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1.
Adv Radiat Oncol ; 8(5): 101230, 2023.
Article in English | MEDLINE | ID: mdl-37179902

ABSTRACT

Purpose: This study analyzes assessments within radiation oncology (RO) to determine characteristics of existing assessment methods and then report resident perceptions of these methods. We hypothesize familiarity with evaluation methods is predictive of the perceived utility of evaluations and behavioral changes. Methods and materials: This study was conducted in 2 phases. Phase 1 involved requesting resident evaluation forms from RO residency programs to assess the Accreditation Council for Graduate Medical Education 6 Core Competencies. Analysis of variance was used to determine any significant differences between institutions or categories of questions. In phase 2, RO residents were surveyed about familiarity with the Accreditation Council for Graduate Medical Education Milestones and their perceptions about the current methods. Responses to questions were further analyzed using linear regression models. Results: In phase 1, forms were obtained from 13 institutions, and they were based on the 6 Core Competencies with an average of 19 questions (standard deviation, 11; range, 5-47) in total. Analysis of variance did not show significant variation in the number of questions between the categories (F = 0.78, P = .6). A significant difference in the mean number of questions used for assessing each of the competencies was found between institutions (F = 6.6, P < .01). In phase 2, a majority of surveyed residents reported being "not" or only "slightly familiar" with the competencies (59.6%) and the factors used to assess them (73.1%). Resident-reported familiarity with the evaluation methods was not found to be a significant predictor of likelihood of changing postevaluation (coefficient = 0.41, P = .204), intimidation from receiving evaluations (coefficient = -0.06, P = .792), stress of receiving evaluations (coefficient = -0.11, P = .62), or usefulness of evaluations (coefficient = -0.02, P = .83). Conclusions: Familiarity with evaluation methods is not correlated with perceptions or behavioral changes necessitating further investigation of alternative predictor variables. Despite the low familiarity with evaluation tools, most residents reported that evaluations were useful and likely to elicit changes in their behaviors and practice, highlighting the value of current evaluation methods.

2.
Brachytherapy ; 22(3): 352-360, 2023.
Article in English | MEDLINE | ID: mdl-36681540

ABSTRACT

PURPOSE: Many current radiotherapy patient education materials are not patient-centered. An interprofessional team developed Communicating the Gynecologic Brachytherapy Experience (CoGBE), a graphic narrative discussion guide for cylinder, intracavitary, and interstitial high-dose-rate (HDR) gynecologic brachytherapy. This study assesses perceived clinical benefits, usability, and anxiety-reduction of CoGBE. METHODS AND MATERIALS: An electronic survey was sent to members of the American Brachytherapy Society. Participants were assigned to assess one of the three modality-specific CoGBE versions using a modified Systems Usability Scale (SUS), modified state-trait anxiety index (mSTAI), and Likert-type questions. Free response data was analyzed using modified grounded theory. RESULTS: Median modified SUS score was 76.3 (interquartile range [IQR], 71.3-82.5) and there were no significant differences between guide types. Median mSTAI was 40 (IQR, 40-43.3) for all guides collectively. The cylinder guide had a significantly higher median mSTAI than the intracavitary and interstitial guides (41.6 vs. 40.0 and 40.0; p = 0.04) suggesting the cylinder guide may have less impact on reducing anxiety. Most respondents reported that CoGBE was helpful (72%), would improve patient understanding (77%) and consultation memorability (82%), and was at least moderately likely to be incorporated into their practice (80%). Qualitative analysis themes included personalization and relatability (positive); generalizability (negative); illustrations (both). CONCLUSIONS: Clinicians rate CoGBE as usable with potential to reduce patient anxiety, especially with more invasive treatment modalities including intracavitary or interstitial high-dose-rate. CoGBE has the potential to improve patient-clinician communication for a wider range of patients due to its accessible, adaptable, and patient-centered design.


