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Objective: To describe the baseline symptom burden(SB) experienced by patients(pts) with recurrent ovarian cancer(ROC) prior and associations with progression free survival (PFS) and overall survival (OS)., Methods: We analysed baseline SB reported by pts. with platinum resistant/refractory ROC (PRR-ROC) or potentially‑platinum sensitive ROC receiving their third or greater line of chemotherapy (PPS-ROC≥3) enrolled in the Gynecologic Cancer InterGroup - Symptom Benefit Study (GCIG-SBS) using the Measure of Ovarian Symptoms and Treatment concerns (MOST). The severity of baseline symptoms was correlated with PFS and OS., Results: The 948 pts. reported substantial baseline SB. Almost 80% reported mild to severe pain, and 75% abdominal symptoms. Shortness of breath was reported by 60% and 90% reported fatigue. About 50% reported moderate to severe anxiety, and 35% moderate to severe depression. Most (89%) reported 1 or more symptoms as moderate or severe, 59% scored 6 or more symptoms moderate or severe, and 46% scored 9 or more symptoms as moderate or severe. Higher SB was associated with significantly shortened PFS and OS; five symptoms had OS hazard ratios larger than 2 for both moderate and severe symptom cut-offs (trouble eating, vomiting, indigestion, loss of appetite, and nausea; p < 0.001)., Conclusion: Pts with ROC reported high SB prior to starting palliative chemotherapy, similar among PRR-ROC and PPS-ROC≥3. High SB was strongly associated with early progression and death. SB should be actively managed and used to stratify patients in clinical trials. Clinical trials should measure and report symptom burden and the impact of treatment on symptom control., Competing Interests: Conflict of interest statement FR acknowledges travel grant from Pfizer. Y-CL acknowledges institutional research grant from Beigene, honoraria from Astra Zeneca for educational event and received honoraria from GSK for participation in advisory board. MF acknowledges institutional grants from Astra Zeneca, Beigene, Novartis; received honoraria from Astra Zeneca, GSK, MSD; consulting fees from Astra Zeneca, Novartis, GSK, Incyclix. JL acknowledges grants from Astra Zeneca, MSD/Merck; advisory board for Astra Zeneca, Clovis Oncology, GSK, Artios Pharma, MSD/Merck, VBL Therapeutics, BMS, Nuvation, Ellipses, Immagene, Incyte, Immunogen; educational events for Astra Zeneca, MSD/Merck, GSK, Eisai, Neopharm, and data safety monitoring board for Mersana. AO acknowledges data safety monitoring board for Morphosys, Astra Zeneca, BMS, and uncompensated leadership role for Ozmosis Research where he is CEO and Board member. FH acknowledges grants from GSK, Astra Zeneca, MSD, PharmaMar, Immunogen, consulting fees from Immunogen, MSD, Astra Zeneca; honoraria from GSK, Astra Zeneca, MSD, Pharma Mar; and has been on data safety monitoring boards for MSD, GSK and Astra Zeneca. JB acknowledges grants from Tesaro, Eisai, Immunogen, Karyopharm. MS acknowledges institutional grants from Astellas, Amgen, Astra Zeneca, Bionomics, BMS, Celgene, Medivation, Merck, Sharp and Dohme, Pfizer, Roche and Sanofi. MK, RO, EA-L, FJ, M-CK, YY, DB and AL declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Tyrosine kinase inhibitors targeting the vascular endothelial growth factor (VEGF) inhibitor pathway with immune checkpoint blockade have shown promising outcomes in managing metastatic renal cancer. However, they increase the risk of a person developing high blood pressure and cardiovascular complications., Case Summary: In this study, we report the case of a 73-year-old woman on axitinib and pembrolizumab for her Stage 4 renal cell carcinoma. She presented with intractable chest pain and high systolic blood pressure, not responding to opiates. Her computed tomography angiography results showed an acute intra-mural haematoma with a rupture in the descending thoracic aorta. She underwent emergency thoracic endovascular aortic repair. Post-operatively, she recovered fully without any neurological or cardiovascular issues., Discussion: The severity of cardiovascular haemodynamic complications arising from the consumption of VEGF inhibitors and from immunotherapy and the lack of anti-hypertensive strategies to adequately manage such events require an unequivocal and urgent assessment of their cardiovascular safety. This case highlights the crucial role of cardiovascular oncology in managing such acute aortic catastrophes., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Competing Interests: Competing interests: None declared.

