tbuckley/cabot-search huggingface dataset:
Health disparity viewed from public historic cancer mortality data in the US: Advocacy for gastrointestinal cancers, for tailored prevention measures, and for inter-agency population data harmonization.
Authors: Tingting Zhang, Tony Hung
Journal: Journal of Clinical Oncology (2024)

152 Background: We searched public datasets released by CDC to answer the question ”Can we have a bird’s-eye view of health disparity in cancer care in the US?” By looking into historic data, we hope to identify not only health disparity reflected by the different cancer mortality rates for major cancer types, but also signs of missing data. Methods: We analyzed 2016-2020 US Cancer Statistics (USCS) cancer burden data to assess cancer disparity as reflected by rates of death in different races or ethnicities. Since the 2022 AACR report on cancer in Asian Americans raised concerns, we then looked into the “Single Race 15” grouping for the underlying cause-of-death data in WONDER@CDC to count liver cancer deaths (ICD10: C22) 2018-2021 among 6 Asian minority groups with population data from 2021 Census ACS data. 2020 GLOBOCAN estimated liver cancer mortality data were also compared. With anecdotal stories suggesting immigrants may seek end-of-life care in the birth country to access culture-concordant services, we looked into how cancer deaths abroad was reported. Results: Gastrointestinal (GI) cancers emerged as an area of cancer health disparity from USCS data. 5 GI cancers (colon and rectum, pancreas, liver and bile duct, stomach, and esophagus) contributed to 1/4 of US cancer deaths, and cancers in the pancreas, liver and bile duct, and esophagus still have poor outcomes. Black non-hispanic Americans are more likely to die from cancers of colon/rectum or pancreas. All minority races or ethnicities are more likely to die from cancers in liver and bile duct, or stomach than white non-Hispanic Americans. Cancers in colon and rectum, liver and bile duct, or stomach also cause high numbers of death in US under-50 population. Liver cancer mortality of US East Asian alone groups shown in the table were lower than GLOBOCAN estimated ASR of 16.1, with the greatest discrepancy in the Chinese (9.1 vs 17.2). Difference between the Vietnamese and Asian Indians may reflect that liver cancer is #1 cause of death in Vietnam, or HepB infection is low in India. Census data excluded expat US citizens, and consulate reports of death abroad have neither cause of death nor race/ethnicity data. Conclusions: We identified gastrointestinal cancers as a focus for cancer health disparity advocacy. Divergent risks for liver cancer in Asian Americans call for tailored prevention measures. Cross-agency death abroad data harmonisation to include race/ethnicity information will complete views of cancer mortality data in US. [Table: see text]
Illness uncertainty, coping, and quality of life in patients with advanced cancer and family caregivers: A dyadic study.
Authors: Ting Guan, Mimi Chapman, Lisa Zerden, Catherine Zimmer, Laurel L. Northouse, Lixin Song
Journal: Journal of Clinical Oncology (2024)