Subject(s)
Brachytherapy , Genital Neoplasms, Female , Uterine Cervical Neoplasms , Humans , Female , Brachytherapy/methods , Radiotherapy Dosage , Genital Neoplasms, Female/radiotherapy , Uterine Cervical Neoplasms/radiotherapy
3.
Blood Adv ; 7(3): 285-292, 2023 02 14.
Article in English | MEDLINE | ID: mdl-35851593

ABSTRACT

Relapse after allogeneic stem cell transplantation (allo-SCT) remains the primary cause of treatment failure. A second SCT can result in long-term survival in a subset of patients, but the relapse rate remains high. We conducted a single-center, phase 1, modified 3 + 3 dose-escalation study of the feasibility of combining intensity-modulated total marrow irradiation (IM-TMI) with fludarabine and melphalan for conditioning. Between December 2015 and May 2020, 21 patients with relapsed hematologic disease undergoing second or greater allo-SCT were treated with IM-TMI doses of 6 Gy, 9 Gy, or 12 Gy. Dose-limiting toxicity was defined as a grade 3 or higher treatment-related adverse event; mucositis was the primary dose-limiting toxicity. The median times to neutrophil and platelet engraftment were 10 and 18 days, respectively. The 1-year cumulative incidence of graft-versus-host disease was 65% (95% confidence interval CI, 38-83). The nonrelapse mortality at 2 years was 17% (95% CI, 4-39). Cumulative incidence of relapse at 2 years was 35% (95% CI, 13-58). Two-year progression-free survival and overall survival were 48% and 50%. We conclude that combining IM-TMI with fludarabine-melphalan is feasible. We recommend 12 Gy of IM-TMI with fludarabine-melphalan for second SCT, although 9 Gy may be used for older or underweight patients.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Hematologic Neoplasms , Hematopoietic Stem Cell Transplantation , Humans , Hematologic Neoplasms/therapy , Hematopoietic Stem Cell Transplantation/adverse effects , Melphalan/therapeutic use , Neoplasm Recurrence, Local/drug therapy , Antineoplastic Combined Chemotherapy Protocols/adverse effects
4.
Adv Radiat Oncol ; 7(6): 100998, 2022.
Article in English | MEDLINE | ID: mdl-36420189

ABSTRACT

Purpose: Patients with cervical cancer who are at high risk for para-aortic lymphatic involvement may receive extended-field chemoradiation (EF-CRT), with inclusion of the para-aortic region. Increased radiation to bone marrow (BM) may heighten hematologic toxicity (HT) and affect timely delivery of chemoradiation. Factors associated with HT in this setting have not been well studied. Methods and Materials: This study was a retrospective analysis of women treated with EF-CRT from 2012 to 2018 with platinum-based chemotherapy. Factors including age, body mass index (BMI), race, Charlson Comorbidity Index (CCI), and nadirs for white blood cell count, absolute neutrophil count, hemoglobin, and platelet count were collected. The BM metrics included V5Gy, V10Gy, V15Gy, V20Gy, V25Gy, V30Gy, V35Gy, V40Gy and V45Gy (VxGy was defined as the percentage of BM volume receiving x Gy). Hematologic toxicity was defined as grade ≥2 (Cooperative Group Common Toxicity Criteria) leukopenia, anemia, neutropenia, or thrombocytopenia. Univariate analysis (UVA) and multivariate analysis (MVA) were performed using the χ2 test, the Fisher exact test, and logistic regression. Previously published dosimetric BM constraints were examined as detailed in each respective study. Results: Fifty-two women underwent EF-CRT with cisplatin. UVA showed no association between HT and age, BMI, or CCI. When accounting for race, V5Gy ≥98% was associated with grade ≥2 leukopenia (P = .02) and grade ≥2 HT (P = .05). Most previously described radiation metrics were not reproduced in our cohort, but a similar constraint, V20Gy <70%, was associated with reduced leukopenia of grade ≥2 on UVA (P = .02) and MVA (P < .05). Conclusions: Acute HT in patients receiving EF-CRT was associated with large volumes of low-dose radiation to the BM and was also associated with race. Restricting the BM V20Gy to less than 70% to 75% may be beneficial in reducing HT, but other pelvic radiation BM constraints may not be applicable to this population.

