Differences In Stage Distribution Research Articles

OP22 Benchmarking Of Population-Based Childhood Cancer Survival By Toronto Stage: Know The Differences To Propose Effective Interventions

IntroductionPediatric cancers are rare tumors, heterogeneous in location and biologically very different from adult cancers. Documented survival variation across European countries and Italian regions shows that there is still room for further improvement by reducing inequalities. We aim to understand why there are differences in survival. The BENCHISTA-ITA project (National Benchmarking of Childhood Cancer Survival by Stage at diagnosis), that is the Italian twin project of the International BENCHISTA, collects stage at diagnosis of solid pediatric tumors, according to the Toronto Guidelines. We will compare how far the cancer has spread at diagnosis and test if differences in tumor stage explain any survival differences between Italian regions.MethodsThe project study involved the stage distribution and the survival of 9 pediatric solid tumors diagnosed between 2013 and 2017 in Italy. All patients therefore had at least 3 years of follow-up in 2021 for life-stage definition. The study involves the identification of all new diagnoses of cancer, evaluation of the clinical documentation of cases eligible for research, and international classification and coding. Analyses of stage distribution and survival rates for each tumor type will be described.ResultsData from 35 population-based cancer registries from 18 out of 20 Italian regions were collected covering about 84 percent of the Italian child population. In particular, data on: imaging/examination performed before any treatment; source used for staging; primary treatment defined as given within one year from diagnosis; relapse/ recurrence/ progression; follow up and status of life. The study tested the applicability of the Toronto Guidelines as a tool to obtain population-level comparable stage information for childhood cancers. There were 1,343 cases collected (242 Neuroblastoma, 124 Wilms Tumour, 145 Medulloblastoma, 148 Osteosarcoma, 135 Ewing sarcoma, 115 Rhabdomyososarcoma, 54 Ependymoma, 47 Retinoblastoma, 333 Astrocytoma). Toronto stage could be assigned in more than 90 percent in the majority of tumors. Tumors in which it was more difficult to assign the stage using the Toronto staging guidelines were ependymoma, astrocytoma, and retinoblastoma. It was easier to retrieve data for patients in the 0-14 years of age range than adolescents (14-18 years). Differences in stage distribution and survival differences between regional grouping were presented.ConclusionsThe Italian BENCHISTA project, improving the connection between pediatric cancer registries, aims to improve care of children with cancer across the nation, reducing possible disparities.The wide adoption of the Toronto Guidelines will facilitate international comparative incidence studies, strengthen the interpretation of survival data, and contribute to more appropriate solutions to improve childhood cancer outcomes.

Regional differences in stage distribution and rates of treatment for adrenocortical carcinoma across United States SEER registries.

We tested for regional differences across United States (US) in rates of adrenalectomy, systemic therapy, and adrenalectomy and systemic therapy combination for adrenocortical carcinoma (ACC) patients. We hypothesized that no differences exist, especially after accounting for baseline patient and tumor characteristics. Within Surveillance, Epidemiology, and End Results (SEER) database (2004-2018), 1275 ACC patients were identified. Distribution of patient age, tumor size, ENSAT (European Network for the Study of Adrenal Tumors) stages, and treatments were tabulated and graphically displayed, according to nine geographical registries, corresponding to the population of specific states, cities or macro areas of the US on which the data are based on. Multinomial models predicted treatment probability for each patient according to registries. Patients count according to registries ranged from 62 to 509. Differences across registries existed for age (range 54-59 years; P=0.4), tumor size (8.5-11.0 cm; P=0.2), ENSAT stage (1-11% vs. 17-35% vs. 18-32% vs. 24-44%, in respectively ENSAT stage I, II, III, and IV), and treatment distribution (35-53% vs. 5-21% vs. 23-42%, in respectively adrenalectomy, systemic therapy, and adrenalectomy and systemic therapy combination; P=0.039). After adjustment for age, stage and year of diagnosis, clinically meaningful residual differences across registries remained for adrenalectomy (33-54%), systemic therapy (4-19%), and adrenalectomy and systemic therapy combination (20-38%). However, most variability originated from registries with smallest sample sizes. We identified important variability in ACC treatment according to SEER geographical registries, even after considering baseline patient and tumor characteristics. These findings may be indicative of differences in quality of care or expertise in ACC management.

Elucidating the genomic and transcriptomic landscape of L858R vs ex19del EGFR-mutated NSCLC.

