Single organ metastatic sites in non-small cell lung cancer: Patient characteristics, treatment patterns and outcomes from a large retrospective Canadian cohort.

BACKGROUND: There is a paucity of information about the characteristics, treatment patterns, and outcomes of non-small cell lung cancer (NSCLC) patients with single organ metastasis (SOM). METHODS: This retrospective cohort study includes all patients with a diagnosis of stage IV NSCLC diagnosed from 2014 to 2016 and treated at Princess Margaret Cancer Centre. We compared baseline characteristics and patterns of metastatic sites between patients with SOM versus multiple (M)OM. Additionally, we identified treatment modalities and outcomes for patients with SOM. Cox multivariable models (MVA) were utilized to evaluate differences in overall survival (OS) between the SOM and MOM cohorts. RESULTS: Of 893 pts analyzed, 457 (51 %) had SOM, while 436 (49 %) had MOM at initial diagnosis. Demographics were comparable between the two groups. Brain was the most common site of metastasis for SOM patients. When compared to the MOM group, the SOM group had lower percentages of liver and adrenal metastases. Amongst SOM patients, 54 % received single modality treatment, and 20 % did not receive any treatment for their SOM. In MVA, patients with liver (HR 2.4), bone (HR 1.8), and pleural (HR 1.7) metastasis as their SOM site had the worst outcomes, with median OS of 6.8 months, 12.1 months, and 13.0 months respectively. Patients with SOM had a significantly improved median OS compared to those with MOM (15.9 months vs. 10.6 months; HR 0.56, 95 % CI 0.47-0.66, p < 0.001). CONCLUSION: In NSCLC patients who presented with SOM, survival correlated with the initial organ involved and was better overall compared to patients with MOM. SOM NSCLC may benefit from specific management strategies and SOM patients could be considered as a specific subgroup for survival analyses in observational and non-randomized interventional studies. In clinical trials, SOM can be considered as a stratification factor in the future.

Nurse-led renal cell carcinoma clinic: a single center review.

BACKGROUND: In 2015 our centre introduced a nurse-led renal cell cancer follow-up protocol and clinic for patients who have undergone partial or radical nephrectomy for organ-confined kidney tumours. The main aims of this clinic were to improve healthcare efficiency and standardize follow-up processes. OBJECTIVES: The primary objective was to assess the effectiveness of a nurse-led renal cell cancer follow up clinic in regard to surveillance protocol compliance and the timely identification and appropriate management of recurrences. A secondary objective was to evaluate this locally developed follow up protocol against the current European Association of Urology (EAU) guidelines surveillance protocol. PATIENT AND METHODS: All patients who underwent a partial or radical nephrectomy between 2015 and 2021 at a single Western Australia institution for a primary renal malignancy were included. Data was collected from local clinical information systems and protocol adherence, recurrence characteristics and management were assessed. The current EAU guidelines were applied to the cohort to assess differences in risk-stratification and theoretical outcomes between the protocols. RESULTS: After a mean follow up period of 31.2 months (range 0-77 months), 75.5% (185/245) of patients had all follow up imaging and reviews within 1 month of the timeframe scheduled on the protocol. 17.1% (42/245) had a delay in their follow up of more than a month at some stage, 5.7% (14/245) did not attend for follow up but had documented attempts to facilitate their compliance, and 0.4% (1/245) were lost to follow up with no evidence of attempted contact. 15.5% (38/245) of patients had recurrence of malignancy detected during follow up and these were all discussed in a multi-disciplinary team (MDT) meeting. The recurrence rate was 2.5% (3/119) for low risk, 17.7% (14/79) for intermediate risk, and 44.7% (21/47) for high risk patients when they were re-stratified according to EAU risk categories. No recurrences were detected through ultrasound (USS) or chest x-ray (CXR) in this cohort and our protocol tended to place patients in higher risk-stratification groups as compared to current EAU guidelines. CONCLUSION: Nurse-led renal cell cancer follow up is a safe, reliable and effective clinical framework that has significant benefits in regard to resource utilization. USS and CXR are ineffective in detecting recurrence and Computerized tomography (CT) should be considered the imaging modality of choice for this purpose. The EAU surveillance protocol appears superior to our protocol, and we have therefore transitioned to the EAU guideline protocol going forward.