In the Republic of Ireland (ROI), BRCA1/BRCA2 genetic testing has been traditionally undertaken in eligible individuals, after pre-test counselling by a Clinical Geneticist/Genetic Counsellor. Clinical Genetics services in ROI are poorly resourced, with routine waiting times for appointments at the time of this pilot often extending beyond a year. The consequent prolonged waiting times are unacceptable where therapeutic decision-making depends on the patient's BRCA status. "Mainstreaming" BRCA1/BRCA2 testing through routine oncology/surgical clinics has been implemented successfully in other centres in the UK and internationally. We aimed to pilot this pathway in three Irish tertiary centres. A service evaluation project was undertaken over a 6-month period between January and July 2017. Eligible patients, fulfilling pathology and age-based inclusion criteria defined by TGL clinical, were identified, and offered constitutional BRCA1/BRCA2 testing after pre-test counselling by treating clinicians. Tests were undertaken by TGL Clinical. Results were returned to clinicians by secure email. Onward referrals of patients with uncertain/pathogenic results, or suspicious family histories, to Clinical Genetics were made by the treating team. Surveys assessing patient and clinician satisfaction were sent to participating clinicians and a sample of participating patients. Data was collected with respect to diagnostic yield, turnaround time, onward referral rates, and patient and clinician feedback. A total of 101  patients underwent diagnostic germline BRCA1/BRCA2 tests through this pathway. Pathogenic variants were identified in 12 patients (12%). All patients in whom variants were identified were appropriately referred to Clinical Genetics. At least 12 additional patients with uninformative BRCA1/BRCA2 tests were also referred for formal assessment by Clinical Geneticist or Genetic Counsellor. Issues were noted in terms of time pressures and communication of results to patients. Results from a representative sample of participants completing the satisfaction survey indicated that the pathway was acceptable to patients and clinicians. Mainstreaming of constitutional BRCA1/BRCA2 testing guided by age- and pathology-based criteria is potentially feasible for patients with breast cancer as well as patients with ovarian cancer in Ireland., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Objective: The Gynecologic Cancer InterGroup (GCIG)-Symptom Benefit Study was designed to evaluate the effects of chemotherapy on symptoms and health-related quality of life (HRQL) in women having chemotherapy for platinum resistant/refractory recurrent ovarian cancer (PRR-ROC) and potentially platinum sensitive with ≥3 lines of chemotherapy (PPS-ROC ≥3)., Methods: Participants completed the Measure of Ovarian Cancer Symptoms and Treatment (MOST) and European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire QLQ-C30 questionnaires at baseline and every 3-4 weeks until progression. Participants were classified symptomatic if they rated ≥4 of 10 in at least one-third of symptoms in the MOST index. Improvement in MOST was defined as two consecutive scores of ≤3 in at least half of the symptomatic items at baseline. Improvement in HRQL was defined as two consecutive scores ≥10 points above baseline in the QLQ-C30 summary score scale (range 0-100)., Results: Of 948 participants enrolled, 910 (96%) completed baseline questionnaires: 546 with PRR-ROC and 364 with PPS-ROC ≥3. The proportions of participants symptomatic at baseline as per MOST indexes were: abdominal 54%, psychological 53%, and disease- or treatment-related 35%. Improvement was reported in MOST indexes: abdominal 40%, psychological 35%, and disease- or treatment-related 38%. Median time to improvement in abdominal symptoms occurred earlier for PRR-ROC than for PPS-ROC ≥3 (4 vs 6 weeks, p=0.044); median duration of improvement was also similar (9.0 vs 11.7 weeks, p=0.65). Progression-free survival was longer among those with improvement in abdominal symptoms than in those without (median 7.2 vs 2.5 months, p<0.0001). Improvements in HRQL were reported by 77/448 (17%) with PRR-ROC and 61/301 (20%) with PPS-ROC ≥3 (p=0.29), and 102/481 (21%) of those with abdominal symptoms at baseline., Conclusion: Over 50% of participants reported abdominal and psychological symptoms at baseline. Of those, 40% reported an improvement within 2 months of starting chemotherapy. Approximately one in six participants reported an improvement in HRQL. Symptom monitoring and supportive care is important as chemotherapy palliated less than half of symptomatic participants., Competing Interests: Competing interests: YCL has received honoraria from GSK for participation on the Advisory Board. FJ acknowledges institutional research grants from GSK and has received honoraria for educational events from AstraZeneca, Astellas, Amgen, BMS, Bayer, Clovis, GSK, Ipsen, MSD, Janssen, Pfizer, and Sanofi. AO acknowledges institutional research grants from MSD K.K., Fuji Pharma, Kissei Pharmaceutical, Meiji Holdings, Taiho Pharmaceutical, Kaken Pharmaceutical, Chugai Pharmaceutical, Tsumura, Daiichi Sankyo, Shinnihonseiyaku, Mochida Pharmaceutical, CMIC Holdings, CMIC Holdings, ASKA Pharmaceutical, Takeda, Pfizer, AstraZeneca, and Terumo; and has received honoraria for educational events from Takeda and AstraZeneca. JL acknowledges institutional research grants from AstraZeneca and MSD/Merck and has received honoraria for educational events from AstraZeneca, Neopharm, GSK and Pfizer and participated on the data safety monitoring board of Regeneron. JS has received honoraria (educational events/travel) from AstraZeneca, Clovis, Clovis and Roche; and has participated on the data safety monitoring board or advisory board for AstraZeneca, Clovis, Eisei, GSK, Novocure, Pfizer, Roche, and Tesaro. MLF acknowledges institutional research grants from AstraZeneca, Novartis, and Beigene; has received honoraria (consultancy/educational events) from AstraZeneca, Novartis, GSK, MSD, Takeda, Lily, and ACT-Genomics; and participated on the data safety monitoring board for AGITG. MTK, RO, AL, FH, AD, FTR, JB, PD, AMO, EA-L, JSB, DB, AF, M-CK, KD and MRS declare no conflict of interest., (© IGCS and ESGO 2022. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ.)

