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BACKGROUND: Sexual health is an important survivorship issue in cervical cancer. We assessed patient-reported sexual health outcomes and correlations with oncologist-assessed vaginal toxicity (VT). METHODS: This was a prospective, cross-sectional study of stage IB-IVA cervical cancer patients treated with definitive chemoradiation, who completed a socio-demographic questionnaire and the following patient-reported-outcomes (PROs): Female Sexual Function Index (FSFI), Female Sexual Distress Scale-Revised (FSDS-R), Menopause Rating Scale (MRS), Hospital Anxiety and Depression Scale (HADS). VT was assessed using the CTCAE v4.0. Sociodemographic, clinical data, PROs and VT were summarized using descriptive statistics; correlations were evaluated using linear regression analyses. RESULTS: Between August 2018 and April 2022, 73 patients were analyzed. Median age was 49 (range 25-81), 57.5% had vaginal involvement at diagnosis and 76.9% were partnered. Sexual dysfunction (FSFI score ≤ 26), sexual distress (FSDS-R ≥ 11), severe menopausal symptoms (MRS ≥ 17), anxiety (HAD-Anxiety >7) and depression (HAS-Depression >7) were reported in 86.3%, 54.5%, 36.2%, 46.6% and 24.7%, respectively. Grade 2+ VT was reported in 27.4%. No significant associations were found between PROs and VT. On multivariable analysis, non-partnered status, use of hormone replacement therapy, and International Commission on Radiation Units and Measurements - rectovaginal dose (ICRU-RV) >65Gy were associated with worse sexual health (p < 0.005). CONCLUSION: Cervical cancer patients self-report high rates of sexual distress, dysfunction and menopause symptoms. Discordance between oncologist-assessed VT and PROs highlights the importance of evaluating the patient's experience. Proactive treatment of menopausal symptoms and attention to radiotherapy doses to the vagina should be considered.
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Perioperative blood transfusion in ovarian cancer patients was associated with a 28% increase in all-cause mortality. The negative impact of perioperative blood transfusion extends beyond the immediate postoperative period. OBJECTIVES: The effect of perioperative blood transfusions on long-term oncologic outcomes of patients with advanced ovarian cancer undergoing cytoreductive surgery remains uncertain. Our study aims to determine the association between perioperative blood transfusion and all-cause mortality in this population. METHODS: Using province-wide administrative databases, patients with advanced ovarian cancer who underwent surgery between 2007 and 2021 as part of first-line treatment were identified. Perioperative transfusion was defined as any transfusion from date of surgery to discharge from hospital. Multivariable Cox proportional hazards regression models were used to determine if there was an independent association of transfusion with all-cause mortality, accounting significant confounders. RESULTS: A total of 5891 patients had cytoreductive surgery for advanced ovarian cancer between 2007 and 2021, of which 2898 (49.2%) had interval cytoreductive surgery (ICS) and 2993 (50.8%) had primary cytoreductive surgery (PCS). Perioperative blood transfusion was given to 37.3% of patients (40.5% ICS and 34.2% PCS). On multivariable analysis, there was an increased hazard of all-cause mortality for patients receiving perioperative transfusion compared to those who did not (hazard ratio: 1.28; 95% CI: 1.20-1.37). The association of increased all-cause mortality was observed starting 1 year after surgery, was sustained thereafter, and seen in both ICS and PCS groups. CONCLUSION: Perioperative blood transfusion after cytoreductive surgery for ovarian cancer is common in Ontario, Canada and was significantly associated with an increase in all-cause mortality. Blood transfusion is a poor prognostic factor, and the negative impact of blood transfusion persists beyond the immediate postoperative period.
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Although the impact of acoustic challenge on speech processing and memory increases as a person ages, older adults may engage in strategies that help them compensate for these demands. In the current preregistered study, older adults (n = 48) listened to sentences-presented in quiet or in noise-that were high constraint with either expected or unexpected endings or were low constraint with unexpected endings. Pupillometry and EEG were simultaneously recorded, and subsequent sentence recognition and word recall were measured. Like young adults in prior work, we found that noise led to increases in pupil size, delayed and reduced ERP responses, and decreased recall for unexpected words. However, in contrast to prior work in young adults where a larger pupillary response predicted a recovery of the N400 at the cost of poorer memory performance in noise, older adults did not show an associated recovery of the N400 despite decreased memory performance. Instead, we found that in quiet, increases in pupil size were associated with delays in N400 onset latencies and increased recognition memory performance. In conclusion, we found that transient variation in pupil-linked arousal predicted trade-offs between real-time lexical processing and memory that emerged at lower levels of task demand in aging. Moreover, with increased acoustic challenge, older adults still exhibited costs associated with transient increases in arousal without the corresponding benefits.