System-level recommendations for improved wellness for gynecologic oncologists: A Society of Gynecologic Oncology Review.

Burnout and its negative sequelae are a persistent problem in gynecologic oncology, threatening the health of our physician workforce. Individual-level interventions such as stress management training, physical activity, and sleep hygiene only partially address this widespread, systemic crisis rooted in the extended work hours and stressful situations associated with gynecologic oncology practice. There is an urgent need for systematic, institution-level changes to allow gynecologic oncologists to continue the crucial work of caring for people with gynecologic cancer. We present recommendations for institution-level changes which are grounded in the framework presented by the National Plan for Health Workforce Well-Being by the National Academy of Medicine. These are aimed at facilitating gynecologic oncologists' well-being and reduction of burnout. Recommendations include efforts to create a more positive and inclusive work environment, decrease administrative barriers, promote mental health, optimize electronic medical record use, and support a diverse workforce. Implementation and regular evaluation of these interventions, with specific attention to at-risk groups, is an important next step.

Auditory Brainstem Implant Outcomes in Tumor and Nontumor Patients: A Systematic Review.

OBJECTIVE: To elucidate the differences in auditory performance between auditory brainstem implant (ABI) patients with tumor or nontumor etiologies. DATA SOURCES: PubMed, Embase, and Web of Science Core Collection from 1990 to 2021. REVIEW METHODS: We included published studies with 5 or more pediatric or adult ABI users. Auditory outcomes and side effects were analyzed with weighted means for closed-set, open-set speech, and categories of auditory performance (CAP) scores. Overall performance was compared using an Adult Pediatric Ranked Order Speech Perception (APROSPER) scale created for this study. RESULTS: Thirty-six studies were included and underwent full-text review. Data were extracted for 662 tumor and 267 nontumor patients. 83% were postlingually deafened and 17% were prelingually deafened. Studies that included tumor ABI patients had a weighted mean speech recognition of 39.2% (range: 19.6%-83.3%) for closed-set words, 23.4% (range: 17.2%-37.5%) for open-set words, 21.5% (range: 2.7%-48.4%) for open-set sentences, and 3.1 (range: 1.0-3.2) for CAP scores. Studies including nontumor ABI patients had a weighted mean speech recognition of 79.8% (range: 31.7%-84.4%) for closed-set words, 53.0% (range: 14.6%-72.5%) for open-set sentences, and 2.30 (range: 2.0-4.7) for CAP scores. Mean APROSPER results indicate better auditory performance among nontumor versus tumor patients (3.5 vs 3.0, P = .04). Differences in most common side effects were also observed between tumor and nontumor ABI patients. CONCLUSION: Auditory performance is similar for tumor and nontumor patients for standardized auditory test scores. However, the APROSPER scale demonstrates better ABI performance for nontumor compared to tumor patients.

Advance care planning for patients with end-stage kidney disease on dialysis: narrative review of the current evidence, and future considerations.

Patients with end-stage kidney disease (ESKD) have a high symptom-burden and high rates of morbidity and mortality. Despite this, evidence has shown that this patient group does not have timely discussions to plan for deterioration and death, and at the end of life there are unmet palliative care needs. Advance care planning is a process that can help patients share their personal values and preferences for their future care and prepare for declining health. Earlier, more integrated and holistic advance care planning has the potential to improve access to care services, communication, and preparedness for future decision-making and changing circumstances. However, there are many barriers to successful implementation of advance care planning in this population. In this narrative review we discuss the current evidence for advance care planning in patients on dialysis, the data around the barriers to advance care planning implementation, and interventions that have been trialled. The review explores whether the concepts and approaches to advance care planning in this population need to be updated to encompass current and future care. It suggests that a shift from a problem-orientated approach to a goal-orientated approach may lead to better engagement, with more patient-centred and satisfying outcomes.