5.
Front Oncol ; 12: 942685, 2022.
Article in English | MEDLINE | ID: mdl-36267964

ABSTRACT

Purpose: Total marrow irradiation (TMI) involves optimization of extremely large target volumes and requires extensive clinical experience and time for both treatment planning and delivery. Although volumetric modulated arc therapy (VMAT) achieves substantial reduction in treatment delivery time, planning process still presents a challenge due to use of multiple isocenters and multiple overlapping arcs. We developed and evaluated a knowledge-based planning (KBP) model for VMAT-TMI to address these clinical challenges. Methods: Fifty-one patients previously treated in our clinic were selected for the model training, while 22 patients from another clinic were used as a test set. All plans used a 3-isocenter to cover sub-target volumes of head and neck (HN), chest, and pelvis. Chest plan was performed first and then used as the base dose for both the HN and pelvis plans to reduce hot spots around the field junctions. This resulted in a wide range of dose-volume histograms (DVH). To address this, plans without the base-dose plan were optimized and added to the library to train the model. Results: KBP achieved our clinical goals (95% of PTV receives 100% of Rx) in a single day, which used to take 4-6 days of effort without KBP. Statistically significant reductions with KBP were observed in the mean dose values to brain, lungs, oral cavity and lenses. KBP substantially improved 105% dose spillage (14.1% ± 2.4% vs 31.8% ± 3.8%), conformity index (1.51 ± 0.06 vs 1.81 ± 0.12) and homogeneity index (1.25 ± 0.02 vs 1.33 ± 0.03). Conclusions: KBP improved dosimetric performance with uniform quality. It reduced dependence on planner experience and achieved a factor of 5 reduction in planning time to produce quality plans to allow its wide-spread clinical implementation.

6.
Adv Radiat Oncol ; 7(2): 100833, 2022.
Article in English | MEDLINE | ID: mdl-35387422

ABSTRACT

Purpose: Patients with cervical cancer are at high risk for opioid use. This study aimed to characterize opioid prescribing patterns at 2 urban hospitals. Methods and Materials: Data from patients with cervical cancer treated with curative intent from 2011 to 2018 were retrospectively collected. Women with unrelated chronic opioid use before diagnosis, persistent/recurrent disease at 3 months after initiation of treatment, or initiation of opioids >6 months after treatment were excluded. Demographics, disease characteristics, treatment, and outpatient prescription practices were collected. Endpoints included duration of opioid use ≥6 and ≥12 months. Results: There were 106 women included, of whom 83% received definitive radiation. Most patients (n = 91, 85.8%) received outpatient opioids. Most common timing of prescriptions were before cancer therapy (35.9%), postprocedure (26.4%), and during radiation therapy (17.0%). Median duration was 3 (interquartile range, 1-11) months; 35.2% of these patients received opioids ≥6 months and 22% received opioids ≥12 months. Greater International Federation of Gynaecology and Obstetrics (FIGO) stage, recurrent/residual disease, initiation of opioids before treatment, history of depression or anxiety, and use of gabapentin or steroids were associated with long-term opioid use. Conclusions: Most patients were prescribed outpatient opioids, many of whom used opioids for 12 months. Improvement in provider communication and education, increased posttreatment monitoring, and further evaluation of nonopioid therapies are needed in this patient population to reduce long-term opioid use.

7.
Gynecol Oncol Rep ; 39: 100925, 2022 Feb.
Article in English | MEDLINE | ID: mdl-35059489

ABSTRACT

BACKGROUND: Primary small cell ovarian cancer of pulmonary type (SCCOPT) remains a rare ovarian tumor. Its aggressive nature is associated with poor survival outcomes. Current treatment algorithms rely on systemic chemotherapy, primarily involving platinum agents. However, given its low incidence, less is known about the potential benefits of other treatments. CASE PRESENTATION: We report a case of an 80-year-old woman who was found to have a complex pelvic mass with a mildly elevated CA-125. She underwent a laparotomy for staging with tumor debulking; she had bulky unresectable adenopathy and pathology was consistent with stage IIIC SCCOPT. Postoperative imaging revealed progression of disease. She received six cycles of carboplatin and etoposide followed by consolidative radiation therapy to her para-aortic lymph nodes. She remains disease-free for over four years after completion of adjuvant therapy. DISCUSSION: Histologically, SCCOPT resembles small cell carcinomas of the lung, which are treated with a combination of chemotherapy and radiation therapy. New approaches that build upon the current treatment approaches and incorporate strategies from non-gynecologic tumor types could be beneficial.

