J. Lea - Academia.edu (original) (raw)

Papers by J. Lea

INTRODUCTION Prognosis is particularly poor for cervical cancer patients who present with large h... more INTRODUCTION Prognosis is particularly poor for cervical cancer patients who present with large hypoxic tumors. While tumor size can be assessed non-invasively, invasive electrodes have been required to measure oxygenation. A noninvasive assessment would be particularly attractive to patients and physicians and potentially allow the design of personalized medicine regimes (1). BOLD (Blood Oxygen Level Dependant) contrast MRI is a non-invasive technique sensitive to tumor vascular oxygenation (2) that we have tested to assess cervical cancer in this study. Deoxyhemoglobin causes T2* shortening and the signal change accompanying an oxygen breathing challenge can indicate vascular oxygen dynamics. This process has been shown to relate to elimination of hypoxic fractions in rat breast tumors (3). We seek to evaluate whether BOLD response to hyperoxic gas challenge has prognostic value for these patients.

Annals of Oncology, 2017

Background: Ovarian cancers have a high rate of mutation in TP53, an alteration that produces a G... more Background: Ovarian cancers have a high rate of mutation in TP53, an alteration that produces a G1/S checkpoint deficiency and increases the level of endogenous DNA abstracts Annals of Oncology

Poster exhibition Day 1, 2019

Introduction/Background Endometrial precancer (endometrioid intraepithelial neoplasia/EIN) diagno... more Introduction/Background Endometrial precancer (endometrioid intraepithelial neoplasia/EIN) diagnosis remains contentious, with variable criteria and frequent disagreements among gynecologic pathologists, potentially leading to under/overtreatment. The endometrium is unique in that diagnostic biopsies do not extirpate neoplastic lesions. Our purpose was to 1) characterize serial genomic alterations along the pre-EIN/EIN/cancer continuum in individual women; 2) determine if genomic analysis adds diagnostic value to histopathological review. Methodology Inclusion criteria were 1) endometrial cancer diagnosis/hysterectomy 2) preceding serial endometrial biopsies (typically over many years) including for some patients an early biopsy before an EIN diagnosis. A comprehensive panel was designed for genes recurrently mutated in endometrial cancer, including hereditary cancer loci. Formalin-fixed/paraffin-embedded specimens for each cancer, preceding samples, and matched germline DNA were subjected to barcoded massively-parallel sequencing to identify mutations, hereditary and acquired, and track their origin and allelic frequency progression. 147 samples from 29 women (5.1 samples/patient) were analyzed. Results In all but two patients mutations in the cancer were detectable in preceding EIN(s). Notably, ≥1 mutations were detectable in 15/19 patients where a pre-EIN biopsy was available. Serial analysis provided unique insights into the progression of various endometrial cancers. In most cases, the presence of ≥1 mutation could be confirmed by immunohistochemistry, providing unique views of histologic correlates. Class-defining mutations (e.g. POLE) were identified in several cases. Germline mutations were identified in patients with known cancer predisposition syndromes. Mutations were not identified in 15 age-matched control (normal) endometria, arguing that with appropriate thresholds, age-related endometrial mutations should not confound analyses. Conclusion Genomic analysis of selected endometrial biopsies has the potential to be a cost-effective and valuable diagnostic adjunct to histology, also replacing in a single assay diverse screening methods to identify cancer predisposition syndromes. Though of considerable promise, further investigations will be required to establish utility and refine diagnostic criteria. Disclosure The authors have no conflicts of interest to disclose. Funding to DHC was provided by the National Institutes of Health/National Cancer Institute (USA), the Cancer Prevention Research Institute of Texas (State of Texas) and the UT Southwestern Stembridge Distinguished Professorship. Abstract P1236 Figure 1 Allelic frequencies for mutations in biopsies up to 8 years prior to cancer dx (single patient)