Survival differences by race and surgical approach in early-stage operable cervical Cancer.

OBJECTIVE: To evaluate if the higher rate of open radical hysterectomy in Black patients, prior to the widespread return to open surgical techniques, mitigated survival disparities and to identify other actionable factors to target for systemic change. METHODS: This is a retrospective cohort study including patients from the National Cancer Database with cervical cancer who underwent radical hysterectomy from 2010 to 2018. Patient demographics, clinical characteristics and survival were compared by race and surgical route. Kaplan-Meier plots were constructed. Cox proportional hazards modeling was used to adjust for covariates. RESULTS: 7201 patients were eligible for inclusion, 687 (9.5%) Black and 4870 (68%) White. We found that 51% of Black patients and 39% of White patients underwent open surgery. Black patients were 10% less likely to receive Guideline Concordant Care (GCC). Those with publicly-funded insurance had a 40% higher hazard of death compared to private insurance (CI 1.19-1.73 p < 0.001). Black patients who had open surgery had similar 5-year survival compared to White patients who had MIS surgery (0.90 vs 0.91, NS). After adjusting for potential confounders including age, insurance, nodal status, and lymphovascular space invasion, Black patients who had surgery had a 40% higher hazard for death (HR 1.40 95% CI 1.10-1.79, p = 0.007) compared to White patients. CONCLUSIONS: A lower 5 and 10-year survival was seen in Black patients, regardless of surgical approach. Adjustment for significant covariates did not resolve this disparity, confirming that these factors do not fully account racial disparities.

Presentation and outcomes of KRASG12C mutant non-small cell lung cancer patients with stage IV disease at diagnosis (de novo) versus at recurrence.

Close monitoring after diagnosis of patients with stage I-III non-small cell lung cancer (NSCLC) may result in fitter patients with lower disease burden at the time of metastatic recurrence or progression compared to patients diagnosed initially as stage IV (de novo). We compared the presentation, treatments, and outcomes of patients with KRASG12C-mutated NSCLC with de novo versus recurrent stage IV disease. Of 109 patients, 94% had a smoking history. When compared to patients with KRASG12C-mutated NSCLC who developed stage IV disease at recurrence (n = 38), de novo stage IV patients (n = 71) had worse ECOG performance status (p = 0.007), greater numbers of extra-thoracic metastatic sites (p = 0.001), and were less likely to receive 2nd/3rd line systemic therapy (p = 0.05, p = 0.002) or targeted therapy (p = 0.001). De novo metastatic patients had shorter overall survival than metastatic patients at recurrence (9.1 versus 24.2 months; adjusted-hazard-ratio=1.94 (95% CI: 1.14-3.28; p = 0.01)). There is a critical need for well-tolerated targeted therapies in the first-line setting for metastatic patients with de novo, high-burden, stage IV KRASG12C-mutated NSCLCs.

Association between duration of smoking abstinence before non-small-cell lung cancer diagnosis and survival: a retrospective, pooled analysis of cohort studies.