Subject(s)
Aging , Electroencephalography , Pupil , Speech Perception , Humans , Aged , Male , Female , Pupil/physiology , Aging/physiology , Speech Perception/physiology , Acoustic Stimulation , Aged, 80 and over , Middle Aged , Memory/physiology , Recognition, Psychology/physiology , Evoked Potentials/physiology , Auditory Perception/physiology , Mental Recall/physiologyABSTRACT
OBJECTIVE: Same day discharge is safe after minimally invasive gynecology oncology surgery. Our quality improvement peri-operative program based on enhanced recovery after surgery principles led to an increase in same day discharge from 30% to 75% over a 12 month period. Twelve months after program implementation, we assessed the sustainability of same day discharge rates, determined post-operative complication rates, and evaluated factors affecting same day discharge rates. METHODS: A retrospective chart review was conducted of 100 consecutive patients who underwent minimally invasive surgery at an academic cancer center from January to 2021 to December 2021. This cohort was compared with the active intervention cohort (n=102) from the implementation period (January 2020 to December 2020). Same day discharge rates and complications were compared. Multivariable analysis was performed to assess which factors remained associated with same day discharge post-intervention. RESULTS: Same day discharge post-intervention was 72% compared with 75% during active intervention (p=0.69). Both cohorts were similar in age (p=0.24) and body mass index (p=0.27), but the post-intervention cohort had longer operative times (p=0.001). There were no significant differences in 30-day complications, readmission, reoperation, or emergency room visits (p>0.05). There was a decrease in 30-day post-operative clinic visits from 18% to 5% in the post-intervention cohort (p=0.007), and unnecessary bowel prep use decreased from 35% to 14% (p<0.001). On multivariable analysis, start time (second case of the day) (OR 0.06; 95% CI 0.01 to 0.35), and ward narcotic use (OR 0.12; 95% CI 0.03 to 0.42) remained associated with overnight admission. CONCLUSION: Same day discharge rate was sustained at 72%, 12 months after the implementation of a quality improvement program to optimize same day discharge rate after minimally invasive surgery, while maintaining low post-operative complications and reducing unplanned clinic visits. To maximize same day discharge, minimally invasive gynecologic oncology surgery should be prioritized as the first case of the day, and post-operative narcotic use should be limited.
Subject(s)
Enhanced Recovery After Surgery , Genital Neoplasms, Female , Gynecologic Surgical Procedures , Minimally Invasive Surgical Procedures , Humans , Female , Middle Aged , Retrospective Studies , Genital Neoplasms, Female/surgery , Enhanced Recovery After Surgery/standards , Gynecologic Surgical Procedures/methods , Gynecologic Surgical Procedures/standards , Gynecologic Surgical Procedures/rehabilitation , Minimally Invasive Surgical Procedures/methods , Postoperative Complications/prevention & control , Aged , Adult , Quality Improvement , Patient DischargeABSTRACT
BACKGROUND: Retrospective data suggest that the incidence of parametrial infiltration is low in patients with early-stage low-risk cervical cancer, which raises questions regarding the need for radical hysterectomy in these patients. However, data from large, randomized trials comparing outcomes of radical and simple hysterectomy are lacking. METHODS: We conducted a multicenter, randomized, noninferiority trial comparing radical hysterectomy with simple hysterectomy including lymph-node assessment in patients with low-risk cervical cancer (lesions of ≤2 cm with limited stromal invasion). The primary outcome was cancer recurrence in the pelvic area (pelvic recurrence) at 3 years. The prespecified noninferiority margin for the between-group difference in pelvic recurrence at 3 years was 4 percentage points. RESULTS: Among 700 patients who underwent randomization (350 in each group), the majority had tumors that were stage IB1 according to the 2009 International Federation of Gynecology and Obstetrics (FIGO) criteria (91.7%), that had squamous-cell histologic features (61.7%), and that were grade 1 or 2 (59.3%). With a median follow-up time of 4.5 years, the incidence of pelvic recurrence at 3 years was 2.17% in the radical hysterectomy group and 2.52% in the simple hysterectomy group (an absolute difference of 0.35 percentage points; 90% confidence interval, -1.62 to 2.32). Results were similar in a per-protocol analysis. The incidence of urinary incontinence was lower in the simple hysterectomy group than in the radical hysterectomy group within 4 weeks after surgery (2.4% vs. 5.5%; P = 0.048) and beyond 4 weeks (4.7% vs. 11.0%; P = 0.003). The incidence of urinary retention in the simple hysterectomy group was also lower than that in the radical hysterectomy group within 4 weeks after surgery (0.6% vs. 11.0%; P<0.001) and beyond 4 weeks (0.6% vs. 9.9%; P<0.001). CONCLUSIONS: In patients with low-risk cervical cancer, simple hysterectomy was not inferior to radical hysterectomy with respect to the 3-year incidence of pelvic recurrence and was associated with a lower risk of urinary incontinence or retention. (Funded by the Canadian Cancer Society and others; ClinicalTrials.gov number, NCT01658930.).
