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PurposeIn March 2020, a 1-week adjuvant breast radiotherapy schedule, 26 Gy in 5 fractions, was adopted to reduce the risk of COVID19 for staff and patients. This study quantifies acute toxicity rates and the effect on linac capacity.Materials and methodsThis is a report of consecutive patients receiving ultrafractionated breast radiotherapy ( ± sequential boost) Mar–Aug 2020. Virtual consultations assessed acute skin toxicity during treatment and weeks 1, 2, 3 and 4 post treatment using CTCAE V5 scoring criteria. The number of linac minutes saved was estimated accounting for boost and DIBH use.ResultsIn total, 128/135 (95%) patients, including 31/33 boost patients, completed at least 3/5 assessments. 0/128 (0%) reported moist desquamation not confined to skin folds or minor bleeding (Grade 3), 41/128 (32%) reported brisk erythema, moist desquamation confined to skin folds or breast swelling (Grade 2), 62/128 (48%) reported faint erythema or dry desquamation (Grade 1) as their worst skin toxicity, with the remaining 20% reporting no skin toxicity. The highest prevalence of grade 2 toxicity occurred week 1 following treatment (20%), reducing to 3% by week 4. There was no difference in toxicity between those who received a boost versus not (p = 1.00). Delivering this schedule to 135 patients over six months saved 21,300 linac minutes and 1485 hospital visits compared to a 3-week schedule.ConclusionRapidly implementing ultrahypofractionated breast radiotherapy is feasible and acute toxicity rates are acceptable even when followed by boost.

The extent of intervention effects on carotid intima-media thickness (CIMT) can predict the degree of atherosclerotic cardiovascular risk-reduction. We hypothesized that regular lipoprotein apheresis over the course of 10 years might slow down progression of CIMT in patients with severe hypercholesterolemia. This case series describes 10 Caucasian patients (mean age 60 ± 9 years, 70% female, 80% statin intolerant) with a severe hypercholesterolemia phenotype treated with lipoprotein apheresis between 2005 and 2020 (mean duration, 10 ± 4 years). The median pretreatment low-density lipoprotein cholesterol (LDL-C) level was 214 mg/100 ml (95% confidence interval, 145 to 248), lipoprotein(a) (Lp[a]), 26 mg/100 ml (15 to 109; 40% with Lp(a)60 mg/100 ml). Three patients were diagnosed with a monogenic cause. The baseline mean CIMT was 850 ± 170 µm, and maximum CIMT was 1,040 ± 220 µm across the age range of 46 to 70 years. Acute effects of lipoprotein apheresis determined as a difference before and immediately after the procedure were estimated as a median of 72 ± 8% and 75 ± 7% reduction in the LDL-C and Lp(a) levels, respectively. Using the imputed trajectories, period-specific on-treatment time-weighted averages for LDL-C and Lp(a) were 141 mg/100 ml (interquartile range, 89 to 152; 38% reduction from the baseline) and 24 mg/100 ml (interquartile range, 12 to 119; 19% reduction from baseline), respectively. The number of patients with CIMT above their "vascular age" decreased from 80% to 30% over the treatment course. In conclusion, an increase in CIMT seen with advanced age and severe hypercholesterolemia was halted with lipoprotein apheresis with an estimated annual rate of change in mean common CIMT of -4 µm/y and maximum CIMT of -3 µm/y.

Adult women require routine care for the acute and chronic health problems found in both sexes, and they require specialized care for women's health problems, including disease prevention, disease screening, and disease management. Internists should direct primary care and participate in specialized care and to the extent possible follow guidelines published by various professional organizations. They should understand the use of ultrasound in breast cancer screening, the management of pregnancy, and other gynecologic problems, including vaginal bleeding, pelvic pain, and investigation for pelvic malignancy. Finally, all management decisions need discussions on the potential benefit or harm in each step of a woman's care with an emphasis on personal preferences.

Objective Niraparib is a poly (ADP-ribose) polymerase inhibitor (PARP) approved for use in maintenance therapy for ovarian cancer that is associated with the unpredictable grade 3/4 thrombocytopenia. This study was conducted to refine patient dosing recommendations for niraparib based upon clinical practice observations of grade 3/4 thrombocytopenia. Methods and materials Six patient cases were reviewed to identify similarities in patient factors. An in vitro study was conducted using healthy volunteer blood spiked with Niraparib concentrations ranging from 0 ng/mL to 5000 ng/mL. Manual platelet counts were evaluated at different time intervals for each concentration and compared to untreated controls. Data was then analyzed based on percent change in platelet count versus untreated control for each concentration/time point. Results In three patients with body weight > 80 kg and platelet count >200 × 109/L, decreased creatinine clearance (CrCl) Conclusion The data suggests that renal insufficiency and hypoalbuminemia may be associated with the development of niraparib-induced thrombocytopenia. Moreover, the preliminary in vitro studies also demonstrated a concentration-dependent relationship between niraparib and direct toxicity to platelets.