185 Background: Illness uncertainty is prevalent among patients with cancer and their family caregivers. While the relationship between illness uncertainty, coping, and quality of life (QOL) has been explored individually for patients or caregivers, it remains largely unexamined within patient-caregiver dyads. Guided by Mishel’s Uncertainty in Illness Theory, this study examined the relationships between illness uncertainty, coping, and QOL among patients with advanced cancer and family caregivers. Methods: This cross-sectional study analyzed the data from a randomized clinical trial that examined the effects of a dyadic-based intervention on psychological outcomes for patients with advanced cancer and family caregivers. Illness uncertainty, coping, and QOL were measured using the shorten version of the Mishel Uncertainty in Illness Scale for Adult, the Brief Cope, and the Functional Assessment of Cancer Therapy, respectively. The actor-partner interdependence mediation model was used to achieve the aim. Results: This study included 484 patient-caregiver dyads, with patients diagnosed with advanced breast (32.4%), lung (29.1%), colorectal (25.4%), and prostate cancer (13.0%). Patients’ avoidant coping mediated the relationship between their own illness uncertainty and QOL ( p &lt; .001). Caregivers’ active coping and avoidant coping mediated the relationship between their own illness uncertainty and QOL ( p &lt; .001). Notably, caregivers’ illness uncertainty was positively associated with patients’ avoidant coping ( b = 0.113; p &lt; .01). Conclusions: This study is one of the first to use a dyadic approach to investigate the relationships between illness uncertainty, coping, and QOL in advanced cancer patients and caregivers. Our findings highlight the importance of viewing patient-caregiver dyads as the unit of care. These findings support targeted interventions offered to both patients and family caregivers to manage their illness uncertainty and improve their QOL. Giving the effect of caregivers’ uncertainty on patients’ coping, healthcare professionals should advocate for additional psychosocial supports for family caregivers. Clinical trial information: NCT00709176 .
Validation of FIGO 2018 staging for cervical cancer: Insights from a Japanese multicenter cohort.
Authors: Kohei Hamada, Koji Yamanoi, Mana Taki, Ryusuke Murakami, Ken Yamaguchi, Junzo Hamanishi, Masaki Mandai
Journal: Journal of Clinical Oncology (2024)

126 Background: The International Federation of Gynecology and Obstetrics (FIGO) updated its staging system for cervical cancer in 2018, introducing major changes such as the establishment of stage IIIC based on lymph node metastasis (LNM), which has been reported to provide a better reflection of prognosis. However, stage IIIC has been reported to be heterogeneous, with prognoses varying depending on LNM extent and local tumor factors. In Japan, where various imaging tests are extensively performed, this revision is expected to lead to numerous cases of stage migration due to LNM. However, there have been few reports on the impact of this revision in Japan. Therefore, this multicenter study aims to assess the validity of FIGO 2018 in a Japanese cohort, focusing on LNM, local tumor factors, and histological types. Methods: Using a unified registry for gynecological malignancies developed by The Japanese Society of Obstetrics and Gynecology, this study involved 1,468 cervical cancer patients treated between 2011 and 2019 across eight designated cancer treatment hospitals. The registry used the FIGO 2009 staging system, and patients with stage IA to IIIB disease were restaged according to the FIGO 2018. Stage IIIC cases were further classified into substages IIIC-T1, IIIC-T2, and IIIC-T3AB based on local tumor factors. Results: After restaging process, A total of 347 cases (27.6%) were upstaged to stage IIIC according to LNM. Survival analysis showed that stage IIIC had a poorer prognosis than stage II (HR, 2.09; 95% CI, 1.27-3.44; p=0.004), but a significantly better prognosis than stage IIIAB (HR, 0.46; 95% CI, 0.27-0.77; p=0.004). There was also a clear difference between subclasses stage IIIC1 and IIIC2, with IIIC2 having a worse prognosis (HR, 2.13; 95% CI, 1.23-3.67; p=0.007). A survival analysis focusing on stageIIIC1 subdivisions (T1, T2, and T3AB) showed varied prognosis among them. Furthermore, IIIC1-T1 and IIIC1-T2 had significantly worse prognoses compared to stages I and II (I vs IIIC1-T1, HR, 3.21; 95% CI, 1.64-6.30; p&lt;0.001. II vs IIIC1-T2, HR, 1.82; 95% CI, 1.03-3.21; p=0.04), while the prognosis of IIIC1-T3AB was similar to stage IIIAB. In the analysis by histological type, there was little difference between IIIC1-T1 and IIIC1-T2 in squamous cell carcinoma, but there was significant difference between IIIC1-T1 and IIIC1-T2 in adenocarcinoma (HR, 5.12; 95% CI, 1.10-23.74; p=0.04). On the other hand, for IIIC2, prognosis was similar across T1, T2, and T3AB, all showing uniformly poor outcomes. Conclusions: We were able to concretely clarify the current situation in Japan and validate the usefulness of FIGO 2018. The comprehensive examination of LNM, local tumor factors, and histological type may further reinforce and complement FIGO 2018.
Exploring depression risk among breast cancer survivors: A nationwide cohort study in South Korea.
Authors: Hea Lim Choi, Bongsung Kim, Kyungdo Han, Dong Wook Shin
Journal: Journal of Clinical Oncology (2024)