BACKGROUND: The association between duration of smoking abstinence before non-small-cell lung cancer (NSCLC) diagnosis and subsequent survival can influence public health messaging delivered in lung-cancer screening. We aimed to assess whether the duration of smoking abstinence before diagnosis of NSCLC is associated with improved survival. METHODS: In this retrospective, pooled analysis of cohort studies, we used 26 cohorts participating in Clinical Outcomes Studies of the International Lung Cancer Consortium (COS-ILCCO) at 23 hospitals. 16 (62%) were from North America, six (23%) were from Europe, three (12%) were from Asia, and one (4%) was from South America. Patients enrolled were diagnosed between June 1, 1983, and Dec 31, 2019. Eligible patients had smoking data before NSCLC diagnosis, epidemiological data at diagnosis (obtained largely from patient questionnaires), and clinical information (retrieved from medical records). Kaplan-Meier curves and multivariable Cox models (ie, adjusted hazard ratios [aHRs]) were generated with individual, harmonised patient data from the consortium database. We estimated overall survival for all causes, measured in years from diagnosis date until the date of the last follow-up or death due to any cause and NSCLC-specific survival. FINDINGS: Of 42 087 patients with NSCLC in the COS-ILCCO database, 21 893 (52·0%) of whom were male and 20 194 (48·0%) of whom were female, we excluded 4474 (10·6%) with missing data. Compared with current smokers (15 036 [40·0%] of 37 613), patients with 1-3 years of smoking abstinence before NSCLC diagnosis (2890 [7·7%]) had an overall survival aHR of 0·92 (95% CI 0·87-0·97), patients with 3-5 years of smoking abstinence (1114 [3·0%]) had an overall survival aHR of 0·90 (0·83-0·97), and patients with more than 5 years of smoking abstinence (10 841 [28·8%]) had an overall survival aHR of 0·90 (0·87-0·93). Improved NSCLC-specific survival was observed in 4301 (44%) of 9727 patients who had quit cigarette smoking and was significant at abstinence durations of more than 5 years (aHR 0·87, 95% CI 0·81-0·93). Results were consistent across age, sex, histology, and disease-stage distributions. INTERPRETATION: In this large, pooled analysis of cohort studies across Asia, Europe, North America, and South America, overall survival was improved in patients with NSCLC whose duration of smoking abstinence before diagnosis was as short as 1 year. These findings suggest that quitting smoking can improve overall survival, even if NSCLC is diagnosed at a later lung-cancer screening visit. These findings also support the implementation of public health smoking cessation strategies at any time. FUNDING: The Alan B Brown Chair, The Posluns Family Fund, The Lusi Wong Fund, and the Princess Margaret Cancer Foundation.

Maternal and childhood medical history and the risk of childhood brain tumours: a case-control study in Ontario, Canada.

BACKGROUND: Studies to date have yielded inconclusive results as to whether maternal medical history during pregnancy, and a child's early-life medical history contribute to the development of childhood brain tumours (CBTs). This study examined associations between maternal and childhood medical history and the risk of CBTs. METHODS: The Childhood Brain Tumour Epidemiology Study of Ontario (CBREO) examined children 0-15 years of age with newly diagnosed CBTs from 1997 to 2003. Multivariable logistic regression analysis determined associations for prenatal medications and childhood medical history, adjusted for child's demographics, and maternal education. Analyses were stratified by histology. A latency period analysis was conducted using 12- and 24-month lead times. RESULTS: Maternal intake of immunosuppressants during the prenatal period was significantly associated with glial tumours (OR 2.73, 95% CI 1.17-6.39). Childhood intake of anti-epileptics was significantly associated with CBTs overall, after accounting for 12-month (OR 8.51, 95% CI 3.35-21.63) and 24-month (OR 6.04, 95% CI 2.06-17.70) lead time before diagnosis. No associations for other medications were found. CONCLUSIONS: This study underscores the need to examine potential carcinogenic effects of the medication classes highlighted and of the indication of medication use. Despite possible reverse causality, increased CBT surveillance for children with epilepsy might be warranted.

The genomic landscape of familial glioma.

Glioma is a rare brain tumor with a poor prognosis. Familial glioma is a subset of glioma with a strong genetic predisposition that accounts for approximately 5% of glioma cases. We performed whole-genome sequencing on an exploratory cohort of 203 individuals from 189 families with a history of familial glioma and an additional validation cohort of 122 individuals from 115 families. We found significant enrichment of rare deleterious variants of seven genes in both cohorts, and the most significantly enriched gene was HERC2 (P = 0.0006). Furthermore, we identified rare noncoding variants in both cohorts that were predicted to affect transcription factor binding sites or cause cryptic splicing. Last, we selected a subset of discovered genes for validation by CRISPR knockdown screening and found that DMBT1, HP1BP3, and ZCH7B3 have profound impacts on proliferation. This study performs comprehensive surveillance of the genomic landscape of familial glioma.