A lab-scale bubble column was investigated as an alternative means to achieve a low-temperature binary solvent swap of solutions containing pharmaceutical materials at atmospheric pressure, for batch and continuous configurations. The rate of solvent evaporation was predicted by first-principles vapor-liquid equilibrium (VLE) thermodynamic modeling and compared to experimentally achieved results. For batch configurations, evaporation rates of up to 5 g/min were achieved at gas flow rates up to 2.5 L/min (0.21 m/s superficial velocity) and temperatures up to 50 °C. This achieved 99 mol % purity of the desired solvent within three "put and take" evaporations from a 50:50 starting mixture. The evaporation rate profiles for the duration of the experiments were calculated, and the changing concentration profile was predicted within satisfactory error margins of <5%. Continuous process modeling explored a multistage equilibrium configuration and could predict the approach to attaining steady-state operation for various operating conditions. All rates of evaporation and resulting changes in solution concentration were measured, and direct comparison of model predictions fell within instrumentation error margins, as previously. This underlined the capability of the model to provide accurate representations of predicted evaporation rates and binary solution concentration changes during operation., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

A continuously operated single-stage mixed suspension-mixed product removal (MSMPR) crystallizer was developed for the continuous cooling crystallization of 2-chloro- N -(4-methylphenyl)propanamide (CNMP) in toluene from 25 to 0 °C. The conversion of the previous batch to a continuous process was key to developing a methodology linking the synthesis and purification unit operations of CNMP and gave further insight in the development of continuous process trains for active pharmaceutical ingredient materials. By monitoring how parameters such as cooling and agitation rates influence particle size and the yield, two batch start-up strategies were compared. The second part of the study focused on developing and optimizing the continuous cooling crystallization of CNMP in the MSMPR crystallizer in relation to the yield by determining the effects of varying the residence time and the agitation rates. During the MSMPR operation, the plot of the focused beam reflectance measurement total counts versus time oscillates and reaches an unusual state of control. Despite the oscillations, the dissolved concentration was constant. The yield and production rate from the system were constant after two residence times, as supported by FTIR data. The overall productivity was higher at shorter residence times (τ), and a productivity of 69.51 g/h for τ = 20 min was achieved for the isolation of CNMP., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

In this work, a diffusion-theory-based model has been devised to simulate dissolution kinetics of a poorly water-soluble drug, ibuprofen. The model was developed from the Noyes-Whitney equation in which the dissolution rate term is a function of the remaining particulate surface area and the concentration gradient across the boundary layer. Other dissolution parameters include initial particle size, diffusion coefficient, material density, and diffusion boundary layer thickness. It is useful for predicting nonsink circumstances under which pure API polydisperse powders are suspended in a well-mixing tank. The model was used to compare the accuracy of simulations using spherical (single dimensional characteristic length) and cylindrical particle (multidimensional characteristic lengths) geometries, with and without size-dependent diffusion layer thickness. Experimental data was fitted to the model to obtain the diffusion layer thickness as well as used for model validation and prediction. The CSDs of postdissolution were also predicted with this model, demonstrating good agreement between theory and experiment., Competing Interests: The authors declare no competing financial interest., (© 2021 The Authors. Published by American Chemical Society.)

Purpose: Ireland's Sláintecare health plan is placing an increased focus on primary care. A community oncology nursing programme was developed to train community nurses to deliver care in the community. While the initial pilot was proven to be clinically safe, no cost evaluation was carried out. This study aims to compare the costs of providing cancer support services in a day-ward versus in the community., Methods: 183 interventions (40 in day-ward and 143 in community) were timed and costed using healthcare professional salaries and the Human Capital method., Results: From the healthcare provider perspective, the day-ward was a significantly cheaper option by an average of €17.13 (95% CI €13.72 - €20.54, p < 0.001). From the societal perspective, the community option was cheaper by an average of €2.77 (95% CI -€3.02 - €8.55), although this was a non-significant finding. Sensitivity analyses indicate that the community service may be significantly cheaper from the societal perspective., Conclusions: Given the demand for cost-viable options for primary care services, this programme may represent a national option for cancer care in Ireland when viewed from the societal perspective., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Potentially platinum sensitive recurrent ovarian cancer (PPS ROC) is defined by a platinum-free interval of >6 months, and usually treated with platinum-based chemotherapy with variable response and benefit in women who have had 3 or more lines of chemotherapy(≥3). We identified baseline characteristics (health-related quality of life[HRQL] and clinicopathological factors), associated with PFS, OS and early progression (within 8 weeks). The goal is to improve patient selection for chemotherapy based on a nomogram predicting PFS., Methods: HRQL was assessed with EORTC QLQ-C30/QLQ-OV28. Associations with PFS and OS were assessed with Cox proportional hazards regression. Variables significant in univariable analysis were included in multivariable analyses using backward elimination to select those significant. Associations with stopping chemotherapy early were assessed with logistic regression., Results: 378 women were enrolled, with median(m)OS and PFS of 16.6 months and 5.3 months, respectively. The majority had ECOGPS 0-1. Chemotherapy was stopped early in 45/378 participants (12%); with mOS 3.4 months (95% CI: 1.7-7.2). Physical function(PF), role function(RF), cognitive function(CF), social function(SF), Global Health Status(GHS) and abdominal/GI symptoms(AGIS) were significant univariable predictors of PFS(p < 0.030). SF remained significant after adjusting for clinicopathological factors; p = 0.03. PF, RF, CF, SF, GHS and AGIS were significant univariable predictors of OS (p < 0.007); PF, RF, SF and GHS remained significant predictors of OS in multivariable models; p < 0.007. Poor baseline PF and GHS were significant univariable predictors of stopping chemotherapy early (p < 0.007) but neither remained significant after adjusting for clinicopathological factors., Conclusion: Baseline HRQL is simple to measure, is predictive of PFS and OS and when used in conjunction with clinicopathological prognostic factors, can assist with clinical decision making and treatment recommendations for women with PPSROC≥3., (Crown Copyright © 2019. Published by Elsevier Inc. All rights reserved.)

