Efficacy of niraparib by time of surgery and postoperative residual disease status: A post hoc analysis of patients in the PRIMA/ENGOT-OV26/GOG-3012 study.

OBJECTIVE: To evaluate the association between surgical timing and postoperative residual disease status on the efficacy of niraparib first-line maintenance therapy in patients with newly diagnosed advanced ovarian cancer at high risk of recurrence. METHODS: Post hoc analysis of the phase 3 PRIMA/ENGOT-OV26/GOG-3012 (NCT02655016) study of niraparib in patients with newly diagnosed primary advanced ovarian, primary peritoneal, or fallopian tube cancer with a complete/partial response to first-line platinum-based chemotherapy. Progression-free survival (PFS) was assessed by surgical status (primary debulking surgery [PDS] vs neoadjuvant chemotherapy/interval debulking surgery [NACT/IDS]) and postoperative residual disease status (no visible residual disease [NVRD] vs visible residual disease [VRD]) in the intent-to-treat population. RESULTS: In PRIMA (N = 733), 236 (32.2%) patients underwent PDS, and 481 (65.6%) received NACT/IDS before enrollment. Median PFS (niraparib vs placebo) and hazard ratios (95% CI) for progression were similar in PDS (13.7 vs 8.2 months; HR, 0.67 [0.47-0.96]) and NACT/IDS (14.2 vs 8.2 months; HR, 0.57 [0.44-0.73]) subgroups. In patients who received NACT/IDS and had NVRD (n = 304), the hazard ratio (95% CI) for progression was 0.65 (0.46-0.91). In patients with VRD following PDS (n = 183) or NACT/IDS (n = 149), the hazard ratios (95% CI) for progression were 0.58 (0.39-0.86) and 0.41 (0.27-0.62), respectively. PFS was not evaluable for patients with PDS and NVRD because of sample size (n = 37). CONCLUSIONS: In this post hoc analysis, niraparib efficacy was similar across PDS and NACT/IDS subgroups. Patients who had NACT/IDS and VRD had the highest reduction in the risk of progression with niraparib maintenance.

Adjuvant chemotherapy and radiation for patients with high-risk stage I endometrial cancer treated with curative intent surgery: impact on recurrence and survival.

BACKGROUND: Survival benefits of post-operative systemic and radiation therapy in high-risk stage I endometrial cancer are uncertain. OBJECTIVE: To compare recurrence patterns and survival outcomes of post-surgical treatment in patients with high-risk stage I endometrial cancer and to determine whether adjuvant therapy significantly improves outcomes. METHODS: High-risk stage I endometrial cancer was defined as either stage IB grade 3 endometrioid histology or myoinvasive non-endometrioid histology. Consecutive patients diagnosed between January 2000 and December 2010 in eight cancer centers were included. Patients, disease, and treatment characteristics were summarized by descriptive statistics. Overall survival, disease-specific survival, and relapse-free survival were examined using Cox's proportional hazards regression and log-rank test. Survival curves were estimated using the Kaplan-Meier method. RESULTS: Of 2317 patients with stage I endometrial cancer, 414 patients had high-risk disease. Use of chemotherapy did not improve overall survival (relative risk (RR) 0.70, 95% CI 0.46 to 1.14, p=0.13) or disease-specific survival (RR 1.06, 95% CI 0.61 to 1.85, p=0.84). Significant improvement in recurrence-free survival was observed in patients who received chemotherapy (RR 0.61, 95% CI 0.39 to 0.95, p=0.03). Use of radiation therapy did not improve overall survival, recurrence-free survival, or disease-specific survival. Patients who received four cycles or fewer of chemotherapy versus five to six cycles had similar overall survival, disease-specific survival, and recurrence-free survival. CONCLUSIONS: Post-operative chemotherapy or radiation in stage I high-risk endometrial cancer is not associated with improved cancer-specific or overall survival. More than four cycles of chemotherapy did not improve survival compared with four cycles or fewer.

Modelling retail inventory pricing policies under service level and promotional efforts during COVID-19.

