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Objectives: Gastric-type endocervical adenocarcinoma (GEA) is a rare form of cervical cancer not associated with human papilloma virus (HPV) infection. We summarize our experience with GEA at a large cancer center., Methods: Clinical and demographic information on all patients diagnosed with GEA between June 1, 2002 and July 1, 2019 was obtained retrospectively from clinical charts. Kaplan-Meier survival analysis was performed to describe progression-free survival (PFS) and overall survival (OS). Tumors from a subset of patients underwent next generation sequencing (NGS) analysis., Results: A total of 70 women with GEA were identified, including 43 who received initial treatment at our institution: of these 4 (9%) underwent surgery alone, 15 (35%) underwent surgery followed by adjuvant therapy, 10 (23%) were treated with definitive concurrent chemoradiation (CCRT), 7 (16%) with chemotherapy alone, and 3 (7%) with neoadjuvant CCRT and hysterectomy with or without chemotherapy. One-third (n = 14) of patients experienced disease progression, of whom 86% (n = 12) had prior CCRT. The median PFS and OS for patients with stage I GEA were 107 months (95% CI 14.8-199.2 months) and 111 months (95% CI 17-205.1 months) respectively, compared to 17 months (95% CI 5.6-28.4 months) and 33 months (95% CI 28.2-37.8 months) for patients with stages II-IV, respectively. On NGS, 4 patients (14%) had ERBB2 alterations, including 2 patients who received trastuzumab., Conclusions: GEA is an aggressive form of cervical cancer with poor PFS and OS when diagnosed at stage II or later. Further investigation is needed to identify the optimal management approach for this rare subtype., Competing Interests: Declaration of Competing Interest Outside the submitted work, B. Weigelt reports ad hoc membership in the scientific advisory board of Repare Therapeutics, outside the scope of the study. C. Friedman reports participation in the scientific advisory boards for Merck (LYNK-002) and Genentech (MyPathway) without compensation, consulting for Seagen and Bristol Myers Squibb, and institutional research funds from Genentech/Roche, Bristol Myers Squibb, Merck, AstraZeneca, and Daiichi. E. Jewell reports personal fee from Covidien/Medtronic. K. Cadoo reports grant funding from the Irish Cancer Society, MSD, and Immunogen; consulting fees from Nextcure, MJH Life Sciences, and GSK; payments/honoraria from GSK, AstraZeneca, and MSD; financial support to attend meetings from Roche, Pfizer, and MSD; advisory board participation at MSD, AstraZeneca, GSK, and Eisai; a voluntary advisory role at the National Cancer Control Programme Ireland; and a voluntary board member at ARC Cancer Support Centers. N. Abu-Rustum reports grant funding from GRAIL paid to the institution. S. issa Bhaloo reports stock or stock options in BioNTech, Moderna, Inc., Inovio, Relief Therapeutics Holding SA, Cansino Biologics, Inc., and Pfizer, Inc. M. Leitao reports personal fees from Medtronic, Intuitive Surgical, Inc., and JnJ/Ethicon. C. Aghajanian has received research grants from Abbvie, Clovis, Genentech, and Astra Zeneca and served on advisory boards for Abbvie, AstraZeneca/Merck, Eisai/Merck, Mersana Therapeutics, Repare Therapeutics, and Roche/Genentech. R. O'Cearbhaill reports honoraria from GSK, Bayer, Regeneron, SeaGen, Fresenius Kabi, Immunogen, MJH Life Sciences and Curio. C. Kyi reports grant funding from Conquer Cancer Foundation; grant funding paid to the institution from Merus, Gritstone, and BMS; and consulting fees from Scenic Immunology B.V. and OncLive. D. Zamarin is an inventor on a patent related to the use of oncolytic Newcastle Disease Virus for cancer therapy, and reports grant funding paid to the institution from AstraZeneca, Roche, Plexxikon, and Synthekine; consulting fees from Memgen, Celldex, Agenus, Astellas, AstraZeneca, Crown Biosciences, Roche, GSK, Hookpia, ImmunOS, Kalvir, Synlogic Therapeutics, Synthekine, Takeda, Targovax, Tessa