Best Oral/Late-Breaking Abstracts 4 – Miscellaneous, 2019

Introduction/Background Introduction: GROINSS-V II investigated whether radiotherapy is a safe al... more Introduction/Background Introduction: GROINSS-V II investigated whether radiotherapy is a safe alternative for inguinofemoral lymphadenectomy (IFL) in vulvar cancer patients with a metastatic sentinel node (SN). Methodology Methods: In GROINSS-V II, a prospective multicentre phase II trial, patients were included with early-stage squamous cell carcinoma (SCC) of the vulva (diameter <4cm) without suspicious lymph nodes at imaging, who had primary surgery with SN-procedure. In case of a metastatic SN (metastasis of any size), radiotherapy was given to the groin(s) (50Gy). In case of a negative SN, patients were followed-up for ≥2 years. Stopping rules were defined for both groups to monitor groin recurrence rate. Results From December 2005 until October 2016, 1552 eligible patients were registered. SN-metastasis occurred in 324/1552 (21%) patients. After 54 months of inclusion the stopping-rule for SN-positive patients was activated; interim analysis showed an increased risk for groin recurrence in case of SN-metastasis >2 mm and/or extranodal extension (ENE). After amendment of the protocol only patients with SN-micrometastasis ≤2 mm received radiotherapy, while those with SN metastasis >2 mm underwent IFL (with radiotherapy if >1 metastasis or ENE). Final analysis after ≥2 years of follow-up revealed six isolated groin recurrences in 157 patients with a SN-micrometastasis (3.8%). Four could not be considered radiotherapy failures: two developed recurrence in the contralateral (SN-negative) groin, two refused radiotherapy. Twenty-eight patients did not get radiotherapy (2 recurrences;7.1%). Among 129 patients who received radiotherapy to the groin(s) only two isolated groin recurrences were diagnosed (1.6%: 95%CI:0–3.8%). The combination of radiotherapy with SN was associated with minimal toxicity: 5/118(4.2%) grade 3 toxicity, no grade 4 or 5 toxicity. In 38/1222 SN-negative patients (3.1%: 95%CI:2.1–4.1%) isolated groin recurrences were diagnosed with clear protocol violations in 6 patients: incomplete treatment of the groin (n=3); primary tumor >4cm (n=1); not all SNs visualized on the lymphoscintigram removed (n=2). After exclusion of these protocol violations an isolated groin recurrence rate of 2.6% (95%CI:1.7–3.5%) was observed. Conclusion Radiotherapy to the groins is a safe alternative for IFL in patients with SN metastasis ≤2 mm, with minimal toxicity. We further established the safety of omitting IFL in patients with SCC of the vulva <4cm and a negative SN. For patients with SN metastasis >2 mm, radiotherapy with a total dose of 50Gy was no safe alternative for IFL; dose escalation and/or chemoradiation should be investigated in these patients. Disclosure Funded by Dutch Cancer Society.