Subject(s)
Carcinoma, Squamous Cell , Hysterectomy , Uterine Cervical Neoplasms , Female , Humans , Canada , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/surgery , Hysterectomy/adverse effects , Hysterectomy/methods , Lymph Nodes/pathology , Neoplasm Recurrence, Local/epidemiology , Neoplasm Staging , Prognosis , Retrospective Studies , Urinary Incontinence/etiology , Urinary Retention/etiology , Uterine Cervical Neoplasms/pathology , Uterine Cervical Neoplasms/surgeryABSTRACT
In speech production research, talkers often perform a speech task several times per recording session with different speaking styles or in different environments. For example, Lombard speech studies typically have talkers speak in several different noise conditions. However, it is unknown to what degree simple repetition of a speech task affects speech acoustic characteristics or whether repetition effects might offset or exaggerate effects of speaking style or environment. The present study assessed speech acoustic changes over four within-session repetitions of a speech production taskset performed with two speaking styles recorded in separate sessions: conversational and clear speech. In each style, ten talkers performed a set of three speech tasks four times. Speaking rate, median fundamental frequency, fundamental frequency range, and mid-frequency spectral energy for read sentences were measured and compared across test blocks both within-session and between the two styles. Results indicate that statistically significant changes can occur from one repetition of a speech task to the next, even with a brief practice set and especially in the conversational style. While these changes were smaller than speaking style differences, these findings support using a complete speech set for training while talkers acclimate to the task and to the laboratory environment.
Subject(s)
Speech Perception , Speech , Acoustics , Noise/adverse effects , Speech IntelligibilityABSTRACT
OBJECTIVES: To assess the impact of the COVID-19 pandemic on endometrial cancer stage and surgical treatment in Ontario, Canada. METHODS: This descriptive study identified cases from January 1, 2017 to December 31, 2021 from endometrial cancer hysterectomy specimens in the Ontario Health-Cancer Care Ontario, ePath system. Endometrial biopsy records from January 1, 2016 to December 31, 2021 were matched to surgical specimens by provincial health card number. Time to surgery and surgical stage were compared before (2017-2019) and during (2020-2021) the COVID-19 pandemic. RESULTS: There were 10 446 women treated with hysterectomy for endometrial cancer in Ontario from 2017-2021. In April and May 2020, corresponding with the provincial state of emergency, there was a 56% relative reduction in endometrial biopsies. Despite this 2-month reduction in endometrial biopsy volume, there was no change in surgical volume for endometrial cancer treatment. The median time from endometrial biopsy to surgery was 56 days (IQR 40, 80) during the pandemic (2020-2021) compared to 58 days (IQR 43, 82) prior to the pandemic (2017-2019) (P < 0.001). There was no upstaging of endometrial cancer during the COVID-19 pandemic. CONCLUSIONS: The Ontario healthcare system continued to prioritize service delivery to endometrial cancer patients during the COVID-19 pandemic, despite the increase in virtual care and decrease in operating room time. There were no significant surgical delays or upstaging of endometrial cancer.
Subject(s)
COVID-19 , Endometrial Neoplasms , Humans , Female , Ontario/epidemiology , Pandemics , Retrospective Studies , Endometrial Neoplasms/epidemiology , Endometrial Neoplasms/surgery , Endometrial Neoplasms/pathologyABSTRACT
PURPOSE: Most cervical cancers are caused by human papilloma virus (HPV), and HPV circulating tumor DNA (ctDNA) may identify patients at highest risk of relapse. Our pilot study using digital polymerase chain reaction (dPCR) showed that detectable HPV ctDNA at the end of chemoradiation (CRT) is associated with inferior progression-free survival (PFS) and that a next-generation sequencing approach (HPV-seq) may outperform dPCR. We aimed to prospectively validate HPV ctDNA as a tool for early detection of residual disease. METHODS: This prospective, multicenter validation study accrued patients with stage IB-IVA cervical cancer treated with CRT between 2017 and 2022. Participants underwent phlebotomy at baseline, end of CRT, 4-6 weeks post-CRT, and 3 months post-CRT for HPV ctDNA levels. Plasma HPV genotype-specific DNA levels were quantified using both dPCR and HPV-seq. The primary end point was 2-year PFS. RESULTS: With a median follow-up of 2.2 (range, 0.5-5.5) years, there were 24 PFS events among the 70 patients with HPV+ cervical cancer. Patients with detectable HPV ctDNA on dPCR at the end of CRT, 4-6 weeks post-CRT, and 3 months post-CRT had significantly worse 2-year PFS compared with those with undetectable HPV ctDNA (77% v 51%, P = .03; 82% v 15%, P < .001; and 82% v 24%, P < .001, respectively); the median lead time to recurrence was 5.9 months. HPV-seq showed similar results as dPCR. On multivariable analyses, detectable HPV ctDNA on dPCR and HPV-seq remained independently associated with inferior PFS. CONCLUSION: Persistent HPV ctDNA after CRT is independently associated with inferior PFS. HPV ctDNA testing can identify, as early as at the end of CRT, patients at high risk of recurrence for future treatment intensification trials.