Therapeutics, and Xencor; stock options in Accurius Therapeutics, Immunos Therapeutics and Calidi Biotherapeutics; and a Merck licensed patent (with personal payments and payments to the institution). All other authors have no potential conflicts of interest to disclose., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Purpose: To describe the development and implementation of a new digital health clinical tool (Gynecologic Survivorship Tool [GST]) for symptom management of women surgically treated for gynecologic cancer; to assess its feasibility; and to conduct a retrospective review of the data., Materials and Methods: The GST was developed on the basis of a comprehensive review of the literature, multidisciplinary expert opinion, and feedback from women with a history of gynecologic cancer. It is composed of 17 questions addressing six main categories-gynecologic health (abnormal bleeding/pain), lymphedema, vaginal/vulvar dryness, sexual health, menopause (hot flushes/sleep difficulties), and bowel/urinary issues. An electronic version using the Memorial Sloan Kettering Cancer Center Engage platform was piloted in two clinics for patients with endometrial or cervical cancer. Health information was generated into clinical summaries and identified concerns for actionable response. Associations of symptom and survey time point were assessed by longitudinal models using generalized estimating equations., Results: From January 1, 2019, to February 29, 2020, 3,357 GST assessments were assigned to 1,405 patients, with a 71% completion rate (90% within 5 minutes). Sixty-eight percent were performed at home via a patient portal, 32% at follow-ups using a clinic iPad. The most common symptoms were bowel problems, swelling/fluid, pain during examination, vaginal or vulvar dryness, and vaginal bleeding. Implementation challenges included improving patient compliance and ensuring that reports were reviewed by all clinical teams. We developed screening e-mails detailing patients whose assessments were due, planned training sessions for multidisciplinary teams, and incorporated feedback on methods for reviewing symptoms reports., Conclusion: The GST demonstrated feasibility, a high completion rate, and minimal time commitment. It was an effective electronic reporting mechanism for patients, enabling the medical team to develop specific strategies for alleviating bothersome symptoms during follow-up., Competing Interests: Nadeem R. Abu-RustumHonoraria: Prime OncologyResearch Funding: Stryker/Novadaq (Inst), GRAIL (Inst)Travel, Accommodations, Expenses: Prime Oncology Ling Y. ChenEmployment: Lyra Andrew J. VickersStock and Other Ownership Interests: OPKO HealthConsulting or Advisory Role: OPKO Diagnostics, Insightec, Steba BiotechPatents, Royalties, Other Intellectual Property: I am named on a patent for a statistical method to detect prostate cancer. This method has been commercialized by OPKO as the 4Kscore. I receive royalties from sales of the 4KscoreTravel, Accommodations, Expenses: OPKO Health Vance BroachOpen Payments Link: https://openpaymentsdata.cms.gov/physician/1162364 Dennis S. ChiLeadership: CSurgeriesStock and Other Ownership Interests: Bovie Medical, Verthermia, Intuitive Surgical, TransenterixHonoraria: Biom'UpConsulting or Advisory Role: Bovie Medical, Verthermia, Biom'upTravel, Accommodations, Expenses: Biom'Up Ginger J. GardnerHonoraria: BioAscentTravel, Accommodations, Expenses: BioAscent Elizabeth L. JewellHonoraria: SurvivornetConsulting or Advisory Role: Intuitive Surgical, Covidien/MedtronicResearch Funding: Summit Biomedical Mario M. Leitao JrHonoraria: Intuitive SurgicalConsulting or Advisory Role: Intuitive Surgical, Ethicon/Johnson & Johnson, Medtronic, TakedaResearch Funding: KCITravel, Accommodations, Expenses: Intuitive Surgical Yukio SonodaPatents, Royalties, Other Intellectual Property: Pending patent for a surgical instrument (uterine manipulator)No other potential conflicts of interest were reported.