Study Objective To compare the accuracy of frozen section diagnosis of borderline ovarian tumors among 3 distinct types of hospital—academic hospital with gynecologic pathologists, academic hospital with nongynecologic pathologists, and community hospital with nongynecologic pathologists—and to determine if surgical staging alters patient care or outcomes for women with a frozen section diagnosis of borderline ovarian tumor. Design Retrospective study (Canadian Task Force classification II-1). Setting Tertiary care, academic, and community hospitals. Patients Women with an intraoperative frozen section diagnosis of borderline ovarian tumor at 1 of 3 types of hospital from April 1998 through June 2016. Interventions Comparison of final pathology with intraoperative frozen section diagnosis. Measurements and Main Results Two hundred twelve women met the inclusion criteria. The frozen section diagnosis of borderline ovarian tumor correlated with the final pathologic diagnosis in 192 of 212 cases (90.6%), and the rate of correlation did not differ among the 3 hospital types (p = .82). Seven tumors (3.3%) were downgraded to benign on final pathologic analysis and 13 (6.1%) upgraded to invasive carcinoma. The 3 hospital types did not differ with respect to the proportion of tumors upgraded to invasive carcinoma (p = .62). Mucinous (odds ratio, 7.1; 95% confidence interval, 2.1–23.7; p = .002) and endometrioid borderline ovarian tumors (odds ratio, 32.4; 95% confidence interval, 1.8–595.5; p = .02) were more likely than serous ovarian tumors to be upgraded to carcinoma. Only 88 patients (41.5%) underwent lymphadenectomy, and only 1 (1.1%) had invasive carcinoma in a lymph node. Conclusions A frozen section diagnosis of borderline ovarian tumor correlates with the final pathologic diagnosis in a variety of hospital types.

Purpose or Objective In March 2020, a 1-week hypofractionated adjuvant breast radiotherapy schedule, 26 Gy in 5 fractions was adopted to reduce the risk of COVID 19 exposure for patients and staff without compromising on cancer outcomes. This study aimed to confirm acceptable acute toxicity rates for patients receiving this 1-week schedule (+/- sequential boost) and to quantify the positive impact of implementing this schedule on linac capacity. Materials and Methods This is a multicentre prospective observational study of consecutive patients receiving 26 Gy in 5 fractions adjuvant breast cancer radiotherapy (+/- boost) Mar-Aug 2020. Consensus was obtained on planning procedure protocols which included dose-volume evaluation and mandatory radiation quality assurance objectives. Standardised virtual consultations assessed acute skin toxicity during treatment and at weeks 1, 2, 3 and 4 post treatment using CTCAE V5 scoring criteria. Toxicity was compared between patients who received a boost and those that did not. The total number of linac minutes saved was estimated accounting for boost and DIBH use Results In total, 135 women were included, 33 (24%) received a boost. 128/135 (95%) patients, including 31/33 boost patients, completed at least 3/5 acute toxicity assessments. 0/128 (0%) reported moist desquamation not confined to skin folds or minor bleeding (grade 3 toxicity). 41/128 (31%) reported brisk erythema, moist desquamation confined to skin folds or breast swelling (Grade 2) and 63/128 (50%) reported faint erythema or dry desquamation (Grade 1) as their worst reported acute skin toxicity. The highest prevalence of grade 2 toxicity occurred at week 1 following treatment (19.5%), which reduced to 2.6% by week 4. There was no statistically significant difference in acute toxicity between boost and no boost patients (p= 1.00). Delivering a 1-week schedule to 135 patients over a six month period led to a saving of 21,300 linac minutes and 1485 hospital visits compared to delivering a moderately hypofractionated regimen of 3 weeks duration. 6,300 LINAC minutes were saved and 462 hospital visits avoided for patients > 70 years and cocooning under national guidance $Φg $Φg Conclusion This study demonstrates the feasibility of rapidly implementing a 1-week hypofractionated adjuvant breast radiotherapy schedule in clinical practice and how this landmark change has a considerable impact on linac capacity. This change in practice has ensured ongoing access to treatment for patients during the COVID-19 pandemic and greatly reduced the risks of infection for patients and staff. It further confirms acceptable acute skin toxicity even when followed by boost.