Endobronchial metastasis from extrapulmonary malignancies are rare and include malignant melanoma. Cases that are complicated by central airway obstruction should follow a patient-centred approach, guided by patient and tumour characteristics. http://bit.ly/32baZvo., Competing Interests: Conflict of interest: S. Cullivan has nothing to disclose. Conflict of interest: J. Bruzzi has nothing to disclose. Conflict of interest: T. McHale has nothing to disclose. Conflict of interest: R. Shatwan has nothing to disclose. Conflict of interest: P. Donnellan has nothing to disclose. Conflict of interest: D.P. Breen has nothing to disclose., (Copyright ©ERS 2019.)

Background: Combining bevacizumab and chemotherapy produced superior response rates compared with chemotherapy alone in metastatic breast cancer. As bevacizumab may cause hypertension (HTN) and increase the risk of cardiac failure, we performed a pilot study to evaluate the feasibility and toxicity of a non-anthracycline-containing combination of docetaxel with cyclophosphamide and bevacizumab in early stage breast cancer patients., Methods: Treatment consisted of four 3-weekly cycles of docetaxel and cyclophosphamide (75/600 mg/m 2 ). Bevacizumab was administered 15 mg/kg intravenously on day 1, and then every 3 weeks to a total of 18 cycles of treatment. Serum biomarker concentrations of vascular endothelial growth factor (VEGF), cardiac troponin-I (cTnI), myeloperoxidase (MPO), and placental growth factor (PlGF) were quantified using enzyme-linked immunosorbent assay (ELISA) in 62 patients at baseline and whilst on treatment to determine their utility as biomarkers of cardiotoxicity, indicated by left ventricular ejection fraction (LVEF)., Results: A total of 106 patients were accrued in nine sites. Median follow up was 65 months (1-72 months). Seventeen protocol-defined relapse events were observed, accounting for an overall disease-free survival (DFS) rate of 84%. The DFS rates for hormone receptor positive (HR+) and triple-negative (TN) patients were 95% versus 43%, respectively. The median time to relapse was 25 (12-54) months in TN patients versus 38 (22-71) months in HR+ patients. There have been 13 deaths related to breast cancer . The overall survival (OS) rate was 88%. The 5-year OS rate in HR+ versus TN was 95% versus 57%. None of the measured biomarkers predicted the development of cardiotoxicity., Conclusions: We observed a low relapse rate in node-positive, HR+ patients; however, results in TN breast cancer were less encouraging. Given the negative results of three large phase III trials, it is unlikely that this approach will be investigated further., Trial Registration: ClinicalTrials.gov Identifier: NCT00911716., Competing Interests: Conflict of interest statement: The authors declare that there is no conflict of interest.

Background: Modified Glasgow Prognostic Score (mGPS) is predictive of survival in many advanced cancers, but has not been evaluated in recurrent ovarian cancer (ROC). The aim was to determine validity of mGPS in ROC, investigate its associations with health related quality of life (HRQL) and ECOG performance status (PS)., Methods: mGPS is based on serum C reactive protein (CRP) and albumin, with scores ranging from 0 (least) to 2 (most). HRQL was measured with EORTC QLQ C-30 and OV-28. χ 2 tests for trend were used to examine the relationship between HRQL, PS and mGPS. Cox proportional hazards regression was used to assess associations between mGPS, HRQL, clinicopathological factors, and overall survival (OS)., Results: Inflammatory markers were available in 516 of 948 patients in GCIG SBS. 200(39%) had potentially platinum sensitive ROC with ≥3 lines of chemotherapy, 316(61%) had platinum resistant ROC. 282(55%), 123(24%), 111(22%) had mGPS of 0, 1, 2, respectively. Median OS (months) was 18.1, 9.6, and 6.6 for mGPS 0, 1, and 2 respectively. mGPS was an independent predictor of OS after adjusting for PS and platinum sensitivity (p<0.001). mGPS remained a predictor of OS after adjusting for physical function, role function, global health status, abdominal/GI symptoms, and multiple clinicopathologic factors (p=0.02). Worse PS and higher mGPS were associated with poorer HRQL (p<0.001). Higher mGPS was associated with worse HRQL, independent of PS., Conclusion: The mGPS is an independent predictor of OS in ROC after adjusting for HRQL and clinicopathological factors. Higher mGPS is associated with worse HRQL independent of PS. mGPS is simple, inexpensive and may be suitable for clinical practice, clinical trial patient selection and stratification., (Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.)

