bluuebunny/crossref_metadata_2025 huggingface dataset:
Pyrotinib plus nab-paclitaxel in patients with HER2-positive advanced or metastatic breast cancer: A multicenter, single-arm, open-label phase 2 trial.
Authors: Li Huan , Li Zhaohui , Yan Min , Cui Xiujie , Ji Xuening , Fang Fenqi , Zhang Yuyang , Wang Xiaoxin , Wang Yan , Guo Xiangyu , Jing Mingxi , Gao Zhichao , Cao Hui , Dong Fangyuan , Wu Jie , Jiang Cui , Duan Yangyang , Li Xiaorui , Jiang Yujun , Sun Tao
Published: June 2022

1035

Background: For human epidermal growth factor receptor 2 (HER2) positive advanced or metastatic breast cancer, the standard therapeutic strategy is HER2-targeted agents combined with a taxane. This multicenter, single-arm phase 2 trial was designed to assess the efficacy and safety of pyrotinib (a brand-new generation, irreversible anti-HER2 tyrosine kinase inhibitor) plus nab-paclitaxel in patients with HER2-positive advanced or metastatic breast cancer. Methods: This was a multicenter, single-arm, open-label phase 2 trial conducted at seven centers in China (ChiCTR1900023653). Women aged 18-75 years, with histologically or cytologically confirmed HER-2 positive (immunohistochemistry [IHC] 3+ or positive confirmed by fluorescence in situ hybridization) advanced or metastatic breast cancer and with Eastern Cooperative Oncology Group performance score (ECOG PS) of 0-1 were enrolled. Patients with primary resistance to trastuzumab and bone-only metastases were excluded. Eligible patients received pyrotinib (400 mg, po, qd) plus nab-paclitaxel (125 mg/m2, iv, day 1/8/15) for each 28-day cycle until disease progression, unacceptable toxicity, consent withdrawal or death. The primary endpoint was objective response rate (ORR), defined as the proportion of patients with complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Secondary endpoints included progression-free survival (PFS), overall survival, safety and quality of life. Results: Between December 2019 and December 2021, 51 patients were enrolled. The median age was 55 years (range 35–72). Twenty-three patients (45.1%) had ECOG PS of 0. Ten patients (19.6%) with metastatic disease had previously received first-line treatment and 28 (54.9%) had received prior treatment with trastuzumab. More than half (29 of 51, 56.9%) had hormone receptor-positive disease. Visceral metastases occurred in 56.9% of the patients (29 of 51) and 26 patients (51.0%) were menopausal. The data cutoff for the present analysis was January 21, 2022. Among 38 evaluable patients, four patients (10.5%) had CR, 27 (71.1%) had PR, six (15.8%) had stable disease, and one (2.6%) had progressive disease. The confirmed ORR was 81.6% (95% CI 65.1-91.7%). The PFS data were still immature. The most common grade ≥3 treatment-emergent adverse events included neutropenia (14 of 51, 27.5%), diarrhea (10 of 51, 19.6%), fatigue (5 of 51, 9.8%) and peripheral neuropathy (4 of 51, 7.8%). Conclusions: Pyrotinib combined with nab-paclitaxel showed a promising antitumor activity with good tolerance in patients with HER2-positive advanced or metastatic breast cancer. Clinical trial information: ChiCTR1900023653.
Updated overall survival (OS) data from the phase 1b study of tebentafusp (tebe) as monotherapy or combination therapy with durvalumab (durva) and/or tremelimumab (treme) in metastatic cutaneous melanoma (mCM).
Authors: Middleton Mark R. , Hamid Omid , Shoushtari Alexander Noor , Meier Friedegund Elke , Bauer Todd Michael , Salama April K.S. , Kirkwood John M. , Ascierto Paolo Antonio , Lorigan Paul , Mauch Cornelia , Orloff Marlana M. , Evans T.R. Jeffry , Abdullah Shaad Essa , Yuan Yuan , Mitchell James , Hassel Jessica Cecile
Published: June 2022

104

Background: Tebe is a T-cell receptor bispecific (gp100 x CD3) against gp100 peptide-HLA-A2 complexes that are overexpressed in uveal (UM)/cutaneous melanoma (CM). Tebe is the only therapy to show an OS benefit (HR 0.51) in a phase (Ph) 3 trial in previously untreated metastatic UM. In a prior Ph 1 trial, tebe demonstrated monotherapy activity in anti-PD1 naïve mCM (1-yr OS, approx. 74%). The safety and initial activity of tebe with dose escalation of durva and/or treme in previously treated mCM has been reported. Here, we present updated OS in the subset of mCM patients (pts) relapsed or refractory to prior anti-PD1, a population where recent reports suggest a benchmark 1-yr OS of approximately 55% and median OS of approximately 14 months (mos). Methods: Patients with HLA-A2+, pre-treated mCM received weekly tebe (IV) monotherapy in Arm 4a or in combination with dose escalation of durva and/or treme (IV) on day 15 of each cycle (Arms 1-3). Primary objective was RP2D, secondary objectives were safety and efficacy. Subgroup analyses were performed for durva doses ≥10 mg/kg, a threshold previously defined by Bavarel et al, 2018. Analysis performed on data cut-off 04 January 2022 with median follow up for 14.3 mos. [NCT02535078] Results: 112 pts were treated with median age 59, 23% were ECOG = 1, 37% were BRAFm (73% received prior BRAFi/MEKi), 55% had LDH > ULN. 92% of pts were 2L+ and 74% 3L+; median 3 prior lines. The safety profile of all therapy arms within this study therapy remains very favorable with no new safety signals identified. 97 of 112 pts were documented as relapsed or refractory to prior anti-PD1 (80% also received ipilimumab). Of these 97 pts, 32 received tebe + durva (Arm 1), 13 received tebe + treme (Arm 2), 26 received triplet therapy (Arm 3), and 20 received tebe monotherapy (Arm 4a). 33 of 97 pts in any arm received durva ≥ 10 mg/kg with 1-yr OS of 79%, 2-yr OS of 34%, and median OS of 20 mos. 64 of 97 pts received durva < 10 mg/kg with 1-yr OS of 53%, 2-yr OS of 24%, and median OS of 13 mos. Tebe + durva doublet therapy had similar OS to triplet therapy with tebe + durva + treme: 1-yr OS of 74% vs. 76%, and 2-yr OS of 32% vs. 27%, respectively. Conclusions: Promising OS is seen in mCM similar to mUM, with both tumor types overexpressing gp100. In mCM relapsed or refractory to prior anti-PD1, tebe with anti–PD-L1 continues to demonstrate promising OS (1-yr, approx. 75%) compared to recent benchmarks (1-yr, approx. 55%). These data provide rationale for a randomized study of tebe with anti-PD(L)1 in mCM. Clinical trial information: NCT02535078.
Brain metastasis as first and only metastatic relapse site portends poor outcomes in patients with advanced HER2+ breast cancer.
Authors: Noteware Laura , Broadwater Gloria , Dalal Nicole , Alder Laura , Herndon James Emmett , Floyd Scott R. , Van Swearingen Amanda E.D. , Anders Carey K. , Sammons Sarah
Published: June 2022