Objectives Surgery is a cornerstone for patients with gynecologic malignancies. Surgical site infections (SSI) remain a source of post-operative morbidity. Consequences range from escalated costs, delay in adjuvant therapy, and increased morbidity. Our primary objective was to evaluate the effectiveness of a cyanoacrylate microbial sealant (CMS) to reduce post-operative SSI following laparotomy for suspected gynecologic malignancy. Methods Patients were randomized using a 1:1 allocation to receive either standard skin preparation or standard preparation with CMS and stratified by BMI. Patients were followed for 6weeks for SSI. Demographic data was collected through the EMR. Associations between SSI, use of CMS, and clinicopathologic factors were explored using descriptive statistics, chi-square and multivariate analysis. Results 300 patients underwent randomization. Median age of the cohort was 58. Arms were matched and there was no difference in rate of medical comorbidities. Mean BMI was 38.8kg/m 2 in patients randomized to BMI≥30 and 26.3kg/m 2 randomized to BMI p =0.18). Multivariate model demonstrated that BMI≥30 ( p p =0.010), transfusion in the OR ( p p =0.0005) were associated with post-operative SSI. Conclusions Patients presenting to a gynecologic oncologist for surgery frequently present with multiple risk factors for SSI and laparotomy is complicated by surgical-site complications in up to 30% of cases. The addition of CMS alone does not appear to reduce risk of overall SSI. Additional risk-reducing strategies including use of antimicrobial agents and optimization of modifiable risk factors prior to surgery should be explored as pathways for reducing this significant post-operative morbidity.

Objectives Previous reviews of phase I clinical trials report limited response rates. Development of novel biologic agents and trials designs have increased these rates. A contemporary appraisal of phase I clinical trials in gynecologic malignancies could help validate these findings. Methods Retrospectively reviewed records for 410 patients with gynecologic malignancies treated in a phase I unit, January 1999 to October 2012. Patient characteristics and treatment outcomes were abstracted and analyzed. Results Patients enrolled in 43 different phase I trials, 17 phase Ia, 17 phase Ib dose escalation and 9 dose expansion. 9 trials (21%) investigated unique cytotoxic delivery methods, 15 (35%) conventional cytotoxic plus novel agents and 19 (44%) novel agents alone. For patients treated in the first-line setting, 90 (74.4%) achieved CR, 20 (16.5%) PR, 9 (7.4%) SD and 2 (1.7%) PD, yielding an overall response rate of 90.9%. In patients treated for recurrent disease, 2 (1.6%) achieved CR, 11 (8.9%) PR, 57 (46.0%) SD and 54 (43.5%) PD, yielding a response rate of 11% and an overall clinical benefit rate of 57%. Response rate for molecular targeted therapies was 11.5% with an overall clinical benefit rate of 46.2%. Patients with prior anti-angiogenic exposure had comparable median PFS to those who had not been previously exposed (3.5 vs. 4.0months, p=0.29). Conclusions Results support referral of gynecologic cancer patients for phase I clinical trials. Patients with advanced, heavily pretreated disease fare at least as well as they do on phase II trials and a proportion of them can attain an objective response or stabilization of their disease.

Objective To determine the progression free survival (PFS), toxicity, and patterns of failure for early stage, high-intermediate risk (H-IR) patients in a phase II trial with adjuvant vaginal cuff brachytherapy (VCB) and three cycles of carboplatin and paclitaxel. Methods Surgically staged patients with stage I-IIb endometrial cancer with H-IR factors were treated with VCB (2100cGy) followed by three cycles of carboplatin (AUC 6) and paclitaxel (175mg/m 2 ). The primary endpoint was PFS at 2years, with toxicity and sites of failure as secondary endpoints. Toxicity was assessed by patient report (CTCAE v. 3) as well as by delays or dose modifications in treatment. Results All patients completed VCB and 19/23 (83%) completed both VCB and 3cycles of chemotherapy. Mean time to complete VCB was 14.5days with minimal acute toxicity noted. At 6months, all toxicity related to VCB had resolved. In total 60cycles of chemotherapy were given, with one dose reduction (1.6%) for grade 2 neuropathy and seven delays (11.6%) in treatment due to hematologic toxicity. At a median follow-up of 44.5months, 91% of patients remained progression free at 2years. Four patients experienced a recurrence; they recurred both locally and distant. Conclusions Adjuvant therapy with VCB and chemotherapy is well tolerated in a population of patients with H-IR endometrial carcinoma and provides 2year PFS of 91%. A randomized trial is currently underway to assess whether combined VCB and chemotherapy reduces the rate of recurrence compared to external beam radiation therapy (EBRT) in this patient population.