Purpose: Gynecologic Cancer Intergroup Symptom Benefit Study (GCIG-SBS) Stage 2 aimed to review, revise, and validate a patient-reported outcome measure (PROM), the Measure of Ovarian Symptoms and Treatment concerns (MOST), developed in GCIG-SBS Stage 1 (MOSTv1, 35 items), and document recurrent ovarian cancer (ROC) symptom burden and benefit., Methods: GCIG-SBS Stage 2 recruited patients with platinum-resistant/refractory ROC (PRR-ROC) or potentially platinum-sensitive ROC with ≥ 3 lines of prior chemotherapy (PPS-ROC ≥ 3). Patients completed MOSTv1, QLQ-C30, QLQ-OV28, and FACT-O/FOSI at baseline and before cycle 3 of chemotherapy (pre-C3), and global assessments of change (MOST-Change) pre-C3. Clinicians rated patients' cancer-related symptoms, performance status, and adverse events. Convergent and divergent validity (Spearman's correlations), discriminative validity (effect sizes between groups classified by clinician-rated characteristics), and responsiveness (paired t tests in patients expected to experience clinically meaningful change) were assessed., Results: Of 948 recruits, 903 completed PROMs at baseline and 685 pre-C3. Baseline symptom burden was substantial for PRR-ROC and PPS-ROC ≥ 3. MOSTv2 has 24 items and five multi-item scales: abdominal symptoms (MOST-Abdo), disease or treatment-related symptoms (MOST-DorT), chemotherapy-related symptoms (MOST-Chemo), psychological symptoms (MOST-Psych), and MOST-Well-being. Correlations confirmed concurrent and divergent validity. Discriminative validity was confirmed by effect sizes that conformed with a priori hypotheses. MOST-Abdo was responsive to improvements in abdominal symptoms and MOST-Chemo detected the adverse effects of chemotherapy., Conclusions: The MOSTv2 validly quantifies patient-reported symptom burden, adverse effects, and symptom benefit in ROC, and as such is fit-for-purpose for clinical trials of palliative chemotherapy in ROC. Further research is required to assess test-retest reliability.

Background: Clinicians and patients often overestimate the benefits of chemotherapy, and overall survival (OS), in platinum resistant/refractory ovarian cancer (PRROC). This study sought to determine aspects of health-related quality of life and clinicopathological characteristics before starting chemotherapy that were associated with stopping chemotherapy early, shortened survival, and death within 30 days of chemotherapy., Materials and Methods: This study enrolled women with PRROC before starting palliative chemotherapy. Health-related quality of life was measured with EORTC QLQ-C30/QLQ-OV28. Chemotherapy stopped within 8 weeks of starting was defined as stopping early. Logistic regression was used to assess univariable and multivariable associations with stopping chemotherapy early and death within 30 days of chemotherapy; Cox proportional hazards regression was used to assess associations with progression-free and OS., Results: Low baseline global health status (GHS), role function (RF), physical function (PF), and high abdominal/gastrointestinal symptom (AGIS) were associated with stopping chemotherapy early (all p  < .007); low PF and RF remained significant after adjusting for clinicopathological factors (both p  < .0401). Most who stopped chemotherapy early had Eastern Cooperative Oncology Group Performance Score 0-1 at baseline (79%); PF, RF, and GHS remained independently significant predictors of stopping chemotherapy early in this subgroup. Death within 30 days of chemotherapy occurred in 14%. Low GHS, RF, and PF remained significantly associated with death within 30 days of chemotherapy after adjusting for clinicopathological factors (all p  < .012)., Conclusion: Women with low GHS, RF, or PF before starting chemotherapy were more likely to stop chemotherapy early, with short OS. Self-ratings of GHS, RF, and PF could improve patient-clinician communication regarding prognosis and help decision-making in women considering chemotherapy for PRROC., Implications for Practice: Measuring aspects of health-related quality of life when considering further chemotherapy in platinum resistant/refractory ovarian cancer (PRROC) could help identify women with a particularly poor prognosis who are unlikely to benefit from chemotherapy and could therefore be spared unnecessary treatment and toxicity in their last months of life. Self-ratings of global health status, role function, and physical function could improve patient-clinician communication regarding prognosis and help decision-making in women considering chemotherapy for PRROC., Competing Interests: Disclosures of potential conflicts of interest may be found at the end of this article., (© AlphaMed Press 2017.)

