Investigator
Houston Methodist
Response to: Correspondence on “Complications of HIPEC for ovarian cancer surgery: evaluation over two time periods” by Lavoue et al
Cardiophrenic lymph nodes in advanced ovarian cancer
Epithelial ovarian cancer most commonly presents at advanced stages, and prognosis is influenced by residual disease following cytoreduction. The significance of cardiophrenic lymph node resection at the time of cytoreductive surgery in advanced ovarian cancer remains a topic of debate. Enlarged cardiophrenic lymph nodes are detected through high-resolution imaging; however, the optimal imaging technique in determining feasibility of node resection remains uncertain. Similarly, the impact of excision of cardiophrenic lymph nodes on progression-free and overall survival remains elusive. The indications for resection of cardiophrenic lymph nodes are not addressed in standard ovarian cancer guidelines. Patients with cardiophrenic lymph nodes exceeding 1 cm in size may be considered for resection if complete intra-abdominal cytoreduction is feasible to no gross residual. The surgical approach might be either by open access or by video-assisted thoracoscopic surgery (minimally invasive approach), and major complications following cardiophrenic lymph nodes resection are low. Pathological cardiophrenic lymph nodes are associated with a poorer overall prognosis and can serve as a prognostic parameter; however, the therapeutic benefit of cardiophrenic lymph nodes resection remains inconclusive.
Highlights from the 24th European Congress on Gynaecological Oncology in Istanbul: an ENYGO-IJGC Fellows compilation
Combination of hormonal-based therapy in endometrial cancer: ready for prime time
Isolated nodal recurrence in endometrial cancer: not so common and very salvageable
ESGO/ESTRO/ESP updated guidelines in cervical cancer
Isolated tumor cells in low-risk endometrial cancer: are we ready for treatment decisions in ‘isolation’?
Surgical and Blood-Based Minimal Residual Disease in Patients with Ovarian Cancer after First-line Therapy: Clinical Outcomes and Translational Opportunities
Abstract Purpose: Minimal residual disease (MRD) after first-line treatment of advanced-stage ovarian cancer remains a long-standing barrier to cure. We investigated the prognostic and translational value of MRD detection by second-look laparoscopy (SLL) and ctDNA at the completion of first-line therapy. Experimental Design: Patients with high-grade epithelial ovarian cancer who had a complete clinical response to first-line therapy and underwent SLL and plasma collection for ctDNA were included. Progression-free survival (PFS) and overall survival (OS) were estimated based on MRD and clinicopathologic status. Spatial transcriptomics (GeoMx and Visium) and proteomics (CODEX) profiling were performed on serial samples from select patients. Results: Forty of 95 (42.1%) patients had surgically detected MRD, which was associated with worse PFS (median PFS 7.4 vs. 23.8 months; P < 0.001) and OS (median OS 33.9 vs. not reached; P < 0.001). SLL positivity was an independent negative prognostic factor for OS (HR, 4.40; 95% confidence interval, 1.37–14.21; P = 0.013) in multivariable analysis. Among 44 patients who underwent SLL and had ctDNA testing, 34% (15/44) were ctDNA-positive, which was associated with worse PFS (6.4 vs. 28.1 months; P < 0.001) and OS (32.4 months vs. not reached; P = 0.008). We demonstrated the feasibility of spatial multiomics in studying MRD and their ability to provide hypothesis-generating observations, implicating the upregulation of the hypoxia signaling pathway, expression of multiple druggable targets (CDK6, GLS, MSLN, ERBB2), and immune exclusion in MRD lesions. Conclusions: Approximately half of patients in clinical remission after first-line therapy have assessable MRD, which can inform prognosis, therapeutic target discovery, and clinical trials.