Differential prognostic significance of sarcopenia in metastatic esophageal squamous and adenocarcinoma.

BACKGROUND: Sarcopenia indicates poor prognosis in various malignancies. We evaluated the association of sarcopenia with overall (OS) and progression-free survival (PFS) in metastatic esophageal cancer (MEC) patients, a population often presenting with poor nutritional status. METHODS: In newly diagnosed MEC patients managed at the Princess Margaret (PM) Cancer Centre (diagnosed 2006-2015), total muscle area, visceral adiposity (VA), and subcutaneous adiposity (SA) were quantified on abdominal computed tomography at L3. Sarcopenia was determined using published cutoffs, based on sex and height. RESULTS: Of 202 MEC patients, most were male (166/82%), < 65 years (116/57%), and had adenocarcinoma histology (141/70%); 110/54% had recurrent MEC after initial curative-intent treatment; 92/46% presented with de novo MEC. At stage IV diagnosis, 20/10% were underweight, 97/48% were normal-weight and 84/42% were overweight/obese; 103/51% were sarcopenic. Sarcopenia was associated with worse median OS (4.6 vs. 7.9 months; log-rank p = 0.03) and 1-year survival, even after adjusting for other body composition variables (e.g., BMI, VA, and SA): adjusted-HR 1.51 [95% CI 1.1-2.2, p = 0.02]. In post hoc analysis, sarcopenia was highly prognostic in adenocarcinomas (p = 0.003), but not squamous cell carcinomas (SCC). In patients receiving palliative systemic treatment (104/51%), sarcopenia was associated with shorter PFS (p = 0.004) in adenocarcinoma patients (75/72%). CONCLUSIONS: In metastatic esophageal adenocarcinomas, sarcopenia is associated with worse PFS and OS. In metastatic esophageal SCC, there was a non-significant trend for worse PFS but no association with OS. In order to offset the poor prognosis associated with sarcopenia particularly in metastatic esophageal adenocarcinoma patients, future research should focus on possible countermeasures.

Respiratory and Cardiometabolic Comorbidities and Stages I to III NSCLC Survival: A Pooled Analysis From the International Lung Cancer Consortium.

INTRODUCTION: We explored the association of respiratory and cardiometabolic comorbidities with NSCLC overall survival (OS) and lung cancer-specific survival (LCSS), by stage, in a large, multicontinent NSCLC pooled data set. METHODS: On the basis of patients pooled from 11 International Lung Cancer Consortium studies with available respiratory and cardiometabolic comorbidity data, adjusted hazard ratios (aHRs) were estimated using Cox models for OS. LCSS was evaluated using competing risk Grey and Fine models and cumulative incidence functions. Logistic regression (adjusted OR [aOR]) was applied to assess factors associated with surgical resection. RESULTS: OS analyses used patients with NSCLC with respiratory health or cardiometabolic health data (N = 16,354); a subset (n = 11,614) contributed to LCSS analyses. In stages I to IIIA NSCLC, patients with respiratory comorbidities had worse LCCS (stage IA aHR = 1.51, confidence interval [CI]: 1.17-1.95; stages IB-IIIA aHR = 1.20, CI: 1.06-1.036). In contrast, patients with stages I to IIIA NSCLC with cardiometabolic comorbidities had a higher risk of death from competing (non-NSCLC) causes (stage IA aHR = 1.34, CI: 1.12-1.69). The presence of respiratory comorbidities was inversely associated with having surgical resection (stage IA aOR = 0.54, CI: 0.35-0.83; stages IB-IIIA aOR = 0.57, CI: 0.46-0.70). CONCLUSIONS: The presence of either cardiometabolic or respiratory comorbidities is associated with worse OS in stages I to III NSCLC. Patients with respiratory comorbidities were less likely to undergo surgery and had worse LCSS, whereas patients with cardiometabolic comorbidities had a higher risk of death from competing causes. As more treatment options for stages I to III NSCLC are introduced into the practice, accounting for cardiometabolic and respiratory comorbidities becomes essential in trial interpretation and clinical management.