Objectives Controversy continues over the importance of lymph node (LN) status in treating and predicting recurrence in endometrial cancer. Several predictive models are available which use uterine factors to stratify risk groups. Our objective was to determine how LN status affects recurrence and survival compared to uterine factors alone. Methods A retrospective review was performed of patients undergoing complete surgical staging for clinical stage 1 endometrioid adenocarcinoma of the uterus. Patients were assessed based on PORTEC 1 high intermediate risk (H-IR) criteria (2 factors : age>60, grade 3, >50% DOI), GOG-99 H-IR criteria (age >70+1 factor, age 50–70+2 factors, any age +3 factors: grade 2 or 3, LVSI, >50% DOI), and PORTEC 2 criteria. Rates of nodal involvement, recurrence rates, PFS, and OS were compared. Results We identified 352 clinical stage I patients with positive LN in 24% (87). 175 patients met PORTEC 1 eligibility and 66 met H-IR criteria. Rates of LN positivity were similar among groups (18.4% vs 19.7%, p =0.83) but recurrence rates were dissimilar (7.4% vs 27.3%, p =0.0004). Only 93 met PORTEC 2 criteria for treatment with no association between LN status, recurrence, and eligibility. 188 patients met H-IR eligibility criteria for GOG-99 with LN positive and recurrence rates higher in the H-IR group compared to GOG-99 eligible (34.6% vs 16.3%, p =0.0004, 28.3% vs. 10.6%, p =0.0002). Conclusions Patients with H-IR disease based on uterine characteristics alone have substantial risk of nodal involvement. Knowledge of LN status may better define risk, prognosis, and postoperative treatment.

The aim of this study was to evaluate the effect of number of chemotherapy cycles and other clinical and pathologic factors on progression-free (PFS) and overall survival (OS) in patients with newly diagnosed cervical cancer.We identified 118 patients with locally advanced cervical cancer (stages IB2-IVA) treated with combination weekly cisplatin (40 mg/m(2)) and radiation therapy (RT) between 2003 and 2007. Kaplan-Meier and Cox proportional hazard models were utilized to evaluate PFS and OS for associations with number of chemotherapy cycles and other factors.The majority of patients had stage IB2 or II disease (70%), squamous histology (91%), and size6 cm (65%). Median RT duration was 50 days and 95% received brachytherapy. Thirty percent of patients completed6 cycles of chemotherapy, and estimated PFS and OS were 63% and 75%, respectively. In multivariate analyses, the number of chemotherapy cycles was independently predictive of PFS and OS. Patients who received6 cycles of cisplatin had a worse PFS (HR 2.65; 95% CI 1.35-5.17; p=0.0045) and OS (HR 4.47; 95% CI 1.83-10.9; p=0.001). Advanced stage, longer time to RT completion, and absence of brachytherapy were also associated with decreased OS and PFS (p0.05). Similar results were found when analysis was conducted using a breakpoint of at least five but not less than five chemotherapy cycles. Higher grade was associated with decreased PFS (p=0.03) but not OS. Age, race, BMI, tumor size, smoking, histology, and IMRT were not statistically significant for OS or PFS.Aggressive supportive care to minimize missed chemotherapy treatments may improve survival after chemoradiation.

To explore the yield and impact of perioperative imaging on management among patients undergoing surgical resection and treatment of uterine sarcomas.A retrospective chart review was done for women with histologically confirmed uterine sarcomas treated at Barnes Jewish Hospital/Washington University from 2001 to 2007. Descriptive statistics, Cox multivariate models, and Kaplan-Meier plots were used to evaluate associations and survival.A total of 92 patients were identified and 55 (60%) were diagnosed with stage III-IV disease. Perioperative imaging was obtained in 84 (91%) cases, including chest X-ray in 66 (72%), computerized tomography (CT) of the abdomen and pelvis in 59 (64%), chest CT in 33 (36%), positron emission tomography (PET) in 8 (9%), and CT of the head, pelvic magnetic resonance imaging (MRI), or bone scan in a total of 2 (2.2%). Imaging identified abnormalities concerning for metastases in 30 (32%) studies. Thirty-four recurrences have been documented, and 21 (62%) of these treatment failures were extrapelvic. Multivariate analysis of this series noted that tomographic evidence of extrauterine disease predicted recurrence (p=0.028) and incomplete surgical resection (p=0.003, HR 6.0 95% CI 1.9-19.9) predicted disease-free survival. Imaging contributed to change in surgical and post-surgical treatment decisions in 8 (9%) patients.Pretreatment imaging studies change management in a minority of patients with newly diagnosed uterine sarcomas.

Preparation of fungal material for microscopical examination of their conidiogenous structures is described below. A modification to the existing methods used coupled with a sporulation medium has proved to be simple to use and successful for the induction of sporulation and subsequent examination of conidiogenous structures in a range of xylariaceous species and in endophytic fungi.

The genus Biscogniauxia, a member of the family Xylariaceae, has a worldwide distribution with over 50 taxa recognised. Biscogniauxia mediterranea is well known as the causative agent of charcoal canker in cork oak and is a serious problem in Portugal. Other species also cause canker under specific conditions. There is good evidence that these species occur in healthy living trees as endophytes and then become invasive under water stress conditions. The ability of B. nummularia, B. nothofagi and B. uniapiculata to cause cankers in Fagus, Nothofagus and Eucalyptus respectively is reported here.