Gynecologic Oncology, 2019

We fit logistic joinpoint models to quantify the probability of 90-day postoperative mortality as... more We fit logistic joinpoint models to quantify the probability of 90-day postoperative mortality as a function of age for women undergoing primary (PCS) and interval (ICS) cytoreductive surgery. We fit separate models to estimate crude and adjusted age-specific relative odds of postoperative death after PCS relative to ICS. Results: We identified 47,117 of whom 37,024 (78.5%) underwent PCS and 10,153 (21.5%) underwent ICS. Overall, 90-day mortality was more common after PCS (7.2%; 2,658 deaths) than ICS (3.1%; 312 deaths). Age-related trends in 90-day mortality differed between PCS and ICS (p interaction b0.001, see Figure). Women age ≤47 experienced no age-related increase in risk of 90-day mortality after ICS (p =0.36) or PCS (p=0.75). Among women who underwent PCS, the odds of 90-day postoperative mortality began rising at age 47, increasing by 5.7% per year (95% CI 5.0-6.5, pb0.001) until age 71, and by 9.9% per year (95% CI 8.8-10.9; pb0.001) thereafter. In contrast, odds of 90-day mortality after ICS began to increase at age 62, and increased steadily by 5.7% per year (95% CI 3.9-7.5, pb0.001). By age 75 the probability of 90-day postoperative mortality after ICS was 4.2% (95% CI 3.6-4.9) compared with 12.3% after PCS (95% CI 11.4-12.7). By age 85 these probabilities increased to 7.2% (95% CI 5.5-9.2) and 26.0% (95 CI 24.1-27.9) respectively. Conclusions: Women undergoing PCS incurred an age-related risk of postoperative mortality at a younger age, and to of a greater magnitude, than those undergoing ICS. Among older women, NACT may reduce the frequency on unbeneficial cytoreductive surgery. Objectives: The objective of this study was to assess the practice patterns of gynecologic oncologists regarding the use of minimally invasive surgery (MIS) for the treatment of ovarian cancer. Methods: An electronic survey using REDCap was sent to all physician members of the Society of Gynecologic Oncologists. Responses were confidential with no identifying information collected from participants. Statistical analysis was descriptive in nature. Study approved by the authors' home Institutional Review Board. Results: There were 234 responses to the survey. Most respondents were part of an academic practice (64.7%) that trained fellows (53.3%) or residents (94%). Practice location was evenly distributed throughout the United States. Number of female and male respondents was evenly split. The vast majority of respondents (88%) reported performing more than half of all surgeries using MIS with 44.4% performing more than three-quarters of all surgeries using MIS. The most common procedures currently performed using MIS were: hysterectomy (98.3%), lymphad-enectomy (95.7%), omentectomy (90.1%), appendectomy (88.5%), and radical hysterectomy (84.5%). Several respondents were currently performing advanced procedures laparoscopically with many others interested in performing these procedures in the future: cytoreductive surgery (34.8%, 16.7%), splenectomy (15.1%, 30.6%), diaphragmatic stripping (18.1%, 26.3%), bowel resection and reanastomosis (19.7%, 42.5%), and low anterior resection (16.7%, 39.1%). Three-quarters (74.8%) of respondents reported currently using MIS for the treatment of ovarian cancer with diagnostic laparoscopy (90.1%), primary staging (76.7%), and interval cytoreductive surgery (72.7%) being the most common procedures performed. The most common cited benefits of MIS for the treatment of ovarian cancer included decreased blood loss (65.1%), decreased hospital LOS (81.2%), and decreased morbidity (76.9%). The most common cited barriers to the treatment of ovarian cancer with MIS included leaving residual disease behind (84.1%) and lack of scientific validation for MIS compared to laparotomy (58.0%). Conclusions: Minimally invasive surgery is currently being used regularly for the treatment of ovarian cancer. Interest among gynecologic oncologists to perform more advanced surgical procedures in the setting of ovarian cancer via minimally invasive routes is high. Our findings underscore the need to validate the use of MIS in ovarian cancer treatment. Objectives: This study was conducted to determine the cost-effectiveness of opportunistic salpingectomy at the time of tubal ligation and hysterectomy and the impact of this procedure on ovarian cancer mortality. Methods: A Markov state transition model was constructed including hysterectomy, tubal ligation, and ovarian cancer. Transition probabilities between the states were informed by previously reported population data. This model was used to predict ovarian cancer incidence and mortality with and without opportunistic salpingectomy at tubal ligation or hysterectomy, as well as the costs associated with these procedures. Results: The recursive Markov model was run from age 20 to 85 in one-year intervals with a half step correction and included age adjusted rates of tubal ligation, hysterectomy (with and without Abstracts / Gynecologic Oncology 153…

Gynecologic Oncology, 2015

Gynecologic Oncology, 2017

The Journal of reproductive medicine

To review outcomes of women with gestational trophoblastic neoplasia (GTN) who presented to an in... more To review outcomes of women with gestational trophoblastic neoplasia (GTN) who presented to an inner-city hospital system, given that the rigorous treatment and follow-up for GTN is often problematic for certain women of low socioeconomic status with limited resources and social support. A retrospective review was performed with IRB approval of patients diagnosed with GTN based on the revised WHO scoring system from 1999-2010 at our institution. SPSS Statistics software was used to perform univariate and multivariate analyses. Forty-nine patients were treated for GTN: 32 low-risk and 17 high-risk. Low-risk patients received an average of 5 cycles of initial single-agent chemotherapy. Six patients had persistent disease and were switched to a second single-agent regimen. One patient required multiagent chemotherapy for normalization of human chorionic gonadotropin levels. No patient had recurrence of disease. All high-risk patients were initially treated with multiagent chemotherapy,...

Journal of Bioinformatics and Computational Biology, 2006

Ovarian cancer recurs at the rate of 75% within a few months or several years later after therapy... more Ovarian cancer recurs at the rate of 75% within a few months or several years later after therapy. Early recurrence, though responding better to treatment, is difficult to detect. Surface-enhanced laser desorption/ionization time-of-flight (SELDI-TOF) mass spectrometry has showed the potential to accurately identify disease biomarkers to help early diagnosis. A major challenge in the interpretation of SELDI-TOF data is the high dimensionality of the feature space. To tackle this problem, we have developed a multi-step data processing method composed of t-test, binning and backward feature selection. A new algorithm, support vector machine-Markov blanket/recursive feature elimination (SVM-MB/RFE) is presented for the backward feature selection. This method is an integration of minimum weight feature elimination by SVM-RFE and information theory based redundant/irrelevant feature removal by Markov Blanket. Subsequently, SVM was used for classification. We conducted the biomarker selec...