Real-World Treatment Sequencing, Toxicities, Health Utilities, and Survival Outcomes in Patients with Advanced ALK-Rearranged Non-Small-Cell Lung Cancer.

OBJECTIVES: This real-world analysis describes treatment patterns, sequencing and clinical effectiveness, toxicities, and health utility outcomes in advanced-stage, incurable ALK-positive NSCLC patients across five different ALK-TKIs. MATERIALS AND METHODS: Clinicodemographic, treatment, and toxicity data were collected retrospectively in patients with advanced-stage ALK-positive NSCLC at Princess Margaret Cancer Centre. Patient-reported symptoms, toxicities, and health utilities were collected prospectively. RESULTS: Of 148 ALK-positive NSCLC patients seen July 2009-May 2021, median age was 58.9 years; 84 (57%) were female; 112 (76%) never-smokers; 54 (47%) Asian and 40 (35%) white; 139 (94%) received at least one ALK-TKI: crizotinib (n = 74; 54%) and alectinib (n = 61; 44%) were administered mainly as first-line ALK-TKI, ceritinib, brigatinib and lorlatinib were administered primarily after previous ALK-TKI failure. Median overall survival (OS) was 54.0 months; 31 (21%) patients died within two years of advanced-stage diagnosis. Treatment modifications were observed in 35 (47%) patients with crizotinib, 19 (61%) with ceritinib, 41 (39%) with alectinib, 9 (41%) with brigatinib and 8 (30%) with lorlatinib. Prevalence of dose modifications and self-reported toxicities were higher with early versus later generation ALK-TKIs (P<.05). The presence of early treatment modification was not negatively associated with progression-free survival (PFS) and OS analyses. CONCLUSION: Serial ALK-TKI sequencing approaches are viable therapeutic options that can extend quality of life and quantity-of-life, though a fifth of patients died within two years. No best single sequencing approach could be determined. Clinically relevant toxicities occurred across all ALK-TKIs. Treatment modifications due to toxicity may not necessarily compromise outcomes, allowing multiple approaches to deal with ALK-TKI toxicities.

Vessel wall magnetic resonance and arterial spin labelling imaging in the management of presumed inflammatory intracranial arterial vasculopathy.

Optimal criteria for diagnosing and monitoring response to treatment for infectious and inflammatory medium-large vessel intracranial vasculitis presenting with stroke are lacking. We integrated intracranial vessel wall MRI with arterial spin labelling into our routine clinical stroke pathway to detect presumed inflammatory intracranial arterial vasculopathy, and monitor disease activity, in patients with clinical stroke syndromes. We used predefined standardized radiological criteria to define vessel wall enhancement, and all imaging findings were rated blinded to clinical details. Between 2017 and 2018, stroke or transient ischaemic attack patients were first screened in our vascular radiology meeting and followed up in a dedicated specialist stroke clinic if a diagnosis of medium-large inflammatory intracranial arterial vasculopathy was radiologically confirmed. Treatment was determined and monitored by a multi-disciplinary team. In this case series, 11 patients were managed in this period from the cohort of young stroke presenters (<55 years). The median age was 36 years (interquartile range: 33,50), of which 8 of 11 (73%) were female. Two of 11 (18%) had herpes virus infection confirmed by viral nucleic acid in the cerebrospinal fluid. We showed improvement in cerebral perfusion at 1 year using an arterial spin labelling sequence in patients taking immunosuppressive therapy for >4 weeks compared with those not receiving therapy [6 (100%) versus 2 (40%) P = 0.026]. Our findings demonstrate the potential utility of vessel wall magnetic resonance with arterial spin labelling imaging in detecting and monitoring medium-large inflammatory intracranial arterial vasculopathy activity for patients presenting with stroke symptoms, limiting the need to progress to brain biopsy. Further systematic studies in unselected populations of stroke patients are needed to confirm our findings and establish the prevalence of medium-large artery wall inflammation.

