Real-world evaluation of access-driven Canadian treatment sequences in progressive prostate cancer (REACTIVATE).

INTRODUCTION: The results of the phase 3 ALSYMPCA trial showed that Radium-223 (Ra-223) improves overall survival (OS) and delays onset of first symptomatic skeletal event vs. placebo in patients with metastatic castration-resistant prostate cancer (mCRPC). The purpose of the REACTIVATE study was to inform the optimal placement of Ra-233 in the treatment sequence by evaluating clinical outcomes and healthcare resource utilization using real-world data from multiple Canadian provinces. METHODS: This retrospective cohort study analyzed patient outcomes according to Ra-223 placement using administrative databases of four Canadian provinces, encompassing 4301 patients with mCRPC who received at least two lines of life-prolonging therapy (LPT) for mCRPC. Outcomes included OS, event-free survival (EFS), and healthcare resource utilization. Each province was analyzed separately. RESULTS: OS, measured from the start of second-line LPT, differed between provinces: those in Ontario receiving second-line Ra-223 had a longer OS vs. those receiving it in third-line or later (hazard ratio [HR] 0.79, 95% confidence interval [CI] 0.66-0.95). There was no difference between lines of therapy in patients in British Columbia (HR 1.165, 95% CI, 0.894-1.518, p=0.2576), and OS was numerically worse but not statistically significant in patients receiving Ra-223 in second-line in Quebec (HR 1.44, 95% CI, 0.93-2.24). Other outcomes also varied across provinces, with second-line use of Ra-223 being associated with longer EFS and reduced healthcare utilization vs. third-line use in Ontario but not in Quebec. CONCLUSIONS: Significant heterogeneity exists in the management and outcomes of mCRPC between provinces, particularly regarding the placement of Ra-223 in the treatment sequence.

BeTTer Outcomes Workgroup Health Quality Initiative to optimize bone health for prostate cancer patients in the British Columbia Cancer System.

INTRODUCTION: Bone-targeted therapies (BTTs) are integral to the management of bone metastases in metastatic castration-resistant prostate cancer (mCRPC). BTTs vary considerably in referral and drug access pathways and optimal BTT use requires multi-specialty consultation and supervision. Health quality improvement (HQI) has become the predominant framework to improve patient care in multidisciplinary settings. METHODS: HQI initiatives on use of BTT in mCRPC were developed and evaluated in five centers of a provincial cancer center network using Plan-Do-Study-Act (PDSA) methodology. Multidisciplinary teams (MDTs) completed a common quality assessment form and an HQI template and then implemented an HQI initiative. Feedback and findings were shared and discussed at regional events. It was subsequently determined whether to adopt, adapt, or abandon initiatives. RESULTS: Patterns of unmet needs varied across type of BTT. Gaps in use of radium-223 were mostly referral and education issues that could be directly addressed at the local level by participating clinician teams. Conversely, most supportive BTT gaps were related to coverage and resourcing support. HQI initiatives selected by each site consisted of implementation or expansion of local MDT meetings, referral documents, databases, and improvement charters. The main HQI initiative was completed in four sites and was adapted or adopted in three. Improvements in BTT use were observed in two of three centers with data on HQI process measures. CONCLUSIONS: Despite the overall heterogenous structure of the groups and metrics used, this study demonstrated that the PDSA framework provides the needed structure for improvements in BTT use in mCRPC across multiple sites.

Treatment patterns and outcomes of patients with locally advanced vulvar or vaginal cancer in British Columbia.

OBJECTIVE: As vulvar and vaginal cancers are rare malignancies, treatment is extrapolated from the cervical cancer field. Further studies are necessary to evaluate whether surgery, radiotherapy (RT), or combined chemoRT is most beneficial. METHODS: A retrospective chart review was conducted on patients diagnosed with vulvar or vaginal cancer in 2000-2017. Descriptive statistics was used to summarize demographic factors. Kaplan-Meier curves, log-rank tests, multivariate analysis with hazard ratios (HR) were conducted to compare survival outcomes, including overall survival (OS), disease-free survival, and cancer-specific survival, between surgery, RT, and chemoRT. RESULTS: This study included 688 patients with either vulvar (n = 560, 81%) or vaginal cancer (n = 128, 19%). Median age of diagnosis was 68 (27-98) years. In multivariate survival analysis, vulvar cancer was associated with more likelihood of death (HR: 1.50, p = 0.042) compared to vaginal cancer. For patients who received definitive RT, median OS was 63.8 months with concurrent chemotherapy vs. 46.3 months without for vulvar cancer (p = 0.75); for vaginal, median OS 100.4 with chemotherapy vs. 66.6 months without (p = 0.31). For vulvar cancer patients who received RT (n = 224), adding chemotherapy (n = 100) was not associated with statistically significant OS improvement (HR: 0.989, p = 0.957). Similarly, vaginal cancer patients who received chemoRT (n = 51) did not have significant OS benefit (HR: 0.720, p = 0.331) over patients who received RT (n = 49). CONCLUSIONS: In this retrospective study, chemoRT was not associated with significant improvements in survival compared to RT in vulvar or vaginal cancer. Future studies investigating novel therapies to treat these cancers are needed to improve patient outcomes.