8530 Background: Epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) is heterogeneous and L858R derive less benefit from osimertinib than ex19del in both the metastatic and adjuvant setting, which remains poorly understood. We sought to examine the genomic and transcriptomic features of L858R vs ex19del. Methods: Consecutive patients with AJCC7 Stage IA-IIIA EGFR-mutated NSCLC diagnosed 1/1/2010 – 31/12/2019 who underwent surgery at National Cancer Centre Singapore were included. Patients who received neoadjuvant therapy were excluded. Fresh frozen tumour and normal samples were subject to whole exome sequencing (WES) at 400X and 100X coverage respectively, with approximately 50 million paired-end reads for RNA-seq per sample. Wilcoxon and Fisher’s exact test were used for association analysis. Results: A total of 203 patients were included. Median age at diagnosis was 66, 66.0% (134/203) were females and 84.2% (171/203) never-smokers. Stage IA comprised 44.3% (90/203), IB 28.6% (58/203), II 15.8% (32/203) and IIIA 11.3% (23/203). Median tumour mutational burden (TMB) was 1.3 mutations/megabase (range 0.3 – 44.3). Ex19del represented 46.3% (94/203) and L858R 41.9% (85/203). Whole genome doubling (WGD) was found in 70.0% (142/203) and was more common in TP53-mutated compared to TP53-wildtype (81.1% vs. 63.6%, p=0.01). TP53 mutations were more common in stage II/IIIA tumours compared with stage IB and IA (50.9% vs 32.8% vs 30.0%, p=0.035). Comparing ex19del and L858R, there was no difference in stage distribution (p=0.337), proportion of TMB≥10 (1.1% vs 5.9%, p=0.103), number of cancer co-driver mutations (p=0.174), TP53 mutations (39.4% vs 32.9%, p=0.437) and WGD (69.1% vs 76.5%, p=0.316). L858R had a higher incidence of smoking mutational signature (median 0.35 vs 0.28, p=0.018) compared to ex19del despite similar smoking history (15.3% vs 12.8%, p=0.67), whereas APOBEC mutational signature was higher in ex19del (median 0.06 vs 0.04, p=0.015). L858R tumors were associated with a higher incidence of co-mutations in RBM10 (21.2% vs 6.38%, p=0.004), RNF213 (10.6% vs 1.06%, p=0.007) and amplification of NTHL1 (15.3% vs 2.13%, p=0.001) and AXIN1 (17.6% vs 3.19%, p=0.002) compared to ex19del. Transcriptomic subtype differed significantly by EGFR mutation with a higher representation of TRU subtype among L858R than ex19del (51.0% vs 35.3%, p=0.010), while GEP score was similar (median 0.189 vs 0.325, p=0.122). Conclusions: L858R have distinct co-mutations and copy number alterations compared to ex19del, in addition to a higher representation of smoking mutational signature and TRU subtype. TP53 co-mutations are more frequently observed in higher stage tumours and are associated with WGD. Our findings highlight the molecular heterogeneity of resected EGFR-mutated NSCLC, which could contribute to the differential outcomes to adjuvant osimertinib between ex19del and L858R.

Age-related differences in colon and rectal cancer survival by stage, histology, and tumour site: An analysis of United States SEER-18 data

Age-related differences in colon and rectal cancer survival have been observed, even after accounting for differences in background mortality. To determine how stage, tumour site, and histology contribute to these differences, we extracted age-specific one-year relative survival ratio (RS) stratified by these factors. We used colon and rectal cancer cases diagnosed between 2012 and 2016 from 18 United States Surveillance Epidemiology and End Results cancer registries. For colon cancer, 1-year RS ranged from 87.8 % [95 % Confidence Interval: 87.5–88.2] in the 50–64-year-olds to 62.3 % [61.3–63.3] in 85–99-year-olds and for rectal cancer ranged from 92.3 % [91.8–92.7] to 65.0 % [62.3–67.5]. With respect to stage, absolute differences in RS between 50-64-year-olds and 75–84-year-olds increased with increasing stage (from 6 [5–7] %-points in localised disease to 27 [25–29] %-points in distant disease) and were the highest for cancers of unknown stage (> 28 %-points). Age-related differences in survival were smallest for persons with tumours in the right-sided colon (8 [7–9] %-points) and largest for tumours of the colon without tumour site further specified (25 [21–29] %-points). With respect to histology, differences ranged from 7.4 % to 10.6 %-points for cancers with one of the three primary histologies (adenocarcinoma, mucinous adenocarcinoma, signet ring cell carcinoma) and were several-fold higher (42 %-points) for those with unknown/other histology (< 6 % of cases). Because age-related differences in survival were observed for all histologies and tumour sites, RS differences are unlikely to be driven by differences in the distribution of these factors by age. Differences in stage distribution by age are likely to contribute toward age-related differences in survival. Within stage groups, age differences in survival could be explained by frailty and/or therapy. Future studies incorporating data on treatment and geriatric conditions including frailty and comorbidity would support further understanding of the age gap in colon and rectal cancer survival.

Abstract P2-13-05: Triple Negative Breast Cancer (TNBC) patients are more likely to digitally explore clinical trial options and prior to receiving treatment for advanced disease compared to non-TNBC patients

