Homologous recombination deficiency should be tested for in patients with advanced stage high-grade serous ovarian cancer aged 70 years and over.

OBJECTIVE: Due to limited data on homologous recombination deficiency (HRD) in older patients (≥ 70 years) with advanced stage high grade serous ovarian cancer (HGSC), we aimed to determine the rates of HRD at diagnosis in this age group. METHODS: From the Phase 3 trial VELIA the frequency of HRD and BRCA1/2 pathogenic variants (PVs) was compared between younger (< 70 years) and older participants. HRD and somatic(s) BRCA1/2 pathogenic variants (PVs) were determined at diagnosis using Myriad myChoice® CDx and germline(g) BRCA1/2 PVs using Myriad BRACAnalysis CDx®. HRD was defined if a BRCA PV was present, or the genomic instability score (GIS) met threshold (GIS ≥ 33 & ≥ 42 analyzed). RESULTS: Of 1140 participants, 21% were ≥ 70 years. In total, 26% (n = 298) had a BRCA1/2 PV and HRD, 29% (n = 329) were HRD/BRCA wild-type, 33% (n = 372) non-HRD, and 12% HR-status unknown (n = 141). HRD rates were higher in younger participants, 59% (n = 476/802), compared to 40% (n = 78/197) of older participants (GIS ≥ 42) [p < 0.001]; similar rates demonstrated with GIS ≥ 33, 66% vs 48% [p < 0.001]. gBRCA PVs observed in 24% younger vs 8% of older participants (p < 0.001); sBRCA in 8% vs 10% (p = 0.2559), and HRD (GIS ≥ 42) not due to gBRCA was 35% vs 31% (p = 0.36). CONCLUSIONS: HRD frequency was similar in participants aged < 70 and ≥ 70 years (35% vs 31%) when the contribution of gBRCA was excluded; rates of sBRCA PVs were also similar (8% v 10%), thus underscoring the importance of HRD and BRCA testing at diagnosis in older patients with advanced HGSC given the therapeutic implications.

End-Effector Contact and Force Detection for Miniature Autonomous Robots Performing Lunar and Expeditionary Surgery.

INTRODUCTION: The U.S. Space Force was stood up on December 20, 2019 as an independent branch under the Air Force consisting of about 16,000 active duty and civilian personnel focused singularly on space. In addition to the Space Force, the plans by NASA and private industry for exploration-class long-duration missions to the moon, near-earth asteroids, and Mars makes semi-independent medical capability in space a priority. Current practice for space-based medicine is limited and relies on a "life-raft" scenario for emergencies. Discussions by working groups on military space-based medicine include placing a Role III equivalent facility in a lunar surface station. Surgical capability is a key requirement for that facility. MATERIALS AND METHODS: To prepare for the eventuality of surgery in space, it is necessary to develop low-mass, low power, mini-surgical robots, which could serve as a celestial replacement for existing terrestrial robots. The current study focused on developing semi-autonomous capability in surgical robotics, specifically related to task automation. Two categories for end-effector tissue interaction were developed: Visual feedback from the robot to detect tissue contact, and motor current waveform measurements to detect contact force. RESULTS: Using a pixel-to-pixel deep neural network to train, we were able to achieve an accuracy of nearly 90% for contact/no-contact detection. Large torques were predicted well by a trained long short-term memory recursive network, but the technique did not predict small torques well. CONCLUSION: Surgical capability on long-duration missions will require human/machine teaming with semi-autonomous surgical robots. Our existing small, lightweight, low-power miniature robots perform multiple essential tasks in one design including hemostasis, fluid management, suturing for traumatic wounds, and are fully insertable for internal surgical procedures. To prepare for the inevitable eventuality of an emergency surgery in space, it is essential that automated surgical robot capabilities be developed.

Standardization of lower extremity quantitative lymphedema measurements and associated patient-reported outcomes in gynecologic cancers.

Practice changing standardization of lower extremity lymphedema quantitative measurements with integrated patient reported outcomes will likely refine and redefine the optimal risk-reduction strategies to diminish the devastating limb-related dysfunction and morbidity associated with treatment of gynecologic cancers. The National Cancer Institute (NCI), Division of Cancer Prevention brought together a diverse group of cancer treatment, therapy and patient reported outcomes experts to discuss the current state-of-the-science in lymphedema evaluation with the potential goal of incorporating new strategies for optimal evaluation of lymphedema in future developing gynecologic clinical trials.