8.
Clin Breast Cancer ; 22(1): e8-e20, 2022 01.
Article in English | MEDLINE | ID: mdl-34257001

ABSTRACT

INTRODUCTION/BACKGROUND: We aimed to update the previous evaluation of hypofractionated whole-breast irradiation (HF-WBI) use over time in the United States and factors related to its adoption for patients undergoing a lumpectomy from 2004 to 2016. MATERIALS AND METHODS: Among the patients who underwent a lumpectomy, we identified 688,079 patients with early-stage invasive breast cancer and 248,218 patients with ductal carcinoma in situ in the National Cancer Database from 2004 to 2016. We defined HF-WBI as 2.5 to 3.33 Gy/fraction to the breast and conventional fractionated whole-breast irradiation as 1.8 to 2.0 Gy/fraction. We evaluated the trend of HF-WBI use and examined factors associated with HF-WBI use using logistic regression models. RESULTS: Among invasive cancer patients, the use of HF-WBI increased exponentially from 0.7% in 2004 to 15.6% in 2013 and then to 38.1% in 2016. Among patients with ductal carcinoma in situ, the use of HF-WBI has increased significantly from 0.42% in 2004 to 13.4% in 2013 and then to 34.3% in 2016. Factors found to be associated with HF-WBI use included age, patient geographical location, race/ethnicity, tumor stage, grade, treating facility type, and volume. CONCLUSION: HF-WBI use in the United States has more than doubled from 2013 to 2016. Although its use is close to that of conventional fractionated whole-breast irradiation, HF-WBI is still far from the preferred standard of care in the United States. We identified several patient and facility factors that can impact the uptake of HF-WBI treatment. Microabstract Using the National Cancer Database from 2004 to 2016, we evaluated the trend of hypofractionated whole-breast radiation therapy use and factors associated with use. Use in the United States has more than doubled from 2013 to 2016, but it has not become the standard of care. We identified several patient and facility factors that impact the uptake of hypofractionated whole-breast radiation therapy treatment.


Subject(s)
Breast Neoplasms/pathology , Breast Neoplasms/radiotherapy , Practice Patterns, Physicians'/statistics & numerical data , Radiation Dose Hypofractionation/standards , Radiation Injuries/prevention & control , Standard of Care , Databases, Factual , Female , Humans , Neoplasm Staging , Radiotherapy, Adjuvant/statistics & numerical data , Severity of Illness Index , Time Factors , United States
9.
Am J Clin Oncol ; 44(11): 565-571, 2021 11 01.
Article in English | MEDLINE | ID: mdl-34456239

ABSTRACT

OBJECTIVE: Historically, external beam parametrial boost (EBPB) has been used in locally advanced cervical cancers to supplement radiation dose. However, it has become controversial in the era of image-guided brachytherapy. Modern 3D imaging and brachytherapy techniques have improved delineation and coverage of tumor. Outcomes with and without parametrial boost were analyzed. METHODS: Women with cervical cancer involving the parametria (clinically or radiographically) diagnosed between 2001 and 2017 were identified. Clinicopathologic and treatment features, survival and patterns of failure data were collected. Univariate and multivariable data analysis was performed to evaluate association of these variables, including parametrial boost, with local failure-free survival and overall survival. Competing risks analysis was performed for cumulative incidence of local failure, with death and other failures treated as competing events. RESULTS: A total of 100 women were identified (median follow-up 26.8 mo). Forty-one (41%) received EBPB; these patients were less likely to have received magnetic resonance imaging, positron emission tomography, interstitial, or high-dose rate brachytherapy. Magnetic resonance imaging, positron emission tomography, dose rate, and treatment era were highly correlated (Cramer's V: 0.43 to 0.68, P<0.01). Two-year overall survival and local failure were 78% and 12% for the entire cohort. While the use of EBPB was not associated with any outcome on multivariable analysis, treatment year after 2009 was highly associated with improved outcomes in all models. CONCLUSIONS: In this study, omission of EBPB did not compromise local control or survival in the modern era, supporting a decreased need for standardized use of parametrial boost.