Most supply chain and production systems faced multiple manufacturing and delivery challenges during COVID-19 and transformed their supply chain for improved customer service. These challenges are mostly related to stocking and managing the inventory flow throughout the supply chain (from manufacturer to end consumer). Due to the COVID-19 travel and movement restrictions, inventory reorganisation is necessary for fulfilling consumer demand with adequate service facilities. The safety and serviceability of inventory consumption is the primary concern of many retail grocery stores and consumers. Maintaining the supply of groceries items during and post COVID-19 time without disruption is a real operational and policy challenge. Therefore, this research tries to solve an inventory pricing mechanism and retailer's profit under the optimal service level and retailers' promotional efforts. The proposed optimisation model is validated in the grocery retail sector. The grocery retail market situation is modelled when the demand for the grocery product (which may be essential items) and selling price depending on the investment in item promotional effort and consumer serviceability. The retail grocery store's investment in the product promotional efforts, such as awareness of the item availability and no-contact delivery which, may attract consumers. Therefore, the proposed inventory consumption is modelled with an optimisation problem to maximise the store profit with the optimal investment in promotional activities and service facilities to the consumers and maintain an optimal replenishment cycle. The optimisation model is tested with three different cases (no investment in promotional efforts, no investment in service facility, and investment in both) of investment to maximise the retailer's profit and stock availability. The optimality results depicted that investment in promotional efforts and service facility givens higher profit to the retailer. The proposed optimisation model's policy implications would help grocery retail store managers to develop operational strategies for maximising profit with the optimal service level and promotional efforts.

Single or two drug combination therapy as initial treatment for low risk, gestational trophoblastic neoplasia. A Canadian analysis.

INTRODUCTION: Low risk gestational trophoblastic neoplasia, WHO prognostic score of 0 to 6, is highly curable. There is no consensus on the optimal chemotherapy. Common regimens are q2wk actinomycin-D (ACT-D), weekly intramuscular methotrexate (MTX) or multi-day MTX. Combination MTX/ACT-D is rarely used. METHODS: A four centre, retrospective cohort study was carried out comparing commonly used regimens: weekly MTX, q2weekly ACT-D and q2 weekly MTX and ACT-D. RESULTS: 412 patients - 196 MTX/ACT-D, 107 MTX, 109 ACT-D - were treated between October 1994 and January 2019. Initial regimen failure (secondary to resistance or toxicity) occurred in 37% (MTX), 21% (ACT-D) and 5% (MTX/ACT-D). Relapse after completion of primary therapy (initial plus switch to another therapy if needed) was rare (0-5%). All eventually were cured. Mean number of cycles required to achieve remission were 10.1 (MTX), 7 (ACT-D) and 5.6 (MTX/ACT-D) with corresponding mean treatment durations of 3.12, 2.9 and 2.26 months. Dosage reductions occurred in 3% (MTX), 0% (ACT-D) and 29% (MTX/ACT-D). Higher failure rates occurred with WHO prognostic scores of 5 to 6 and HCG levels ≥10,000. SUMMARY: Initial regimen failure ie the need to switch to an alternative treatment was more common with MTX. ACT-D and MTX/ACT-D were similar within prognostic score 0-4 or HCG < 10,000. ACT-D then appears the better initial choice with its superior convenience. Above these levels primary failure rates are less with MTX/ACT-D, making it a better choice.

Immediate-term cognitive impairment following intravenous (IV) chemotherapy: a prospective pre-post design study.

BACKGROUND: Cognitive impairment is commonly reported in patients receiving chemotherapy, but the acuity of onset is not known. This study utilized the psychomotor vigilance test (PVT) and trail-making test B (TMT-B) to assess cognitive impairment immediately post-chemotherapy. METHODS: Patients aged 18-80 years receiving first-line intravenous chemotherapy for any stage of breast or colorectal cancer were eligible. Patient symptoms, peripheral neuropathy and Stanford Sleepiness Scale were assessed. A five-minute PVT and TMT-B were completed on a tablet computer pre-chemotherapy and immediately post-chemotherapy. Using a mixed linear regression model, changes in reciprocal transformed PVT reaction time (mean 1/RT) were assessed. A priori, an increase in median PVT reaction times by > 20 ms (approximating PVT changes with blood alcohol concentrations of 0.04-0.05 g%) was considered clinically relevant. RESULTS: One hundred forty-two cancer patients (73 breast, 69 colorectal, median age 55.5 years) were tested. Post-chemotherapy, mean 1/RT values were significantly slowed compared to pre-chemotherapy baseline (p = 0.01). This corresponded to a median PVT reaction time slowed by an average of 12.4 ms. Changes in PVT reaction times were not correlated with age, sex, cancer type, treatment setting, or use of supportive medications. Median post-chemotherapy PVT reaction time slowed by an average of 22.5 ms in breast cancer patients and by 1.6 ms in colorectal cancer patients. Post-chemotherapy median PVT times slowed by > 20 ms in 57 patients (40.1%). Exploratory analyses found no statistically significant association between the primary outcome and self-reported anxiety, fatigue or depression. TMT-B completion speed improved significantly post-chemotherapy (p = 0.03), likely due to test-retest phenomenon. CONCLUSIONS: PVT reaction time slowed significantly immediately post-chemotherapy compared to a pre-chemotherapy baseline, and levels of impairment similar to effects of alcohol consumption in other studies was seen in 40% of patients. Further studies assessing functional impact of cognitive impairment on patients immediately after chemotherapy are warranted.