GOG 244 - The Lymphedema and Gynecologic cancer (LeG) study: The impact of lower-extremity lymphedema on quality of life, psychological adjustment, physical disability, and function.

OBJECTIVE: To assess quality of life (QOL) in patients who developed lower-extremity lymphedema (LLE) after radical gynecologic cancer surgery on prospective clinical trial GOG 244. METHODS: The prospective, national, cooperative group trial GOG-0244 determined the incidence of LLE and risk factors for LLE development, as well as associated impacts on QOL, in newly diagnosed patients undergoing surgery for endometrial, cervical, or vulvar cancer from 6/4/2012-11/17/2014. Patient-reported outcome (PRO) measures of QOL (by the Functional Assessment of Cancer Therapy [FACT]), body image, sexual and vaginal function, limb function, and cancer distress were recorded at baseline (within 14 days before surgery), and at 6, 12, 18, and 24 months after surgery. Assessments of LLE symptoms and disability were completed at the time of lower limb volume measurement. A linear mixed model was applied to examine the association of PROs/QOL with a Gynecologic Cancer Lymphedema Questionnaire (GCLQ) total score incremental change ≥4 (indicative of increased LLE symptoms) from baseline, a formal diagnosis of LLE (per the GCLQ), and limb volume change (LVC) ≥10%. RESULTS: In 768 evaluable patients, those with a GCLQ score change ≥4 from baseline had significantly worse QOL (p < 0.001), body image (p < 0.001), sexual and vaginal function (p < 0.001), limb function (p < 0.001), and cancer distress (p < 0.001). There were no significant differences in sexual activity rates between those with and without LLE symptoms. CONCLUSIONS: LLE is significantly detrimental to QOL, daily function, and body image. Clinical intervention trials to prevent and manage this chronic condition after gynecologic cancer surgery are needed.

GOG 244-The lymphedema and gynecologic cancer (LEG) study: Incidence and risk factors in newly diagnosed patients.

OBJECTIVES: To evaluate the incidence and risk factors for lymphedema associated with surgery for gynecologic malignancies on GOG study 244. METHODS: Women undergoing a lymph node dissection for endometrial, cervical, or vulvar cancer were eligible for enrollment. Leg volume was calculated from measurements at 10-cm intervals starting 10 cm above the bottom of the heel to the inguinal crease. Measurements were obtained preoperatively and postoperatively at 4-6 weeks, and at 3-, 6-, 9-, 12-, 18-, and 24- months. Lymphedema was defined as a limb volume change (LVC) ≥10% from baseline and categorized as mild: 10-19% LVC; moderate: 20-40% LVC; or severe: >40% LVC. Risk factors associated with lymphedema were also analyzed. RESULTS: Of 1054 women enrolled on study, 140 were inevaluable due to inadequate measurements or eligibility criteria. This left 734 endometrial, 138 cervical, and 42 vulvar patients evaluable for LVC assessment. Median age was 61 years (range, 28-91) in the endometrial, 44 years (range, 25-83) in the cervical, and 58 years (range, 35-88) in the vulvar group. The incidence of LVC ≥10% was 34% (n = 247), 35% (n = 48), and 43% (n = 18), respectively. The peak incidence of lymphedema was at the 4-6 week assessment. Logistic regression analysis showed a decreased risk with advanced age (p = 0.0467). An exploratory analysis in the endometrial cohort showed an increased risk with a node count >8 (p = 0.033). CONCLUSIONS: For a gynecologic cancer, LVC decreased with age greater than 65, but increased with a lymph node count greater than 8 in the endometrial cohort. There was no association with radiation or other risk factors.

GOG 244 - The LymphEdema and Gynecologic cancer (LEG) study: The association between the gynecologic cancer lymphedema questionnaire (GCLQ) and lymphedema of the lower extremity (LLE).