Abstract Introduction: Triple-negative breast cancer (TNBC), an aggressive form of breast cancer (BC) that is associated with poor prognosis, accounts for 10-15% of all BCs. Chemotherapy remains the standard of care (SOC) for advanced disease, with limited clinical benefit. Oncology clinical trials (CTs) are globally recommended and encouraged as the preferred treatment (tx) option for any cancer patient (pt). ‘TrialJectory’ (TJ) is an artificial intelligence (AI)-based technology that matches pts to oncology CTs. Here, we identified distinct characteristics of TNBC pts who signed up to the TJ platform compared to non-TNBC pts. Methods: Using AI and an unsupervised natural language processing approach, the TJ platform clinically matches pts to CTs. Matching is achieved by pt response to an online dynamic questionnaire (www.trialjectory.com) that collects detailed clinical data including clinico-pathologic characteristics, tx history, general health, and comorbidities. Those are compared to the eligibility criteria of available CTs to yield a high-quality actionable matched-trial list. Results: Between 1/2020 and 12/2021, out of 9796 BC pts that signed up, 2688 were TNBC pts (27%). There was no significant difference in age at sign-up between TNBC and non-TNBC patients (median age of 57 years vs 58 years, respectively). Consistently with Non-hispanic black (NHB) race prevalence in the different molecular subtypes in the general US population, NHB race had higher signup rate in TNBC compared to non-TNBC (9.95% vs 5.76%, respectively). TNBC pts signed up at a later disease stage compared to non-TNBC pts (19% of TNBC reported having a stage 1 disease compared to 27% of non-TNBC pts, p&amp;lt; 0.001).A significantly higher percentage of pts with advanced/metastatic TNBC signed up to the TJ platform before starting tx compared to non-TNBC patients (34% vs 22%, respectively, p&amp;lt; 0.001). Furthermore, there was a significant difference in the willingness to travel any distance within the US for a matched clinical trial between TNBC and non-TNBC pts (39% vs 34%, respectively, p&amp;lt; 0.001). Conclusions: In this study, we found significant differences in the characteristics of TNBC vs non-TNBC pts that have signed up to the TJ platform. There was an up to 2-fold enrichment of TNBC on the TJ platform pts compared to their frequency in the general population. While previous studies do not show a difference in stage distribution between different subtypes, TNBC patients initiated their search for CTs at a higher stage. In addition, advanced TNBC patients started their search earlier in their journey, before starting chemotherapy. This may reflect the lack of effective SOC and possibly, the motivation to avoid the use of chemotherapy. This is also supported by the willingness of TNBC patients to travel farther in order to identify and enroll in a CT compared to non-TNBC pts. Importantly, the motivation of TNBC pts to travel any distance has not been reduced despite the COVID-19 pandemic, reflecting a strong drive of this pt population to enroll in CTs. It also demonstrates that with the right access, diverse patient populations are willing to participate in clinical trials. In sum, TNBC pts are more likely to explore CT options, in the advanced stage setting, earlier in their journey. This study demonstrates the power of TJ platform for clinico-pathologic characterization and diverse pt groups, including their drivers and behavioral choices during their battle with cancer. Citation Format: Michal Safran, Yelena Lapidot, Tzvia Bader, Avital Gaziel. Triple Negative Breast Cancer (TNBC) patients are more likely to digitally explore clinical trial options and prior to receiving treatment for advanced disease compared to non-TNBC patients [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-13-05.

Regional differences in stage distribution and rates of treatment for adrenocortical carcinoma across United States SEER registries

Regional differences in stage distribution and rates of treatment for adrenocortical carcinoma across United States SEER registries

Abstract A007: Trends and racial and ethnic disparities in colorectal cancer by anatomic subsite and stage at diagnosis, 2000-2019

Abstract Introduction: Subsite-specific incidence rates (IRs) of colorectal cancer (CRC) vary considerably by race/ethnicity and patterns of stage at diagnosis by anatomic subsite may reflect access to CRC screening. We examine racial and ethnic trends and differences in CRC IRs by stage and subsite in a screening eligible population. Methods: The Surveillance, Epidemiology, and End Results 17 registries database identified 374,582 patients aged 50-74 diagnosed with adenocarcinoma CRC from 2000-2019. Stage-specific (In situ/localized, regional, distant), age-adjusted IRs were computed by subsite (proximal, distal, rectal) and race/ethnicity (White, Black, Asian/Pacific Islander [API], American Indian/Alaskan Native [AIAN], and Hispanic). Trends in IRs were measured using annual percentage change (APC) and absolute change. Proportional stage distribution (percent contribution of each cancer stage) were calculated and compared using chi-squared tests. Supplemental analyses compared differences in stage distribution within API subgroups (Filipino, Chinese, Japanese, Korean, Vietnamese, Pacific Islander). Results: From 2000-2019, IRs decreased across all CRC subsites and racial and ethnic groups except for AIAN patients. For AIAN patients, the incidence of rectal cancer increased over time (APC=1.24, p&amp;lt;0.05), while IRs for proximal and distal colon cancer remained stable over time. When stratified by stage, the steepest percent decreases in IRs were among in situ/localized and regional stages, with smaller declines for distant stage tumors across all race/ethnic groups. As of 2018-2019, IRs of distant stage tumors of the proximal (IRR=2.09, p&amp;lt;0.001) and distal colon (IRR=1.51, p&amp;lt;0.001) cancers remained 1.5 to 2 times higher among Black patients compared to White patients, while API and Hispanic patients had similar or lower distant stage IRs for proximal and distal subsites. In contrast, stage-specific rectal cancer IRs were similar across race/ethnic groups. Proportional stage analysis revealed an increase in distant stage tumors and a decrease in in situ/localized stage tumors over time among distal colon and rectal subsites across all race/ethnic groups. As of 2018-2019, Black patients had higher percentages of distant stage tumors and lower percentages of in situ/localized tumors compared to other race/ethnic groups, and this was consistent across all three subsites. In supplemental analysis, Pacific Islander patients had higher percentages of distant stage CRC (22.6%), while Japanese patients had higher percentages of in situ/localized CRC (16.85%). Conclusions: Our findings suggest that racial and ethnic disparities in CRC vary by subsite, with Black patients experiencing higher rates of distant stage tumors of the proximal and distal colon. While decreases in CRC IRs highlight the positive impact of CRC screening and early detection efforts, more work is needed to reduce persistent disparities for Black patients. Variation by stage within API subgroups emphasizes the need to examine disparities among disaggregated racial and ethnic groups. Citation Format: Kristin M. Primm, Andrea Malabay, Taylor Curry, Shine Chang. Trends and racial and ethnic disparities in colorectal cancer by anatomic subsite and stage at diagnosis, 2000-2019 [abstract]. In: Proceedings of the AACR Special Conference on Colorectal Cancer; 2022 Oct 1-4; Portland, OR. Philadelphia (PA): AACR; Cancer Res 2022;82(23 Suppl_1):Abstract nr A007.