Subject(s)
Circulating Tumor DNA , Papillomavirus Infections , Uterine Cervical Neoplasms , Female , Humans , Circulating Tumor DNA/genetics , Uterine Cervical Neoplasms/therapy , Human Papillomavirus Viruses , Prospective Studies , Papillomavirus Infections/complications , Papillomavirus Infections/diagnosis , Pilot Projects , Neoplasm Recurrence, Local/pathology , Biomarkers, Tumor/geneticsABSTRACT
Surgical staging with total hysterectomy, bilateral salpingo-oophorectomy, and lymph node assessment is the standard of care for patients with clinical early-stage endometrial cancer. Traditionally, complete pelvic and para-aortic lymphadenectomy (LND) was performed to assess for nodal metastases; however, numerous prospective studies have demonstrated that sentinel lymph node biopsy has similar diagnostic accuracy, and is an acceptable alternative to complete LND. This has led to a paradigm shift in endometrial cancer staging.
Subject(s)
Endometrial Neoplasms , Sentinel Lymph Node , Female , Humans , Lymph Nodes/surgery , Lymph Nodes/pathology , Sentinel Lymph Node/surgery , Sentinel Lymph Node/pathology , Prospective Studies , Sentinel Lymph Node Biopsy , Lymph Node Excision , Endometrial Neoplasms/pathology , Neoplasm StagingABSTRACT
OBJECTIVES: Abnormalities in mismatch repair have been described in ovarian cancer, but few studies have examined the causes of mismatch repair deficiency (MMRd). To address this, we completed targeted mutational and methylation sequencing on MMRd ovarian cancer cases. The objective of this study was to explore the molecular mechanism of MMRd using our targeted next generation sequencing panel. METHODS: Newly diagnosed non-serous/mucinous ovarian cancers (n=215) were prospectively recruited from three cancer centers in Ontario, Canada, between 2015 and 2018. Tumors were reflexively assessed for mismatch repair protein by immunohistochemistry. Matched tumor-normal MMRd cases were analyzed on a custom next generation sequencing panel to identify germline and somatic mutations, copy number variants, rearrangements, and promoter methylation in mismatch repair and associated genes. RESULTS: Of 215 cases, 28 (13%) were MMRd. The MMRd cohort had a median age of 52.3 years (range 33.6-62.2), with mostly stage I (50%) and grade 1 or 2 endometrioid histotype (57%). Of the 28 cases, 22 were available for molecular analysis, and Lynch syndrome was detected in 50% of MMRd cases (11/22; seven ovarian cancer and four synchronous ovarian and endometrial cancer: seven MSH6, two MLH1, one PMS2, and one MSH2). An explanation for the observed mismatch repair phenotype was available for 22/22 deficient cases, including 12 MLH1/PMS2 deficient (nine somatic methylation, one bi-allelic somatic deletion, and two pathogenic germline variant), one PMS2 deficient (one pathogenic germline variant), seven MSH6 deficient (seven pathogenic germline variant), and two MSH2/MSH6 deficient (one pathogenic germline variant and one bi-allelic somatic mutation). Concordance between clinical germline testing and panel sequencing results was 100%. CONCLUSIONS: Use of our custom next generation sequencing panel allowed for the streamlined assessment of hereditary and somatic causes of MMRd in ovarian cancers.
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Relationships between extended high-frequency (EHF) thresholds and speech-in-spatialized noise were examined in firefighters with a history of occupational noise and airborne toxin exposure. Speech recognition thresholds were measured for co-located and spatially separated (±90° azimuth) sentences in a competing signal using the Listening in Spatialized Noise-Sentences test. EHF hearing was significantly correlated with the spatial advantage, indicating that firefighters with poorer EHF thresholds experienced less benefit from spatial separation. The correlation between EHF thresholds and spatial hearing remained significant after controlling for age. Deficits in EHF and spatial hearing suggest firefighters may experience compromised speech understanding in job-related complex acoustic environments.