Objective: To compare oncologic and perioperative outcomes in patients who underwent minimally invasive surgery (MIS) compared to laparotomy for newly diagnosed early-stage cervical carcinoma., Methods: We retrospectively identified patients who underwent radical hysterectomy for stage IA1 with lymphovascular invasion (LVI), IA2, or IB1 cervical carcinoma at our institution from 1/2007-12/2017. Clinicopathologic characteristics and surgical and oncologic survival outcomes were compared using appropriate statistical testing. Multivariable Cox regression analysis was used to control for potential confounders., Results: We identified 196 evaluable cases-117 MIS (106 robotic [90.6%]) and 79 laparotomy cases. Cohorts had similar age, BMI, substage, histologic subtype, clinical and pathologic tumor size, positive margins, and presence of LVI. The MIS group had more cases with no residual tumor in the hysterectomy (24.8% vs. 10.1%, P = 0.01). The laparotomy group had more cases with positive nodes (29.1% vs. 17.1%, P = 0.046) and more patients who received adjuvant therapy (53.2% vs. 33.3%, P = 0.006). Median follow-up was ~4 years. Five-year disease-free survival (DFS) rates were 87.0% in the MIS group and 86.6% in the laparotomy group (P = 0.92); 5-year disease-specific survival (DSS) rates were 96.5% and 93.9%, respectively (P = 0.93); and 5-year overall survival (OS) rates were 96.5% and 87.4%, respectively (P = 0.15). MIS was not associated with DFS, DSS, or OS on multivariable regression analysis. The rate of postoperative complications was significantly lower in the MIS cohort (11.1% vs. 20.3%; P = 0.04)., Conclusions: MIS radical hysterectomy for cervical carcinoma did not confer worse oncologic outcomes in our single-center and concurrent series of patients with early-stage cervical carcinoma., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objectives: Radical trachelectomy has enabled select women with stage I cervical cancer to maintain fertility after treatment. Tumor size greater than 2 cm has been considered a contraindication, and those patients denied trachelectomy. We report our trachelectomy experience with tumors measuring 2 to 4 cm., Methods: We retrospectively reviewed the medical records of all patients planned for fertility-sparing radical trachelectomy. Largest tumor dimension was determined by physical examination, preoperative magnetic resonance imaging, or pathologic evaluation. No patient received neoadjuvant chemotherapy., Results: Twenty-nine (26%) of 110 patients had stage IB1 disease with tumors 2 to 4 cm. Median age was 31 years (range, 22-40 years), and 83% were nulliparous. Thirteen patients (45%) had squamous cell carcinoma, 12 patients (41%) had adenocarcinoma, and 4 patients (14%) had adenosquamous carcinoma. Thirteen (45%) of 29 patients had positive pelvic nodes. All para-aortic nodes were negative. Owing to intraoperative frozen section, 13 patients (45%) underwent immediate hysterectomy and 1 patient (3%) definitive chemoradiation. Owing to high-risk features on final pathology, 6 patients (21%) who had retained their uterus received chemoradiation. Nine patients (31%) underwent a fertility-sparing procedure. At a median follow-up of 44 months (range, 1-90 months), there was one recurrence., Conclusions: Expanding radical trachelectomy inclusion criteria to women with 2- to 4-cm tumors allows for a fertility-sparing procedure in 30% of patients who would otherwise have been denied the option, with no compromise in oncologic outcome.

Objective: A recent phase III trial reported gemcitabine with cisplatin chemoradiation followed by 2 cycles of gemcitabine and cisplatin (G) significantly improved progression-free (PFS) and overall survival (OS) compared to standard cisplatin chemoradiation (C) for locally advanced cervix cancer. We evaluate the cost effectiveness (CE) of these treatment regimens., Methods: A modified Markov model was constructed comparing CE between treatment arms using the published trial's five-year OS and treatment-related toxicity rates. Quality of life (QOL) utility scores during treatment were obtained from published literature and modeled for sensitivity analysis. Cost data was obtained from Medicare reimbursement figures and the Healthcare Cost and Utilization Project. One-way sensitivity analyses assessed variations in cost and adverse events., Results: Mean cost was $41,330 (US$) for C versus $60,974 for G. Incremental cost-effectiveness ratio (ICER) for G compared to C was $33,080 per quality-adjusted life year (QALY). In sensitivity analyses (SA), the ICER increased to common willingness-to-pay thresholds of 50 K and 100 K when QOL utility scores during G active treatment declined to 0.64 and 0.53 (baseline 0.76), respectively. The model was insensitive to changes in adverse event rates, costs of treatment, or adverse event hospitalization costs., Conclusions: Gemcitabine with cisplatin chemoradiation followed by 2 cycles of adjuvant gemcitabine and cisplatin is a cost effective treatment for locally advanced cervix cancer compared to standard cisplatin chemoradiation. Common willingness to pay thresholds are exceeded during sensitivity analyses with realistic declines in QOL. Our results support ongoing investigations of novel adjuvants to standard cisplatin chemoradiation with potentially less toxicity., (Published by Elsevier Inc.)