Follow-Up Imaging Guidelines for Patients with Stage III Unresectable NSCLC: Recommendations Based on the PACIFIC Trial.

The PACIFIC trial showed a survival benefit with durvalumab through five years in stage III unresectable non-small cell lung cancer (NSCLC). However, optimal use of imaging to detect disease progression remains unclearly defined for this population. An expert working group convened to consider available evidence and clinical experience and develop recommendations for follow-up imaging after concurrent chemotherapy and radiation therapy (CRT). Voting on agreement was conducted anonymously via online survey. Follow-up imaging was recommended for all suitable patients after CRT completion regardless of whether durvalumab is received. Imaging should occur every 3 months in Year 1, at least every 6 months in Year 2, and at least every 12 months in Years 3-5. Contrast computed tomography was preferred; routine brain imaging was not recommended for asymptomatic patients. The medical oncologist should follow-up during Year 1 of durvalumab therapy, with radiation oncologist involvement if pneumonitis is suspected; medical and radiation oncologists can subsequently alternate follow-up. Some patients can transition to the family physician/community primary care team at the end of Year 2. In Years 1-5, patients should receive information regarding smoking cessation, comorbidity management, vaccinations, and general follow-up care. These recommendations provide guidance on follow-up imaging for patients with stage III unresectable NSCLC whether or not they receive durvalumab consolidation therapy.

Patient, disease, and survival outcomes for stage IB to stage IV cervical cancer-A population study.

BACKGROUND: Factors that impact recurrence in stages IB to IV include larger tumor, high-risk histology, older age, and lymphovascular invasion (LVI); however, local studies on risk factors for recurrence in British Columbia and our local recurrence patterns have not been well studied. Furthermore, the efficacy of treatment modalities including surgery and chemoradiation in the different stages of cervical cancer have not been clarified in this population. OBJECTIVES: The purpose of this study is to determine the disease and treatment characteristics of stages IB to IV cervical cancer which are associated with survival differences within British Columbia. METHODS/DESIGN: We performed a retrospective population study. A chart review on cervical cancer patients in British Columbia between 1 January 2010 and 31 December 2017 was done. Demographic data and treatment details were collected. Data were analyzed using multivariate Cox regressions, pairwise comparison using the Log-Rank test, and chi-square tests. RESULTS: We included 780 patients (stage I: 31.5%, II: 20.0%, III: 34.5%, and IV: 3.3%). LVI and p16 negativity were associated with decreased overall survival (OS), and multivariate analyses show them to be independent risk factors for poorer survival. Surgical resection in stage I was associated with improved survival, but not with stages II-IV. The use of radical radiation therapy (RT), brachytherapy, and concurrent chemotherapy were independently associated with improved survival in stages II-IV. Peri-RT chemotherapy was not associated with survival benefit in adeno/adenosquamous carcinoma. There were 180 recurrences (23.1%), mostly distant metastases (42.8%). There were fewer recurrences after resection of tumors <2 cm compared to tumors 2 cm or larger (6.49% vs 31.3%, p = 0.00011). Only 37.7% of recurrence/metastases were treated with first-line carboplatin/paclitaxel/bevacizumab, but it was associated with better OS compared to other regimens (median OS 40.1 vs 24.8 months, p = 0.03). CONCLUSION: A significant portion of patients with localized cervical cancer relapse despite radical therapy, with LVI and p16 negativity associated with poorer survival. Surgical resection may still play a role in stage IB disease, while RT, brachytherapy, and concurrent chemotherapy should be considered first-line therapy in stage II-IV diseases. First-line carboplatin, paclitaxel, and bevacizumab for recurrence shows improved survival.