OBJECTIVE: To explore whether patient-reported lymphedema-related symptoms, as measured by the Gynecologic Cancer Lymphedema Questionnaire (GCLQ), are associated with a patient-reported diagnosis of lymphedema of the lower extremity (LLE) and limb volume change (LVC) in patients who have undergone radical surgery, including lymphadenectomy, for endometrial, cervical, or vulvar cancer on Gynecologic Oncology Group (GOG) study 244. METHODS: Patients completed the baseline and at least one post-surgery GCLQ and LVC assessment. The 20-item GCLQ measures seven symptom clusters-aching, heaviness, infection-related, numbness, physical functioning, general swelling, and limb swelling. LLE was defined as a patient self-reported LLE diagnosis on the GCLQ. LVC was measured by volume calculations based on circumferential measurements. A linear mixed model was fitted for change in symptom cluster scores and GCLQ total score and adjusted for disease sites and assessment time. RESULTS: Of 987 eligible patients, 894 were evaluable (endometrial, 719; cervical, 136; vulvar, 39). Of these, 14% reported an LLE diagnosis (endometrial, 11%; cervical, 18%; vulvar, 38%). Significantly more patients diagnosed versus not diagnosed with LLE reported ≥4-point increase from baseline on the GCLQ total score (p < 0.001). Changes from baseline were significantly larger on all GCLQ symptom cluster scores in patients with LLE compared to those without LLE. An LVC increment of >10% was significantly associated with reported general swelling (p < 0.001), heaviness (p = 0.005), infection-related symptoms (p = 0.002), and physical function (p = 0.006). CONCLUSIONS: Patient-reported symptoms, as measured by the GCLQ, discerned those with and without a patient-reported LLE diagnosis and demonstrated predictive value. The GCLQ combined with LVC may enhance our ability to identify LLE.

A randomized phase II study of cabozantinib versus weekly paclitaxel in the treatment of persistent or recurrent epithelial ovarian, fallopian tube or primary peritoneal cancer: An NRG Oncology/Gynecologic Oncology Group study.

INTRODUCTION: Cabozantinib is a receptor tyrosine kinases inhibitor that targets MET (c-MET), VEGF receptor 2 (VEGFR2), RET, AXL, KIT, FLT-3, and TIE-2 and previously showed promising single agent activity in recurrent ovarian cancer. METHODS: This was an open label, 1:1 randomized study of cabozantinib 60 mg orally (PO) daily versus weekly paclitaxel 80 mg/m2 given 3 out of 4 weeks (NCT01716715); 111 patients were enrolled. Eligibility included persistent or recurrent epithelial ovarian, fallopian tube, or primary peritoneal carcinoma and at least one but no >3 prior chemotherapy regimens. RESULTS: Median PFS was similar for both treatment groups and was 5.3 months for cabozantinib and 5.5 months for weekly paclitaxel (HR 1.11 (90% CI 0.77-1.61, p = 0.64)). Secondary analyses of overall survival (OS) and event free survival (EFS) showed that cabozantinib did not perform as well as weekly paclitaxel. Median OS for cabozantinib was 19.4 months and was not reached for weekly paclitaxel (HR 2.27 (90% CI 1.17-4.41, p = 0.04). EFS was also worse in the cabozantinib arm, 3.5 months, compared to weekly paclitaxel at 5.0 months (HR 1.81 (90% CI 1.24-2.63, p = 0.01). Overall response rate (ORR) was less for cabozantinib compared to weekly paclitaxel (7% versus 24.1%). Gastrointestinal toxicities, specifically nausea, diarrhea, and abdominal pain were worse in the cabozantinib arm. CONCLUSIONS: Median PFS was similar for cabozantinib and weekly paclitaxel. However, OS, EFS, and ORR were worse for cabozantinib compared to weekly paclitaxel. Cabozantinib given at this dose and schedule cannot be recommended as a treatment for recurrent ovarian cancer.

A phase II study of frontline paclitaxel/carboplatin/bevacizumab, paclitaxel/carboplatin/temsirolimus, or ixabepilone/carboplatin/bevacizumab in advanced/recurrent endometrial cancer.