Subject(s)
Noise, Occupational , Sound Localization , Speech Perception , Hearing , Hearing Tests , Humans , Young Adult , Adult , Middle AgedABSTRACT
Purpose: Non-invasive ventilation (NIV) provides respiratory support without invasive endotracheal intubation but can hinder patients' ability to communicate effectively. The current study presents preliminary results using a novel in-mask ventilator microphone to enhance talker intelligibility while receiving NIV.Method: A proof-of-concept study assessed sentence intelligibility of five healthy adult talkers using a prototype model of the microphone under continuous positive airway pressure (CPAP; 5/5 cm H2O) and bilevel positive airway pressure (BiPAP; 8/4 cm H2O) ventilator conditions. A pilot study then assessed intelligibility, subjective comprehensibility and naturalness, and patient- and conversation partner-reported communication outcomes for eight patients undergoing therapeutic NIV while being treated in an intensive care unit (ICU).Result: Intelligibility increased significantly with the microphone on in the BiPAP condition for healthy volunteers. For patients undergoing NIV in an ICU, intelligibility, comprehensibility, and patient and conversation partner ratings of conversation satisfaction significantly improved with the microphone on. Patients with lower baselines without the microphone in certain measures (intelligibility, comprehensibility) generally showed a greater microphone benefit than patients with higher baselines.Conclusion: Use of a novel microphone integrated into NIV improved intelligibility during ventilation for both healthy volunteers and patients undergoing therapeutic NIV. Additional clinical studies will define precise benefits and implications of such improved intelligibility.
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Purpose: To examine Canadian physiotherapists' experiences in adapting their delivery of patient care during the COVID-19 pandemic. We examine the level of strain on the profession and barriers and enablers to virtual care and provide strategies to support future virtual care implementation. Methods: From May to October 2020, a series of eight cross-sectional survey cycles were distributed every 2-4 weeks through branches and divisions of the Canadian Physiotherapy Association, social media, and personal networks. Descriptive statistics summarized the main findings. Open ended questions were first analyzed inductively using thematic analysis, then deductively mapped to the Capability-Opportunity-Motivation Behavioural (COM-B) Model. Results: Between 1,820 (cycle 1) and 334 (cycle 7) physiotherapists responded. Median strain level was 5/5 (cycle 1) and dropped to median 3/5 (cycles 5-8). In cycle 1, 55% of physiotherapists had ceased in-person care, while 41% were providing modified in-person care. Of these physiotherapists, 79% were offering virtual care. As modified in-person care increased, virtual care continued as a substantial aspect of practice. Physiotherapists identified barriers (e.g., lack of hands-on care) and enabling factors (e.g., greater accessibility to patients) for virtual care. In-depth examination of the barriers and enablers through the COM-B lens identified potential interventions to support future virtual care implementation, including education and training resources for physiotherapists and communication and advocacy to patients and the public on the value of virtual care. Conclusions: Canadian physiotherapists exhibited high adaptability in response to COVID-19 through the rapid and widespread use of virtual care. By creating an in-depth understanding of the barriers and enablers to virtual care, along with potential interventions, this work will facilitate future opportunities to support and enhance physiotherapists' delivery of virtual care.
Objectif : examiner les expériences des physiothérapeutes canadiens qui ont adapté la prestation de leurs soins aux patients pendant la pandémie de COVID-19. Les auteurs ont examiné le degré de pression sur la profession de même que les obstacles et les incitations aux soins virtuels et ils proposent des stratégies pour appuyer la future mise en Åuvre des soins virtuels. Méthodologie : de mai à octobre 2020, toutes les deux à quatre semaines, les auteurs ont distribué une série de huit cycles de sondages transversaux aux sections et divisions de l'Association canadienne de physiothérapie, aux réseaux sociaux et à leurs réseaux personnels. Ils ont utilisé des statistiques descriptives pour résumer leurs principales observations. Ils ont d'abord procédé à l'examen inductif des questions ouvertes par une analyse thématique, puis ont entrepris la cartographie déductive du modèle comportemental de capacité-possibilité-motivation (COM-B). Résultats : entre 1 820 (cycle 1) et 334 (cycle 7) physiothérapeutes ont répondu. Le degré médian de pression a atteint 5/5 (cycle 1), pour reculer à 3/5 (cycles 5 à 8). Au cours du cycle 1, 55 % des physiothérapeutes ont interrompu leurs soins en présentiel, tandis que 41 % ont fourni des soins modifiés en présentiel. Par ailleurs, 79 % de tous ces physiothérapeutes ont offert des soins virtuels. Alors que les soins modifiés en présentiel ont augmenté, les soins virtuels ont continué de représenter un volet substantiel de la pratique. Les physiothérapeutes ont relevé des obstacles (p. ex., absence de soins manuels) et des incitatifs (p. ex., plus grande accessibilité aux patients) aux soins virtuels. L'examen approfondi des obstacles et des incitatifs en fonction du modèle COM-B a permis d'extraire des interventions possibles pour appuyer la future mise en Åuvre des soins virtuels, y compris des ressources d'éducation et de formation pour les physiothérapeutes et les communications et la promotion de la valeur des soins virtuels auprès des patients et du public. Conclusions : les physiothérapeutes canadiens ont fait preuve d'une grande adaptabilité en réponse à la COVID-19 grâce au recours rapide et généralisé aux soins virtuels. Par une compréhension approfondie des obstacles et des incitations aux soins virtuels et des interventions potentielles, la présente étude favorisera les futures occasions de soutenir et d'améliorer la prestation des soins virtuels par des physiothérapeutes.