Subject(s)
Brachytherapy/methods , Radiotherapy, Image-Guided , Uterine Cervical Neoplasms/radiotherapy , Adult , Female , Humans , Middle Aged , Neoplasm Staging , Radiotherapy Dosage , Retrospective Studies , Uterine Cervical Neoplasms/pathology , Uterus
10.
JAMA Oncol ; 7(6): 845-852, 2021 Jun 01.
Article in English | MEDLINE | ID: mdl-33885704

ABSTRACT

IMPORTANCE: Stereotactic body radiotherapy (SBRT) for oligometastases is hypothesized to improve survival and is increasingly used. Little evidence supports its safe use to treat patients with multiple metastases. OBJECTIVE: To establish safety of SBRT dose schedules in patients with 3 to 4 metastases or 2 metastases in close proximity to each other. DESIGN, SETTING, AND PARTICIPANTS: This phase 1 trial opened on August 4, 2014, and closed to accrual on March 20, 2018. Metastases to 7 anatomic locations were included: bone/osseous (BO), spinal/paraspinal (SP), peripheral lung (PL), central lung (CL), abdominal-pelvic (AP), mediastinal/cervical lymph node (MC), and liver (L). Six patients could be enrolled per anatomic site. The setting was a consortium of North American academic and community practice cancer centers participating in NRG Oncology trials. Patients with breast, prostate, or non-small cell lung cancer with 3 to 4 metastases or 2 metastases in close proximity (≤5 cm) amenable to SBRT were eligible for this phase 1 study. Statistical analyses were performed from December 31, 2017, to September 19, 2019. INTERVENTIONS: The starting dose was 50 Gy in 5 fractions (CL, MC), 45 Gy in 3 fractions (PL, AP, L), and 30 Gy in 3 fractions (BO, SP). MAIN OUTCOMES AND MEASURES: The primary end point was dose-limiting toxicity (DLT) defined by the Common Terminology Criteria for Adverse Events, version 4.0, as specific adverse events (AEs) of grades 3 to 5 (definite or probable per the protocol DLT definition) related to SBRT within 180 days of treatment. Dose levels were considered safe if DLTs were observed in no more than 1 of 6 patients per location; otherwise, the dose at that location would be de-escalated. RESULTS: A total of 42 patients enrolled, 39 were eligible, and 35 (mean [SD] age, 63.1 [14.2] years; 20 men [57.1%]; 30 White patients [85.7%]) were evaluable for DLT. Twelve patients (34.3%) had breast cancer, 10 (28.6%) had non-small cell lung cancer, and 13 (37.1%) had prostate cancer; there was a median of 3 metastases treated per patient. Median survival was not reached. No protocol-defined DLTs were observed. When examining all AEs, 8 instances of grade 3 AEs, most likely related to protocol therapy, occurred approximately 125 to 556 days from SBRT initiation in 7 patients. CONCLUSIONS AND RELEVANCE: This phase 1 trial demonstrated the safety of SBRT for patients with 3 to 4 metastases or 2 metastases in close proximity. There were no treatment-related deaths. Late grade 3 AEs demonstrate the need for extended follow-up in long-surviving patients with oligometastatic disease. Treatment with SBRT for multiple metastases has been expanded into multiple ongoing randomized phase 2/3 National Cancer Institute-sponsored trials (NRG-BR002, NRG-LU002). TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02206334.


Subject(s)
Breast Neoplasms , Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Prostatic Neoplasms , Radiosurgery , Breast Neoplasms/pathology , Carcinoma, Non-Small-Cell Lung/pathology , Female , Humans , Lung Neoplasms/pathology , Male , Prostatic Neoplasms/pathology , Radiosurgery/adverse effects , Radiosurgery/methods
11.
J Appl Clin Med Phys ; 21(12): 146-154, 2020 Dec.
Article in English | MEDLINE | ID: mdl-33124774