Real-world experience managing unresectable or metastatic small cell carcinoma of the prostate.

INTRODUCTION: Unresectable and metastatic small cell carcinoma of the prostate (SCPC) is a rare and aggressive disease that is under-represented in clinical trials. We carried out a retrospective chart review of metastatic or unresectable SCPC patients at British Columbia (BC) Cancer centers, studying diagnosis and treatment patterns. METHODS: Drug-dispensing records from the six BC Cancer centers were obtained from 2002-2017. For each patient, information was collected on baseline information prior to therapy and for each line of treatment. Treatments at each line were compared regarding time to progression and overall survival by Kaplan-Meier curves. RESULTS: Forty-one patients received treatment; 65.6% had metastatic disease and 61% had pure small cell carcinoma. Median time from treatment to death was 10 months (95% confidence interval [CI] 6-16). Patients with initially prostate-confined disease had a better median overall survival (mOS) of 21 months (95% CI 13-34) compared to those with initially locally advanced (mOS 19 months, 95% CI 5-37) and metastatic disease (mOS 8 months, 95% CI 6-10) (log-rank p=0.0364). All patients received either cisplatin- or carboplatin-based combination chemotherapy as the first-line treatment and 36.7% received second-line therapy. Time to second-line therapy was eight months for those who presented with metastatic SCPC, compared to 13 months for those with initial non-metastatic SCPC. CONCLUSIONS: This single-province, multi-institution cohort reports data on unresectable and metastatic SCPC and highlights the poor prognosis of this rare disease entity.

Survival Outcomes Associated with First and Second-Line Palliative Systemic Therapies in Patients with Metastatic Bladder Cancer.

BACKGROUND: Real-world data on palliative systemic therapies (PST) in treating metastatic bladder cancer (mBC) is limited. This study investigates current trends in treating mBC with first- (1L) and second-line (2L) chemotherapy (CT) and immunotherapy (IT). METHODS: A chart review was conducted on patients diagnosed with stage II-IV bladder cancer in 2014-2016. Survival outcomes were compared between chemotherapy, immunotherapy, and supportive care. RESULTS: out of 297 patients, 77% were male. 44% had stage IV disease at diagnosis. Median age at metastasis was 73 years. 40% of patients received 1L PST and 34% received 2L PST. Median overall survival (mOS) was longer in those receiving PST versus no treatment (p < 0.001). Patients receiving CT and IT sequentially had the longest mOS (18.99 months). First-line IT and CT mOS from treatment start dates were 5.03 and 9.13 months, respectively (p = 0.81). Gemcitabine with cisplatin (8.88 months) or carboplatin (9.13 months) were the most utilized 1L chemotherapy regimens (p = 0.85). 2L IT and CT mOS from treatment start dates were 6.72 and 3.78 months, respectively (p = 0.15). CONCLUSION: real-world mOS of >1.5 years in mBC is unprecedented and supports using multiple lines of PST. Furthermore, immunotherapy may be a comparable alternative to chemotherapy in both 1L and 2L settings.

Serious Illness Conversation-Evaluation Exercise: A Novel Assessment Tool for Residents Leading Serious Illness Conversations.

Background/Objectives: The serious illness conversation (SIC) is an evidence-based framework for conversations with patients about a serious illness diagnosis. The objective of our study was to develop and validate a novel tool, the SIC-evaluation exercise (SIC-Ex), to facilitate assessment of resident-led conversations with oncology patients. Design: We developed the SIC-Ex based on SIC and on the Royal College of Canada Medical Oncology milestones. Seven resident trainees and 10 evaluators were recruited. Each trainee conducted an SIC with a patient, which was videotaped. The evaluators watched the videos and evaluated each trainee by using the novel SIC-Ex and the reference Calgary-Cambridge guide (CCG) at months zero and three. We used Kane's validity framework to assess validity. Results: Intra-class correlation using average SIC-Ex scores showed a moderate level of inter-evaluator agreement (range 0.523-0.822). Most evaluators rated a particular resident similar to the group average, except for one to two evaluator outliers in each domain. Test-retest reliability showed a moderate level of consistency among SIC-Ex scores at months zero and three. Global rating at zero and three months showed fair to good/very good inter-evaluator correlation. Pearson correlation coefficients comparing total SIC-Ex and CCG scores were high for most evaluators. Self-scores by trainees did not correlate well with scores by evaluators. Conclusions: SIC-Ex is the first assessment tool that provides evidence for incorporating the SIG guide framework for evaluation of resident competence. SIC-Ex is conceptually related to, but more specific than, CCG in evaluating serious illness conversation skills.