Gynecologic Oncology, 2013

Gynecologic Oncology, 2002

To determine if performing an endocervical curettage (ECC) at the time of conization is a useful ... more To determine if performing an endocervical curettage (ECC) at the time of conization is a useful diagnostic tool for predicting residual cervical adenocarcinoma in situ (AIS) among women who might wish to preserve their fertility. All patients diagnosed with AIS from 1995 to 2000 at four institutions were identified. Data were retrospectively extracted from clinical records. Women included in the statistical analysis were (1) younger than 40 years, (2) had an ECC performed at the time of the initial cone biopsy, (3) had a clearly demarcated surgical margin pathologically, and (4) underwent a second surgical procedure. Twenty-nine (24%) of 123 AIS patients met criteria for inclusion. The median age was 33 years (range, 17 to 39) and 13 (46%) were nulliparous. Initial surgery was a cold-knife conization (n = 17) or loop electrosurgical excision procedure (n = 12). Twelve (41%) ECCs and 15 (52%) cone margins were histologically positive. Sixteen patients underwent a repeat conization; 13 underwent hysterectomy. Thirteen (45%) patients had residual AIS at the time of their second surgical procedure. ECC had a superior positive predictive value (100% vs 47%; P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.01) and negative predictive value (94% vs 57%; P = 0.01) compared to cone margin in predicting residual AIS. None of the women undergoing fertility-sparing surgery developed recurrent AIS or adenocarcinoma. ECC performed at the time of conization may be a useful tool for predicting residual AIS in women considering fertility preservation.

Gynecologic Oncology, 2012

ABSTRACT Objectives: Survival outcomes for endometrioid adenocarcinoma of the uterus are far bett... more ABSTRACT Objectives: Survival outcomes for endometrioid adenocarcinoma of the uterus are far better than those of papillary serous (UPSC) or clear cell carcinoma (CC) of a comparable stage. In the recurrent setting, patients with diverse histologic types of epithelial endometrial cancer are commonly grouped together when evaluating treatment regimes. The purpose of this study was to compare survival outcomes after recurrence between endometrioid adenocarcinoma and UPSC/CC of the uterus. Methods: This was a retrospective review of patients with recurrent endometrioid, UPSC, or CC carcinoma of the uterus that were treated with chemotherapy from 1999–2011 at our institution. Descriptive statistics were performed using Microsoft Excel 2011 and Fisher's exact test. Kaplan Meier analyses were used to compare disease free and overall survival. Results: A total of 53 patients with recurrent endometrial cancer treated with chemotherapy were identified: 25 with endometrioid and 28 with UPSC/CC histology. All patients initially underwent a total abdominal hysterectomy, bilateral salpingo-oophorectomy ± staging. Adjuvant therapy in the endometrioid group consisted of chemotherapy in 9 (36%) patients, whole pelvic radiation in 6 (24%) patients, brachytherapy in 3 (12%) patients, hormonal treatment in 2 (8%) patients, and no treatment in 5 (20%) patients. In the UPSC/CC group, 16 (57%) patients received adjuvant chemotherapy, 4 (14%) received chemotherapy and pelvic radiation, 4 (14%) received pelvic radiation alone, 1 (4%) received brachytherapy, and 3 (11%) received no adjuvant therapy. The mean number of salvage regimens was greater for those in the endometrioid group compared to the UPSC/CC group (2.2 vs. 1.4, p = 0.003). There was no statistically significant difference in median progression free survival between groups (20.6 vs. 10.0 months, p = 0.31). There was a trend towards significance in median overall survival from time of recurrence between the endometrioid (median = 24.63 months, range = 2–79) and the UPSC/CC groups (median = 14.9 months, range = 1–56) (p = 0.08). Conclusion: Even in the recurrent setting, papillary serous and clear cell carcinomas of the uterus continue to have a more aggressive clinical course than their endometrioid counterparts and portend a worse prognosis from recurrence to death. Investigators studying novel regimens for the treatment of recurrent uterine cancer should consider stratifying on histologic cell type.