1045

Background: In patients (pts) with stable or no extracranial disease (ECD) presenting with breast cancer brain metastases (BCBrMs), current guidelines recommend pts receive local therapy with radiation +/- surgery, without changing systemic therapy. However, preliminary studies suggest that pts with isolated HER2+ BCBrM without ECD have inferior overall survival (OS) compared to pts with concurrent ECD. Our study further explores the implications of ECD status on intracranial progression free survival (iPFS) and OS. Methods: Retrospective analysis was performed on data from 153 pts diagnosed with initial HER2+ BCBrM who received CNS radiation at Duke between 2008 and 2020. Demographics, dates of metastatic and BCBrM diagnosis, ECD status at first CNS event, systemic therapy, and outcomes were collected. The primary endpoint was iPFS defined as the time from first CNS radiation to the subsequent documentation of intracranial progression (RANO-BM). OS was defined as time from first CNS radiation and first metastatic disease to date of death or last known contact. ECD status was defined by RECIST1.1 from systemic staging scans within 30 days of first CNS event. Results: In this cohort of 153 pts with HER2+ BCBrMs undergoing CNS radiation, > 70% of pts with known ECD status had controlled systemic disease: either no ECD (27%) or stable/responding disease (44%). 64% of pts’ tumors were ER+. Median age was 50 years (range 24 – 75). Most pts (59%) developed first CNS event during adjuvant or 1st/2nd line metastatic therapy. CNS radiation treatment included 48% of pts receiving SRS only, 9% WBRT only, and 43% SRS and WBRT. All pts with no ECD presented with isolated BCBrMs as first metastatic disease. Among pts with known ECD status, OS from initial metastatic disease to death was markedly worse for pts with isolated brain metastases or no ECD (median = 28.4m, 95% CI: 18.1 to not reached) compared to those with progressive or stable/responding ECD (48.8m, 95% CI: 40.5 to 65.0; and 68.1m, 95% CI: 55.2 to 85.7, respectively; log-rank p = 0.004). OS from first CNS involvement to death was significantly worse for pts with progressive ECD (17.8m, 95% CI: 13.7 to 28.8) versus stable/responding (36.6m, 95% CI: 29.7 to 45.2) or no ECD (28.4m, 95% CI: 18.1 to not reached; log-rank p = 0.008). iPFS did not differ statistically among subgroups of pts with known ECD status: progressive ECD (median = 7.7m), no ECD (8.3m), or stable/responding ECD (11.2m) (log-rank p = 0.15). Conclusions: Overall survival in pts with HER2+ isolated BCBrM was markedly inferior to that of pts with progressive or stable/responding ECD. Studies investigating initiation of brain penetrable HER2-targeted therapies earlier in the disease course of isolated HER2+ BCBrMs pts are warranted.
Democratizing germline genetic testing and its impact on prostate cancer clinical decision-making.
Authors: Shore Neal D. , Gazi Mukaram , Pieczonka Christopher Michael , Heron Sean , Cahn David J , Belkoff Laurence , Berger Aaron D. , Mazzarella Brian , Veys Joseph , Morris David , Engelman Alexander , Dato Paul , Bevan-Thomas Richard , Cornell Robert , Layman Paige , Hatchell Kathryn E. , Heald Brandie , Nielsen Sarah M. , Nussbaum Robert Luke , Esplin Edward D.
Published: June 2022

