PurposeThis randomized, multicenter, phase III noninferiority trial was designed to test the efficacy and safety of the combination of pegylated liposomal doxorubicin (PLD) with carboplatin (CD) compared with standard carboplatin and paclitaxel (CP) in patients with platinum-sensitive relapsed/recurrent ovarian cancer (ROC).Patients and MethodsPatients with histologically proven ovarian cancer with recurrence more than 6 months after first- or second-line platinum and taxane-based therapies were randomly assigned by stratified blocks to CD (carboplatin area under the curve [AUC] 5 plus PLD 30 mg/m2) every 4 weeks or CP (carboplatin AUC 5 plus paclitaxel 175 mg/m2) every 3 weeks for at least 6 cycles. Primary end point was progression-free survival (PFS); secondary end points were toxicity, quality of life, and overall survival.ResultsOverall 976 patients were recruited. With median follow-up of 22 months, PFS for the CD arm was statistically superior to the CP arm (hazard ratio, 0.821; 95% CI, 0.72 to 0.94; P = .005); median PFS was 11.3 versus 9.4 months, respectively. Although overall survival data are immature for final analysis, we report here a total of 334 deaths. Overall severe nonhematologic toxicity (36.8% v 28.4%; P < .01) leading to early discontinuation (15% v 6%; P < .001) occurred more frequently in the CP arm. More frequent grade 2 or greater alopecia (83.6% v 7%), hypersensitivity reactions (18.8% v 5.6%), and sensory neuropathy (26.9% v 4.9%) were observed in the CP arm; more hand-foot syndrome (grade 2 to 3, 12.0% v 2.2%), nausea (35.2% v 24.2%), and mucositis (grade 2-3, 13.9% v 7%) in the CD arm.ConclusionTo our knowledge, this trial is the largest in recurrent ovarian cancer and has demonstrated superiority in PFS and better therapeutic index of CD over standard CP.

EGFR-TKIs therapy statistically significantly delays disease progression in EGFRmut(+) patients but has no demonstrable impact on OS. EGFR mutation is a predictive biomarker of PFS benefit with EGFR-TKIs treatment in all settings. These findings support EGFR mutation assessment before initiation of treatment. EGFR-TKIs should be considered as front-line therapy in EGFRmut(+) advanced NSCLC patients.

AimChemotherapy side effects are often reported in clinical trials; however, there is little evidence about their incidence in routine clinical care. The objective of this study was to describe the frequency and severity of patient-reported chemotherapy side effects in routine care across treatment centres in Australia.MethodsWe conducted a prospective cohort study of individuals with breast, lung or colorectal cancer undergoing chemotherapy. Side effects were identified by patient self-report. The frequency, prevalence and incidence rates of side effects were calculated by cancer type and grade, and cumulative incidence curves for each side effect computed. Frequencies of side effects were compared between demographic subgroups using chi-squared statistics.ResultsSide effect data were available for 449 eligible individuals, who had a median follow-up of 5.64 months. 86% of participants reported at least one side effect during the study period and 27% reported a grade IV side effect, most commonly fatigue or dyspnoea. Fatigue was the most common side effect overall (85%), followed by diarrhoea (74%) and constipation (74%). Prevalence and incidence rates were similar across side effects and cancer types. Age was the only demographic factor associated with the incidence of side effects, with older people less likely to report side effects.ConclusionThis research has produced the first Australian estimates of self-reported incidence of chemotherapy side effects in routine clinical care. Chemotherapy side effects in routine care are common, continue throughout chemotherapy and can be serious. This work confirms the importance of observational data in providing clinical practice-relevant information to decision-makers.

Objective: The aim of the study was to determine the efficacy of laparoscopic rectal resection (Lap) versus open laparotomy and rectal resection (Open) for rectal cancer on locoregional recurrence (LRR) and disease-free survival (DFS) at 2 years. Summary background data: Although a Lap approach to colon cancer surgery may offer similar oncological outcomes to Open with potentially less morbidity, this remains to be clearly established for the treatment of rectal cancer. Methods: A randomized, multicenter noninferiority phase 3 trial of 475 patients with T1 to T3 rectal adenocarcinoma <15 cm from anal verge, given Lap or Open and followed for a minimum 2 years to assess LRR, DFS, and overall survival (OS). Results: Secondary endpoint analyses included 450 patients (95%) without metastases at baseline (mean age 64; 34% women) who received Lap (n = 225) or Open (n = 225). Median follow-up was 3.2 years (range: 0.1–5.4 yrs). LRR cumulative incidence at 2 years: Lap 5.4%; Open 3.1% [difference, 2.3%; 95% confidence interval (CI), −1.5% to 6.1%; hazard ratio (HR) 1.7; 95% CI, 0.74–3.9]. DFS at 2 years: Lap 80%; Open 82% (difference, 2.0%; 95% CI, −9.3% to 5.4%; HR for recurrence or death, 1.17; 95% CI, 0.81–1.68; P = 0.41). After adjustment for baseline factors HR = 1.07 (95% CI, 0.7–1.6). OS at 2 years: Lap 94%; Open 93% (difference 0.9%; 95% CI, −3.6% to 5.4%). Conclusions: Laparoscopic surgery for rectal cancer did not differ significantly from open surgery in effects on 2-year recurrence or DFS and OS. Confidence intervals included potentially clinically important differences favoring open resection, so that the combination of primary and secondary study endpoints may not support laparoscopic resection of rectal cancer as a routine standard of care and further follow-up is required.