ABSTRACT

PURPOSE: To evaluate the dosimetric impact of daily positioning variations measured with cone-beam computed tomography (CBCT) on whole-breast radiotherapy patients treated in the prone position. METHODS: Daily CBCT was prospectively acquired for 30 consecutive patients positioned prone. Treatment for early-stage (≤II) breast cancer was prescribed with standard dose (50 Gy/25 fractions) or hypofractionation (42.56 Gy/16 fractions) for 13 and 17 patients, respectively. Systematic and random errors were calculated from the translational CBCT shifts and used to determine population-based setup margins. Mean translations (±one standard deviation) for each patient were used to simulate the dosimetric impact on targets (PTV_eval and lumpectomy cavity), heart, and lung. Paired Student's t tests at α = 0.01 were used to compare dose metrics after correction for multiple testing (P < 0.002). Significant correlation coefficients were used to identify associations (P < 0.01). RESULTS: Of 597 total fractions, 20 ± 13% required patient rotation. Mean translations were 0.29 ± 0.27 cm, 0.41 ± 0.34 cm, and 0.48 ± 0.33 cm in the anterior-posterior, superior-inferior, and lateral directions leading to calculated setup margins of 0.63, 0.88, and 1.10 cm, respectively. Average three-dimensional (3D) shifts correlated with the maximum distance of breast tissue from the sternum (r = 0.62) but not with body-mass index. Simulated shifts showed significant, but minor, changes in dose metrics for PTV_eval, lung, and heart. For left-sided treatments (n = 18), mean heart dose increased from 109 ± 75 cGy to 148 ± 115 cGy. Shifts from the original plan caused PTV_eval hotspots (V105%) to increase by 5.2% ± 3.8%, which correlated with the total MU of wedged fields (r = 0.59). No significant change in V95% to the cavity was found. CONCLUSIONS: Large translational variations that occur when positioning prone breast patients had small but significant dosimetric effects on 3DCRT plans. Daily CBCT may still be necessary to correct for rotational variations that occur in 20% of treatments. To maintain planned dose metrics, unintended beam shifts toward the heart and the contribution of wedged fields should be minimized.


Subject(s)
Breast Neoplasms , Radiotherapy, Conformal , Breast Neoplasms/diagnostic imaging , Breast Neoplasms/radiotherapy , Cone-Beam Computed Tomography , Female , Humans , Prone Position , Radiotherapy Dosage , Radiotherapy Planning, Computer-Assisted
13.
Gynecol Oncol Rep ; 33: 100593, 2020 Aug.
Article in English | MEDLINE | ID: mdl-32577490

ABSTRACT

•Extensive nodal metastases from uterine serous carcinoma can lead to SVC syndrome.•Prevention of nodal metastases is an important goals of care discussion.•Radiation, steroids and/or chemotherapy must all be considered in this setting.

14.
Br J Radiol ; 93(1111): 20190640, 2020 Jul.
Article in English | MEDLINE | ID: mdl-32286849

ABSTRACT

While it is well-established that hypoxia is a major factor that affects clinical outcomes in cervical cancer, widespread usage of clinically available methods to detect and evaluate hypoxia during the course of treatment have not been established. This review compares these methods, summarizes their strengths and weaknesses, and assesses the pathways for their useful employment to alter clinical practice. We conducted a search on PubMed for literature pertaining to imaging hypoxic cervical cancer, and implemented keywords related to oxygen measurement tools to improve the relevance of the search results.Oxygenation level-dependent applications of MRI have demonstrated hypoxia-induced radioresistance, and changes in cervix tumor oxygenation from hyperoxic therapy.The hypoxic areas within tumors can be indirectly identified in dynamic contrast-enhanced images, where they generally display low signal enhancement, and diffusion-weighted images, which demonstrates areas of restricted diffusion (which correlates with hypoxia). Positron emmision tomography, used independently and with other imaging modalities, has demonstrated utility in imaging hypoxia through tracers specific for low oxygen levels, like Cu-ATSM tracers and nitroimidazoles. Detecting hypoxia in the tumors of patients diagnosed with cervical cancer via medical imaging and non-imaging tools like electron paramagnetic resonance oximetry can be utilized clinically, such as for guiding radiation and post-treatment surveillance, for a more personalized approach to treatment. The merits of these methods warrant further investigation via comparative effectiveness research and large clinical trials into their clinical applications.