10500

Background: Approximately 10-15% of prostate cancer (PCa) patients (pts) have a pathogenic germline variant (PGV). Identification of a PGV has important implications affecting decisions regarding cancer screening, treatment selection, and family cascade testing. There exists limited data documenting real world recommendations post germline genetic testing (GGT). This study was designed to collect clinician reported outcomes from PCa pts who underwent GGT. Methods: An IRB-approved, nationwide, prospective registry recruited unselected PCa pts from 15 community and academic urology practices. Pts underwent an 84-gene panel test, with clinical outcomes collected via clinician-completed case report forms > 1-month post GGT. Statistical significance was determined by two-tailed Fisher’s exact test. Results: 982 predominantly white (75.9%), non-metastatic (80.7%) males with PCa were recruited; 56.9% met National Comprehensive Cancer Network (NCCN) GGT criteria. Average age was 65.3 years at PCa diagnosis. PGVs, most commonly CHEK2 (17) and BRCA2 (10), were identified in 100 (10.2%) pts; 34 (34%) of these did not meet NCCN GGT criteria. Among PGV positive pts, 241 recommendations were made (Table). They were more likely to have changes to treatment (p < 0.0001), follow up (p < 0.0001) and cascade testing recommendations (p < 0.0001) than those with negative/variant of uncertain significance (VUS) results. There were no significant differences in changes to treatment (p = 0.4471) or follow up (p = 0.861) for pts who met NCCN criteria versus those who did not. 7 pts with PGVs received targeted therapy or were referred to a clinical trial. 5 pts with VUS results were also referred to a clinical trial. Among these 12 pts, 6 (50%, 2 CHEK2 PGV, 1 ATM PGV, 1 VUS each ATM, BLM, CHEK2) did not meet NCCN GGT criteria. Referral to a genetic counselor was the most common follow up recommendation for those with PGV (38 patients, 38%) and VUS results (66, 13.7%). The most commonly reported impact to health outcomes for those with negative results was knowledge/reassurance (38, 7.88%). Conclusions: This study showed that GGT did influence PCa pts care. Appropriately, pts with PGVs received a greater number of recommendations for relatives, changes to follow up and treatment. [Table: see text]
Racial and regional disparities in metastatic breast cancer.
Authors: Singhal Sachi , Desai Devashish , Khosla Akshita , Lanade Oladimeji , Potdar Rashmika
Published: June 2022

10516

Background: Breast cancer is the most commonly diagnosed malignancy in American women, with about 281,500 new reported cases this year, 3.8 million women living with an active or history of breast cancer, and a lifetime occurrence of 1 in 8 women in this nation. Racial disparities persist despite the advent and implementation of screening by national agencies. AA females are less likely to be diagnosed with breast cancer, and yet bear an arbitrarily high burden of mortality of this malignancy. Socioeconomic variables and lifestyle are the most plausible explanations of this discrepancy. Even in clinical trials, there remains an underrepresentation of all ethnic minorities. Encouragement of guideline based screening for all along with constant follow ups, access to health insurance and a more uniform representation in trials are the cornerstone of eliminating these disparities. Methods: Data for this study was obtained from the 2016-18 Nationwide Inpatient Sample (NIS) which comprises 20% of the total US hospital discharges. We identified all patients with a primary diagnosis of Malignant Neoplasms of Breast. In-hospital mortality, race and hospital regions for the given patients were studied. Baseline characteristics of participants were summarized using descriptive statistics. The patient population was stratified as per race, hospital region, gender, therapy they received and family history. Logistic regression was performed to derive the odds ratio while adjusting for different variables. Further details: https://www.hcup-us.ahrq.gov/ . Results: 99, 543 patients with metastatic breast cancer were identified, and almost 99% of them were females. 67% of the population was comprised of Caucasians, 16.91% African Americans (AA), 9.14% Hispanics and 3.28% Asians and Pacific Islanders (API). AAs had the most reported deaths at 5.54%, followed by APIs at 4.80% and Caucasians 4.09% (p < 0.0001). The odds of dying were significantly higher in AA population when compared to Caucasian population (OR 1.391 (1.286-1.504)), and the odds were consistently higher across all regions of the US. In terms of regional variation, it was seen that races identifying as “others' ' had significantly higher odds of dying in the North East (OR 1.646 (1.238-2.189)) and the West (OR 1.503 (1.059-2.133)). Conclusions: It is crucial to identify racial disparities in diagnosis, treatment and mortality before we devise a blueprint to tackle this incongruity. This highlights the significance of universal screening and better health insurance coverage in addition to recognition of reasons behind these differences.
Increase in incidence of advanced-stage breast cancer in Asian women versus White women: Can this be explained by the lower utilization of mammograms?
Authors: Liao Cheng-I , Caesar Michelle Ann P. , Lee Danny , Chan Chloe , Kapp Daniel Stuart , Chan John K
Published: June 2022

10524

Background: To examine trends in postmenopausal breast cancer and mammogram utilization in Asian and White women in the United States. Methods: Data on postmenopausal breast cancer was obtained from the United States Cancer Statistics Public Use Database from 2001 and 2018. Rates of mammogram screening for women ages 18 and older were evaluated using the Behavioral Risk Factor Surveillance System (BRFSS) between 2000 and 2018. Obesity rates for women ages 18 and older were extracted from BRFSS between 2001 and 2016. SEER*Stat 8.3.8 and Joinpoint regression program 4.8.0.1 were used to calculate incidence trends. Breast cancer incidence and trends were described using average annual percent change (AAPC). Mammogram screening trends were described using average biennial percent change (ABPC). Obesity trends were described using AAPC. Age groups were divided into five-year or ten-year intervals. Results: The incidence of metastatic postmenopausal breast cancer in women was 19.48/100,000 in 2018 has increased by 1.03% annually over the past eighteen years (p = 0.000). In 2018, the incidence of advanced-stage breast cancer in Asian and White women was 12.17/100,000 and 19.17/100,000 respectively. Over time, the incidence of advanced-stage breast cancer has increased in Asian women by 2.19% annually (p = 0.000), but remained stable in White women. In a subset analysis of early-stage breast cancer, there was no difference in both Asian and White women. Using the BRFSS data, we evaluated the utilization of mammograms. In the overall population, 20.92% were newer screened and this was higher in Asian women at 40.99% compared to 18.17% in White women in the year 2018. Given the potential association of obesity and breast cancer, we then evaluated the rate of obesity in these two groups. Our data showed that the incidence of obesity was low in Asian women at 12.8% compared to 28.13% in White women. Conclusions: There is an increased incidence of advanced-stage breast cancer in Asian women in the U.S. Although Asian women are less obese but they are also less likely to undergo screening compared to White women.
Designing a decision aid for cancer prevention.
Authors: Milton Shakira R , Macrae Finlay , McIntosh Jennifer , Saya Sibel , Emery Jon D.
Published: June 2022