ABSTRACT
Contextual factors such as patient expectations and financial pressures are overlooked challenges for Physiotherapists (PTs) and other rehabilitation professionals trying to implement evidence-based practice (EBP), particularly in private practice settings. In today's hypercompetitive pain management market, PTs may risk detrimental impacts to their reputation and livelihood if they do not give patients what they want, even if what they want does not align with clinical guidelines and research evidence. The aim of this professional practice paper is to shed light on these real-world challenges and encourage discussion among the PT community about strategies to increase uptake of EBP that involve multiple stakeholders such as PT training programs, professional organizations, researchers and clinic owners, which all have a role to play in supporting the translation of evidence into practice in our profession.
Subject(s)
Financial Stress , Physical Therapists , Humans , Motivation , Evidence-Based PracticeABSTRACT
Sex related differences in the incidence or severity of infection have been described for multiple viruses. With herpes simplex viruses, the best example is HSV-2 genital infection where women have a higher incidence of infection and can have more severe infections than men. HSV-1 causes several types of infections including skin and mucosal ulcers, keratitis, and encephalitis in humans that do not appear to have a strong biological sex component. Given that mouse strains differ in their MHC loci it is important to determine if sex differences occur in multiple strains of mice. Our goal was to answer two questions: Are virus related sex differences present in BALB/C mice and does virulence of the viral strain have an effect? We generated a panel of recombinant HSV-1 viruses with differing virulence phenotypes and characterized multiple clinical correlates of ocular infection in BALB/c mice. We found no sex-specific differences in blepharitis, corneal clouding, neurovirulence, and viral titers in eye washes. Sex differences in neovascularization, weight loss and eyewash titers were observed for some recombinants, but these were not consistent across the phenotypes tested for any recombinant virus. Considering these findings, we conclude that there are no significant sex specific ocular pathologies in the parameters measured, regardless of the virulence phenotype following ocular infection in BALB/c mice, suggesting that the use of both sexes is not necessary for the bulk of ocular infection studies.
Subject(s)
Eye Infections , Herpes Simplex , Herpesvirus 1, Human , Keratitis, Herpetic , Humans , Female , Male , Animals , Mice , Herpesvirus 1, Human/genetics , Mice, Inbred BALB C , Eye/pathology , Keratitis, Herpetic/pathologyABSTRACT
BACKGROUND: We previously developed the Integrated Prediction Model using a 4-step algorithm of unresectable stage IVB, patient factors, surgical resectability, and surgical complexity to predict outcome of <1 cm cytoreduction in advanced epithelial ovarian cancer, and triaged patients to neoadjuvant chemotherapy or primary cytoreductive surgery. OBJECTIVE: To validate the Integrated Prediction Model on a retrospective cohort of patients. METHODS: A retrospective cohort study of 107 patients with advanced ovarian cancer treated between January 2017 and September 2018 was carried out. The above mentioned 4-step algorithm determined cut-off points using the Youden Index. This validation study reports sensitivity, specificity, negative and positive predictive value on an external cohort. RESULTS: Among 107 patients, 61 had primary surgery and 46 had neoadjuvant chemotherapy. Compared with primary surgery, patients treated with neoadjuvant chemotherapy were significantly older (63.5 vs 61, p=0.037), more likely to have stage IV disease (52% vs 18%, p<0.001), Eastern Cooperative Oncology Group (ECOG) score >1 (30% vs 11%, 0.045), lower pre-operative albumin (37 vs 40, p<0.001), and higher CA-125 (970 vs 227.5, p<0.001). They also had higher patient factors (2 vs 0, p=0.013), surgical resectability (4 vs 1, p<0.001), and anticipated surgical complexity (8 vs 5, p<0.001). There was no significant difference in outcome of cytoreduction (<1 cm residual disease: 85% for primary surgery vs 87% interval surgery, p=0.12)In this validation cohort, triaging patients with patient factors ≤2, surgical resectability score ≤5, and surgical complexity score ≤9 to primary surgery had a sensitivity of 91% for optimal cytoreduction <1 cm and a specificity of 81%. The positive predictive value, negative predictive value, and accuracy were 83%, 90%, and 86%, respectively. Application of the Integrated Prediction Model would have prevented five patients from receiving suboptimal cytoreduction and triaged them to neoadjuvant chemotherapy. CONCLUSIONS: We validated the proposal that a triage algorithm integrating patient factors, surgical complexity, and surgical resectability in advanced ovarian cancer had high sensitivity and specificity to predict optimal cytoreduction <1 cm.