MYB-NFIB gene fusions identified in archival adenoid cystic carcinoma tissue employing NanoString analysis: an exploratory study.

BACKGROUND: Adenoid cystic carcinoma (ACC) is a slow growing salivary gland malignancy that is molecularly characterized by t(6:9)(q22-23;p23-24) translocations which predominantly result in MYB-NFIB gene fusions in nearly half of tumours. Detection of MYB-NFIB transcripts is typically performed with fresh ACC tissue using conventional RT-PCR fragment analysis or FISH techniques, which are prone to failure when only archival formalin fixed paraffin embedded (FFPE) tissue is available. The purpose of this pilot study was to evaluate the utility of NanoString probe technology for the detection of MYB-NFIB transcripts in archival ACC tissue. METHODS: A NanoString probeset panel was designed targeting the junctions of three currently annotated MYB-NFIB fusion genes as well as 5'/3' MYB probesets designed to detect MYB gene expression imbalance. RNA isolated from twenty-five archival ACC specimens was profiled and analyzed. RT-qPCR and sequencing were performed to confirm NanoString results. MYB protein expression was analyzed by immunohistochemistry. RESULTS: Of the 25 samples analyzed, 11/25 (44%) expressed a high degree of MYB 5'/3' imbalance and five of these samples were positive for at least one specific MYB-NFIB variant in our panel. MYB-NFIB variant detection on NanoString analysis was confirmed by direct cDNA sequencing. No clinical correlations were found to be associated with MYB fusion status. CONCLUSION: We conclude that the application of NanoString digital probe counting technology is well suited for the detection and quantification of MYB-NFIB fusion transcripts in archival ACC specimens.

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

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

Small cell carcinoma of cervix: A population-based study evaluating standardized provincial treatment protocols.

OBJECTIVES: To describe the patient characteristics, patterns of treatment, and outcome of patients with small cell carcinoma of Cervix (SmCC) treated with radical radiotherapy from a provincial cancer registry database. METHODS: Overall 25 patients with SmCC were treated with radical radiotherapy (with or without chemotherapy) from January 1, 1994 to December 31, 2013. Nineteen patients had pure SmCC while 6 had additional neuroendocrine component. Patients were treated with combined chemo-radiotherapy using multi-agent chemotherapy with pelvic or combined pelvic and para-aortic radiotherapy. All patients received brachytherapy. Use of prophylactic cranial irradiation was dependent on physician discretion. Survival was estimated using Kaplan-Meier method and compared using log-rank test. RESULTS: We report a median overall survival of 53.8 months for our cohort. After a median follow-up of 54 months for surviving patients, the overall survival (OS) and progression free survival (PFS) at 5-years were 48% and 46.4% respectively. Patients with stage I-IIA disease had superior 5-year PFS (67.3% vs. 11.1%; p = .004) and 5-year OS (62.5% vs. 22.2%; p = .006). Patients with node-negative disease had a trend towards better 5-year PFS (55.7% vs. 19%; p = .07) and OS (61.1% vs. 14.3% at 5-years; p = .06) Distant metastasis was the predominant site of disease progression (n = 12; 48%). CONCLUSION: Distant metastasis is the predominant pattern of failure for patients with SmCC treated with radical chemo-radiotherapy. With modern chemo-radiotherapy protocols we can expect a 5 year survival of around 50%. Early stage and node-negative status appear to be favorable prognostic factors with survival rates at 5-year over 60%.

Causes of mortality in older patients with stage 3 colon cancer.