10531

Background: Australian guidelines recommend those aged 50 to 70-years-old without contraindications, consider taking low-dose aspirin (100 mg – 300 mg per day) for at least 2.5 years to reduce their risk of colorectal cancer. To increase uptake of the new guidelines, we hypothesized that a decision aid (DA) would help facilitate a discussion between clinicians and patients about aspirin chemoprevention. We aimed to design a DA with clinician and consumer input including state-of-the-art expected frequency trees (EFTs). We aimed to explore clinicians’ opinions about using EFTs with their patients during consultations and gain consumers feedback on DAs including their understanding and their hypothetical decision to take aspirin or not. Methods: Semi-structured interviews were conducted with relevant clinicians including familial cancer clinic staff (geneticists, oncologists and genetic counsellors), gastroenterologists, pharmacists, and general practitioners (GPs). Focus groups were conducted with consumers in the target age range of the guidelines. DAs were developed through an iterative process. The clinician and focus group interview schedules covered ease of comprehension, design, potential effects on decision making, and approaches to implementation of the DA. Coding was inductive and the focus group interviews were independently coded by two researchers. Themes were developed through consensus between the authors. Final versions of the DAs were proposed to consumers for their final approval after all changes were made. Results: Sixty-four interviews were completed with clinicians between March and October 2019. Twelve consumers, aged 50 to 70 years, participated in two focus groups in February and March 2020. The clinicians agreed that the EFTs would be helpful to facilitate a discussion with patients but suggested including an additional estimate of the effects of aspirin on all-cause mortality. Clinicians agreed that patients would benefit from being shown the EFT in a consultation. The consumers felt favorable about the DA, especially if used with a clinician, and suggested some additional changes to the design and wording to improve ease of comprehension. Conclusions: We have designed a DA using novel approaches to communicate risks and benefits of low dose aspirin for cancer and cardiovascular disease prevention. The DAs are currently being trialled in the SITA trial in general practice to determine its impact on informed decision-making and aspirin uptake.
Socioeconomic status for predicting COVID-19-related changes in cancer prevention behaviors.
Authors: Elsaid Mohamed I. , Zhang Xiaochen , DeGraffinreid Cecilia , Paskett Electra D.
Published: June 2022

10547

Background: Disruptions of daily life activities during the CVOID-19 pandemic have adversely affected cancer-prevention behaviors. Socioeconomic status (SES) impacts on changes in cancer prevention behaviors have not been fully investigated. To tackle this gap, we examined the effects of SES on COVID-19 related changes in cancer prevention behaviors. Methods: We invited participants from previous studies conducted at the Ohio State University Comprehensive Cancer Center who agreed to be re-contacted to participate in a survey assessing the impact of COVID-19 on various behaviors between June and November 2020. Participants reported current cancer prevention behaviors, including physical activity, daily fruit and vegetable intake, alcohol consumption, and tobacco use. In addition, participants reported qualitative changes in current behaviors relative to pre-COVID levels. We combined current behaviors with COVID-related changes to construct a 24-point cancer prevention score. Participants were classified into low, middle, or high SES based on household income, education, and employment status. Adjusted multinomial logistic regression was used to examine the association between SES and COVID-19 related changes in cancer prevention behaviors. Results: The study sample included 6136 eligible participants. The average age was 57 years, 67% were female, 89% were non-Hispanic White, and 33% lived in non-metro counties. The proportion of participants in the lowest cancer prevention behavior quartile decreased significantly with higher SES [low SES vs. high SES; 32% vs. 28%; P-value <.001]. Relative to pre-COVID-19 levels, higher SES was significantly associated with increases in post-COVID-19 prevalence of more physical activity [low SES vs. high SES; 12% vs. 28%; P-value <.001], higher fruit and vegetable intake [low SES vs. high SES; 12% vs. 14%; P-value <.001], and more alcohol consumption [low SES vs. high SES; 15% vs. 22%; P-value <.001]. Higher SES was associated with lower tobacco use prevalence [low SES vs. high SES; 5% vs. 2%; P-value <.001]. Relative to the highest prevention score quartile, the adjusted odds of scoring in the lowest prevention score quartile were: adjusted odds ratio (aOR) 1.55 (95% CI: 1.27 - 1.89) and aOR 1.40 (95% CI: 1.19 - 1.66), respectively higher for low and middle SES. Low SES was significantly associated with higher odds of less frequent physical activity (aOR = 1.87; 95% CI: 1.49 - 2.35) and less fruit and vegetable consumption (aOR = 1.56; 95% CI: 1.15 - 2.12). Middle SES relative to high SES was associated with lower odds of more alcohol consumption (aOR = 0.64; 95% CI: 0.49 - 0.85) and higher odds of binge drinking (aOR = 1.32; 95% CI: 1.09 - 1.59). Conclusions: The adverse impacts of COVID-19 on cancer prevention behaviors were seen most in those with lower SES. Public health efforts are currently needed to promote cancer prevention behaviors, especially amongst lower SES adults.
Higher obesity and lower screening rates in Hispanic women and associated increased breast cancer in the United States.
Authors: Caesar Michelle Ann P. , Liao Cheng-I , Lee Danny , Chan Ava , Kapp Daniel Stuart , Chan John K
Published: June 2022