Bevacizumab in Metastatic, Recurrent, or Persistent Cervical Cancer: The BC Cancer Experience.

OBJECTIVE: We conducted a population-based analysis of patient outcomes following treatment with bevacizumab and platinum-based chemotherapy for metastatic, recurrent, or persistent cervical carcinoma. METHODS: Eligible cases were identified using the BC Cancer provincial pharmacy database. Cases with small cell component or inadequate clinical follow-up were excluded. Overall response to therapy, progression-free survival (PFS), overall survival (OS), and toxicities were documented. RESULTS: Twenty-seven eligible cases were included with a median follow-up of 12.1 months. The median age at recurrence/metastatic diagnosis was 49 years (range, 27-83 years). Twenty-three of 27 women received carboplatin, paclitaxel, and bevacizumab as first-line treatment, and 4 of 27 as second-line treatment. The median number of cycles of bevacizumab delivered was 5.5 (range, 1-21). The overall response rate was 44% (12/27), with 11% (3/27) complete response and 33% (9/27) partial response. Median PFS and OS for the entire cohort were 5.3 and 12.1 months, respectively. In first-line therapy, the median PFS and OS were 6.3 and 17.5 months, respectively. Common toxicities included anemia (grade 1/2) 73% (19/27), and the following grade 2 or greater: neutropenia 38% (n = 10) with 1 occurrence of febrile neutropenia, hypertension 30% (n = 8), and thrombosis 22% (n = 6). The fistula rate was 3.7% (n = 1). CONCLUSIONS: In this population-based analysis, the combination of bevacizumab and platinum-based chemotherapy as first-line therapy for metastatic, recurrent, or persistent cervical carcinoma was safely delivered and had outcomes comparable to results from the GOG 240 phase III trial.

Survival Benefit of Adjuvant Radiotherapy: An Analysis of Low-Stage Invasive Ovarian Mucinous Carcinomas.

OBJECTIVE: Our aim was to evaluate the population-based outcomes of stages I and II invasive ovarian mucinous carcinomas (MCs) treated with adjuvant platinum-based chemotherapy and abdominopelvic radiotherapy (XRT). METHODS: International Federation of Gynecology and Obstetrics stage I/II MC cases referred to the British Columbia Cancer Agency between 1984 and 2014 were reviewed. Chemotherapy (minimum of 3 cycles) and XRT were the institutional policy for stages IA/B (grade 2/3) and IC/II (any grade). Physician patterns of practice determined XRT use in eligible patients, allowing for the comparison of outcomes based on receipt of XRT treatment on disease-free survival (DFS) and overall survival (OS). RESULTS: We identified 129 patients. Univariate analyses on substages IA, IC no rupture, IC with intraoperative rupture, and IC with preoperative rupture demonstrated 10-year DFS rates of 67%, 67%, 67%, and 27% (P = 0.004), respectively, and OS rates of 72%, 72%, 67%, and 38% (P = 0.01), respectively. For all patients, adjuvant XRT demonstrated improved 10-year DFS (78% vs 36%, P = 0.05) and OS (83% vs 36%, P = 0.02). Subgroup analysis did not detect a benefit of adjuvant therapy for stage IA grade 1/2. Multivariate analysis confirmed the benefit of XRT on DFS (hazard ratio, 0.14; 95% confidence interval, 0.02-0.98; P = 0.047) and a trend to improved OS (hazard ratio, 0.12; 95% confidence interval, 0.009-1.64; P = 0.11), whereas decision tree analysis demonstrated a reduced rate of relapse (33% vs 77%) and death (20% vs 46%) with the use of XRT, exclusive of patients with preoperative rupture. CONCLUSIONS: This population-based retrospective study is the first to demonstrate that the use of adjuvant abdominopelvic XRT after chemotherapy can improve survival in patients diagnosed as having stage I/II MC. Patients with stage IA grade 1 and grade 2 MC can have adjuvant therapy omitted.

Adjuvant chemotherapy use and outcomes of patients with high-risk versus low-risk stage II colon cancer.