OBJECTIVE: Paclitaxel and carboplatin (PC) is a standard initial therapy for advanced endometrial cancer. We evaluated the efficacy and tolerability of incorporating three novel agents into initial therapy. METHODS: In this randomized phase II trial, patients with chemotherapy-naïve stage III/IVA (with measurable disease) and stage IVB or recurrent (with or without measurable disease) endometrial cancer were randomly assigned to treatment with PC plus bevacizumab (Arm 1), PC plus temsirolimus (Arm 2) or ixabepilone and carboplatin (IC) plus bevacizumab (Arm 3). The primary endpoint was progression-free survival (PFS). Comparable patients on the PC Arm of trial GOG209 were used as historical controls. Secondary endpoints were response rate, overall survival (OS), and safety. RESULTS: Overall, 349 patients were randomized. PFS duration was not significantly increased in any experimental arm compared with historical controls (p > 0.039). Treatment HRs (92% CI) for Arms 1, 2, and 3 relative to controls were 0.81 (0.63-1.02), 1.22 (0.96-1.55) and 0.87 (0.68-1.11), respectively. Response rates were similar across arms (60%, 55% and 53%, respectively). Relative to controls, OS duration (with censoring at 36 months), was significantly increased in Arm 1 (p < 0.039) but not in Arms 2 and 3; the HRs (92% CIs) were 0.71 (0.55-0.91), 0.99 (0.78-1.26), and 0.97 (0.77-1.23), respectively. No new safety signals were identified. Common mutations and rates of mismatch repair protein loss are described by histotype. Potential predictive biomarkers for temsirolimus and bevacizumab were identified. CONCLUSION: PFS was not significantly increased in any experimental arm compared to historical controls. NRG Oncology/Gynecologic Oncology Group Study GOG-86P.

Pre-operative assessment and post-operative outcomes of elderly women with gynecologic cancers, primary analysis of NRG CC-002: An NRG oncology group/gynecologic oncology group study.

INTRODUCTION: CC-002 is a prospective cooperative group study conducted by NRG Oncology to evaluate whether a pre-operative GA-GYN score derived from a predictive model utilizing components of an abbreviated geriatric assessment (GA) is associated with major post-operative complications in elderly women with suspected ovarian, fallopian tube, primary peritoneal or advanced stage papillary serous uterine (GYN) carcinoma undergoing primary open cytoreductive surgery. METHODS: Patients 70 years or older with suspected advanced gynecologic cancers undergoing evaluation for surgery were eligible. A GA-GYN score was derived from a model utilizing the GA as a pre-operative tool. Patients were followed for six weeks post-operatively or until start of chemotherapy. Post-operative events were recorded either directly as binary occurrence (yes or no) using CTCAE version 4.0. RESULTS: There were 189 eligible patients, 117 patients with primary surgical intervention and 37 patients undergoing interval cytoreduction surgery. The association between higher GA-GYN score and major postoperative complications in patients undergoing primary surgery was not significant (p = 0.1341). In a subgroup analysis of patients with advanced staged malignant disease who underwent primary cytoreductive surgery, there was a trend towards an association with the GA-GYN score and post-operative complications. CONCLUSION: The pre-operative GA-GYN score derived from a predictive model utilizing components of an abbreviated geriatric assessment was not predictive of major post-operative complications in elderly patients undergoing primary open cytoreductive surgery. However, there was an association between GA-GYN score and post-operative complications in a subgroup of patients with advanced staged malignant disease.

Antibody targeting of phosphatidylserine for the detection and immunotherapy of cancer.

Phosphatidylserine (PS) is a negatively charged phospholipid in all eukaryotic cells that is actively sequestered to the inner leaflet of the cell membrane. Exposure of PS on apoptotic cells is a normal physiological process that triggers their rapid removal by phagocytic engulfment under noninflammatory conditions via receptors primarily expressed on immune cells. PS is aberrantly exposed in the tumor microenvironment and contributes to the overall immunosuppressive signals that antagonize the development of local and systemic antitumor immune responses. PS-mediated immunosuppression in the tumor microenvironment is further exacerbated by chemotherapy and radiation treatments that result in increased levels of PS on dying cells and necrotic tissue. Antibodies targeting PS localize to tumors and block PS-mediated immunosuppression. Targeting exposed PS in the tumor microenvironment may be a novel approach to enhance immune responses to cancer.

In-Home Behavioral Monitoring Using Simultaneous Localization and Activity Detection.