10555

Background: To evaluate trends in postmenopausal breast cancer and mammogram utilization in Hispanic and White women in the United States. Methods: Data on postmenopausal breast cancer was obtained from the United States Cancer Statistics Public Use Database between 2001 and 2018. Rates of mammogram screening for women ages 18 and older were evaluated using the Behavioral Risk Factor Surveillance System (BRFSS) from 2000 and 2018. Obesity rates for women ages 18 and older were extracted from BRFSS between 2001 and 2016. SEER*Stat 8.3.8 and Joinpoint regression program 4.8.0.1 were used to calculate incidence trends. Breast cancer and obesity incidence and trends were described using average annual percent change (AAPC). Mammogram screening trends were described using average biennial percent change (ABPC). Age groups were divided into five-year or ten-year intervals. Results: Over the past eighteen years, early-stage breast cancer in Hispanic women has increased annually by 1.06% (p = 0.000) and advanced-stage has also increased annually by 0.81% (p = 0.000). In contrast, there was no increase in early-stage cancer in White women, however, advanced stage increased by 1.06% annually (p = 0.000). Compared to White woomen, Hispanic women are more likely to be unscreened with mammograms (18.17% vs. 40.06%). Over time, the unscreened population is decreasing at 3.43% for White women compared to only 1.24% in Hispanic women (p = 0.000, p = 0.001). Overall in the U.S., the never-screened population has decreased biennially by 2.88% (p = 0.000). In 2016, 33.16% of Hispanic women and 28.13% of White women were considered obese, and this obesity rate has been increasing at 2.6% and 2.4%, respectively (p = 0.000). Conclusions: Our data showed that early- and advanced-stage breast cancer has been increasing in Hispanic women in the United States. Hispanic women were also more likely to be obese and less likely to undergo screening compared to White women.
Early mortality in real-life nationwide epidemiological study on lung cancer in non-academic French public hospitals.
Authors: Debieuvre Didier , Marquette David , Crequit Jacky , Le Treut Jacques , Portel Laurent , Chikouche Reda , François Hugues , Dayen Charles , Rizzo Claudia , Goarant Eric , Turlotte Amélie , Jarjour Baihas , Masson Philippe , Jaafar Mohamad , Marty Clothilde , Stoven Luc , Belmont Laure , Le Foll Christine , Renault David
Published: June 2022

10557

Background: Each decade since 2000, the French College of General Hospital Pulmonologists (CPHG) conducts a real-life nationwide prospective epidemiological, observational, multicenter study on lung cancer (LC). In 2020, the CPHG constituted the third cohort, KBP-2020-CPHG. We reported here the data on one-month and three-month mortality among general population of this cohort and compared them with 2010 cohort. Methods: Collection of all consecutive LC histologically or cytologically confirmed between 01/01 and 12/31/2020 in non-academic public hospital pulmonology or oncology units in France. A Scientific Committee controlled inclusion exhaustivity and quality in each center. Results: 82 centers collected 8,999 patients in 2020. One-month mortality was 8.8% (734/8,999) and 9.7% (680/7,051) in 2010. Three-month mortality was 21.5% (1,771/8,999) in 2020 and 23.3% (1,624/7,051) in 2010 (Table 1). According to sex, mortality at one and three months mainly affected men (525/734; 71.5% and 1,259/1,771; 71.1% respectively). Mean age at diagnosis was older than in the cohort population (67.8 y-o); respectively 69.9 and 69.8 at one and three months. At diagnosis, patients were in poorer ECOG mainly grade 2 (211/697; 30.3%) or 3 (194/697; 27.8%) for one-month and mainly grade 1 (549/1,703; 32.2%) or 2 (547/1,703; 32.1%) for three-month mortality. Among ECOG grade 3 and 4, 34.8% (194/557) and 57.1% (93/163) were dead at one month respectively; 63.5% (350/551) and 83.4% (136/163) respectively were dead at three months. According to histology, adenocarcinoma was the most common (308/734; 42%), followed by small cell lung cancer (170/734; 23.2%) at one-month; adenocarcinoma was also the most common (822/1,771; 46.4%), followed by squamous cell carcinoma (380/1771; 21.5%) at three-month mortality. Most patients who died early were stage 4, metastatic/disseminated (respectively 625/702; 89% and 1,488/1,715; 86.8% for one- and three-month mortality). In patients with COVID19 infection (n=547), mortality at one and three months was respectively 36.4% (174/478) and 46.7% (228/488). Conclusions: Early mortality has not improved over the two decades and remains high. KBP-2020-CPHG study was performed during COVID-19 pandemic, which may have generated delays in diagnosis and limited access to care and hospital. Early mortality at one and three months concerned mostly men, mean age nearly 70 y-o, adenocarcinoma, metastatic disease and frail patients. This confirms the potential value of LC screening program in a targeted population. [Table: see text]
Impact of the COVID-19 pandemic on stage at diagnosis of patients with breast cancer: An analysis of 11,752 patients from Oncoclínicas.
Authors: Resende Cristiano Augusto Andrade de , Dienstmann Rodrigo , Barrios Carlos H. , Ferrari Bruno Lemos , Goncalves Aline Coelho , Cascelli Fanny , Souto Andreza Karine , Costa e Silva Matheus , Cruz Heloisa , Oliveira Leandro Carvalho , Andrade Diocesio Alves Pinto de , Millen Eduardo Camargo , Zerwes Felipe , Reinert Tomas , Moraes Paulo , Mano Max S.
Published: June 2022