Accuracy of pre-operative tumor size assessment compared to final pathology and frequency of adjuvant treatment in patients with FIGO 2018 stage IB2 cervical cancer
The primary aim of our study was to compare tumor size assessment by pre-operative evaluation (physical examination and/or imaging) with tumor size on final pathology. As a secondary outcome, we evaluated the rate of adjuvant treatment in patients who underwent radical hysterectomy whose tumor size was ≥3 cm on final pathology. Patient details were collected from three separate databases: the University of Texas MD Anderson Cancer Center Radical Hysterectomy Database, the SUCCOR Study Group Database, and the Multi-institutional Database LATAM (encompassing Latin America and Europe). Patients with International Federation of Gynecology and Obstetrics (FIGO) 2018 stage IB2 cervical cancer on pre-operative evaluation (physical examination or imaging) who underwent radical hysterectomy with a therapeutic intent were included. Any histological subtype, any tumor grade, and pre-operative evaluation with clinical evaluation and/or imaging (ultrasound, MRI, CT, or PET/CT) was considered. A total of 675 patients met eligibility criteria (SUCCOR=350, LATAM=250, MD Anderson=75). The median age was 46 years (range 22-82) and the median body mass index was 25.6 kg/m Our study showed that there is a high concordance between tumor size assessment by physical examination and MRI, as well as estimates of measurement by MRI and final pathology. In addition, we noted that the majority of patients with FIGO 2018 stage IB2 received adjuvant therapy after radical hysterectomy.
Metastasized inflammatory myofibroblastic tumor of uterine origin
Assessing minimally invasive simple hysterectomy in low risk cervical cancer: set up for the LASH trial
After the publication of the Laparoscopic Approach to Cervical Cancer (LACC) trial, open surgery has become the standard approach for radical hysterectomy in early stage cervical cancer. Recent studies assessed the role of a non-radical approach in low risk cervical cancer and showed no survival difference compared with radical hysterectomy. However, there is a gap in knowledge regarding the oncologic outcomes of minimally invasive simple hysterectomy in low risk cervical cancer. This review offers an overview of the current evidence on the role of the minimally invasive approach in low risk cervical cancer and raises the need for a new clinical trial in this setting.
Recurrent low-grade uterine sarcoma: a diagnostic and therapeutic challenge
Complications of HIPEC for ovarian cancer surgery: evaluation over two time periods
Cytoreductive surgery in conjunction with hyperthermic intraperitoneal chemotherapy (HIPEC) is being explored in the upfront, interval, and recurrent setting in patients with ovarian cancer. The objective of this systematic review was to assess the rate of complications associated with HIPEC in epithelial ovarian cancer surgery over two time periods. This study was registered in PROSPERO (CRD42022328928). A systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist. Ovid/Medline, Ovid/Embase, Web of Science, Scopus, and Cochrane Central Register of Controlled Trials were searched from January 2004 to April 2022. We included studies reporting on patients with advanced primary or recurrent epithelial ovarian cancer who underwent cytoreductive surgery and HIPEC. We evaluated two different time periods: 2004-2013 and 2014-2022. A random-effects meta-analysis was used to produce an overall summary. Subgroup analyses were planned according to recruited period for each specific complication type. Heterogeneity was assessed using the I A total of 4928 patients were included from 69 studies for this systematic review; 19 published from 2004-2013, and 50 published from 2014-2022. No significant differences were found between the two time periods in terms of blood transfusions (33% vs 51%; p=0.46; I Our review showed that overall complications have not changed over time for patients undergoing HIPEC in the setting of primary or recurrent ovarian cancer. There was no decrease in the rates of ICU admissions, reoperations, or deaths.
LACC Trial: Final Analysis on Overall Survival Comparing Open Versus Minimally Invasive Radical Hysterectomy for Early-Stage Cervical Cancer
Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. The aim of this study was to compare overall survival between open and minimally invasive radical hysterectomy with participants followed for 4.5 years. The primary objective was to evaluate whether minimally invasive surgery was noninferior in disease-free survival (DFS) to abdominal radical hysterectomy. Secondary outcomes included overall survival. Sample size was based on DFS of 90% at 4.5 years and 7.2% noninferiority margin for minimally invasive surgery. A total of 631 patients were enrolled: 319 assigned to minimally invasive and 312 to open surgery. Of these, 289 (90.6%) patients underwent minimally invasive surgery and 274 (87.8%) patients open surgery. At 4.5 years, DFS was 85.0% in the minimally invasive group and 96% in the open group (difference of –11.1; 95% CI, –15.8 to –6.3; P = .95 for noninferiority). Minimally invasive surgery was associated with lower rate of DFS compared with open surgery (hazard ratio [HR], 3.91 [95% CI, 2.02 to 7.58]; P < .001). Rate of overall survival at 4.5 years was 90.6% versus 96.2% for the minimally invasive and open surgery groups, respectively (HR for death of any cause = 2.71 [95% CI, 1.32 to 5.59]; P = .007). Given higher recurrence rate and worse overall survival with minimally invasive surgery, an open approach should be standard of care.