Shifting demographics in the U.S. has created an urgent need to reform the policies, practices, and technology associated with delivering healthcare to geriatric populations. Automated monitoring systems can improve the quality of life while reducing healthcare costs for individuals aging in place. For these systems to be successful, both activity detection and localization are important, but most existing research focuses on only one of these technologies and systems that do collect both data treat these data sources separately. Here, we present SLAD {Simultaneous Localization and Activity Detection a novel framework for simultaneously processing data collected from localization and activity classification systems. Using a hidden Markov model and machine learning techniques, SLAD fuses these two sources of data in realtime using a probabilistic likelihood framework, which allows activity data to refine localization, and vice-versa. To evaluate the system, a wireless sensor network was deployed to collect RSSI data and IMU data concurrently from a wrist-worn watch; the RSSI data was processed using a radial basis function neural network localization algorithm, and the resulting position likelihoods were combined with the likelihoods from an IMU acitivty classification algorithm. In an experiment conducted in an indoor office environment, the proposed method produces 97% localization accuracy and 85% activity classification.

Smart watch RSSI localization and refinement for behavioral classification using laser-SLAM for mapping and fingerprinting.

As a first step toward building a smart home behavioral monitoring system capable of classifying a wide variety of human behavior, a wireless sensor network (WSN) system is presented for RSSI localization. The low-cost, non-intrusive system uses a smart watch worn by the user to broadcast data to the WSN, where the strength of the radio signal is evaluated at each WSN node to localize the user. A method is presented that uses simultaneous localization and mapping (SLAM) for system calibration, providing automated fingerprinting associating the radio signal strength patterns to the user's location within the living space. To improve the accuracy of localization, a novel refinement technique is introduced that takes into account typical movement patterns of people within their homes. Experimental results demonstrate that the system is capable of providing accurate localization results in a typical living space.

Real-time three-dimensional soft tissue reconstruction for laparoscopic surgery.

BACKGROUND: Accurate real-time 3D models of the operating field have the potential to enable augmented reality for endoscopic surgery. A new system is proposed to create real-time 3D models of the operating field that uses a custom miniaturized stereoscopic video camera attached to a laparoscope and an image-based reconstruction algorithm implemented on a graphics processing unit (GPU). METHODS: The proposed system was evaluated in a porcine model that approximates the viewing conditions of in vivo surgery. To assess the quality of the models, a synthetic view of the operating field was produced by overlaying a color image on the reconstructed 3D model, and an image rendered from the 3D model was compared with a 2D image captured from the same view. RESULTS: Experiments conducted with an object of known geometry demonstrate that the system produces 3D models accurate to within 1.5 mm. CONCLUSIONS: The ability to produce accurate real-time 3D models of the operating field is a significant advancement toward augmented reality in minimally invasive surgery. An imaging system with this capability will potentially transform surgery by helping novice and expert surgeons alike to delineate variance in internal anatomy accurately.

A compact high-definition low-cost digital stereoscopic video camera for rapid robotic surgery development.

Robotic surgical platforms require vision feedback systems, which often consist of low-resolution, expensive, single-imager analog cameras. These systems are retooled for 3D display by simply doubling the cameras and outboard control units. Here, a fully-integrated digital stereoscopic video camera employing high-definition sensors and a class-compliant USB video interface is presented. This system can be used with low-cost PC hardware and consumer-level 3D displays for tele-medical surgical applications including military medical support, disaster relief, and space exploration.

A low-cost, reliable, high-throughput system for rodent behavioral phenotyping in a home cage environment.

Inexpensive, high-throughput, low maintenance systems for precise temporal and spatial measurement of mouse home cage behavior (including movement, feeding, and drinking) are required to evaluate products from large scale pharmaceutical design and genetic lesion programs. These measurements are also required to interpret results from more focused behavioral assays. We describe the design and validation of a highly-scalable, reliable mouse home cage behavioral monitoring system modeled on a previously described, one-of-a-kind system. Mouse position was determined by solving static equilibrium equations describing the force and torques acting on the system strain gauges; feeding events were detected by a photobeam across the food hopper, and drinking events were detected by a capacitive lick sensor. Validation studies show excellent agreement between mouse position and drinking events measured by the system compared with video-based observation--a gold standard in neuroscience.

A quality process study of lymph node evaluation in endometrial cancer.