OBJECTIVES: Life expectancy plays a key role in the selection of patients with stage III colon cancer for adjuvant chemotherapy, but little is known about causes of mortality in older patients with colon cancer. We aimed to examine causes of death in this population and compare these causes between patients who received chemotherapy and those who did not. Specifically, we chose to examine the rates of death related to recurrent colon cancer versus non colon cancer. MATERIALS AND METHODS: Patients aged 50 and older diagnosed with stage III colon cancer between 2005 and 2009 were included. Patients were divided into "younger" (aged 50-69) and "older" (aged 70+). Causes of death, which were categorized into colon cancer versus non-colon cancer related. RESULTS: 1361 patients were included, 50% of whom were 70 or older. Younger patients were more likely to receive adjuvant chemotherapy (90% vs. 60%). 601 patients died in the follow up period. Deceased patients in the younger group were more likely to die from colon cancer (81% vs. 62%). The most common cause of non-colon cancer death was other primary malignancies in younger patients and cardiovascular diseases in older patients. In older patients who received chemotherapy, 41% died; 89% of these deaths were related to colon cancer. In older patients who did not receive chemotherapy 72% died, with 38% of patients ultimately dying from colon cancer. CONCLUSIONS: Older patients remain under-treated with chemotherapy. Although non-colon cancer deaths were more frequent in older patients with cancer, colon cancer was a still a significant cause of mortality. These deaths may be preventable with adjuvant chemotherapy.

Whole-genome and transcriptome profiling of a metastatic thyroid-like follicular renal cell carcinoma.

Thyroid-like follicular renal cell carcinoma (TLFRCC) is a rare cancer with few reports of metastatic disease. Little is known regarding genomic characteristics and therapeutic targets. We present the clinical, pathologic, genomic, and transcriptomic analyses of a case of a 27-yr-old male with TLFRCC who presented initially with bone metastases of unknown primary. Genomic DNA from peripheral blood and metastatic tumor samples were sequenced. A transcriptome of 280 million sequence reads was generated from the same tumor sample. Tumor somatic expression profiles were analyzed to detect aberrant expression. Genomic and transcriptomic data sets were integrated to reveal dysregulation in pathways and identify potential therapeutic targets. Integrative genomic analysis with The Cancer Genome Atlas (TCGA) data set revealed the following outliers in gene expression profiles: CDK6 (81st percentile), MYC (99th percentile), AR (100th percentile), PDGFRA and PDGFRB (99th and 100th percentiles, respectively), and MAP2K2 (86th percentile). The patient received first-line sunitinib to target PDGFRA and PDGFRB and had stable disease for >6 mo, followed by nivolumab upon progression. To the authors' knowledge, this is the first reported case of comprehensive somatic genomic analyses in a patient with metastatic TLFRCC. Somatic analyses provided molecular confirmation of the primary site of cancer and potential therapeutic strategies in a rare disease with little evidence of efficacy on systemic therapy.

Recent advances in circulating tumor cells and cell-free DNA in metastatic prostate cancer: a review.

INTRODUCTION: The treatment landscape of metastatic prostate cancer has changed dramatically over the past five years. As new discoveries are made and further novel therapies become available, there is a heightened urgency to develop biomarkers that can guide prognoses and predict therapy responses. Circulating tumor cells (CTCs) and cell-free circulating tumor DNA (ctDNA) in the blood have emerged as potential promising tumor avatars. Areas covered: In this review, we describe technological breakthroughs and clinical implementation of the CTCs and ctDNA. We also discuss the key challenges that must be overcome before circulating blood-based biomarkers can be universally adopted into the management of patients with metastatic prostate cancer. Expert commentary: Both CTCs and ctDNA have the potential to be incorporated into routine patient care, with increasing numbers of prospective trials incorporating them into clinical designs. CTCs and ctDNA will thus have an increasingly valuable role in augmenting our understanding of prostate cancer at a molecular level, aiding in prognostication of prostate cancer patients, acting as a surrogate for OS in clinical trials, and helping us prioritize our treatment selections by elucidating resistance mechanisms.

Disease characteristics and survival outcomes of extragonadal primary germ cell tumour in two Canadian tertiary cancer centres.