Background: Body composition is an important predictor of drug toxicity and outcome. Ipilimumab (Ipi), a monoclonal antibody used to treat metastatic melanoma, has specific toxicities. No validated biomarkers that predict Ipi toxicity and efficacy exist. Also, the impact of Ipi on body composition has not been established., Methods: Patients with metastatic melanoma treated with Ipi between 2009 and 2015 were included. Body composition was assessed by computed tomography at baseline and after four cycles of Ipi. Sarcopenia and low muscle attenuation (MA) were defined using published cut-points. All adverse events (AEs) and immune-related AEs (irAEs) were recorded (Common Terminology Criteria For Adverse Event V.4.0)., Results: Eighty-four patients were included in this study (62% male, median age 54 years). At baseline, 24% were sarcopenic and 33% had low MA. On multivariate analysis, sarcopenia and low MA were significantly associated with high-grade AEs (OR=5.34, 95% CI: 1.15-24.88, P=0.033; OR=5.23, 95% CI: 1.41-19.30, P=0.013, respectively), and low MA was associated with high-grade irAEs (OR=3.57, 95% CI: 1.09-11.77, P=0.036). Longitudinal analysis (n=59) revealed significant reductions in skeletal muscle area (SMA), total body fat-free mass, fat mass (all P<0.001) and MA (P=0.030). Mean reduction in SMA was 3.3%/100 days (95% CI: -4.48 to -1.79%, P<0.001). A loss of SMA ⩾7.5%/100 days (highest quartile) was a significant predictor of overall survival in multivariable Cox regression analysis (HR: 2.1, 95% CI: 1.02-4.56, P=0.046)., Conclusions: Patients with sarcopenia and low MA are more likely to experience severe treatment-related toxicity to Ipi. Loss of muscle during treatment was predictive of worse survival. Treatments to increase muscle mass and influence outcome warrant further investigation.

Background: Melanoma in situ (MIS) accounts for up to 27% of all melanomas. MIS has no metastatic potential and the aim should be to excise the lesion completely with a clear histological margin, although margin clearance remains undefined. We aimed to assess the relation of histological excision margins of MIS to recurrence and progression to invasive disease., Methods: We analyzed all patients with MIS excised by wide local excision or staged excision in our institution over a 5-year period from December 2008 to January 2014 using a prospectively maintained database. Clinicopathologic details included patient demographics, anatomical site of lesion, melanoma subtype, histological excision margin, and recurrence., Results: A total of 410 patients had MIS excised during this time, the majority of which were lentigo maligna subtype (79%). The average histological excision margin was 3.7 mm. The rate of recurrence was 2.2% (9/410), with a median follow-up of 23 months. Lentigo maligna had a similar rate of recurrence to non-lentigo MIS (2.3% vs 1.2%) (P = 0.69). The mean excision margin of those that recurred was 1.9 mm compared with an average of 3.8 mm in those that did not. The rate of recurrence of MIS with histological excision margin ≤3.00 mm was 3.8% compared with 0.5% in those with a histological margin >3.00 mm (P = 0.03). One case of MIS recurred as invasive disease., Conclusion: At institutions using wide local excision or staged excision for MIS, a histological margin of >3.0 mm is required to achieve a low recurrence rate.

Introduction: Although there is a lack of established survival benefit of sentinel lymph node biopsy (SLNB), this technique has been increasingly applied in the staging of patients with thin (≤1.00 mm) melanoma (T1Nx), without clear supportive evidence., Methods: We review the guidelines and available literature on the indications and rationale for performing SLNB in thin melanoma., Results: As a consequence of the paucity of evidence of SLNB in thin melanoma, there is considerable variability in the guidelines. It is difficult to define clinicopathologic factors that reliably predict the presence of nodal metastasis. SLNB does not yet inform management in thin melanoma to improve survival outcome., Conclusion: Based on available evidence, high risk patients with melanomas between 0.75 and 1.00 mm may be appropriate candidates to be considered for SLN biopsy after discussing the likelihood of finding evidence of nodal progression, the risks of sentinel node biopsy, and the lack of proven survival benefit from any form of surgical nodal staging.