Separation of radium and actinium using zirconia.

Zirconia was investigated as a radiation-resistant support for radium and actinium aqueous ion separations. Acetate and total metal ion concentrations were experimentally evaluated as factors that could affect retention using La and Ba surrogates. Pseudo-second order rate constants were derived and the uptake of La was determined to be endothermic. Elution profiles containing Ba, La, 228Ra, 228Ac, and 212Pb are presented and discussed.

Treatment patterns and outcomes in early-stage ALK-rearranged non-small cell lung cancer.

INTRODUCTION: We evaluated the baseline demographics, treatment patterns, and outcomes of patients with ALK-rearranged early stage (Stage I-III) non-small cell lung cancer (NSCLC). We also evaluated the efficacy and toxicity of durvalumab consolidation treatment in patients with ALK-rearranged unresectable stage III disease. METHODS: Retrospective chart-review analysis of all patients with histologically confirmed stage I-III reflexively tested ALK-rearranged NSCLC managed with curative intent at two Canadian Centers. RESULTS: Of 48 patients, 19 (40%) were stage I, 5 (10%) were stage II and 24 (50%) were stage-III. Median progression-free survival (PFS) was 27.6 months overall (95%CI: 20.5-51.4) and 144.4 months in stage-I, 27.6 months in stage-II and 14.9 months in stage III patients. Of 20 patients with unresectable stage-III disease treated with chemoradiation (9 also received durvalumab consolidation), 18/90% have relapsed. Median PFS was 10.9 months (95%CI:5.9-22.5). A non-significant trend toward improved PFS was seen in patients receiving additional durvalumab compared to patients treated with chemoradiation alone (median PFS, 12.5 vs 5.9 months, p = 0.16). Toxicity-related treatment modifications on subsequent first ALK-TKI at time of metastatic disease were needed in three (33%) patients who had received chemoradiation alone and two (29%) patients with consolidation durvalumab; no relevant pulmonary or hepato-toxicity was observed overall. CONCLUSION: Treatment strategies and PFS of patients with Stage I-III ALK-rearranged NSCLC are similar to patients without molecular driver alterations. Durvalumab consolidation treatment appears generally safe in patients with unresectable stage III ALK-rearranged disease; however, the degree of benefit of such an approach remains unclear.

Accounting for EGFR Mutations in Epidemiologic Analyses of Non-Small Cell Lung Cancers: Examples Based on the International Lung Cancer Consortium Data.

BACKGROUND: Somatic EGFR mutations define a subset of non-small cell lung cancers (NSCLC) that have clinical impact on NSCLC risk and outcome. However, EGFR-mutation-status is often missing in epidemiologic datasets. We developed and tested pragmatic approaches to account for EGFR-mutation-status based on variables commonly included in epidemiologic datasets and evaluated the clinical utility of these approaches. METHODS: Through analysis of the International Lung Cancer Consortium (ILCCO) epidemiologic datasets, we developed a regression model for EGFR-status; we then applied a clinical-restriction approach using the optimal cut-point, and a second epidemiologic, multiple imputation approach to ILCCO survival analyses that did and did not account for EGFR-status. RESULTS: Of 35,356 ILCCO patients with NSCLC, EGFR-mutation-status was available in 4,231 patients. A model regressing known EGFR-mutation-status on clinical and demographic variables achieved a concordance index of 0.75 (95% CI, 0.74-0.77) in the training and 0.77 (95% CI, 0.74-0.79) in the testing dataset. At an optimal cut-point of probability-score = 0.335, sensitivity = 69% and specificity = 72.5% for determining EGFR-wildtype status. In both restriction-based and imputation-based regression analyses of the individual roles of BMI on overall survival of patients with NSCLC, similar results were observed between overall and EGFR-mutation-negative cohort analyses of patients of all ancestries. However, our approach identified some differences: EGFR-mutated Asian patients did not incur a survival benefit from being obese, as observed in EGFR-wildtype Asian patients. CONCLUSIONS: We introduce a pragmatic method to evaluate the potential impact of EGFR-status on epidemiological analyses of NSCLC. IMPACT: The proposed method is generalizable in the common occurrence in which EGFR-status data are missing.

