CancerSpectrum Knowledge Environment

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ISSN / EISSN : 00278874 / 14602105
Current Publisher: Oxford University Press (OUP) (10.1093)
Total articles ≅ 29,187
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Alice W Lee, Stacey Rosenzweig, Ashley Wiensch, Susan J Ramus, Usha Menon, Aleksandra Gentry-Maharaj, Argyrios Ziogas, Hoda Anton-Culver, Alice S Whittemore, Weiva Sieh, et al.
Journal of the National Cancer Institute; doi:10.1093/jnci/djaa099

The publisher has not yet granted permission to display this abstract.
JNCI: Journal of the National Cancer Institute; doi:10.1093/jnci/djaa086

Correction to “Contribution of Germline Predisposition Gene Mutations to Breast Cancer Risk in African American Women” by Julie R Palmer et al. JNCI J Natl Cancer Inst (2020),
JNCI: Journal of the National Cancer Institute; doi:10.1093/jnci/djaa045

Corrigendum: Sebuødegard S, E Botteri, Hofvind S. Breast cancer mortality after implementation of organized population-based breast cancer screening in Norway. J Natl Cancer Inst. 2020;112(8):djz220.
Nicolas Wentzensen, Bernd Lahrmann, Megan A Clarke, Walter Kinney, Diane Tokugawa, Nancy Poitras, Alex Locke, Liam Bartels, Alexandra Krauthoff, Joan Walker, et al.
Journal of the National Cancer Institute; doi:10.1093/jnci/djaa066

Background With the advent of primary human papillomavirus testing followed by cytology for cervical cancer screening, visual interpretation of cytology slides remains the last subjective analysis step and suffers from low sensitivity and reproducibility. Methods We developed a cloud-based whole-slide imaging platform with a deep-learning classifier for p16/Ki-67 dual-stained (DS) slides trained on biopsy-based gold standards. We compared it with conventional Pap and manual DS in 3 epidemiological studies of cervical and anal precancers from Kaiser Permanente Northern California and the University of Oklahoma comprising 4253 patients. All statistical tests were 2-sided. Results In independent validation at Kaiser Permanente Northern California, artificial intelligence (AI)-based DS had lower positivity than cytology (P < .001) and manual DS (P < .001) with equal sensitivity and substantially higher specificity compared with both Pap (P < .001) and manual DS (P < .001), respectively. Compared with Pap, AI-based DS reduced referral to colposcopy by one-third (41.9% vs 60.1%, P < .001). At a higher cutoff, AI-based DS had similar performance to high-grade squamous intraepithelial lesions cytology, indicating a risk high enough to allow for immediate treatment. The classifier was robust, showing comparable performance in 2 cytology systems and in anal cytology. Conclusions Automated DS evaluation removes the remaining subjective component from cervical cancer screening and delivers consistent quality for providers and patients. Moving from Pap to automated DS substantially reduces the number of colposcopies and also achieves excellent performance in a simulated fully vaccinated population. Through cloud-based implementation, this approach is globally accessible. Our results demonstrate that AI not only provides automation and objectivity but also delivers a substantial benefit for women by reduction of unnecessary colposcopies.
Hildur Helgadottir, Karolin Isaksson, Ildiko Fritz, Christian Ingvar, Jan Lapins, Veronica Höiom, Julia Newton-Bishop, Håkan Olsson
JNCI: Journal of the National Cancer Institute; doi:10.1093/jnci/djaa088