Laparoscopic secondary cytoreductive surgery: let’s not make the same assumptions
Patient outcomes following interval and delayed cytoreductive surgery in advanced ovarian cancer: protocol for a multicenter, international, cohort study (Global Gynaecological Oncology Surgical Outcomes Collaborative)
The Global Gynecological Oncology Surgical Outcomes Collaborative (GO SOAR) has developed a network of gynecological oncology surgeons, surgical departments, and other interested parties that have the long-term ability to collaborate on outcome studies. Presented is the protocol for the GO SOAR2 study. To compare survival following interval and delayed cytoreductive surgery, between delayed cytoreductive surgery and no surgery (chemotherapy alone); and international variations in access to cytoreductive surgery for women with stage III-IV epithelial ovarian cancer. There is no difference in survival following interval and delayed cytoreductive surgery; there is poorer survival with no surgery compared with delayed cytoreductive surgery; and there are international disparities in prevalent practice and access to cytoreductive surgery in women with stage III-IV epithelial ovarian cancer. International, multicenter, mixed-methods cohort study. Participating centers, will review medical charts/electronic records of patients who had been consecutively diagnosed with stage III-IV ovarian cancer between January 1, 2006 and December 31, 2021. Qualitative interviews will be conducted to identify factors determining international variations in prevalent practice and access to cytoreductive surgery. Inclusion criteria include women with stage III-IV epithelial ovarian cancer, undergoing interval (after 3-4 cycles of chemotherapy) or delayed (≥5 cycles of chemotherapy) cytoreductive surgeries or no cytoreductive surgery (≥5 cycles of chemotherapy alone). Overall survival (defined from date of diagnosis to date of death); progression-free survival (defined from date of diagnosis to date of first recurrence); facilitator/barriers to prevalent practice and access to cytoreductive surgery. In order to determine whether there is a difference in survival following interval and delayed cytoreductive surgery and no surgery, data will be abstracted from 1000 patients. It is estimated that recruitment will be completed by 2023, and results published by 2024. NCT05523804.
MILACC study: could undetected lymph node micrometastases have impacted recurrence rate in the LACC trial?
The etiology of inferior oncologic outcomes associated with minimally invasive surgery for early-stage cervical cancer remains unknown. Manipulation of lymph nodes with previously unrecognized low-volume disease might explain this finding. We re-analyzed lymph nodes by pathologic ultrastaging in node-negative patients who recurred in the LACC (Laparoscopic Approach to Cervical Cancer) trial. Included patients were drawn from the LACC trial database, had negative lymph nodes on routine pathologic evaluation, and recurred to the abdomen and/or pelvis. Patients without recurrence or without available lymph node tissue were excluded. Paraffin tissue blocks and slides from all lymph nodes removed by lymphadenectomy were re-analyzed per standard ultrastaging protocol aimed at the detection of micrometastases (>0.2 mm and ≤2 mm) and isolated tumor cells (clusters up to 0.2 mm or <200 cells). The study included 20 patients with median age of 42 (range 30-68) years. Most patients were randomized to minimally invasive surgery (90%), had squamous cell carcinoma (65%), FIGO 2009 stage 1B1 (95%), grade 2 (60%) disease, had no adjuvant treatment (75%), and had a single site of recurrence (55%), most commonly at the vaginal cuff (45%). Only one patient had pelvic sidewall recurrence in the absence of other disease sites. The median number of lymph nodes analyzed per patient was 18.5 (range 4-32) for a total of 412 lymph nodes. A total of 621 series and 1242 slides were reviewed centrally by the ultrastaging protocol. No metastatic disease of any size was found in any lymph node. There were no lymph node low-volume metastases among patients with initially negative lymph nodes who recurred in the LACC trial. Therefore, it is unlikely that manipulation of lymph nodes containing clinically undetected metastases is the underlying cause of the higher local recurrence risk in the minimally invasive arm of the LACC trial.