Abstract B114: Impact of nativity on survival among blacks with hepatocellular carcinoma in California (1988-2016)

Abstract Introduction/Objective The most striking racial/ethnic disparity among those with hepatocellular carcinoma (HCC) in the United States (US) is worse survival among black Americans. However, existing literature does not consider birthplace among blacks. Differences in risk factors for HCC between US-born (USB) and foreign-born (FB) blacks may influence the natural history of the disease. Our objective was to examine impact of nativity on survival among blacks with HCC utilizing a population-based cohort from California. Methods We identified cases of HCC (ICD-O-3: C220 and 8170) diagnosed between 1988 and 2016 in the statewide California Cancer Registry (CCR). Non-Hispanic black HCC cases with available birthplace information were included in this study (9.7% unknown excluded). Cases were identified as foreign-born if reported or estimated birthplace was outside of the US or its territories. Primary outcome was overall survival after HCC diagnosis. We examined distributions of sociodemographic and tumor characteristics by nativity including disease stage at diagnosis (localized, regional, or distant) and type of therapy received (none, surgical, or non-surgical). The association between nativity and survival was examined using Kaplan-Meier survival curves and multivariable Cox regression. Other factors associated with survival were also evaluated. Results A total of 4019 non-Hispanic black HCC cases were identified in CCR, of which 254 (12.6%) were FB. FB were more likely than USB to be female (30 vs 24%, p=0.02) and more likely to be diagnosed under the age of 40 (10 vs 1%) or between ages 40-50 (15 vs 7%, p&amp;lt;0.001). FB were also more likely to be of higher socioeconomic status (SES) (30 vs 21%, p&amp;lt;0.001). No obvious differences in stage distribution were noted between USB and FB with ~40% localized, ~25% regional, and ~24% distant disease. Nearly half of those in both groups received no treatment. Among those that received treatment, 19% of FB versus 24% of USB received surgical treatment (p=0.54). Overall 75% (191/253) of FB and 90% (3386/3761) of USB died, with median survival of 6 months (IQR 1-32) and 5 months (IQR 1-19), respectively. In multivariable analysis adjusting for age, sex, marital status, SES, tumor stage, and treatment type, FB had improved survival compared to USB (HR 0.8, p=0.006). For both FB and USB, localized stage of disease and receipt of any therapy type were associated with improved survival (p&amp;lt;0.001). Female sex and higher SES were associated with improved survival among USB (p&amp;lt;0.01). No association between age at diagnosis and survival was found for either group. Conclusion FB blacks in California more commonly present with HCC at younger age (&amp;lt;50) than USB. Overall survival was significantly better in FB than USB blacks, though remains low for both groups, and those diagnosed at younger age did not demonstrate improved survival. This study highlights the need to enhance our understanding of factors that contribute to poor outcomes among blacks with HCC. Citation Format: Kali Zhou, Ziwei Song, Norah A Terrault, Lihua Liu. Impact of nativity on survival among blacks with hepatocellular carcinoma in California (1988-2016) [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr B114.

Medicaid expansion and trends in cancer stage at diagnosis.

e14129 Background: Cancer stage distribution offers an early window into the effect of the ACA’s 2014 Medicaid expansion. If Medicaid expansion enabled uninsured adults to access preventive care, then the proportion of cancers diagnosed at early stage should be higher in states that adopted it. Methods: Patient level data were retrieved from SEER-18, New York and Texas cancer registries from January 2010 to December 2015, for eight common tumor types; including N = 2,493,589 (breast, cervical, colorectal, prostate, lung) screen detectable and N = 369,203 (testis, kidney and uterine corpus) not detected by routine screening. Patients were categorized by residence in states that were: 1) Non-expanders; 2) Expanders - income eligibility thresholds increased from 0% to 138% of the federal poverty level (FPL) in 2014; and 3) Pre-Expanders, with pre-2014 eligibility thresholds &gt; 70% of FPL. Stage distributions were compared before and after January 2014, categorized by AJCC stage and using ordinal stage equivalent (OSE) which assigns a numeric score based on AJCC stage. Difference in difference in difference (D3) methods compared patients ≥65 versus &lt; 65, and screen-detectable versus not. Multivariable logistic regression was used to adjust for variation in age, sex, race, ethnicity and tumor site across states. Results: No differences in stage distribution were observed across the three categories of state. (Table). D3 analysis revealed no difference between trends in the over 65s, or for screen-detectable cancers. Adjustment for age, sex, race, ethnicity and tumor site made no significant difference to these results. Conclusions: States’ Medicaid expansion status in 2014 was not associated with a significant difference in early stage diagnoses for adults with cancer diagnosed before age 65. Obstacles to early cancer detection other than financial access must be addressed to improve population-level outcomes. [Table: see text]