Subject(s)
Cell Hypoxia/physiology , Uterine Cervical Neoplasms/diagnosis , Contrast Media , Diffusion Magnetic Resonance Imaging , Female , Humans , Multimodal Imaging/methods , Oximetry/methods , Oxygen/metabolism , Positron-Emission Tomography , Uterine Cervical Neoplasms/metabolism
15.
Int J Radiat Oncol Biol Phys ; 107(3): 487-498, 2020 07 01.
Article in English | MEDLINE | ID: mdl-32151670

ABSTRACT

PURPOSE: This study assessed the safety and tolerability of therapeutic immunization against the human papillomavirus (HPV) viral oncoproteins E6 and E7 in patients with cervical cancer after chemoradiation. METHODS AND MATERIALS: MEDI0457 (INO-3112) is a DNA-based vaccine targeting E6 and E7 of HPV-16/18 that is coinjected with an IL-12 plasmid followed by electroporation with the CELLECTRA 5P device. At 2 to 4 weeks after chemoradiation, patients with newly diagnosed stage IB1-IVA (cohort 1) or persistent/recurrent (cohort 2) cervical cancers were treated with 4 immunizations of MEDI0457 every 4 weeks. The primary endpoints were incidence of adverse events and injection site reactions. Immune responses against HPV antigens were measured by ELISpot for interferon-γ (IFNγ), enzyme-linked immunosorbent assay for antibody responses and multiplexed immunofluorescence for immune cells in cervical biopsy specimens. RESULTS: Ten patients (cohort 1, n = 7; cohort 2, n = 3) with HPV16 (n = 7) or HPV18 (n = 3) cervical cancers received MEDI0457 after chemoradiation. Treatment-related adverse events were all grade 1, primarily related to the injection site. Eight of 10 patients had detectable cellular or humoral immune responses against HPV antigens after chemoradiation and vaccination: 6 of 10 patients generated anti-HPV antibody responses and 6 of 10 patients generated IFNγ-producing T cell responses. At the completion of chemoradiation and vaccination, cervical biopsy specimens had detectable CD8+ T cells and decreased PD-1+CD8+, PD-L1+CD8+, and PD-L1+CD68+ subpopulations. All patients cleared detectable HPV DNA in cervical biopsies by completion of chemoradiation and vaccination. CONCLUSIONS: Adjuvant MEDI0457 is safe and well tolerated after chemoradiation for locally advanced or recurrent cervical cancers, supporting further investigation into combining tumor-specific vaccines with radiation therapy.


Subject(s)
Chemoradiotherapy , Human papillomavirus 16/immunology , Human papillomavirus 18/immunology , Safety , Uterine Cervical Neoplasms/therapy , Uterine Cervical Neoplasms/virology , Vaccines, DNA/adverse effects , Adult , DNA-Binding Proteins/immunology , Female , Human papillomavirus 16/drug effects , Human papillomavirus 16/physiology , Human papillomavirus 16/radiation effects , Human papillomavirus 18/drug effects , Human papillomavirus 18/physiology , Human papillomavirus 18/radiation effects , Humans , Middle Aged , Oncogene Proteins, Viral/immunology , Papillomavirus E7 Proteins/immunology , Repressor Proteins/immunology , Uterine Cervical Neoplasms/prevention & control
16.
Semin Radiat Oncol ; 30(1): 29-38, 2020 01.
Article in English | MEDLINE | ID: mdl-31727297

ABSTRACT

An interstitial brachytherapy approach for gynecologic cancers is typically considered for patients with lesions exceeding 5 mm within tissue or that are not easily accessible for intracavitary applications. Recommendations for treating gynecologic malignancies with this approach are available through the American Brachytherapy Society, but vary based on available resources, staffing, and logistics. The intent of this manuscript is to share the collective experience of 3 academic centers that routinely perform interstitial gynecologic brachytherapy. Discussion points include indications for interstitial implants, procedural preparations, applicator selection, anesthetic options, imaging, treatment planning objectives, clinical workflows, timelines, safety, and potential challenges. Interstitial brachytherapy is a complex, high-skill procedure requiring routine practice to optimize patient safety and treatment efficacy. Clinics planning to implement this approach into their brachytherapy practice may benefit from considering the discussion points shared in this manuscript.