10559

Background: As a reaction to the COVID-19 pandemic, a nation-wide lockdown was enforced in Brazil in March 2020, cancer care was impacted, and cancer screening reduced. Therefore, an increase in cancer diagnoses at more advanced stages was expected. In this study, we extracted data from our nationwide real-world database to evaluate the impact of the COVID-19 pandemic on the stage at diagnosis of breast cancer (BC) cases. Methods: We explored curated electronic medical record data of female patients, over 18 years of age, diagnosed with BC and with established disease stage based on the AJCC 8th edition, who started treatment or follow-up in the Oncoclínicas (OC) between Jan 1, 2018, and Dec 31, 2021. The primary objective was to compare stage distribution at first visit during COVID-19 pandemic (2020-2021) with a historical control cohort from a period prior to the pandemic (2018-2019). We investigated stage distribution according to age at diagnosis and tumor ER/HER2 subtype in univariate models. Associations were considered significant if they had a minimum significance (P < 0.1 in Chi-square test). The historical numbers of patients with BC at OC make it possible to identify differences in the prevalence of stages in the order of 5% comparing pre and post pandemic periods with a statistical power greater than 80%. Results: We collected data for 11,752 patients with initial diagnosis of BC, with 6,492 patients belonging to the pandemic (2020-2021) and 5,260 patients to the pre-pandemic period (2018-2019). For both ER+/ HER2- and HER2+ tumors, there was a lower percentage of patients with early-stage (defined as stage I-II) in the years 2020-2021 vs 2018-2019 and a considerable increase in advanced-stage disease (defined as stage IV). For triple negative BC (TNBC), there was a significant higher percentage of patients with advanced-stage disease in the pandemic vs pre-pandemic period (table 1). Age over 50 years was associated with a greater risk of advanced stage at diagnosis after the onset of the pandemic, with an absolute increase of 7% (P two-sided <0.01) Conclusions: We observed a substantial increase in cases of advanced-stage BC in OC institutions as a result of delays in BC diagnoses due to the COVID-19 pandemic. The impact appeared greater in older adults, potentially because of stricter confinement in this group. [Table: see text]
Sociodemographic trends in COVID-19 mortality in patients with cancer: A nationwide analysis.
Authors: Jambunathan Sree , Lang Jacob , Mays Malik , Hadziahmetovic Mersiha , Ukaegbu Oke Oluchi , Ekwenna Obi
Published: June 2022

10571

Background: The COVID-19 pandemic has caused unprecedented disruptions in medical care, especially in those with cancer. Prior studies have demonstrated a higher risk of mortality in patients with cancer and COVID-19, which could be due to factors such as immunosuppression and higher burden of co-morbidities. However, there are limited studies examining the impact of sociodemographic factors including race, gender, rurality, and region on mortality in patients with COVID-19 and cancer. This study aims to characterize and analyze sociodemographic trends in COVID-19 mortality in patients with cancer. Methods: Data on patients with COVID-19 and cancer listed on death certificates from the Multiple Cause of Death Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research (CDC WONDER) database were extracted. Age-adjusted mortality rates (AAMR) were calculated and compared across sociodemographic groups. Results: A total of 18,467 total deaths occurred in patients with COVID-19 and cancer listed on multiple cause of death certificates in 2020, with overall AAMR of 4.4 (95% CI: 4.4-4.5). AAMR for patients with COVID-19 and cancer was significantly higher in Non-Hispanic (NH) Black or African American (7, 95% CI: 6.8-7.3), NH American Indian or Alaska Native (6.4, 95% CI: 5.4-7.3), and Hispanic or Latino (5.4, 95% CI: 5.2-5.7) groups than NH White (4, 95% CI: 3.9-4.1) and NH Asian or Pacific Islander (2.5, 95% CI: 2.3-2.7). AAMR was also higher in males (5.9, 95% CI: 5.8-6.1) and those in Northeast (5.6, 95% CI: 5.4-5.8) and Midwest (5.3, 95% CI: 5.2-5.5) census regions. Those in medium metro counties had significantly lower AAMR (3.8, 95% CI: 3.7-4) compared to other locations based on the NCHS Urban-Rural Classification Scheme for Counties. Conclusions: AAMR in patients with any cancer and COVID-19 was significantly higher in NH Black or African American, NH American Indian or Alaskan, and Hispanic or Latino race/ethnicity groups, as well as in males. Regional and rurality disparities also exist. This study highlights persistent disparities in COVID-19 and cancer outcomes and identifies groups at higher risk of mortality. Future studies examining sociodemographic trends in COVID-19 mortality in patients with specific cancers are necessary. [Table: see text]
Impact of germline mutations on surgical decision-making in women with DCIS.
Authors: Ellsworth Rachel E , Turza Lauren , Lovejoy Leann A , Turner Clesson E , Shriver Craig D
Published: June 2022