Potential gain in life years for Swedish women with breast cancer if stage and survival differences between education groups could be eliminated – Three what-if scenarios

Many studies have found evidence of socioeconomic differences in breast cancer survival. This study aimed to quantify the impact of removing differences in stage distribution and stage-specific relative survival between education groups in Swedish women with breast cancer. Using information from a breast cancer research database, the study population contained 62 121 women diagnosed with breast cancer in three healthcare regions of Sweden from 1992 to 2012. The loss in expectation of life and life years lost due to breast cancer were estimated using flexible parametric relative survival models by education group and age at diagnosis. The potential gain in life years and postponable deaths were calculated by applying the 1) stage distribution, 2) stage-specific relative survival, and 3) both stage distribution and stage-specific relative survival of the high education group to the low and medium education groups. For a cohort of around 3500 women diagnosed with breast cancer residing in three Swedish healthcare regions in a typical calendar year, we estimated that removing stage differences would postpone an additional 25 deaths at five years after diagnosis, and result in a gain of approximately 573 life years. Alternatively, if stage-specific breast cancer survival could be equated, approximately 692 life years could be saved and an additional 26 deaths could be postponed five years after diagnosis. Results such as these can help guide decisions on interventions intended to minimise socioeconomic differences in breast cancer outcomes.

Impact of laterality and mucinous histology on relapse-free and overall survival in a registry-based colon cancer series

Recent data suggest that tumor laterality and mucinous histology may be clinically relevant. We investigated how both variables impact on the prognosis and the response to therapies in a large population-based cohort of cancer patients. Incidence data, clinical and pathological features, and outcome were systematically collected from the Tumor Registry of Parma over the years 2004–2009. Survival data were modeled by multivariable analysis. 1358 patients affected by stage I–IV colon cancer were considered; 661 (49%) had right-sided and 697 (51%) left-sided tumors. 144 (11%) had mucinous (MAC) and 1214 (89%) non-mucinous (NMAC) histology. MACs and NMACs of the right colon showed no difference in stage distribution, whereas left colon MACs were more frequently in an advanced stage (stage IV) (p = 0.008). Stage IV right colon tumors had a poorer overall survival than stage IV left-sided colon cancers (75th percentile 20 vs 34 months, p < 0.001). At relapse, MACs were less responsive to systemic therapy and had worse survival compared with NMACs regardless of tumor side (7.1 vs 13.1 months, p = 0.018). Right-sided colon cancers had poorer survival compared to left-sided tumors; the effect was mainly attributable to NMACs. At relapse, MACs had unfavorable prognosis regardless of the primary tumor-side.

Treatment and Survival From Colorectal Cancer in Denmark, England, Norway, and Sweden: A Population-Based Study

Background: Colorectal cancer (CRC) patients in Denmark and England have historically had worse outcomes than patients diagnosed in other high-income countries with similar healthcare coverage. This survival deficit may be partly explained by differences in stage distribution due to delays in cancer diagnosis, however, differences in stage-specific survival suggest that differences in treatment also explain the survival gap. Aim: We aim to provide a comparison of stage-specific survival of CRC patients diagnosed in Denmark, England, Norway and Sweden, and compare the probability of receiving potentially curative surgery (PCS) by patient and tumor characteristics to understand whether differences in stage and treatment help explain the international differences in survival. Methods: Population-based information on patients aged 18-99 years diagnosed with primary malignant colon or rectal cancer in Denmark, England, Norway, and Sweden during 2010-2012 was extracted from national CRC registries. We compared the prevalence of PCS by stage and age category, and estimated the probability of receiving it using multivariate logistic regression. Age-standardized net survival was estimated using a multivariable modeling approach. Results: There were 13,230 patients diagnosed with CRC in Denmark, 99,869 in England, 11,754 in Norway, and 17,584 in Sweden between 2010 and 2012. The proportion of patients with missing stage information was higher in England than in the other countries. Stage distribution was otherwise similar. Survival of patients with stage I-II tumors was generally comparable between the countries, but lower in England and - to a lesser degree - in Denmark for stage III-IV disease. Patients with unknown stage had lower survival than staged patients in all countries. We found marked disadvantages in the probability of receiving PCS in older patients with stage II-IV disease in England, and stage IV colon cancer patients in Denmark. The proportion of surgically-treated rectal cancer patients (and their survival) was comparable between Denmark, Norway and Sweden for each combination of age group and stage, except for patients diagnosed with stage I disease. The proportion of patients receiving surgery and survival from rectal cancer was generally lower in England. Conclusion: Denmark seems to be catching up with Norway and Sweden, especially in rectal cancer survival. Despite recent improvements, CRC survival in England remains lower than in Sweden and Norway. Survival generally paralleled countries' relative performance in the provision of potentially curative surgery. Differences in patient selection for surgery, especially in older patients and/or with advanced disease, may partly explain the survival deficit. Increases in the proportion treated, in combination with efforts in postoperative care and with other treatment modalities, may translate into better longer-term outcomes, especially for frail patients.