Subject(s)
Brachytherapy/methods , Genital Neoplasms, Female/radiotherapy , Brachytherapy/instrumentation , Female , Genital Neoplasms, Female/pathology , Humans , Magnetic Resonance Imaging , Practice Guidelines as Topic , Radiotherapy Dosage , Tomography, X-Ray Computed , United States , Workflow
17.
Gynecol Oncol ; 155(3): 429-435, 2019 12.
Article in English | MEDLINE | ID: mdl-31610885

ABSTRACT

OBJECTIVE: To report on patterns of care as well as evaluate the two treatment regimens using a large retrospective hospital-based registry to identify possible subgroups of patients who may experience benefit with VBT + CT vs. EBRT. METHODS: Patients from the National Cancer Database (NCDB) were identified who met the inclusion criteria for GOG 249 and were treated with either VBT + CT or WPRT. Demographic, clinicopathologic, and treatment factors were collected. Association of treatment type and other variables with overall survival was analyzed using Cox proportional hazards model. Subset analyses were performed based on a variety of risk factors, including high risk pathologies, surgical nodal sampling, and grade. RESULTS: A total of 4,602 patients were included in the analysis, with 41% receiving VBT + CT and 59% receiving WPRT. For the entire cohort, VBT + CT was associated with improved survival, with 3-year overall survival 89.6% vs. 87.8% (hazard ratio 1.24, 95%CI 1.01-1.52, p = 0.04). On subset analysis, patients with serous histology experienced benefit with VBT + CT, while high-grade endometrial patients without lymph node dissection experienced improved survival associated with EBRT. After exclusion of serous histology, there was no survival difference associated with treatment type. CONCLUSIONS: VBT + CT was associated with superior survival outcomes in patients with early-stage serous carcinoma. For non-serous histology, treatment modality was not associated with a difference in survival, although patients with high-grade disease and no nodal dissection experienced benefit from EBRT.


Subject(s)
Brachytherapy/methods , Endometrial Neoplasms/drug therapy , Endometrial Neoplasms/radiotherapy , Aged , Carcinoma, Endometrioid/drug therapy , Carcinoma, Endometrioid/pathology , Carcinoma, Endometrioid/radiotherapy , Chemoradiotherapy , Cystadenocarcinoma, Serous/drug therapy , Cystadenocarcinoma, Serous/pathology , Cystadenocarcinoma, Serous/radiotherapy , Endometrial Neoplasms/pathology , Female , Humans , Middle Aged , Neoplasm Staging , Radiotherapy, Adjuvant , Risk Factors , Treatment Outcome
18.
Int J Radiat Oncol Biol Phys ; 105(4): 904-905, 2019 11 15.
Article in English | MEDLINE | ID: mdl-31655659
19.
Pract Radiat Oncol ; 9(6): 479-491, 2019 Nov.
Article in English | MEDLINE | ID: mdl-31302301

ABSTRACT

PURPOSE: Guidelines for the care of women undergoing pelvic radiation therapy (RT) recommend vaginal dilator therapy (VDT) to prevent radiation-induced vaginal stenosis (VS); however, no standard protocol exists. This review seeks to update our current state of knowledge concerning VS and VDT in radiation oncology. METHODS AND MATERIALS: A comprehensive literature review (1972-2017) was conducted using search terms "vaginal stenosis," "radiation," and "vaginal dilator." Information was organized by key concepts including VS definition, time course, pathophysiology, risk factors, and interventions. RESULTS: VS is a well-described consequence of pelvic RT, with early manifestations and late changes evolving over several years. Strong risk factors for VS include RT dose and volume of vagina irradiated. Resultant vaginal changes can interfere with sexual function and correlational studies support the use of preventive VDT. The complexity of factors that drive noncompliance with VDT is well recognized. There are no prospective data to guide optimal duration of VDT, and the consistency with which radiation oncologists monitor VS and manage its consequences is unknown. CONCLUSIONS: This review provides information concerning VS definition, pathophysiology, and risk factors and identifies domains of VDT practice that are understudied. Prospective efforts to monitor and measure outcomes of patients who are prescribed VDT are needed to guide practice.


Subject(s)
Constriction, Pathologic/radiotherapy , Dilatation/methods , Radiation Oncology/methods , Vagina/abnormalities , Vagina/radiation effects , Female , Humans , Vagina/pathology
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