Background:The host inflammatory response has a vital role in carcinogenesis and tumour progression. We examined the prognostic value of inflammatory markers (albumin, white-cell count and its components, and platelets) in pre-treated patients with advanced renal cell carcinoma (RCC).Methods:Using data from a randomised trial, multivariable proportional hazards models were generated to examine the impact of inflammatory markers and established prognostic factors (performance status, calcium, and haemoglobin) on overall survival (OS). We evaluated a new prognostic classification incorporating additional information from inflammatory markers.Results:Of the 416 patients, 362 were included in the analysis. Elevated neutrophil counts, elevated platelet counts, and a high neutrophil–lymphocyte ratio were significant independent predictors for shorter OS in a model with established prognostic factors. The addition of inflammatory markers improves the discriminatory value of the prognostic classification as compared with established factors alone (C-statistic 0.673 vs 0.654, P=0.002 for the difference), with 25.8% (P=0.004) of patients more appropriately classified using the new classification.Conclusion:Markers of systemic inflammation contribute significantly to prognostic classification in addition to established factors for pre-treated patients with advanced RCC. Upon validation of these data in independent studies, stratification of patients using these markers in future clinical trials is recommended.

In this large cross-continental study, comorbidity in OCD was common. The high rates of comorbid major depression and anxiety disorders emphasize the need for clinicians to assess and monitor for these disorders. Earlier ages of onset of OCD, specific phobia and social phobia may indicate some relatedness between these disorders, but this requires further study. Although there do not appear to be significant cultural variations in rates or patterns of comorbidity and suicidality, further research using similar recruitment strategies and controlling for demographic and clinical variables may help to determine whether any sociocultural factors protect against suicidal ideation or psychiatric comorbidity in patients with OCD.

ObjectivesTo compare the risk profile of women giving birth in private and public hospitals and the rate of obstetric intervention during birth compared with previous published rates from a decade ago.DesignPopulation-based descriptive study.SettingNew South Wales, Australia.Participants691 738 women giving birth to a singleton baby during the period 2000 to 2008.Main outcome measuresRisk profile of women giving birth in public and private hospitals, intervention rates and changes in these rates over the past decade.ResultsAmong low-risk women rates of obstetric intervention were highest in private hospitals and lowest in public hospitals. Low-risk primiparous women giving birth in a private hospital compared to a public hospital had higher rates of induction (31% vs 23%); instrumental birth (29% vs 18%); caesarean section (27% vs 18%), epidural (53% vs 32%) and episiotomy (28% vs 12%) and lower normal vaginal birth rates (44% vs 64%). Low-risk multiparous women had higher rates of instrumental birth (7% vs 3%), caesarean section (27% vs 16%), epidural (35% vs 12%) and episiotomy (8% vs 2%) and lower normal vaginal birth rates (66% vs 81%). As interventions were introduced during labour, the rate of interventions in birth increased. Over the past decade these interventions have increased by 5% for women in public hospitals and by over 10% for women in private hospitals. Among low-risk primiparous women giving birth in private hospitals 15 per 100 women had a vaginal birth with no obstetric intervention compared to 35 per 100 women giving birth in a public hospital.ConclusionsLow-risk primiparous women giving birth in private hospitals have more chance of a surgical birth than a normal vaginal birth and this phenomenon has increased markedly in the past decade.

IMPORTANCE Complex surgical interventions are inherently prone to variation yet they are not objectively measured. The reasons for outcome differences following cancer surgery are unclear.OBJECTIVE To quantify surgical skill within advanced laparoscopic procedures and its association with histopathological and clinical outcomes. DESIGN, SETTING, AND PARTICIPANTSThis analysis of data and video from the Australasian Laparoscopic Cancer of Rectum (ALaCaRT) and 2-dimensional/3-dimensional (2D3D) multicenter randomized laparoscopic total mesorectal excision trials, which were conducted at 28 centers in Australia, the United Kingdom, and New Zealand, was performed from 2018 to 2019 and included 176 patients with clinical T1 to T3 rectal adenocarcinoma 15 cm or less from the anal verge. Case videos underwent blinded objective analysis using a bespoke performance assessment tool developed with a 62-international expert Delphi exercise and workshop, interview, and pilot phases.INTERVENTIONS Laparoscopic total mesorectal excision undertaken with curative intent by 34 credentialed surgeons.MAIN OUTCOMES AND MEASURES Histopathological (plane of mesorectal dissection, ALaCaRT composite end point success [mesorectal fascial plane, circumferential margin, Ն1 mm; distal margin, Ն1 mm]) and 30-day morbidity. End points were analyzed using surgeon quartiles defined by tool scores. RESULTSThe laparoscopic total mesorectal excision performance tool was produced and shown to be reliable and valid for the specialist level (intraclass correlation coefficient, 0.889; 95% CI, 0.832-0.926; P< .001). A substantial variation in tool scores was recorded (range, 25-48). Scores were associated with the number of intraoperative errors, plane of mesorectal dissection, and short-term patient morbidity, including the number and severity of complications. Upper quartile-scoring surgeons obtained excellent results compared with the lower quartile (mesorectal fascial plane: 93% vs 59%; number needed to treat [NNT], 2.9, P = .002; ALaCaRT end point success, 83% vs 58%; NNT, 4; P = .03; 30-day morbidity, 23% vs 50%; NNT, 3.7; P = .03). CONCLUSIONS AND RELEVANCEIntraoperative surgical skill can be objectively and reliably measured in complex cancer interventions. Substantial variation in technical performance among credentialed surgeons is seen and significantly associated with clinical and pathological outcomes.