Re: Characterization of Clinical Cases of Advanced Papillary Renal Cell Carcinoma via Comprehensive Genomic Profiling

Abstract Background Papillary renal cell carcinoma (PRCC) is a rare subset of RCC. The Cancer Genome Atlas (TCGA) data largely reflect localized disease, and there are limited data for advanced PRCC. Objective To characterize the frequency of genomic alterations (GAs) in patients with advanced PRCC for whom comprehensive genomic profiling (CGP) was performed in the context of routine clinical care. Design, setting, and participants Formalin-fixed, paraffin-embedded tissue was obtained for 169 consecutive patients with confirmed PRCC. DNA was extracted and comprehensive genomic profiling was performed in a certified central laboratory. Measurements Hybrid-capture, adaptor ligation-based libraries of up to 315 genes were sequenced to a median coverage of 648×. All classes of GAs were identified, including substitutions, insertions/deletions, copy number alterations, and rearrangements. Results and limitations From 169 patients, either primary tumor tissue (102 patients, 60%) or metastatic tissue (67 patients, 40%) was collected. In patients with type 1 PRCC, commonly altered genes were MET (33%; 8 activating mutations, 5 amplifications at >6 copies), TERT (30%), CDKN2A/B (13%), and EGFR (8%). In patients with type 2 PRCC, commonly altered genes were CDKN2A/B (18%), TERT (18%), NF2 (13%), and FH (13%); MET GAs (5 mutations, 3 amplifications) were observed in 7% of type 2 cases. Notable differences from TCGA data include higher frequencies of MET , NF2 , and CDKN2A/B GAs, association of alterations in SWI/SNF complex genes with type 2 PRCC, and observation of frequent CDKN2A/B alterations in both type 1 and type 2 disease. Conclusions Both the current study and the TCGA experience represent similarly sized cohorts of patients with PRCC. Key differences in GA frequency probably underscore the marked difference in stage distribution between these data sets. These results may inform planned precision medicine trials for metastatic PRCC. Patient summary Papillary renal cell carcinoma (PRCC) is a rare subtype of kidney cancer, and understanding of the biology of advanced PRCC is limited. This report highlights some of the unique biologic features of PRCC that may inform on future use of targeted therapies for the treatment of metastatic disease.

Endometrial Serous Carcinoma With Clear-Cell Change: Frequency and Immunohistochemical Analysis.

The diagnostic distinction between endometrial serous carcinoma (ESC) and endometrial clear-cell carcinoma (CCC) may occasionally be problematic, and one potentially contributing factor is the finding of clear cells in otherwise classic cases of ESC. This study aimed to define the frequency of this finding and comparatively assessed the immunophenotype of the clear cells. A review of 56 cases of ESC identified 8 (14.28%) with clear cells, representing 1% to 20% (median 7.5) of tumoral volume in these cases. In only 3 cases were clear cells discernible at low (×20) magnification. There was no significant difference in stage distribution or age between ESC patients with and without clear cells. The immunophenotypes of ESC-associated clear cells (group 1) were compared with foci of conventional ESC on another tissue block within the same case (group 2; n = 8) as well as a randomly selected cohort of CCC cases (group 3; n = 8). Groups 1 and 2 showed no significant differences regarding p53, ER, PR, Napsin-A, p504S, and hepatocyte nuclear factor 1β (HNF1β) expression, or regarding mitotic indices or Ki67 proliferation rate. In contrast, group 1 cases showed an immunophenotypic profile that was notably different from that of group 3 cases, with the former showing statistically significantly higher/more frequent expression of ER, PR, Ki67, and p53 and lower/less frequent expression of Napsin-A, p504S, and HNF1β. We conclude that clear-cell change is seen in 14% of ESCs and is discernible at low magnification in only 5%; these areas show an immunophenotype that is essentially identical to the associated background conventional ESC and are phenotypically dissimilar to CCC.

Characterization of Clinical Cases of Advanced Papillary Renal Cell Carcinoma via Comprehensive Genomic Profiling