Objectives: To determine utility scores for health states relevant to the treatment of early-stage, high-risk cervical cancer., Methods: Seven descriptive health states incorporating the physical and emotional aspects of medical treatment, recovery, and prognosis were developed. Forty-five female volunteers valuated each health state using the visual analogue score (VAS) and time trade off (TTO) methods. Treatment options were ranked by mean and median TTO scores. The 95% confidence intervals were calculated to determine the statistical significance of ranking preferences. The Wilcoxon rank-sum test was used to compare central tendencies related to age, race, parity, and subject history of abnormal cervical cytology., Results: VAS and TTO scores were highly correlated. Volunteers ranked minimally invasive radical hysterectomy with low-risk features as most preferred (mean TTO = 0.96; median TTO = 1.00) and aborted radical hysterectomy followed by chemoradiation as least preferred (mean TTO = 0.69; median TTO = 0.83). Health states that included radical surgery were ranked higher than those that included chemoradiation, either in the adjuvant or primary setting. When survival was comparable, volunteers rated radical hysterectomy with high-risk pathology followed by adjuvant chemoradiation (mean TTO = 0.78; median TTO = 0.92; 95% CI: 0.69-0.87) similarly to chemoradiation alone (mean TTO = 0.76; median TTO 0.90; 95% CI: 0.66-0.86; p = NS). Utility scores for the majority of health states were not significantly associated with age, race, parity, or subject history of abnormal cervical cytology., Conclusion: Subjects consistently preferred surgical excision to treat early-stage, high-risk cervical cancer and chose a minimally invasive approach. Such utility scores can be used to incorporate quality-of-life effects into comparative-effectiveness models for cervical cancer., (Copyright © 2011 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.)

Objectives: To estimate the relative cost-effectiveness of treatments for patients with FIGO stage IB2 cervical cancer and no evidence of metastasis as determined by combination of positron emission tomography/computed tomography (PET/CT)., Methods: A Markov state transition model was constructed to compare two strategies: (1) radical hysterectomy and pelvic lymphadenectomy with tailored adjuvant therapy (RH+TA); (2) primary chemoradiation (CR). Five-year survival estimates for FIGO stage IB2 cervical cancer were obtained from literature. Medicare reimbursement rates and Agency for Healthcare Research and Quality database were used to obtain costs of treatment regimens and grades 3-5 adverse events. Strategies were compared using incremental cost per year of life saved (YLS). Extensive sensitivity analyses were performed., Results: Overall survival estimates were 78.9% for CR; 79.6% for RH+TA. Mean cost for CR at 5 years was $21,403 compared to $27,840 for RH+TA. RH+TA cost $63,689 per additional year of life saved (YLS) compared to CR. Results were most sensitive to survival estimates and the costs associated with high dose rate (HDR) versus low dose rate (LDR) brachytherapy. If 90% of patients with intermediate pathologic risk factors at surgery were assumed to receive adjuvant CR, the ICER of RH+TA rose to $100,000 per YLS compared to CR., Conclusions: RH+TA is potentially cost effective when compared to CR for patients with stage IB2 cervical cancer without metastatic disease by PET/CT imaging. Key factors in the cost-effectiveness of treatments include physician's expected recommendation of adjuvant therapy, brachytherapy modality employed for primary CR and quality of life related to both treatment and its complications.