Background Over the past decades many regions have experienced a steady increase in the incidence of cutaneous melanoma. Here, we report on incidence trends for subsequent primary melanoma. Methods In this nationwide population-based study, patients diagnosed with a first primary cutaneous melanoma reported to the Swedish Cancer Registry, were followed for up to ten years for a diagnosis of subsequent primary melanoma. Patients were grouped with patients diagnosed with first melanoma in the same decade (1960s, 1970s, 1980s, 1990s and 2000s, respectively). Frequencies, incidence rates (IRs), standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) for second melanomas were calculated. All tests of statistical significance were two-sided. Results 54,884 patients with melanoma were included and 2,469 were diagnosed, within ten years, with subsequent melanomas. Over the five decades there was a statistically significant steady increase in the frequency, IR and SIR for second primary melanoma. For example, in the 1960s cohort, <1% (1.0 (95% CI = 0.5-1.7) and 1.1 (95% CI = 0.5-1.9) per 1,000 person-years in women and men, respectively) had second primary melanoma and this rose to 6.4% (7.5 (95% CI = 6.8-8.3) per 1,000 person-years) in the women and 7.9% (10.3 (95% CI = 9.3-11.2) per 1,000 person-years) in the men in the 2000s cohort. This rise was seen, independent of age, sex, invasiveness or site of the melanoma. Further, in patients diagnosed with a second melanoma, the frequency of those having >2 melanomas increased statistically significantly and was 0.0% in the 1960s and rose to 18.0% in the 2000s (P <.001). Conclusions This is the first study to evaluate and report on a rising trend for subsequent primary melanoma. Additional primary melanomas worsen the patients’ survival and precautions are needed to turn this steep upgoing trend.
Ben O’Leary, Rosalind J Cutts, Xin Huang, Sarah Hrebien, Yuan Liu, Fabrice André, Sibylle Loibl, Sherene Loi, Isaac Garcia-Murillas, Massimo Cristofanilli, et al.
JNCI: Journal of the National Cancer Institute; doi:10.1093/jnci/djaa087

Background There are no established molecular biomarkers for patients with breast cancer receiving combination endocrine and CDK4/6 inhibitor (CDK4/6i). We aimed to determine whether genomic markers in circulating tumor DNA (ctDNA) can identify patients at higher risk of early progression on fulvestrant therapy with or without palbociclib, a CDK4/6i. Methods PALOMA-3 was a phase III multicenter double-blind randomized controlled trial of palbociclib plus fulvestrant (n = 347) versus placebo plus fulvestrant (n = 174) in patients with endocrine pre-treated ER+ breast cancer. Pre-treatment plasma samples from 459 patients were analyzed for mutations in 17 genes, copy number in 14 genes, and circulating tumor fraction. Progression free survival (PFS) was compared in patients with circulating tumor fraction above or below a pre-specified cut off of 10%, and with or without a specific genomic alteration. All statistical tests were two-sided. Results Patients with high ctDNA fraction had worse PFS on both palbociclib plus fulvestrant (HR = 1.62, 95%CI 1.17–2.24, p=.004) and placebo plus fulvestrant (HR = 1.77, 95%CI 1.21–2.59, p=.004. In multivariable analysis high circulating tumor fraction was associated with worse PFS (HR = 1.20 per 10% increase in tumor fraction, 95%CI 1.09–1.32, p<.001, as were TP53 mutation (HR = 1.84, 95%CI 1.27– 2.65, p=.001 and FGFR1 amplification (HR = 2.91, 95%CI 1.61–5.25, p<.001. No interaction with treatment randomization was observed. Conclusions Pre-treatment ctDNA identified patients identified a group of high-risk patients with poor clinical outcome despite the addition of CDK4/6 inhibition. These patients might benefit from inclusion in future trials of escalating treatment, with therapies that may be active in these genomic contexts.
Janet S De Moor, Erin E Kent, Timothy S McNeel, Katherine S Virgo, Jennifer Swanberg, J Kathleen Tracy, Matthew P Banegas, Xuesong Han, Jin Qin, K Robin Yabroff
JNCI: Journal of the National Cancer Institute; doi:10.1093/jnci/djaa084

The publisher has not yet granted permission to display this abstract.
Doris Howell, Deborah K Mayer, Richard Fielding, Manuela Eicher, Irma M Verdonck-De Leeuw, Christoffer Johansen, Enrique Soto-Perez-De-Celis, Claire Foster, Raymond Chan, Catherine M Alfano, et al.
JNCI: Journal of the National Cancer Institute; doi:10.1093/jnci/djaa083

The publisher has not yet granted permission to display this abstract.
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