Subject(s)
Ovarian Neoplasms , Humans , Female , Carcinoma, Ovarian Epithelial/pathology , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/surgery , Ovarian Neoplasms/pathology , Cytoreduction Surgical Procedures , Retrospective Studies , Neoadjuvant Therapy , Algorithms , Neoplasm StagingABSTRACT
OBJECTIVES: The study aimed to define the accuracy of intraoperative frozen section (FS) for the detection of metastases in sentinel lymph node biopsy (SLNB) and describe the pattern of lymph node (LN) spread and relation to molecular classifiers in patients with high-grade endometrial cancer (EC). METHODS: We performed a secondary outcome of clinicopathologic data from the Sentinel Lymph Node Biopsy versus Lymphadenectomy for Intermediate- and High-Grade Endometrial Cancer Staging (SENTOR) prospective cohort study evaluating SLNB in patients with clinical stage I high-grade EC (ClinicalTrials.gov ID: NCT01886066). The primary outcome was the sensitivity of FS of the sentinel lymph node (SLN) specimen, compared to a standardized ultrastaging protocol. Secondary outcomes included the pattern and characteristics of LN spread. RESULTS: There were 126 patients with high-grade EC with a median age of 66 years (range:44-86) and a median Body Mass Index (BMI) of 26.9 kg/m2 (range:17.6-49.3). FS was performed on surgical specimens from 212 hemipelves; SLNs were identified in 202 specimens (95.7%) and fatty tissue alone was identified in 10 specimens (4.7%). Of the 202 hemipelves in which SLNs were identified, 24 were positive for metastatic disease on final pathology. Initial FS correctly identified only 12, yielding a sensitivity of 50% (12/24, 95% CI 29.6-70.4) and a negative predictive value of 94% (178/190, 95% CI 89-96.5). A total of 24 patients (19%) had LN metastases: 16 (13%) had isolated pelvic metastases, 7 (6%) had both pelvic and para-aortic metastases and 1 (0.8%) had an isolated para-aortic metastasis. CONCLUSIONS: Intraoperative FS of SLNs in high-grade EC patients has poor sensitivity. Since isolated para-aortic metastases are rare, para-aortic lymphadenectomy may be omitted in patients in which SLNs were successfully mapped to the pelvis.
Subject(s)
Endometrial Neoplasms , Sentinel Lymph Node , Female , Humans , Adult , Middle Aged , Aged , Aged, 80 and over , Frozen Sections , Prospective Studies , Sentinel Lymph Node Biopsy/methods , Lymph Nodes/surgery , Lymph Nodes/pathology , Lymph Node Excision/methods , Sentinel Lymph Node/surgery , Sentinel Lymph Node/pathology , Endometrial Neoplasms/surgery , Endometrial Neoplasms/pathology , Neoplasm StagingABSTRACT
OBJECTIVE: Most fear of cancer recurrence (FCR) interventions have small effects, and few target FCR. This randomized controlled trial (RCT) with breast and gynecological cancer survivors evaluated the efficacy of a cognitive-existential fear of recurrence therapy (FORT) compared to an attention placebo control group (living well with cancer [LWWC]) on FCR. METHOD: One hundred and sixty-four women with clinical levels of FCR and cancer distress were randomly assigned to 6-weekly, 120 min FORT (n = 80) or LWWC (n = 84) group sessions. They completed questionnaires at baseline (T1), posttreatment (T2; primary endpoint), 3 (T3), and 6 months (T4) posttreatment. Generalized linear models were used to compare group differences in the fear of cancer recurrence inventory (FCRI) total score and secondary outcomes. RESULTS: FORT participants experienced greater reductions from T1 to T2 on FCRI total with a between-group difference of -9.48 points (p = .0393), resulting in a medium effect of -0.530, with a maintained effect at T3 (p = .0330) but not at T4. For the secondary outcomes, improvements were in favor of FORT, including FCRI triggers (p = .0208), FCRI coping (p = .0351), cognitive avoidance (p = .0155), need for reassurance from physicians (p = .0117), and quality of life (mental health; p = .0147). CONCLUSIONS: This RCT demonstrated that FORT, compared to an attention placebo control group, resulted in a greater reduction in FCR posttreatment and at 3 months posttreatment in women with breast and gynecological cancer, indicating its potential as a new treatment strategy. We recommend a booster session to sustain gains. (PsycInfo Database Record (c) 2023 APA, all rights reserved).