BACKGROUND: Adjuvant chemotherapy (AC) is frequently considered in patients with stage II colon cancer who are considered to be at high risk. However, to the authors' knowledge, the survival benefits associated with AC in these patients remain largely unproven. In the current study, the authors sought to examine the use of AC in patients with AJCC stage II colon cancer and to compare the impact of AC on outcomes in patients with high-risk versus low-risk disease in a population-based setting. METHODS: Patients with stage II colon cancer who were evaluated at 1 of 5 regional cancer centers in British Columbia from 1999 to 2008 were analyzed. Kaplan-Meier and Cox regression methods were used to correlate high-risk versus low-risk status and receipt of AC with recurrence-free survival (RFS), disease-specific survival (DSS), and overall survival (OS). RESULTS: A total of 1697 patients were identified: 1286 (76%) with high-risk and 411 (24%) with low-risk disease, among whom 373 (29%) and 51 (12%),respectively, received AC. Individuals with high-risk disease treated with AC were younger (median age, 62 years vs 72 years; P<.001) and had better Eastern Cooperative Oncology Group performance status (0/1: 47% vs 33%; P = .001). For high-risk patients, AC was associated with improved OS (hazard ratio [HR], 0.65; 95% confidence interval [95% CI], 0.50-0.83 [P = .001]). However, no significant benefits with regard to RFS or DSS were observed. Subgroup analyses revealed that AC in patients with T4 disease was associated with significantly improved RFS (HR, 0.63; 95% CI, 0.42-0.95 [P = .03]), DSS (HR, 0.59; 95% CI, 0.37-0.93 [P = .02]), and OS (HR, 0.50; 95% CI, 0.33-0.77 [P = .002]). For patients with low-risk disease, AC was associated with inferior RFS (HR, 2.18; 95% CI, 1.00-4.79 [P = .05]) and DSS (HR, 3.01; 95% CI, 1.10-8.23 [P = .03]). CONCLUSIONS: In this population-based analysis, AC was associated with an OS advantage in high-risk patients, most likely due to patient selection. RFS, DSS, and OS benefits were mainly observed in patients with T4 disease, suggesting a limited role for AC in patients deemed to be high risk by non-T4 features.

Early-stage endometrioid ovarian carcinoma: population-based outcomes in British Columbia.

OBJECTIVE: Specific outcomes for early-stage ovarian endometrioid carcinoma (OEC) have not been well characterized. In addition, the benefit of any type of postsurgical therapy remains unclear. Our aims were to delineate (1) potential prognostic factors and (2) the impact of adjuvant treatment on survival in such patients. METHODS: Women with FIGO stages I and II OEC referred to one of the centers of the British Columbia Cancer Agency from 1984 to 2008 were included in a retrospectively abstracted computerized database. Irradiation (abdominal-pelvic) in addition to chemotherapy (3 cycles of platinum combination) was to be given for stage IA/B, grade 2/3; stage IC, any grade; and stage II, any grade, except from 1989 to 1994 when irradiation was dropped from the paradigm for all patients. Univariate analysis and a multivariate analysis, using a decision tree analysis, were carried out of disease-free survival (DFS). RESULTS: One hundred seventy-two patients were identified. Twelve percent were grade 3; 55%, 85%, and 89% of stages IA/B, IC, and II received postoperative adjuvant treatment. Five-year DFS was 95%, 84%, and 74% for stages IA/B and IC based upon rupture alone, IC other (cytologic positivity and/or surface involvement), and II, respectively. No benefit in DFS was accrued in stage IA/B from adjuvant treatment. Decision tree analysis defined 2 poor prognostic groups: those 55 years or older with stage IC based upon positive washings or surface involvement and any patient with stage II disease; in these, an apparent DFS benefit from irradiation was seen (relative risk (RR), 1.77; 95% confidence interval (CI), 0.74-4.24). CONCLUSION: Omission of adjuvant treatment can be considered in most early-stage OECs.

Prevalence of Refractive Errors Among School-Going Children in Urban Versus Rural Areas.

BACKGROUND: The most common cause of visual impairment globally is refractive error. The prevalence of refractive error has been on the rise since the coronavirus disease 2019 (COVID-19) pandemic, possibly due to increased indoor activities and excessive use of electronic devices. Impaired vision during childhood can affect the overall development of a child adversely, and it often remains unreported due to the inability of children to complain about impaired vision. AIM: The main aim of this study was to assess the prevalence of refractive errors among school-going children in urban and rural areas. METHODS: This was a cross-sectional study that included 2024 children going to schools situated in urban and rural areas. All study subjects were tested for visual acuity for distance using Snellen's chart with and without glasses after taking a brief history regarding visual complaints. All children who had visual acuity less than 6/6 on Snellen's chart underwent refraction check-ups. Retinoscopy was performed in all study subjects. Analysis of the collected data was done using SPSS for Windows, Version 16.0 (Released 2007; SPSS Inc., Chicago, United States). The analysis of numerical data was done by an unpaired t-test, and the analysis of categorical data was done by a chi-square test. A P-value of less than 0.05 was considered statistically significant. RESULTS: The mean age of the children was 10.92 ± 2.73 years, with 10.93 ± 2.73 years in urban and 10.91 ± 2.73 years in rural groups. Females (n=1031; 50.93%) were more in number than males (n=993; 49.06%). The overall prevalence of refractive error was 17.43%. The prevalence was higher in urban areas (22.14%) than in rural areas (12.71%). The age group below 10 years comprised 886 (43.77%) study subjects, and 218 (62.1%) children with refractive error had no ocular complaints. The most common refractive error found in this study was simple myopia in both groups, and the least common was astigmatism. The prevalence of uncorrected refractive error was higher in urban school-going children as compared to rural children. CONCLUSION: The prevalence of refractive error was 17.43% in our study. The prevalence was high in urban areas (22.67%) as compared to rural areas (13.12%). Regular screening of school-going children for refractive errors should be done. Also, awareness regarding the use of electronic gadgets must be raised, especially among urban children.