10576

Background: Ductal carcinoma in situ (DCIS) is both a malignant, yet pre-invasive disease of the breast. While the majority of DCIS have a low risk of recurrence, a subset of women with germline pathogenic variants (PV) in cancer predisposition genes are at increased risk for breast cancer recurrence. Uptake of genetic testing and treatment with risk-reducing surgeries (RRS), including bilateral mastectomy (BM), in women with DCIS, has not been well-studied. The aim of this study was to determine the prevalence of PVs in women with DCIS and the impact on surgical decision making. Methods: All women diagnosed with unilateral DCIS 2001-2020 enrolled in the Clinical Breast Care Project were identified. Demographic, genetic test results and surgical procedures were extracted from the database. Test-eligibility was assigned using National Comprehensive Cancer Network (NCCN) criteria. Panel genetic testing was performed in the research setting using DNA from 465 women. Statistical analyses were performed using Fisher’s exact tests and Chi-square analyses with p < 0.05 defining significance. Results: The overall PV frequency in women with DCIS was 8.1%. Within the test-eligible group, 35.1% pursued clinical genetic testing, including 13.2% who pursued testing only after a second cancer event. Of the 39 women with PV, 20 (51.3%) were detected only in the research setting, with 11 (28.2%) of these women not eligible for genetic testing based on NCCN criteria. In the 419 women who did not undergo BM at diagnosis, recurrence was significantly higher (p = 0.001) in women with PV (33.3%) compared to those without PV (11.6%). Conclusions: Genetic testing is suboptimal in women with a primary diagnosis of DCIS. Twenty percent of women with PV, who may have benefited from BM, did not undergo genetic testing at the time of diagnosis and recurred. These data suggest that genetic testing at the time of diagnosis should be standard for all women with DCIS.
Constitutional MLH1 promotor hypermethylation: Clinical characteristics and testing frequency of a poorly recognized mechanism for Lynch-associated malignancies.
Authors: Biswas Rakesh , DeMarco Tiffani , Winer Arthur , Wadlow Raymond Couric , Randall Jamie , Rashkin Misha , Urban Rhianna , Cannon Timothy Lewis
Published: June 2022

10581

Background: MSI-H colorectal cancer is most often a result of deleterious mutations in mismatch repair genes, but can also occur through repressed gene transcription due to hypermethylation of the MLH1 promoter, often associated with BRAF V600E mutations. However, there is a subset of patients who have a “constitutional epimutation”, resulting in hypermethylation of MLH1 throughout normal tissue. We observed a young patient develop a second primary Lynch associated malignancy (see Table 1) who was found to have a constitutional epimutation in MLH1 that prompted us to review the frequency with which the test was ordered and the positivity rate, as well as outline the clinical history in the positive cases. Methods: We reviewed all of the testing ordered for MLH1 hypermethylation of peripheral blood (MLHPB) at the Mayo Clinic Laboratory between 09/01/2020 and 09/01/2021. To the best of our knowledge, this is the only clinically available testing lab in the United States. We reviewed positive casesfor characteristics including the number of malignancies, age of diagnosis, and family history. Results: 33 MLHPB total tests were ordered in the United States at the Mayo Clinic laboratories between 09/01/2020 and 09/01/2021. Three of the tests were positive, including the single test ordered by our institution, and one of the two additional positive tests was available for detailed review. Our institution’s positive test case was a 41 year old women who developed T4N2M0 colorectal cancer 5 years after being treated for endometrial cancer. She had endometrial cancer with absence of MLH1 and PMS2 staining and had a negative germline cancer risk panel at age 36. Five years later, she developed a T4N2 colorectal cancer after which repeat germline testing with RNA sequencing was negative and she was found to have constitutional MLH1 promoter hypermethylation. We were able to obtain clinical information about two of the three individuals with positive tests (See Table). Conclusions: Recognition of constitutional MLH1 hypermethylation may allow for earlier recognition of Lynch related malignancies in affected patients and families. Testing appears infrequent and this condition often goes unrecognized. Specific consensus guidelines may improve recognition and cancer screening in this population. [Table: see text]
Relative disclosure of information on hereditary cancer syndromes: A systematic review and meta-analysis.
Authors: Ahsan Muhammad Danyal , Bergeron Hannah , Lin Jenny , Narayan Priyanka , Nelson Becky Baltich , Li Xuan , Thomas Charlene , Christos Paul J. , Chapman-Davis Eloise , Cantillo Evelyn , Holcomb Kevin , Sharaf Ravi , Frey Melissa Kristen
Published: June 2022

10592

Background: Evidence-based guidelines recommend that patients (probands) diagnosed with a hereditary cancer syndrome share the information with blood relatives as relatives can have 50% risk for harboring the same pathogenic mutation. This information offers the opportunity for relatives to undergo genetic counseling, genetic testing, early detection, and prevention of cancer. Limited literature on this topic suggests underutilization of recommended family member disclosure. We sought to evaluate rates of familial disclosure of hereditary cancer syndrome information in the first meta-analysis on this topic. Methods: We conducted a systematic review and meta-analysis in accordance with PRISMA guidelines (PROSPERO no.: CRD42020134276). We searched key electronic databases to identify studies evaluating hereditary cancer cascade relative disclosure. Eligible trials were subjected to meta-analysis. Results: Thirty studies met inclusion criteria. This review included 3,779 probands and 12,751 at-risk relatives. Among 12,751 included relatives, 72% (CI 64-79%) received information about the hereditary cancer syndrome identified in their family and 28% (CI 19-37%) underwent genetic testing. On meta-analysis, there was a higher rate of disclosure among female vs male relatives (79% [73% - 84%] vs 67% [57% - 75%]) and a higher rate among first-degree vs. second degree relatives (83% [77% - 88%] vs 58% [45 – 69%]). The data regarding the contribution of race/ethnicity to disclosure were limited and inconsistent, with two studies demonstrating non-White vs. White relatives being less likely to have results disclosure and two studies finding no correlation; however, both studies finding no difference were limited by small sample sizes. Finally, one study found that higher proband annual income was associated with improved familial disclosure. Conclusions: Despite a growing understanding of the importance of cascade genetic counseling and testing, probands do not disclosure information on hereditary cancer syndromes to most at-risk relatives. Very few relatives complete genetic testing, representing a critical missed opportunity for precision cancer prevention. Future studies are needed to elucidate barriers to hereditary cancer syndrome disclosure and create innovative strategies to facilitate this essential process.
Evaluation of Lynch syndrome risk models in a multicenter diverse population.
Authors: Lu Jenny , Knapp Stephen , Seymour Gubidxa Gutierrez , Wang Cathy , Huang Theodore , Liang Jane , Yang Kai , Castillo Danielle , Herzog Josef , Parmigiani Giovanni , Gruber Stephen B. , Braun Danielle , Idos Gregory
Published: June 2022