Our objective was to analyze the reported lymph node counts between surgeons, histology prosectors, and pathologists using a cohort of patients enrolled on a national protocol that standardized surgical intent.This is a retrospective review of patients with uterine cancer who underwent a standardized formal staging procedure as dictated by a National Cancer Institute sponsored protocol. Patients were staged using the International Federation of Gynecology and Obstetrics 1988 guidelines. All patients required a hysterectomy, bilateral salpingo-oophorectomy, and bilateral pelvic and para-aortic lymphadenectomy. Lymphadenectomy specimens were separated by the following regions: external iliac, obturator, common iliac, and periaortic. Lymph node counts were analyzed by region, surgeon, histology prosector, and pathologist.There were 78 patients enrolled in the protocol during the study period. Of them, 72 (92%) patients met the inclusion criteria. A total of 2397 lymph nodes were counted, with an average total number of 33 (SD=9) lymph nodes dissected per patient. Surgeons A, B, and C had an average lymph node count of 32, 33, and 35, respectively, with no significant difference in mean node count (P=0.66). Prosectors 1 to 4 dissected an average of 34, 33, 28, and 35 lymph nodes, respectively (P=0.091). There were 2 pathologists with ≥ 10 cases. Their mean lymph node counts were 35 and 30, respectively, with no significant difference in mean node count (P=0.079).This systematic review did not identify a discrepancy in nodal count among surgeons, prosectors, or pathologists at our institution. The methods used may be helpful in structuring interdepartmental reviews for completeness of nodal dissections in cases where surgical intent has been standardized.

Consumers' use of HCAHPS ratings and word-of-mouth in hospital choice.

OBJECTIVE: To investigate the impact of the HCAHPS report of patient experiences and word-of-mouth narratives on consumers' hospital choice. DATA SOURCES: Online consumer research panel of U.S. adults ages 18 and older. STUDY DESIGN/DATA COLLECTION/EXTRACTION METHODS: In an experiment, 309 consumers were randomly assigned to see positive or negative information about a hospital in two modalities: HCAHPS graphs and a relative's narrative e-mail. Then they indicated their intentions to choose the hospital for elective surgery. PRINCIPAL FINDINGS: A simple, one-paragraph e-mail and 10 HCAHPS graphs had similar impacts on consumers' hospital choice. When information was inconsistent between the HCAHPS data and e-mail narrative, one modality attenuated the other's effect on hospital choice. CONCLUSIONS: The findings illustrate the power of anecdotal narratives, suggesting that policy makers should consider how HCAHPS data can be affected by word-of-mouth communication.

Bilateral and multinodular signet-ring stromal tumor of the ovary.

BACKGROUND: Signet-ring stromal tumor of the ovary is a rare, benign sex cord stromal tumor that is typically unilateral. Its distinction from malignant signet-ring cell adenocarcinoma metastatic to the ovary (Krukenberg tumor), is critical. CASE: A 69-year-old gravida 5 woman presented with a 1-week history of right lower abdominal pain. Ultrasonography revealed a 4-cm right adnexal mass. Serum CA 125 and carcinoembryonic antigen were within normal limits. An exploratory laparotomy, partial omentectomy, bilateral salpingo-oophorectomy and peritoneal washing were performed. Solid multinodular masses in both ovaries were identified that histologically corresponded to bilateral signet-ring stromal tumors. CONCLUSION: We report a rare example of signet-ring stromal tumor that is bilateral and multinodular mimicking a Krukenberg tumor. Awareness of this unusual presentation can help prevent incorrect diagnosis.

Advanced cytoreductive surgery: American perspective.

Over the past 3 to 4 decades a special knowledge and understanding of the pathophysiology and behavior of gynecologic peritoneal surface malignancies has led to a significant improvement of the relevant treatment modalities, mirroring advances in chemotherapy approaches and improved knowledge of tumor biology. The surgical management of advanced ovarian, primary peritoneal, and fallopian tube cancers has evolved from the performance of basic gynecologic procedures to the incorporation of more comprehensive surgical procedures. This extensive surgical approach is of great importance for estimating the prognosis and guiding further treatment of affected patients. These complex procedures involving multi-organ resections are generally long and require excellent knowledge of upper abdominal anatomy. This article will focus on the role and program development of advanced cytoreductive surgery in patients with gynecologic peritoneal malignancies. This review is an attempt to provide guidance for the rationale and strategic approach to develop the surgical skill set, meet institutional requirements, and implement the concept of a comprehensive cytoreductive surgical team.