Survival after sentinel node biopsy alone in early-stage cervical cancer: a systematic review
To assess the oncologic outcomes of sentinel lymph node biopsy alone as part of surgical management in patients with early-stage cervical cancer. A systematic search of the literature was performed following the PRISMA checklist. MEDLINE (through PubMed), EMBASE, and Scopus databases were searched from June 1991 to May 2023. Studies of women with early-stage cervical cancer International Federation of Gynecology and Obstetrics (FIGO) 2009 stage IA-IIA, of any age or histology, and articles only in English language were included. After the removal of duplicates, only articles including sentinel node mapping alone compared with full pelvic lymphadenectomy were retained. Four studies with a total of 2226 patients were included. Among these, 354 (15.9%) underwent sentinel lymph node biopsy alone. A total of 2210 (99.2%) patients had FIGO 2009 stage I disease and 1514 (68%) patients had squamous cell carcinoma. Median body mass index was 25.5 kg/m In patients with early-stage cervical cancer, performing sentinel lymph node biopsy alone compared with pelvic lymphadenectomy does not appear to independently confer a higher risk or recurrence.
Definitive pelvic radiotherapy for patients with newly diagnosed stage IVB cervical cancer: a systematic review
The objective of this systematic review was to assess the oncologic outcomes of patients with International Federation of Gynecology and Obstetrics (FIGO) 2018 stage IVB cervical cancer receiving definitive pelvic radiotherapy compared with systemic chemotherapy (with or without palliative pelvic radiotherapy). This study was registered in PROSPERO (registration number CRD42022333433). A systematic literature review was conducted following the MOOSE checklist. MEDLINE (through Ovid), Embase, and Cochrane Central Register of Controlled Trials were searched from inception until August 2022. The inclusion criteria were patients with metastatic FIGO 2018 stage IVB cervical cancer, a histologic subtype of squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma that received definitive pelvic radiotherapy (≥45 Gy) as part of management compared with systemic chemotherapy with or without palliative (30 Gy) pelvic radiotherapy. Randomized controlled trials and observational studies with two arms of comparison were considered. The search identified 4653 articles; 26 studies were considered potentially eligible after removing duplicates, and 8 met the selection criteria. In total, 2424 patients were included. There were 1357 and 1067 patients in the definitive radiotherapy and chemotherapy groups, respectively. All included studies were retrospective cohort studies, and two were database population studies. The median overall survival reported in seven studies for the definitive radiotherapy arm versus systemic chemotherapy groups were 63.7 months versus 18.4 months (p<0.01), 14 months versus 16 months (p value not reported), 17.6 months versus 10.6 months (p<0.01), 32 months versus 24 months (p<0.01), 17.3 months versus 10 months (p<0.01), and 41.6 months versus 17.6 months (p<0.01), and not reached versus 19 months (p=0.13) respectively, favoring the groups that received definitive pelvic radiotherapy. The high clinical heterogeneity precluded the performance of meta-analysis, and all studies were at serious risk of bias. Definitive pelvic radiotherapy as part of treatment in patients with stage IVB cervical cancer may improve oncologic outcomes compared with systemic chemotherapy (with or without palliative radiotherapy); however, this is based on low-quality data. Prospective evaluation would be ideal before the adoption of this intervention in standard clinical practice.
Sentinel lymph node mapping with indocyanine green using SPY-PHI in open radical hysterectomy or trachelectomy
To evaluate the detection rate of at least one sentinel lymph node (SLN) in patients with early cervical cancer who underwent open radical hysterectomy or trachelectomy using indocyanine green (ICG) with the SPY Portable Handler Imager (SPY-PHI) system. We retrospectively reviewed patients with cervical cancer FIGO 2018 stage IA1 with lymphovascular invasion up to stage IIIC1p who underwent SLN mapping and open radical hysterectomy or trachelectomy from March 2018 through August 2022 at The University of Texas MD Anderson Cancer Center. ICG was the only tracer used with the SPY-PHI system. Patient demographics, surgical approach, and tumor factors were analyzed. Overall detection, bilateral detection, and empty lymph node packet rates were determined. A total of 106 patients were included. Ninety-four (88.7%) patients underwent open radical hysterectomy and 12 (11.3%) open radical trachelectomy. Median age was 40 years (range, 23-71). Median body mass index was 28.8 kg/m SLN mapping using ICG with the SPY-PHI system in open radical hysterectomy or trachelectomy is reliable and results in high overall and bilateral detection rates in patients with early cervical cancer.