10597

Background: Lynch syndrome (LS) is the most common cause of hereditary colorectal cancer (CRC) with an increased CRC lifetime risk of 70-80%. LS affects 1:250 individuals and is caused by pathogenic variants in the mismatch repair (MMR) genes. Statistical prediction models such as MMRpro and PREMM5 are widely used to identify LS carriers. However, these models are trained and validated in mostly white populations, and there remains a gap in understanding their performance in Hispanic populations. The purpose of this study was to evaluate the performance of MMRpro and PREMM5 on a large Hispanic cohort from the Clinical Cancer Genomics Community Research Network (CCGCRN). Methods: We validated MMRpro and PREMM5 on 3,490 CCGCRN families, of which 1,122 are Hispanic and 2,062 Non-Hispanic. The two models were evaluated for discrimination using the C-statistic, calibration using the observed to expected ratio (O/E), and overall performance using the root Brier score and negative and positive predictive value (NPV/PPV) at the 5% carrier probability threshold. Evaluations were stratified by ethnicity, and 95% confidence intervals were obtained via bootstrapping for all measures. Results: The C-statistic is 0.90 for both MMRpro (95% CI: 0.88, 0.92) and PREMM5 (95% CI: 0.87, 0.92). When stratified by ethnicity, the C-statistics are 0.96 (95% CI: 0.94, 0.97) and 0.86 (95% CI: 0.83, 0.89) for Hispanics and Non-Hispanics, respectively, in MMRpro, and 0.96 (95% CI: 0.94, 0.97) and 0.84 (95% CI: 0.79, 0.88) in PREMM5. Both models underpredict mutation probabilities, with O/E ratios ranging from 1.79 to 1.96. At a 5% threshold, variations in PPV between Hispanics and Non-Hispanics are observed in both models: 0.72 (95% CI: 0.63, 0.80) and 0.43 (95% CI: 0.37, 0.50) in Hispanic and Non-Hispanic groups in MMRpro; 0.50 (95% CI: 0.43, 0.57) and 0.25 (95% CI: 0.20, 0.30) in PREMM5. We observe less variation and higher values in NPVs in both models. Conclusions: Overall, MMRpro and PREMM5 perform well in this cohort in predicting the probability of having a pathogenic variant in an MMR gene, with modest underprediction. While these results offer reassurance for the clinical use of MMRpro and PREMM5 in Hispanic populations, further validation studies in underrepresented racial and ethnic populations are crucial.
A study of AK104 (an anti-PD1 and anti-CTLA4 bispecific antibody) combined with standard therapy for the first-line treatment of persistent, recurrent, or metastatic cervical cancer (R/M CC).
Authors: Wang Jing , Lou Hanmei , Cai Hong-Bing , Huang Xin , Li Guiling , Wang Li , Liu Ting , Liu Wei , Li Baiyong , Xia Yu
Published: June 2022

106

Background: Current first-line standard therapy (SOC) for R/M CC is platinum-based chemotherapy +/- bevacizumab (bev). AK104 monotherapy has shown promising efficacy and tolerable toxicity in pretreated R/M CC (NCT04380805). In this study, we report the efficacy and safety of AK104 combined with SOC for the first-line treatment of R/M CC (NCT04868708). Methods: The multicenter, open-label, phase II study enrolled R/M CC pts without previous systemic therapy. Eligible pathological types were squamous cell carcinoma, adenocarcinoma, or adenosquamous cell carcinoma. Pts were assigned to 3 cohorts (A-15/A-10: AK104 15/10 mg/kg + PTX 175mg/m2 + DDP 50 mg/m2/CBP AUC 5, q3w; B-10: AK104 10 mg/kg + PTX 175 mg/m2 + DDP 50 mg/m2/CBP AUC 5 + bev 15 mg/kg, q3w). All pts received AK104 until PD or unacceptable toxicity. The primary endpoint was safety. Secondary endpoints included ORR, PFS per RECIST1.1, and OS, etc. Results: 45 pts were enrolled at 6 centers from Jun 3, 2021, to Nov 5, 2021. As of Jan 10, 2022, we assessed safety in all pts and efficacy in pts with at least one tumor assessment result. TRAEs of any grade occurred in 43 (95.6%) pts. Grade ≥3 TRAEs occurred in 23 (51.1%) pts. The most common TRAEs were anemia (55.6%), white blood cell count decreased (46.7%), rash (24.4%), and hypoesthesia (24.4%). The most common grade ≥ 3 TRAEs were anemia (15.6%), white blood cell count decreased (11.1%), neutrophil count decreased (8.9%), and platelet count decreased (8.9%). TRSAE occurred in 17 (37.8%) pts. IrAEs of any grade, assessed by INV, occurred in 24 (53.3%) pts. Grade ≥ 3 irAE occurred in 8 (17.8%) pts. One death due to hemorrhagic shock occurred in cohort B-10 and was judged as treatment-related. ORR were 73.3% (11/15) for A-15, 68.8% (11/16) for A-10, 92.3% (12/13) for B-10, respectively. The response to the treatment was favorable regardless of CPS (Table). PFS or OS data are not mature by cut-off date. Conclusions: AK104 combined with standard therapy was well tolerated, with encouraging antitumor activity in pts with R/M CC. Meanwhile, long-term safety evaluation still needs following up. A phase III trial is ongoing to evaluate the efficacy of AK104 plus standard therapy in first-line treatment for R/M CC (NCT04982237). Clinical trial information: NCT04868708. [Table: see text]