Gynecologic Oncology, 2012

ABSTRACT Objectives: Despite advances in cytoreductive surgery and adjuvant chemotherapy the majo... more ABSTRACT Objectives: Despite advances in cytoreductive surgery and adjuvant chemotherapy the majority of patients with advanced stage epithelial ovarian cancer will recur. Multiple clinical trials have identified salvage regimens with response rates between 10–30%, however the natural course of the disease after multiple regimens has not been studied. Our objective was to describe the clinical course of epithelial ovarian cancer after two salvage chemotherapy regimens. Methods: This was a retrospective review of patients treated for epithelial ovarian cancer who had received at least two salvage regimens at our institution between 1991–2010. Patients were identified from tumor registries and institutional databases. Descriptive statistics were performed using Microsoft Excel 2011 and Instat was used to perform Fisher's exact test. Kaplan Meier survival analyses were used to compare survival statistics. Results: Sixty-five patients were identified as receiving at least 2 salvage chemotherapy regimens. The mean age was 57 years and the mean follow up time was 65 months. Eleven of the 65 patients received neoadjuvant chemotherapy and all patients underwent primary debulking. The distribution of stage is as follows: 2 stage IIC, 5 stage IIIB, 45 stage IIIC, 13 stage IV. All patients received a platinum/taxane-based regimen for their first line chemotherapy. Thirty-nine patients were characterized as platinum sensitive, 12 as platinum resistant, 13 as platinum refractory, and 1 did not receive chemotherapy. Patients received an average of 4 salvage regimens (range 2–11). There was no difference in the number of salvage regimens between the platinum sensitive and the platinum refractory/resistant groups (4 vs 4, p = 0.33). Overall survival was 33.4 months in the platinum refractory/resistant and 61.2 months in the platinum sensitive group (p < 0.0001). Overall survival after second line salvage therapy was 16.4 months in the platinum sensitive versus 9.9 months in the platinum resistant/refractory group (p = 0.05). The most common reasons for cessation of treatment were progressive disease with decreased performance status or patient's choice for decreased quality of life (59 out of 65 patients). Conclusion: Patients treated for recurrent epithelial ovarian cancer have an average survival of 10–16 months after two salvage regimens. Most patients terminate treatment secondary to a decreased quality of life; therefore further research to discover agents with an acceptable response rate and minimal side effects is crucial.

Yearbook of Obstetrics, Gynecology and Women's Health

Journal of Clinical Oncology

e13078 Background: This study describes the in vitro drug response of gynecologic sarcomas and cl... more e13078 Background: This study describes the in vitro drug response of gynecologic sarcomas and clinical implications of in vitro testing. Methods: Ovarian or uterine sarcomas were analyzed for response to any of 7 drugs (carboplatin [Carb], cisplatin [Cis], paclitaxel [Ptx], docetaxel [Dtx], doxorubicin [Dox], gemcitabine [Gem], Ifosfamide [Ifo]) with a chemosensitivity assay (ChemoFx, Precision Therapeutics, Inc, Pittsburgh PA). In combination therapy, tumors were considered sensitive if responsive to at least 1 drug. Results: 68 tumors were analyzed (21 ovarian and 47 uterine; 54 primary and 14 recurrent; carcinosarcoma [n=53], leiomyosarcoma [n=13], other [n=2]). 24% of tumors were responsive to Carb, 30% to Cis, 33% to Ptx, 9% to Dtx, 18% to Dox, 26% to Gem, 27% to Ifo, 40% to Carb+Ptx, 39% to Cis+Ifo, 48% to Ptx+Ifo, 24% to Gem+Dtx, and 27% to Gem+Dox (Table). Ovarian sarcomas were more responsive than uterine sarcomas and primary more than recurrent tumors. Carcinosarcomas were more responsive than leiomyosarcomas to Ifo (P=0.02). Conclusions: In vitro tumor response testing may enable physicians to individualize chemotherapy regimens for their patients. [Table: see text]

Annals of Oncology, 2017

Poster exhibition Day 1, 2019

Best Oral/Late-Breaking Abstracts 4 – Miscellaneous, 2019

Gynecologic Oncology, 2019

Gynecologic Oncology, 2015

Gynecologic Oncology, 2017

The Journal of reproductive medicine

Journal of Bioinformatics and Computational Biology, 2006

Gynecologic Oncology, 2013

Gynecologic Oncology, 2002

Gynecologic Oncology, 2012

Yearbook of Obstetrics, Gynecology and Women's Health

Journal of Clinical Oncology