed by a critical review of the literature.
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http://dx.doi.org/10.1002/pbc.25252DOI Listing
March 2015

Hypofractionated radiation therapy for breast ductal carcinoma in situ.

Int J Radiat Oncol Biol Phys 2013 Dec 8;87(5):1058-63. Epub 2013 Oct 8.

Department of Radiation Oncology, Hôpital Maisonneuve-Rosemont, Centre affilié à l'Université de Montréal, Montreal, Quebec, Canada.

Purpose: Conventional radiation therapy (RT) administered in 25 fractions after breast-conserving surgery (BCS) is the standard treatment for ductal carcinoma in situ (DCIS) of the breast. Although accelerated hypofractionated regimens in 16 fractions have been shown to be equivalent to conventional RT for invasive breast cancer, few studies have reported results of using hypofractionated RT in DCIS.

Methods And Materials: In this multicenter collaborative effort, we retrospectively reviewed the records of all women with DCIS at 3 institutions treated with BCS followed by hypofractionated whole-breast RT (WBRT) delivered in 16 fractions.

Results: Between 2003 and 2010, 440 patients with DCIS underwent BCS followed by hypofractionated WBRT in 16 fractions for a total dose of 42.5 Gy (2.66 Gy per fraction). Boost RT to the surgical bed was given to 125 patients (28%) at a median dose of 10 Gy in 4 fractions (2.5 Gy per fraction). After a median follow-up time of 4.4 years, 14 patients had an ipsilateral local relapse, resulting in a local recurrence-free survival of 97% at 5 years. Positive surgical margins, high nuclear grade, age less than 50 years, and a premenopausal status were all statistically associated with an increased occurrence of local recurrence. Tumor hormone receptor status, use of adjuvant hormonal therapy, and administration of additional boost RT did not have an impact on local control in our cohort. On multivariate analysis, positive margins, premenopausal status, and nuclear grade 3 tumors had a statistically significant worse local control rate.

Conclusions: Hypofractionated RT using 42.5 Gy in 16 fractions provides excellent local control for patients with DCIS undergoing BCS.
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http://dx.doi.org/10.1016/j.ijrobp.2013.08.026DOI Listing
December 2013

Localization of the surgical bed using supine magnetic resonance and computed tomography scan fusion for planification of breast interstitial brachytherapy.

Radiother Oncol 2011 Sep 14;100(3):480-4. Epub 2011 Sep 14.

Department of Radiotherapy, Hôpital Charles Lemoyne, University of Sherbrooke, Québec, Canada.

Purpose: To evaluate the feasibility of supine breast magnetic resonance imaging (MR) for definition and localization of the surgical bed (SB) after breast conservative surgery. To assess the inter-observer variability of surgical bed delineation on computed tomography (CT) and supine MR.

Materials And Methods: Patients candidate for breast brachytherapy and no contra-indications for MR were eligible for this study. Patients were placed in supine position, with the ipsilateral arm above the head in an immobilization device. All patients underwent CT and MR in the same implant/treatment position. Four points were predefined for CT-MRI image fusion. The surgical cavity was drawn on CT then MRI, by three independent observers. Fusion and analysis of CT and MR images were performed using the ECLIPSE treatment planning software.

Results: From September 2005 to November 2008, 70 patients were included in this prospective study. For each patient, we were able to acquire axial T1 and T2 images of good quality. Using the predefined fusion points, the median error following the fusion was 2.7 mm. For each observer, volumes obtained on MR were, respectively, 30%, 38% and 40% smaller than those derived from CT images. A highly significant inter-observer variability in the delineation of the SB on CT was demonstrated (p<0.0001). On the contrary, all three observers agreed on the volume of the SB drawn on MR.

Conclusion: Supine breast MRI yields a more precise definition of the SB with a smaller inter-observer variability than CT and may obviate the need for surgical clips. The volume of the SB is smaller with MRI. In our opinion, CT-MRI fusion should be used for SB delineation, in view of partial breast irradiation.
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http://dx.doi.org/10.1016/j.radonc.2011.08.024DOI Listing
September 2011

Analysis of seed loss and pulmonary seed migration in patients treated with virtual needle guidance and robotic seed delivery.

Am J Clin Oncol 2011 Oct;34(5):449-53

Department of Radiation Oncology, University of Montreal Medical, CHUM, Quebec, Canada.

Purpose And Background: To determine whether automated seed delivery system and real-time intraoperative (IO) virtual needle guidance reduce seed loss and pulmonary seed migration.

Patients And Methods: We analyzed 279 patients with low and intermediate risk prostate cancer treated in our institution with radioactive iodine (I-125) permanent seed implants. Loose seeds were exclusively used. To account for lost seeds, pelvic fluoroscopic imaging from 3 different angles was done 30 days after the implant. Posteroanterior and lateral chest x-rays were done when seed loss was confirmed. Patients were compared using the χ(2) test and Fisher exact test.

Results: At least 1 seed was lost in 31.5% of patients with a migration rate of 1.02%; 9.3% of patients had at least 1 seed in the lung with a migration rate of 0.22%. The population was divided into 3 groups according to the order in which they were treated. Seed loss (P=0.02) and pulmonary seed embolization (P=0.008) were significantly lower in the second hundred than in the first hundred patients. No difference was noted between groups 1 and 3 (patient, 201-279). Peri- or extracapsular seed placement was not correlated to seed loss (P=0.780 and P=0.092, respectively). No serious complications from seed migration were reported. Seed loss did not influence dosimetry parameters (V100, V150, and D90).

Conclusion: Our pulmonary seed migration and total seed loss rates are comparable to the ones reported in the literature. Virtual needle guidance and automated seed delivery system are in our hand as accurate as the manual technique.
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http://dx.doi.org/10.1097/COC.0b013e3181ec63c5DOI Listing
October 2011
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