Cervical cancer: a new era
Cervical cancer is a major global health issue, ranking as the fourth most common cancer in women worldwide. Depending on stage, histology, and patient factors, the standard management of cervical cancer is a combination of treatment approaches, including (fertility- or non-fertility-sparing) surgery, radiotherapy, platinum-based chemotherapy, and novel systemic therapies such as bevacizumab, immune checkpoint inhibitors, and antibody-drug conjugates. While ambitious global initiatives seek to eliminate cervical cancer as a public health problem, the management of cervical cancer continues to evolve with major advances in imaging modalities, surgical approaches, identification of histopathological risk factors, radiotherapy techniques, and biomarker-driven personalized therapies. In particular, the introduction of immune checkpoint inhibitors has dramatically altered the treatment of cervical cancer, leading to significant survival benefits in both locally advanced and metastatic/recurrent settings. As the landscape of cervical cancer therapies continues to evolve, the aim of the present review is to provide a comprehensive discussion of the current state and the latest practice-changing updates in cervical cancer.
Consensus on surgical technique for sentinel lymph node dissection in cervical cancer
The purpose of this study was to establish a consensus on the surgical technique for sentinel lymph node (SLN) dissection in cervical cancer. A 26 question survey was emailed to international expert gynecological oncology surgeons. A two-step modified Delphi method was used to establish consensus. After a first round of online survey, the questions were amended and a second round, along with semistructured interviews was performed. Consensus was defined using a 70% cut-off for agreement. Twenty-five of 38 (65.8%) experts responded to the first and second rounds of the online survey. Agreement ≥70% was reached for 13 (50.0%) questions in the first round and for 15 (57.7%) in the final round. Consensus agreement identified 15 recommended, three optional, and five not recommended steps. Experts agreed on the following recommended procedures: use of indocyanine green as a tracer; superficial (with or without deep) injection at 3 and 9 o'clock; injection at the margins of uninvolved mucosa avoiding vaginal fornices; grasping the cervix with forceps only in part of the cervix is free of tumor; use of a minimally invasive approach for SLN biopsy in the case of simple trachelectomy/conization; identification of the ureter, obliterated umbilical artery, and external iliac vessels before SLN excision; commencing the dissection at the level of the uterine artery and continuing laterally; and completing dissection in one hemi-pelvis before proceeding to the contralateral side. Consensus was also reached in recommending against injection at 6 and 12 o'clock, and injection directly into the tumor in cases of the tumor completely replacing the cervix; against removal of nodes through port without protective maneuvers; absence of an ultrastaging protocol; and against modifying tracer concentration at the time of re-injection after mapping failure. Recommended, optional, and not recommended steps of SLN dissection in cervical cancer have been identified based on consensus among international experts. These represent a surgical guide that may be used by surgeons in clinical trials and for quality assurance in routine practice.
Gestational choriocarcinoma
Gestational choriocarcinoma accounts for 5% of gestational trophoblastic neoplasms. Approximately 50%, 25%, and 25% of gestational choriocarcinoma occur after molar pregnancies, term pregnancies, and other gestational events, respectively. The FIGO scoring system categorizes patients into low (score 0 to 6) and high risk (score 7 or more) choriocarcinoma. Single-agent and multi-agent chemotherapy are used in low- and high-risk patients, respectively. Chemotherapy for localized disease has a goal of eradication of disease without surgery and is associated with favorable prognosis and fertility preservation. Most patients with gestational choriocarcinoma are cured with chemotherapy; however, some (<5.0%) will die as a result of multi-drug resistance, underscoring the need for novel approaches in this group of patients. Although there are limited data due to its rarity, the treatment response with immunotherapy is high, ranging between 50-70%. Novel combinations of immune checkpoint inhibitors with targeted therapies (including VEGFR-2 inhibitors) are under evaluation. PD-L1 inhibitors are considered a potential important opportunity for chemo-resistant patients, and to replace or de-escalate chemotherapy to avoid or minimize chemotherapy toxicity. In this review, the Rare Tumor Working Group and the European Organization for Research and Treatment of Cancer evaluated the current landscape and further perspective in the management of patients diagnosed with gestational choriocarcinoma.
Patient Outcomes Following Interval and Delayed Cytoreductive Surgery in Advanced Ovarian Cancer
To compare patient outcomes following interval and delayed cytoreductive surgeries and no surgery (neoadjuvant chemotherapy alone) and international variations in access to cytoreductive surgeries in women with advanced stage ovarian cancer.
Laparoscopic Approach to Cervical Cancer
The goal of this clinical research study is to compare the long-term outcomes of different surgical methods for the treatment of cervical cancer. The long-term outcome of a total abdominal radical hysterectomy (TARH) will be compared against laparoscopy. In this study, the laparoscopy will be done with or without robotic technology.