Angiogenesis inhibitors have become standard of care for advanced and/or metastatic renal cell carcinoma (RCC), but data on the impact of adverse events (AEs) and treatment modifications associated with these agents are limited. Medical records were abstracted at 10 tertiary oncology centers in Europe for 291 patients ≥ 18 years old treated with sunitinib as first-line treatment for advanced RCC (no prior systemic treatment for advanced disease). Logistic regression models were estimated to compare dose intensity among patients who did and did not experience AEs during the landmark periods (18, 24, and 30 weeks). Cox proportional hazard models were used to explore the possible relationship of low-dose intensity (defined using thresholds of 0.7, 0.8, and 0.9) and treatment modifications during the landmark periods to survival. 64.4% to 67.9% of patients treated with sunitinib reported at least one AE of any grade, and approximately 10% of patients experienced at least one severe (grade 3 or 4) AE. Patients reporting severe AEs were statistically significantly more likely to have dose intensities below either 0.8 or 0.9. Dose intensity below 0.7 and dose discontinuation during all landmark periods were statistically significantly associated with shorter survival time. This study of advanced RCC patients treated with sunitinib in Europe found a significant relationship between AEs and dose intensity. It also found correlations between dose intensity and shorter survival, and between dose discontinuation and shorter survival. These results confirm the importance of tolerable treatment and maintaining dose intensity., (© 2014 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Purpose: This study was conducted to evaluate the extent to which quality of life (QoL) assessment has been incorporated into clinical trials of patients with advanced non-small cell lung cancer (NSCLC) receiving palliative chemotherapy., Patients and Methods: Phase III trials for patients with NSCLC treated with palliative chemotherapy were identified by a literature search of PubMed. All abstracts and relevant articles from August 1986 to October 2011 were reviewed. The primary focus was on (a) whether these articles had incorporated QoL as an endpoint, (c) what instruments were used to measure QoL and (c) impact of chemotherapy on QoL., Results: There were 3,780 items indexed under 'quality of life and lung cancer'. One hundred three studies were identified which measured QoL using validated QoL instruments. Fifty-five of these trials assessed the effects of palliative chemotherapy on QoL in patients with advanced NSCLC. The European Organisation for Research and Treatment of Cancer-Quality of Life Questionnaire was the most widely used questionnaire; other commonly used measurement scales used were the Functional Assessment of Cancer Therapy-Lung and the Lung Cancer Symptom Scale. The majority of studies showed that chemotherapy had a positive impact on QoL and disease-specific symptoms., Conclusion: It is now widely accepted that QoL should be considered as a primary endpoint of treatment in patients with advanced lung cancer both in clinical practice and clinical trials to further define meaningful response. As the traditional outcome measures of survival and tumour response are poor in this population, QoL assessment may offer a more comprehensive approach to evaluating the relative risks and benefits associated with treatments.

The aim of this study was to assess the treatment patterns and safety of sunitinib, sorafenib and bevacizumab in real-world clinical settings in US, Europe and Asia. Medical records were abstracted at 18 community oncology clinics in the US and at 21 tertiary oncology centers in US, Europe and Asia for 883 patients ≥ 18 years who had histologically/cytologically confirmed diagnosis of advanced RCC and received sunitinib (n=631), sorafenib (n=207) or bevacizumab (n=45) as first-line treatment. No prior treatment was permitted. Data were collected on all adverse events (AEs) and treatment modifications, including discontinuation, interruption and dose reduction. Treatment duration was estimated using Kaplan-Meier analysis. Demographics were similar across treatment groups and regions. Median treatment duration ranged from 6.1 to 10.7 months, 5.1 to 8.5 months and 7.5 to 9.8 months for sunitinib, sorafenib and bevacizumab patients, respectively. Grade 3/4 AEs were experienced by 26.0, 28.0 and 15.6% of sunitinib, sorafenib and bevacizumab patients, respectively. Treatment discontinuations occurred in 62.4 (Asia) to 63.1% (US) sunitinib, 68.8 (Asia) to 90.0% (Europe) sorafenib, and 66.7 (Asia) to 81.8% (US) bevacizumab patients. Globally, treatment modifications due to AEs occurred in 55.1, 54.2 and 50.0% sunitinib, sorafenib and bevacizumab patients, respectively. This study in a large, global cohort of advanced RCC patients found that angiogenesis inhibitors are associated with high rates of AEs and treatment modifications. Findings suggest an unmet need for more tolerable agents for RCC treatment.

Based on promising preclinical efficacy of bortezomib in mesothelioma, a single-arm phase II trial (Ireland Cooperative Oncology Research Group 05-10 study), with Simon's two-stage design, was undertaken to assess efficacy of bortezomib monotherapy in the first-line (poor performance status) and second-line settings. The Bcl-2 homology domain 3-only protein Noxa has been implicated as a key inducer of apoptosis by bortezomib. Thus, in a biomarker research substudy, we hypothesized that deficiency in Noxa expression might correlate with resistance. In the second-line setting, 23 patients were enrolled. Partial response was confirmed in one patient (4.8%) who received four cycles of bortezomib. One patient had stable disease; however, progression occurred in the majority of patients within the first two cycles. Median progression-free survival and overall survival were 2.1 and 5.8 months, respectively. In the first-line setting, ten patients were accrued, and there was no evidence of objective response. In the tumor analysis, expression of Noxa was seen in all biopsies. Bortezomib monotherapy exhibits insufficient activity to warrant further investigation in unselected patients with mesothelioma.

Background: Traditionally, carboplatin dosage is based on the Calvert formula. Glomerular filtration rate (GFR) and creatinine clearance (CrCl) are often used interchangeably in this formula. The modification of diet in renal disease (MDRD) equation is now routinely available to estimate GFR (eGFR)., Methods: We performed a retrospective analysis of carboplatin dosage in our institute. Calvert formula derived carboplatin dose using eGFR calculated from the MDRD equation was compared to estimated CrCl from the Cockcroft-Gault and Jelliffe equations., Results: Ninety-two carboplatin treatment episodes were recorded. eGFR and CrCl correlated reasonably well with a correlation coefficient (r) of 0.88. The correlation was weakest at lower levels of serum creatinine. Correcting eGFR for body surface area resulted in a tighter correlation (r = 0.94)., Conclusion: The MDRD derived eGFR is readily available and may prove very useful in calculating carboplatin dosage for patients with impaired renal function.