Longitudinal Assessment of Health Utility Scores, Symptoms and Toxicities in Patients with Small Cell Lung Cancer Using Real World Data.

INTRODUCTION: Recent advances in small cell lung cancer (SCLC) treatments necessitate a better understanding of real-world health utility scores (HUS) in patients treated under current standards to facilitate robust pharmaco-economic assessments. METHODS: In this single institution cohort observational study, HUS were evaluated in patients with SCLC through EQ-5D questionnaires at outpatient visits (encounters). In addition, patients completed questionnaires relating to treatment toxicities and cancer symptoms. Clinical and pathological variables were abstracted from electronic medical records and disease status at each patient visit was documented. The impact of these variables on HUS were explored. RESULTS: There were 282 clinical encounters (12% newly diagnosed; 37% stable on treatment; 22% progressing on treatment; 29% stable off therapy/other) in 111 SCLC patients (58% male; 64% extensive stage (ES) SCLC). At the first encounter 29% of patients had an ECOG performance status (PS) ≥ 2. ES-SCLC, bone metastases, female sex, progressive disease and/or PS were each significantly associated with decreased HUS in multivariable analyses. Patients clinically stable on first line therapy had generally steady HUS longitudinally, with differences in HUS between limited disease (LD) and ES patients emerging as treatment progressed. Decreased HUS were associated with increased severity of the majority of measured symptoms (fatigue/tiredness, loss of appetite, pain, drowsiness, shortness of breath, anxiety, depression, and overall well-being; each p<0.001), supporting the value of EQ-5D-derived HUS in assessing health utility. CONCLUSION: Our HUS values in chemotherapy-treated SCLC are clinically relevant and are associated with specific clinico-demographic, symptom and toxicity factors.

Childhood head trauma and the risk of childhood brain tumours: A case-control study in Ontario, Canada.

Head trauma in early childhood has been hypothesized as a potential risk factor for childhood brain tumours (CBTs). However, head trauma has not been extensively studied in the context of CBTs and existing studies have yielded conflicting results. A population-based and hospital-based case-control study of children 0 to 15 years with newly diagnosed CBTs from 1997 to 2003 recruited across Ontario through paediatric oncology centres was conducted. Controls were frequency-matched with cases by age, sex and geographical region. The association was assessed based on multivariable logistic regressions, accounting for child's age, sex, ethnicity, highest level of maternal education and maternal pack-years of smoking during the pregnancy. Analyses were conducted separately based on age of first head trauma, sex and histology. A latency period analysis was conducted. Overall, based on 280 cases and 919 controls, CBTs were not significantly associated with previous history of head trauma (OR 1.34, 95% CI 0.96, 1.86), head trauma severity, number of head injuries, or head or neck X-rays or computed tomography (CT) examinations. Results were consistent across sexes and histological subtypes. However, head trauma within the first year of life was significantly associated with CBTs (OR 2.00, 95% CI 1.01, 3.98), but the association diminished when adjusted for X-ray or CT occurring during the same time period (OR 1.62, 95% CI 0.75, 3.49), albeit limited sample size. Overall, no association was observed between head trauma and CBTs among all children, while head trauma occurring within first year of life may warrant further investigation in future research.