BackgroundPapillary renal cell carcinoma (PRCC) is a rare subset of RCC. The Cancer Genome Atlas (TCGA) data largely reflect localized disease, and there are limited data for advanced PRCC. ObjectiveTo characterize the frequency of genomic alterations (GAs) in patients with advanced PRCC for whom comprehensive genomic profiling (CGP) was performed in the context of routine clinical care. Design, setting, and participantsFormalin-fixed, paraffin-embedded tissue was obtained for 169 consecutive patients with confirmed PRCC. DNA was extracted and comprehensive genomic profiling was performed in a certified central laboratory. MeasurementsHybrid-capture, adaptor ligation-based libraries of up to 315 genes were sequenced to a median coverage of 648×. All classes of GAs were identified, including substitutions, insertions/deletions, copy number alterations, and rearrangements. Results and limitationsFrom 169 patients, either primary tumor tissue (102 patients, 60%) or metastatic tissue (67 patients, 40%) was collected. In patients with type 1 PRCC, commonly altered genes were MET (33%; 8 activating mutations, 5 amplifications at >6 copies), TERT (30%), CDKN2A/B (13%), and EGFR (8%). In patients with type 2 PRCC, commonly altered genes were CDKN2A/B (18%), TERT (18%), NF2 (13%), and FH (13%); MET GAs (5 mutations, 3 amplifications) were observed in 7% of type 2 cases. Notable differences from TCGA data include higher frequencies of MET, NF2, and CDKN2A/B GAs, association of alterations in SWI/SNF complex genes with type 2 PRCC, and observation of frequent CDKN2A/B alterations in both type 1 and type 2 disease. ConclusionsBoth the current study and the TCGA experience represent similarly sized cohorts of patients with PRCC. Key differences in GA frequency probably underscore the marked difference in stage distribution between these data sets. These results may inform planned precision medicine trials for metastatic PRCC. Patient summaryPapillary renal cell carcinoma (PRCC) is a rare subtype of kidney cancer, and understanding of the biology of advanced PRCC is limited. This report highlights some of the unique biologic features of PRCC that may inform on future use of targeted therapies for the treatment of metastatic disease.

Comprehensive genomic profiling (CGP) of advanced papillary renal cell carcinoma (PRCC) to reveal distinctions from TCGA dataset.

4517 Background: Biologic characterization of PRCC by TCGA reveals alterations in MET in type 1 disease, and CDKN2Asilencing, SETD2 mutations and TFE3 fusions in type 2 disease. A limitation of TCGA data is that of 161 pts analyzed, 73% and 3% had M0 and M1 disease, respectively. We present the gene alterations (GA) identified in pts with advanced PRCC.Methods: FFPE tissue was obtained from 169 patients with PRCC. Diagnosis and PRCC subtyping was centrally confirmed by 2 board-certified pathologists. DNA was extracted and comprehensive genomic profiling (CGP) was performed (median coverage, 648X) in a CLIA-certified central laboratory. Results: Of 169 pts with advanced PRCC, 39 (23%) were type 1, 108 (64%) were type 2 and 22 (13%) were unclassified. 66 samples (39%) were from a metastatic site biopsy, and 103 were from the kidney (61%). An average of 2.4 GA/tumor were detected. In type 1 pts, commonly altered genes were MET (33%: 8 activating mutations, 5 amplifications), TERT (30%), CDKN2A/B (13%), and EGFR (8%). In type 2 pts, commonly altered genes were CDKN2A/B (18%), TERT (18%), NF2 (13%) and FH (13%); METGAs (5 mutations, 3 amplifications) were observed in 7.4% of type 2 pts. MET GA was significantly associated with type 1 PRCC (p = 0.0002) and NF2 GA and alterations in SWI/SNF complex genes were both significantly associated with type2 PRCC (p = 0.02 and p = 0.007, respectively). Overall, frequent alterations were found in genes involved in SWI/SNF complexes (25%), chromatin modification (23%) and cell cycle regulation (22%). RAS/RAF pathway (9%) and PI3K/mTOR pathway (8%). Notable differences with TCGA include higher frequencies of MET and NF2 GAs, association of GAs in the SWI/SNF with type 2 PRCC, and frequent CDKN2A/B alteration in both type 1 and type 2 disease. MET alteration was lower in metastases vs primary (type 1: 15% vs 38%; type 2: 4% vs 10%). Conclusions: In a cohort of PRCC patients slightly larger than the TCGA experience, key differences in CRGA frequency were observed. These likely underscore the marked difference in stage distribution between datasets. Results of this study may inform trials of relevant targeted therapy in metastatic PRCC.

Tumour stage distribution and survival of malignant melanoma in Germany 2002-2011.

BackgroundOver the past two decades, there has been a rising trend in malignant melanoma incidence worldwide. In 2008, Germany introduced a nationwide skin cancer screening program starting at age 35. The aims of this study were to analyse the distribution of malignant melanoma tumour stages over time, as well as demographic and regional differences in stage distribution and survival of melanoma patients.MethodsPooled data from 61 895 malignant melanoma patients diagnosed between 2002 and 2011 and documented in 28 German population-based and hospital-based clinical cancer registries were analysed using descriptive methods, joinpoint regression, logistic regression and relative survival.ResultsThe number of annually documented cases increased by 53.2% between 2002 (N = 4 779) and 2011 (N = 7 320). There was a statistically significant continuous positive trend in the proportion of stage UICC I cases diagnosed between 2002 and 2011, compared to a negative trend for stage UICC II. No trends were found for stages UICC III and IV respectively. Age (OR 0.97, 95% CI 0.97–0.97), sex (OR 1.18, 95% CI 1.11–1.25), date of diagnosis (OR 1.05, 95% CI 1.04–1.06), ‘diagnosis during screening’ (OR 3.24, 95% CI 2.50–4.19) and place of residence (OR 1.23, 95% CI 1.16–1.30) had a statistically significant influence on the tumour stage at diagnosis. The overall 5-year relative survival for invasive cases was 83.4% (95% CI 82.8–83.9%).ConclusionsNo distinct changes in the distribution of malignant melanoma tumour stages among those aged 35 and older were seen that could be directly attributed to the introduction of skin cancer screening in 2008.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-2963-0) contains supplementary material, which is available to authorized users.