Effects of head posture on intraocular pressure and heart rate of human beings.

BACKGROUND: The study analyzed the association of head posture on intraocular pressure (IOP). The study aimed to evaluate and measure the changes in IOP and heart rate (HR) of human beings on head-down posture. The study included 105 patients at the department of ophthalmology of a tertiary care center in India. SUBJECTS AND METHODS: Patients underwent applanation tonometry and HR variability (HRV) analysis before and after 20 min of head-down posture (approximately 20°). The IOP and HRV were measured. STATISTICAL ANALYSIS USED: The statistical methods of Paired t-test and linear regression analysis were applied. P < 0.05 was defined as statistically significant. RESULTS: After 20 min of the 20° head-down position, an increase in IOP was significant from 15.0 ± 2.0 mmHg to 18.0 ± 2.3 mmHg (P < 0.001). A decrease in HR was also significant from 78 ± 10.48 bpm to 72 ± 10.52 bpm after the head-down position for 20 min (P < 0.05). CONCLUSIONS: These outcomes presented the first evidence of the activation of the parasympathetic nervous system in the head-down position which might cause decreased HR and the collapse of Schlemm's canal lumen, which in turn leads to the increased IOP.

Impact of the adjuvant management and risk factors on survival in FIGO stage 3 endometrial cancer patients.

Objective: Patients with FIGO stage III endometrial cancer routinely receive adjuvant therapy. The purpose of this study was to evaluate overall survival (OS) and disease-free survival (DFS) in patients with stage IIIA to IIIC2 patients by treatment modality received and risk factors. Materials/methods: Patients with stage III endometrial cancer treated from 2000-2010 were identified in the provincial cancer registry. Clinicopathologic characteristics, adjuvant treatments and outcomes were compared using descriptive and multivariable analyses. Results: 261 patients had stage 3 endometrial cancer, 132 with stage IIIA, 9 with IIIB, 85 with IIIC1 and 35 with IIIC2. 39 had FIGO grade 1 disease; 73, grade 2; 147, grade 3. 160 had endometrioid and 35 had serous carcinoma. 161 patients received sequential adjuvant chemotherapy (CT) and radiotherapy (RT); 33 received RT only; 32 received CT only; 35 received neither. 5-year (5Y) DFS and OS were similar among stage IIIA (DFS 46.7%, OS 58.5%), IIIB (DFS 50.8%, OS 58.5%), IIIC1 (DFS 44%, OS 49.9%) and IIIC2 (DFS 42%, OS 41.6%). Use of adjuvant RT was associated with improved median DFS (53.7 vs 14.7m, p<0.00001) and OS (61.9 vs 25.7m, p<0.00001) compared to no RT. Likewise, use of adjuvant CT was also associated with improved DFS (54.8 vs 16.5m, p<0.00001) and OS (62.9 vs 26.5m, p<0.00001) compared to no CT. Those who received both chemotherapy and radiotherapy had better outcomes with 5-year DFS (58.3%) and OS (65.2%), compared with those who received monotherapy. On multivariate analysis, grade 3 disease, deep myometrial invasion >50%, and no adjuvant RT or CT were identified as adversely impacting DFS and OS. Conclusion: In stage III endometrial cancer patients, use of both chemotherapy and radiation therapy was associated with improved DFS and OS and therefore should be recommended in all eligible patients after resection.

Building risk mitigation strategies for circularity adoption in Indian textile supply chains.