INTRODUCTION: Extragonadal germ cell tumours (EGCTs) are a heterogeneous group with distinct natural history and responses to treatment modalities. We sought to evaluate characteristics and survival outcomes in men with EGCTs. METHODS: We performed a retrospective analysis on a consecutive list of men diagnosed with EGCT in two Albertan cancer centres between 1990 and 2013. Demographic characteristics and outcomes, stratified by primary site, were evaluated. RESULTS: Sixty-nine cases were identified. The median age was 29 (range 15-76) and 48 cases (70%) were non-seminomatous. Twenty-four (35%) belonged to International Germ Cell Cancer Collaborative Group (IGCCCG) favourable risk group, 14 (20%) to intermediate, and 31 (45%) to poor. Thirty (43%) had mediastinal primary (MPs); 29 were treated with first-line bleomycin, etopo-side, and cisplatin (BEP). Seventeen (57%) relapses occurred, of which three patients achieved long-term survival. Seventeen (25%) had a central nervous system (CNS) primary, with eight (47%) classic germinoma. Seven (41%) received primary chemotherapy alone; 5 (29%) received primary radiotherapy alone, and 5 (29%) received both. Nineteen (28%) had a retroperitoneal primary (RPs) and received first-line chemotherapy; all but two received BEP and eight (42%) had surgical resection. Three (5%) had other or unknown primary. Five-year overall survival (OS) and disease-free survival for all patients were 56% and 44%, respectively; for MPs, 44% and 34%; for CNS primary, 76% and 53%; for RPs, 58% and 53%. Factors that correlated with decreased OS were elevated alpha fetoprotein (AFP) (p<0.001) or human chorionic gonadotropin (HCG) (p=0.001), lactate dehydrogenase (LDH) levels (p=0.028), bone metastasis (p<0.001), lung metastasis (p<0.001), and IGCCCG poor risk (p=0.001). CONCLUSIONS: EGCT is a rare, but important subset of GCT. Patients with EGCTs, despite aggressive treatments, still have poorer outcomes than gonadal primary.

Conditional Survival of Patients With Metastatic Testicular Germ Cell Tumors Treated With First-Line Curative Therapy.

PURPOSE: The International Germ Cell Cancer Collaborative Group (IGCCCG) criteria prognosticate survival outcomes in metastatic testicular germ cell tumor (MT-GCT), but how the initial risk changes over time for those who survived since curative treatment is unknown. PATIENTS AND METHODS: We assessed patients eligible for first-line therapy for MT-GCT at five tertiary cancer centers from 1990 to 2012 for 2-year conditional overall survival (COS) and conditional disease-free survival (CDFS), defined as the probability of surviving, or surviving and being disease free, respectively, for an additional 2 years at a given time point since the initial diagnosis. RESULTS: For all patients (N = 942), 2-year COS increased from 92% (95% CI, 91% to 94%) at 0 months to 98% (95% CI, 97% to 99%), and 2-year CDFS increased from 83% (95% CI, 81% to 86%) at baseline to 98% (95% CI, 97% to 99%) at 24 months after diagnosis. Two-year COS improved by 2% (97% at 0 months, 99% at 24 months) in the IGCCCG favorable-risk group, by 5% (94% at 0 months, 99% at 24 months) in the intermediate-risk group, and by 22% (71% at 0 months to 93% at 24 months) in the poor-risk group. Two-year CDFS improved significantly at 12 months for each risk group (favorable, 91% baseline v 95% at 12 months; intermediate, 84% v 95%; poor, 55% v 85%). Baseline IGCCCG risk stratification was not associated with long-term COS or CDFS for patients who survived to greater than 2 years post therapy. No significant differences in COS and CDFS were noted between seminoma and nonseminoma; patients ≥ 40 years old had inferior 2-year COS from 0 to 12 months, but no differences were noted at 18 months. CONCLUSION: Our data suggest that the concept of conditional survival applies to patients with MT-GCT treated with curative therapy. Patients with MT-GCT who survived and remained disease free more than 2 years after the diagnosis had an excellent chance of staying alive and disease free in additional subsequent years, regardless of the initial IGCCCG risk stratification.

Reasons for Underuse of Adjuvant Chemotherapy in Elderly Patients With Stage III Colon Cancer.