We conducted a randomized phase II trial of SRL172 (Mycobacterium vaccae) +/- low-dose interleukin-2 (IL-2) as treatment for stage IV malignant melanoma. The objectives were to establish the safety and efficacy of SRL172 with and without IL-2. All patients had measurable metastatic disease and none received concurrent chemotherapy, radiotherapy, corticosteroids or any other investigational agent. Sixteen patients were randomized into each arm of the trial prior to closure. The trial was halted prematurely when no responses were seen in the first 16 patients receiving SRL172 alone, predicting a response rate of less than 20%. Three partial remissions were seen in the 16 patients receiving SRL172 + IL-2. These patients remained on monthly SRL172 + IL-2, with disease progression at 12, 15 and 23 months. They continued on the trial regimen following surgical management of their disease progression. This trial provides preliminary evidence of a new, non-toxic, immunotherapeutic regimen in the management of malignant melanoma. Further trials are required to establish a definitive response rate and to compare the combination regimen with the regimen of low-dose IL-2 used in this trial. A biological basis for the responses seen in the SRL172 + IL-2 arm also needs to be established.

Truly informed consent is a difficult thing to achieve! Patients are not healthy volunteers and their vulnerability challenges their ability to assess the risk/benefit of health choices. In this paper we consider some or the issues surrounding this important aspect of modern practice, and offer some suggestions on how to improve the process, with the goal of increasing participation in clinical research, and enhancing patients' confidence in their medical advisors.

Painful ejaculation ("odynorgasmia") is not well recognized. When it occurs it may indicate the precise site of pathology.

Cytomegalovirus (CMV) pneumonia in the setting of non-transplantation patients is a rarity. We present a case of CMV pneumonitis in a woman with stage IV breast cancer, with brain metastases, receiving both chemotherapy and systemic corticosteroids. A review of the literature reveals this as a unique case. Potential viral etiologies should therefore be considered in cancer patients with pneumonia receiving non-transplantation chemotherapy-regimens, particularly if steroids are a component of their therapy.

The modest antitumor activity and clinical benefit of conventional platinum-containing multidrug regimens in locally advanced and metastatic non-small cell lung cancer have provided the impetus for the development of novel combinations. The promising single-agent activity of docetaxel makes it an obvious candidate for incorporation into active programs. The Irish Clinical Oncology Research Group is conducting a phase I-II evaluation of a three-drug combination of docetaxel, ifosfamide, and cisplatin with lenograstim support in patients with stages III-IV non-small cell lung cancer. Preliminary results indicate that the regimen is feasible and tolerable up to a maximum tolerated dose level of 3,000 mg/m2 ifosfamide, 75 mg/m2 cisplatin, and 75 mg/ m2 docetaxel. The regimen appears to be quite active, with nine of 12 evaluable patients responding in the phase I component of the trial. This dose level is currently being explored in a phase II trial.

Non-small cell lung cancer is the most common cause of cancer death in the western world. Non-small cell lung cancer is modestly sensitive to chemotherapy with a small survival benefit in locally advanced and metastatic disease. Newer agents such as docetaxel are yielding encouraging response rates both as single agents and in combination. A phase I/II study is in progress in our institution to determine the maximum tolerated dose and noncomparative efficacy of the combination of docetaxel (Taxotere; Rhône-Poulenc Rorer, Antony, France), ifosfamide, and cisplatin, with mesna and lenograstim support, in the treatment of patients with advanced non-small cell lung cancer. To date, nine patients have received 37 cycles of treatment at increasing dose levels (no intrapatient dose escalation). Treatment was administered to patients on an inpatient basis every 3 weeks, with lenograstim on days 3 to 10. Dose-limiting toxicity has not occurred at levels I to III (dose level III: docetaxel 75 mg/m2, cisplatin 75 mg/m2, and ifosfamide 3 g/m2). These preliminary results suggest that the combination of docetaxel, ifosfamide, and cisplatin, with lenograstim support, is well tolerated in the doses evaluated. Preliminary efficacy results show a response rate of 67% (six of nine patients). The study continues to determine the maximum tolerated dose of this regimen in preparation for a phase II evaluation.

Sixteen of 194 premenopausal woman with breast cancer developed the disease in association with pregnancy. Eight were pregnant as diagnosis and eight were post-partum. There were significant delays in referral for surgical opinion and treatment among both groups. Two of the eight pregnant patients were diagnosed during the first trimester and one during the second trimester. The rest were at or close to term. Standard surgical therapy without irradiation was employed for early stage disease. Adjuvant chemotherapy posed some problems. One of the patients in the first trimester declined all treatment while the other opted for surgery only until after delivery. There was a favourable obstetrical outcome in all cases and survival for this group of patients is similar to that reported in the medical literature. None of the group had a further pregnancy. The incidence of breast cancer related to pregnancy in this premenopausal group was 8% with 1% occurring in the first trimester. This would mean three or four such cases per annum in Ireland.