Textile industries are among the most polluting and demand urgent management measures to mitigate their negative environmental impact. Thus, it is imperative to incorporate the textile industry into the circular economy and to foster sustainable practices. This study aims to establish a comprehensive, compliant decision framework to analyse risk mitigation strategies for circular supply chain (CSC) adoption in India's textile industries. The Situations Actors Processes and Learnings Actions Performances (SAP-LAP) technique analyses the problem. However, interpreting the interacting associations between the SAP-LAP model-based variables is somewhat lacking in this procedure, which might skew the decision-making process. As a result, in this study, the SAP-LAP method is accompanied by a novel ranking technique, namely, the Interpretive Ranking Process (IRP), which reduces decision-making issues in the SAP-LAP method and aids in evaluating the model by determining the ranks of variables; furthermore, the study also offers causal relationships among the various risks and risk factors and various identified risk-mitigation actions by constructing Bayesian Networks (BN) based on conditional probabilities. The study's originality represents the findings using an instinctive and interpretative choice approach to address significant concerns in risk perception and mitigation techniques for CSC adoption in the Indian textile industries. The suggested SAP-LAP and the IRP-based model would assist firms in addressing risk mitigation techniques for CSC adoption concerns by providing a hierarchy of the various risks and mitigation strategies to cope with. The simultaneously proposed BN model will help visualise the conditional dependency of risks and factors with proposed mitigating actions.

Incidence and association of ocular manifestations with the disease severity in COVID-19 patients of northern region of India.

PURPOSE: Our study aims to find the incidence of ocular manifestations and to investigate the relation of ocular manifestations with the disease severity among coronavirus disease 2019 (COVID-19) patients. MATERIAL AND METHODS: Our study is a cross-sectional study done between May 15, 2020, and April 15, 2021, at Hind Institute of Medical Sciences, Lucknow, India. All COVID-19 patients who got admitted to our center between May 15, 2020, and April 15, 2021, were included in our study. We included 261 patients in our study. Diagnosis of COVID-19 was made by testing the nasal and pharyngeal swabs by (reverse transcriptase-polymerase chain reaction [RT-PCR]). An RT-PCR test positive was the criteria for admission in the COVID ward. Statistical analyses were performed using the Mann-Whitney U-test, Chi-square test, and Kolmogorov-Smirnov test. P < 0.01 was considered statistically significant. RESULTS: We included 261 patients in our study. Out of 261 patients, ocular manifestations were found in 43 (16.4%) patients. The patients with ocular manifestations had higher neutrophil counts, erythrocyte sedimentation rate (ESR), procalcitonin (PCT), C-reactive protein (CRP), and D-dimer values (P < 0.001). Patients with ocular manifestations were relatively more symptomatic concerning fever and myalgia. CONCLUSION: The incidence of ocular manifestations in COVID-19 patients was 16.4%. Ocular manifestation was significantly associated with raised neutrophil counts, CRP, ESR, PCT, and D-dimer values. Ocular manifestation was also significantly associated with higher body temperature and higher mean age. The findings of the study are suggestive of more severe disease in patients of COVID-19 with ocular manifestations.

Chemotherapy is of Value in Second Line and Beyond, Relapsed High-grade, Serous Epithelial Ovarian Cancer: An Analysis of Outcomes Obtained With Oral Etoposide.

BACKGROUND: Epithelial ovarian cancer is chemotherapy responsive, and multiple lines of chemotherapy are often given. However, there are few data with regard to its effectiveness in later lines. Our aim was to assess its benefit in the high-grade, serous subtype relative to the line of therapy, using etoposide as the example. METHODS: Women treated with oral etoposide at the British Columbia Cancer Agency upon recurrence/progression in the years 2000 to 2010 were reviewed. Kaplan-Meier and Cox regression methods were used to correlate line of therapy with overall survival, progression-free survival, and interval between etoposide initiation and next progression or death (EPFS). RESULTS: A total of 219 women, median age 61, received etoposide as second (17%), third (30%), fourth (26%), fifth (17%), and sixth to eighth (11%) lines of therapy. The median number of cycles was 2 to 4. Patients who received etoposide as fourth-line to eighth-line treatment had a significantly longer median overall survival and initial progression-free survival (from diagnosis to first relapse) when compared with those who received it as second-line to third-line treatment (47.8 vs. 25.8 mo, P<0.0001; and 16.1 vs. 12.1 mo, P<0.0001, respectively); that is, a selected population of survivors received it later in the course of their disease. On univariate analysis, there was no significant difference in median EPFS (range, 2 to 2.9 mo) on the basis of line of therapy. On multivariate analysis, the hazard ratios improved through the third, fourth, and fifth lines (hazard ratios: 0.82, 0.77, and 0.34, respectively), and was statistically significant in the fifth line. The a priori-defined endpoint of clinical benefit was the "percentage not progressing at 3 months," and this was achieved in 32% to 48%. CONCLUSIONS: In this retrospective study, a similar degree of benefit from etoposide, as defined by the percentage remaining progression free at 3 months, was seen in all lines of therapy.

Impact of Duration of Neoadjuvant Radiation on Rectal Cancer Survival: A Real World Multi-center Retrospective Cohort Study.