BACKGROUND: Undertreatment has been frequently reported in the elderly cancer patient population. For this reason, we aimed to characterize adjuvant chemotherapy (AC) use among elderly patients (EPs) with stage III colon cancer (CC) and to identify potential reasons for undertreatment. PATIENTS AND METHODS: Patients diagnosed with stage III CC between 2008 and 2010 were included in this review. Multivariate Cox regression models were constructed to evaluate the associations between AC and cancer-specific, disease-free, and overall survival and to determine whether these were modified by age. RESULTS: We identified 810 patients: 423 (52%) men, 423 (52%) young patients (YPs), and 603 (74%) received AC. Compared with YPs, EPs were less likely to receive AC (57% vs. 91%; P < .01), particularly 5-fluorouracil and oxaliplatin (FOLFOX) (32% vs. 74%, P < .01). Frequent reasons for nontreatment included age, comorbidities, and perceived minimal benefit from AC. When AC was given, EPs had similar rates of treatment discontinuations (34% vs. 26%; P > .05) and dose reductions (63% vs. 61%; P > .05) as YPs. Reasons for treatment interruptions included side effects, progressive disease, and patient choice. Receipt of either FOLFOX or capecitabine was correlated with improved cancer-specific survival, disease-free survival, and overall survival compared with surgery alone; this effect was not modified by age. CONCLUSION: Elderly patients with stage III CC frequently received either no AC or capecitabine monotherapy because of advanced age and comorbidities. The effect of AC on survival was similar across age groups, with comparable side effects and rates of treatment modifications. AC should not be withheld because of advanced age alone.

The International Metastatic Renal Cell Carcinoma Database Consortium model as a prognostic tool in patients with metastatic renal cell carcinoma previously treated with first-line targeted therapy: a population-based study.

BACKGROUND: Previous prognostic models for second-line systemic therapy in patients with metastatic renal cell carcinoma have not been studied in the setting of targeted therapy. We sought to validate the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) model in patients with metastatic renal cell carcinoma receiving next-line targeted therapy after progression on first-line targeted therapy. METHODS: In this population-based study, we analysed patients who received second-line targeted therapy for metastatic renal cell carcinoma at 19 centres in Canada, USA, Greece, Japan, Singapore, South Korea, and Denmark. The primary endpoint was overall survival since the initiation of second-line therapy. We compared the prognostic performance of the IMDC model with the three-factor MSKCC model used for previously treated patients for overall survival since the start of second-line targeted therapy. FINDINGS: Between Jan 1, 2005, and Nov 30, 2012, we included 1021 patients treated with second-line targeted therapy. Median overall survival since the start of second-line targeted therapy was 12·5 months (95% CI 11·3-14·3). Five of six predefined factors in the IMDC model (anaemia, thrombocytosis, neutrophilia, Karnofsky performance status [KPS] <80, and <1 year from diagnosis to first-line targeted therapy) were independent predictors of poor overall survival on multivariable analysis. The concordance index using all six prognostic factors (ie, also including hypercalcaemia) was 0·70 (95% CI 0·67-0·72) with the IMDC model and was 0·66 (95% CI 0·64-0·68) with the three-factor MSKCC model. When patients were divided into three risk categories using IMDC criteria, median overall survival was 35·3 months (95% CI 28·3-47·8) in the favourable risk group (n=76), 16·6 months (14·9-17·9) in the intermediate risk group (n=529), and 5·4 months (4·7-6·8) in the poor risk group (n=261). INTERPRETATION: The IMDC prognostic model can be applied to patients previously treated with targeted therapy, in addition to previously validated populations in first-line targeted therapy. The IMDC prognostic model in the second-line targeted therapy setting has an improved prognostic performance and is applicable to a more contemporary patient cohort than that of the three-factor MSKCC model. FUNDING: DF/HCC Kidney Cancer SPORE P50 CA101942-01, Kidney Cancer Research Network of Canada, Canadian Institute for Health Research, Trust Family, Loker Pinard, Michael Brigham, and Gerald DeWulf.

Getting the word out: advice on crying and colic in popular parenting magazines.

The objective of this study is to determine whether advice in parenting magazines reflects current evidence-based understanding of early infant crying and colic, where (1) "colic" is the upper end of a spectrum of crying behavior reflective of normal infant development, and (2) physical abuse--in particular, shaken baby syndrome (SBS)--is a serious medical consequence of early crying. All available issues of 11 popular Canadian parenting magazines published between January 2000 and December 2004 were hand-searched and systematically reviewed. Fifty-one articles were found with information on: (1) causes of, (2) responses to, and/or (3) mention of SBS or abuse as a consequence of crying and/or colic. There were 105 specific causes suggested, but almost no agreement concerning the causes of crying and colic. Similarly, there were 231 specific responses to crying and colic mentioned, but little agreement among the suggested responses. For both crying and colic together, the consequence of abuse was mentioned only 7 times, and SBS only twice. Making the advice literature a truly helpful vehicle for parents concerning normal behavioral development and its consequences for their new infant seems to be a significant challenge. Arguably, this is an important shared responsibility of physicians, researchers, and journalists.