A first look at relative survival by stage for colorectal and lung cancers in Canada.

Monitoring and reporting on cancer survival provides a mechanism for understanding the effectiveness of Canada's cancer care system. Although 5-year relative survival for colorectal cancer and lung cancer has been previously reported, only recently has pan-Canadian relative survival by stage been analyzed using comprehensive registry data. This article presents a first look at 2-year relative survival by stage for colorectal and lung cancer across 9 provinces. As expected, 2-year age-standardized relative survival ratios (arsrs) for colorectal cancer and lung cancer were higher when the cancer was diagnosed at an earlier stage. The arsrs for stage i colorectal cancer ranged from 92.2% in Nova Scotia [95% confidence interval (ci): 88.6% to 95.1%] to 98.4% in British Columbia (95% ci: 96.2% to 99.3%); for stage iv, they ranged from 24.3% in Prince Edward Island (95% ci: 15.2% to 34.4%) to 38.8% in New Brunswick (95% ci: 33.3% to 44.2%). The arsrs for stage i lung cancer ranged from 66.5% in Prince Edward Island (95% ci: 54.5% to 76.5%) to 84.8% in Ontario (95% ci: 83.5% to 86.0%). By contrast, arsrs for stage iv lung cancer ranged from 7.6% in Manitoba (95% ci: 5.8% to 9.7%) to 13.2% in British Columbia (95% ci: 11.8% to 14.6%). The available stage data are too recent to allow for meaningful comparisons between provinces, but over time, analyzing relative survival by stage can provide further insight into the known differences in 5-year relative survival. As the data mature, they will enable an assessment of the extent to which interprovincial differences in relative survival are influenced by differences in stage distribution or treatment effectiveness (or both), permitting targeted measures to improve population health outcomes to be implemented.

Survival of patients with skin melanoma in Europe increases further: Results of the EUROCARE-5 study

BackgroundIn Europe skin melanoma (SM) survival has increased over time. The aims were to evaluate recent trends and differences between countries and regions of Europe. MethodsRelative survival (RS) estimates and geographical comparisons were based on 241,485 patients aged 15years and over with a diagnosis of invasive SM in Europe (2000–2007). Survival time trends during 1999–2007 were estimated using the period approach, for 213,101 patients. Age, gender, sub-sites and morphology subgroups were considered. ResultsIn European patients, estimated 5-year RS was 83% (95% confidence interval, CI 83–84%). The highest values were found for patients resident in Northern (88%; 87–88%) and Central (88%; 87–88%) Europe, followed by Ireland and United Kingdom (UK) (86%; 85–86%) and Southern Europe (83%; 82–83%). The lowest survival was in Eastern Europe (74%; 74–75%). Within regions the intercountry absolute difference in percentage points of RS varied from 4% (North) to 34% (East). RS decreased markedly with patients’ age and was higher in women than men. Differences according to SM morphology and skin sub-sites also emerged. Survival has slightly increased from 1999 to 2007, with a small improvement in Northern and the most pronounced improvement in Eastern Europe. DiscussionSM survival is high and still increasing in European patients. The gap between Northern and Southern and especially Eastern European countries, although still present, diminished over time. Differences in stage distribution at diagnosis may explain most of the geographical differences. However, part of the improvement in survival may be attributed to overdiagnosis from early diagnosis practices.

Optimal management of cervical cancer in HIV-positive patients: a systematic review.

The clinical management of cervical cancer in HIV-positive patients has challenges mainly due to the concerns on immune status. At present, their mode of management is similar to HIV-seronegative patients involving the use of chemotherapy and radiotherapy concurrently as indicated. HIV infection, cancer, radiotherapy, and chemotherapy lower immunity through reduction in CD4 cell counts. At present there are no treatment guidelines for HIV-positive patients. This study was done to systematically review the literature on cervical cancer management in HIV-positive patients and treatment outcomes. A systematic literature search was done in the major databases to identify studies on the management of HIV-positive patients with cervical cancer. Identified studies were assessed for eligibility and inclusion in the review following the guidelines of The Cochrane Handbook for Systematic Reviews and CRD's (Centre for Reviews and Dissemination) guidance for undertaking reviews in health care. Eight eligible studies were identified from the literature. Three of them were prospective while five were retrospective studies. Notably, the average age at diagnosis of cervical cancer in HIV-positive patients was a decade lower than in seronegative patients. There was no difference in distribution of stages of disease at presentation between HIV-positive and negative patients. Mild acute toxicity (Grades 1 and 2) was higher in HIV-positive patients than in HIV-negative patients in hematopoietic system. In the grades 3 and 4 reactions, anemia was reported in 4% versus 2% while gastrointestinal reactions were reported in 5% versus 2% respectively. In general, patients who were started early on HAART had higher rates of treatment completion. The study supports the suggestion that HAART should be commenced early at cervical cancer diagnosis in HIV-positive patients diagnosed with cervical cancer to ensure less toxicity and better treatment compliance.