BACKGROUND: The utility of neoadjuvant radiotherapy (nRT) for the treatment of stage II and III rectal cancer is well-established. However, the optimal duration of nRT in this setting remains controversial. Using a population-based cohort of patients with stage II and III rectal cancer (RC) treated with curative intent, our aims were to (1) examine the patterns of nRT use and (2) explore the relationship between different nRT schedules and survival in the real-world setting. METHODS: This is a multi-center retrospective cohort study based on population-based data from 5 regional comprehensive cancer centers in British Columbia, Canada. We analyzed patients diagnosed with clinical stage II or III RC from 2006 to 2010 and treated with either short-course (SC) or long-course (LC) nRT prior to curative intent surgery. Logistic regression models were constructed to determine the factors associated with the course of nRT delivered to patients. Kaplan-Meier methods and Cox regression that accounted for known prognostic factors were used to evaluate the relationship between nRT schedule and overall (OS), disease-free (DFS), local recurrence-free (LRFS), and distant recurrence-free survival (DRFS). RESULTS: We identified 427 patients: the median age was 65 years (range, 31 to 94 years), 67% were men, 87% had T3 or T4 tumors, and 74% had N1 or N2 disease. Among them, 241 (56%) received SC and 186 (44%) received LC. Adjusting for confounders, patients with N1 or N2 disease were more likely to undergo LC (odds ratio [OR], 5.08; 95% confidence interval [CI], 2.51-11.22; P < .0001 and OR, 8.35; 95% CI, 3.35-22.39; P < .0001, respectively), whereas older age patients were less likely to receive LC (OR, 0.95; 95% CI, 0.94-0.98; P < .0001). In Kaplan-Meier analysis, there were no significant differences observed in OS, DFS, LRFS, and DRFS between SC and LC. Likewise, multivariate analyses demonstrated that OS (hazard ratio [HR], 0.91; 95% CI, 0.61-1.37; P = .66), DFS (HR, 1.06; 95% CI, 0.68-1.64; P = .80), LRFS (HR, 0.79; 95% CI, 0.39-1.57; P = .50) and DRFS (HR, 0.99; 95% CI, 0.60-1.61; P = .95) were similar regardless of nRT schedules. Additional baseline clinical and tumor characteristics did not influence outcomes (all P > .05). CONCLUSION: Appropriate preoperative selection of SC versus LC nRT for locally advanced RC based on patient and tumor characteristics was not associated with differences in survival outcomes in the real-world setting.

Compliance with adjuvant capecitabine in patients with stage II and III colon cancer: comparison of administrative versus medical record data.

We aimed to examine the frequency of treatment delays as well as the reasons and appropriateness of such delays in early stage colon cancer patients receiving adjuvant capecitabine by comparing data from pharmacy dispensing versus medical records. Patients diagnosed with stage II or III colon cancer from 2008 to 2012 and who received at least two cycle of adjuvant capecitabine were reviewed for treatment delays. Data from pharmacy dispensing and patient medical records were compared. Multivariate regression models were constructed to identify predictors of treatment delays. A total of 697 patients were analyzed: median age was 70 years (IQR 30-89), 394 (57%) were men, 598 (86%) reported Eastern Cooperative Oncology Group 0/1, and 191 (27%) had stage II disease. In this study cohort, 396 (57%) patients experienced at least 1 treatment delay during their adjuvant treatment. Upon medical record review, half of treatment delays identified using pharmacy administrative data were actually attributable to side effects, of which over 90% were considered clinically appropriate for patients to withhold rather than to continue the drug. The most prevalent side effects were hand-foot syndrome and diarrhea which occurred in 176 (44%) and 67 (17%) patients, respectively. Multivariate analysis revealed a statistically significant association between stage and inappropriate treatment delays whereby patients with stage II disease were more likely to experience drug noncompliance (OR 1.79, 95% CI: 1.27-2.53, P < 0.001) than those with stage III disease. Compliance with adjuvant capecitabine was reasonable. Adherence ascertained from pharmacy administrative data differs significantly from that obtained from medical records.

PROSPECT Eligibility and Clinical Outcomes: Results From the Pan-Canadian Rectal Cancer Consortium.