Subject(s)
Cancer Survivors , Neoplasms , Female , Humans , Adaptation, Psychological , Databases, Factual , Fear , RecurrenceABSTRACT
OBJECTIVE: Investigating for mismatch repair protein deficiency (MMRd), microsatellite instability (MSI), and Lynch syndrome (LS) is widely accepted in endometrial cancer, but knowledge is limited on its value in epithelial ovarian cancer (EOC). The primary objective was to evaluate the prevalence of mismatch repair protein deficiency (MMRd), microsatellite instability (MSI)-high, and Lynch syndrome (LS) in epithelial ovarian cancer (EOC), as well as the diagnostic accuracy of LS screening tests. The secondary objective was to determine the prevalence of MMRd, MSI-high, and LS in synchronous ovarian endometrial cancer and in histological subtypes. METHODS: We systematically searched the MEDLINE, Epub Ahead of Print, MEDLINE In-Process and Other Non-Indexed Citations, Cochrane Central Register of Controlled Trials, and Embase databases. We included studies analysing MMR, MSI, and/or LS by sequencing. RESULTS: A total of 55 studies were included. The prevalence of MMRd, MSI-high, and LS in EOC was 6% (95% confidence interval (CI) 5-8%), 13% (95% CI 12-15%), and 2% (95% CI 1-3%) respectively. Hypermethylation was present in 76% of patients with MLH1 deficiency (95% CI 64-84%). The MMRd prevalence was highest in endometrioid (12%) followed by non-serous non-mucinous (9%) and lowest in serous (1%) histological subtypes. MSI-high prevalence was highest in endometrioid (12%) and non-serous non-mucinous (12%) and lowest in serous (9%) histological subtypes. Synchronous and endometrioid EOC had the highest prevalence of LS pathogenic variants at 7% and 3% respectively, with serous having lowest prevalence (1%). Synchronous ovarian and endometrial cancers had highest rates of MMRd (28%) and MSI-high (28%). Sensitivity was highest for IHC (91.1%) and IHC with MSI (92.8%), while specificity was highest for IHC with methylation (92.3%). CONCLUSION: MMRd and germline LS testing should be considered for non-serous non-mucinous EOC, particularly for endometrioid. PRECIS: The rates of mismatch repair deficiency, microsatellite instability high, and mismatch repair germline mutations are highest in endometrioid subtype and non-serous non-mucinous ovarian cancer. The rates are lowest in serous histologic subtype.
Subject(s)
Carcinoma, Endometrioid , Colorectal Neoplasms, Hereditary Nonpolyposis , Endometrial Neoplasms , Ovarian Neoplasms , Protein Deficiency , Humans , Female , Colorectal Neoplasms, Hereditary Nonpolyposis/genetics , Carcinoma, Ovarian Epithelial , Microsatellite Instability , Ovarian Neoplasms/pathology , Carcinoma, Endometrioid/pathology , Endometrial Neoplasms/pathology , DNA Mismatch Repair , MutL Protein Homolog 1/geneticsABSTRACT
Reflex genetic testing of tumor tissue is being completed to direct cancer treatment; however, the patient impact of this genetic testing model is unknown. This survey study evaluates psychological outcomes following tumor and germline genetic testing in individuals with a new diagnosis of high-grade serous ovarian cancer (HGSOC). Individuals were recruited from two hospitals in Toronto, Canada. Participants completed surveys 1 week after receiving tumor results and 1 week after receiving germline results (which included genetic counseling). Outcomes included cancer-related distress (Impact of Events Scale: IES), genetic testing-related distress (Multidimensional Impact of Cancer Risk Assessment: MICRA), and patient satisfaction. Paired t-tests were used to evaluate differences in outcomes following each genetic test result; Cohen's d was used to evaluate effect size. Subgroup analyses were undertaken according to age at diagnosis (<60 years vs. ≥60 years) and test results (any positive vs. both negative). McNemar's test assessed differences in satisfaction. Fifty-two individuals were included in the analyses. Mean IES scores were similar following disclosure of tumor and germline results (27.39 vs. 26.14; p = 0.481; d = 0.101). Compared to following tumor result disclosure, MICRA scores were significantly lower following receipt of germline results with genetic counseling (27.23 vs. 22.69; p = 0.007; d = 0.435). Decreases in MICRA scores from tumor to germline result disclosure were greater for those diagnosed <60 years or those who received only negative test results. Most individuals were satisfied/highly satisfied following tumor (85.7%) and germline (89.8%) results disclosure (p = 0.774). Reflex tumor, and subsequent germline, genetic testing is a new model of care for cancer patients. In our cohort, genetic testing-related distress decreased significantly following receipt of germline results with genetic counseling, especially for individuals diagnosed under 60 years and those receiving only negative results. Most individuals were satisfied with this model of care.