BACKGROUND: The PROSPECT trial (N1048) is evaluating the selective use of chemoradiation in patients with cT2N1 and cT3N0-1 rectal cancer undergoing sphincter-sparing low anterior resection. We evaluated outcomes of PROSPECT-eligible and -ineligible patients from a multi-institutional database. PATIENTS AND METHODS: Data from patients with locally advanced rectal cancer who received chemoradiation and low anterior resection from 2005 to 2014 were retrospectively collected from 5 Canadian centers. Overall survival, disease-free survival (DFS), recurrence-free survival (RFS), and time to local recurrence (LR) were estimated using the Kaplan-Meier method, and a multivariate analysis was performed adjusting for prognostic factors. RESULTS: A total of 566 (37%) of 1531 patients met the PROSPECT eligibility criteria. Eligible patients were more likely to have better PS (P = .0003) and negative circumferential resection margin (P < .0001). PROSPECT eligibility was associated with improved DFS (hazard ratio [HR], 0.75; 95% confidence interval [CI], 0.61-0.91), overall survival (HR, 0.73; 95% CI, 0.57-0.95), and RFS (HR, 0.68; 95% CI, 0.54-0.86) in univariate analyses. In multivariate analysis, only RFS remained significantly improved for PROSPECT-eligible patients (HR, 0.75; 95% CI, 0.57-1.00, P = .0499). The 3-year DFS and freedom from LR for PROSPECT-eligible patients were 79.1% and 97.4%, respectively, compared to 71.1% and 96.8% for PROSPECT-ineligible patients. CONCLUSION: Real-world data corroborate the eligibility criteria used in the PROSPECT study; the criteria identify a subgroup of patients in whom risk of recurrence is lower and in whom selective use of chemoradiation should be actively examined.

Palliative oxaliplatin-based chemotherapy after exposure to oxaliplatin in the adjuvant setting for colon cancer.

BACKGROUND: Little is known regarding the efficacy of oxaliplatin-based chemotherapy for metastatic colon cancer patients who have already received adjuvant oxaliplatin-based chemotherapy. METHODS: We retrospectively reviewed 22 consecutive patients who developed recurrence after adjuvant oxaliplatin-based chemotherapy for stage III colon cancer and received another course of oxaliplatin-based chemotherapy for their metastatic disease. The main endpoint was progression-free survival (PFS). RESULTS: A total of 635 patients received oxaliplatin-based chemotherapy for stage III colon cancer at the British Columbia Cancer Agency from 2006 to 2011. A total of 176 patients recurred, 22 (12.5%) of whom were re-exposed to oxaliplatin in the metastatic scenario. Oxaliplatin in combination with fluoropyrimidine was given as first, second and third line in in 3 (13.6%), 14 (63.6%), and 5 (22.7%) patients respectively. Median time from the last cycle of adjuvant oxaliplatin-based chemotherapy to the first cycle of palliative oxaliplatin-based chemotherapy was 44.3 months. Median PFS and overall survival (OS) were 3.3 (95% CI, 1.4-5.1) and 10.0 months (95% CI, 5.3-14.6), respectively. There was no difference in PFS for patients re-exposed to oxaliplatin less than 36 months compared to longer (3.6 versus 3.1 months, P=0.793, HR =0.88). CONCLUSIONS: In this population-based study, only a small proportion of pts who recurred after oxaliplatin-based adjuvant therapy received oxaliplatin in the metastatic setting. Re-exposure of oxaliplatin in combination with fluoropyrimidine is associated with only modest PFS benefit. Larger studies evaluating the role of oxaliplatin re-exposure are needed.

Effect of delay in adjuvant oxaliplatin-based chemotherapy for stage III colon cancer.

BACKGROUND: Less than 8 weeks has been recommended as the optimal time to initiate AC based on 2 meta-analyses that suggested worse survival with delayed AC. However, neither study included patients treated with an oxaliplatin-based chemotherapy. We aimed to investigate the effect of delay in initiating oxaliplatin-based chemotherapy on RFS and CSS for stage III colon cancer. PATIENTS AND METHODS: Records of patients who initiated oxaliplatin-based AC for stage III colon cancer between 2006 and 2011 at the British Columbia Cancer Agency were retrospectively reviewed. Cox proportional models were used to analyze the effect of time to AC (TTAC) on RFS and CSS. TTAC was categorized into ≤ 8 weeks (G1) and > 8 weeks (G2). RESULTS: Six hundred thirty-five patients were included (G1, n = 291; G2, n = 344). Median time from surgery to initiation of AC was 8.3 weeks. At a median follow-up of 57.9 months, 176 patients (27.7%) had disease recurrence and 118 (18.6%) had died. Five-year RFS was 70.9% (95% confidence interval [CI], 65.2-76.5) for G1 and 72.1% (95% CI, 67.2-77) for G2. Five-year CSS was 82% for G1 (95% CI, 87.09-76.91) and 82.8% for G2 (95% CI, 78.30-87.30). On multivariate analysis, delayed TTAC did not have prognostic significance on either RFS (hazard ratio [HR], 1.08; P = .609) or CSS (HR, 1.02; P = .893). CONCLUSION: In our population-based study, TTAC after stage III colon cancer resection did not have an effect on RFS or CSS. Contrary to most of the existing data, which are primarily based on 5-fluorouracil-based AC, delay of oxaliplatin-based AC beyond 8 weeks did not appear to be associated with inferior outcomes.