19 Background: With advances in early diagnosis and treatment, the population of breast cancer survivors globally continues to grow. Depression among these survivors poses a significant concern for their long-term survivorship and overall quality of life. This study aims to investigate the incidence of depression among breast cancer survivors and identify associated risk factors. Methods: We used the National Health Insurance Service database of Korea from 2010 to 2016 and examined 59,340 breast cancer survivors and 1:2 age-matched individuals without breast cancer to investigate the incidence of depression. Cox proportional hazards regression was used to calculate the hazard ratio (HR) and 95% confidence interval (CI). The risk of depression was assessed based on age, categorizing individuals as under or over 50 years old. We conducted 1-year, 3-year, and 5-year lag sensitivity analysis to demonstrate changes in risk over time. The study identified risk factors for developing depression through multivariable Cox regression, and Kaplan-Meier analysis was conducted to illustrate the incidence probabilities of depression in breast cancer survivors. Results: Breast cancer survivors exhibited a 39% increased risk of depression compared to individuals without breast cancer, and those under the age of 50 years facing higher risk than their older counterparts (HR 1.64, 95% CI 1.58-1.70 and HR 1.23, 95% CI 1.20-1.27, respectively). Chemotherapy (anthracycline and taxane) and endocrine therapy (tamoxifen and aromatase inhibitor) emerged as potential risk factors for depression among breast cancer survivors. Sensitivity analysis revealed a decreasing trend in depression risk over time, particularly among survivors aged older than 50 years. Conclusions: This study highlights a significant increase in depression risk among breast cancer survivors, particularly those under 50 years old. Specific treatments such as chemotherapy and endocrine therapy were identified as potential risk factors. These findings emphasize the necessity for targeted interventions and support strategies to address the heightened risk of depression in breast cancer survivors, ultimately improving their long-term well-being and quality of life.
Neoadjuvant treatment with trastuzumab and pertuzumab plus fulvestrant in older patients with HER2-positive, ER-positive early breast cancer.
Authors: Juan Jose Celis, Vanessa Rodriguez, Crismar Rodriguez
Journal: Journal of Clinical Oncology (2024)

13 Background: The prevalence of breast cancer in older adults (≥70 years) is increasing and worse outcomes compared to younger patients could be explained by advanced presentation, late diagnosis, deterioration of organ function, and the presence of multimorbidities. Older patients are under-represented in clinical trials. Therefore, the risks and benefits of anticancer therapy should be carefully evaluated. The CREATE-X36 and KATHERINE37 trials enrolled few older individuals but did not show any new safety concerns, older patients should be considered for trastuzumab in case of residual HER2-positive disease following neoadjuvant systemic therapy; neoadjuvant endocrine therapy for at least 4-6 months is useful for older patients who are not immediately suitable for surgery and aromatase inhibitors are favored over tamoxifen in view of better response rate. Although adjuvant trastuzumab is beneficial regardless of age, anti-HER2 (neo)adjuvant strategies remain poorly investigated in patients age 65 years or older. Pertuzumab can be considered for high-risk individuals, but diarrhoea can be debilitating in older adults, similarly with adjuvant neratinib. Age is associated with increased cardiac toxicity rates with trastuzumab,80 with 15–40% of patients requiring early discontinuation, particularly patients who are age 80 years or older and have multimorbidities. Methods: Open-label, exploratory, phase 2 study done at one center in Venezuela. Patients were eligible if they had previously untreated, histologically confirmed, unilateral, invasive, cN0, HER2-positive, ER-positive breast cancer and older &gt;70y. Patients were treated every 3 weeks with intravenous trastuzumab (8 mg/kg loading dose followed by 6 mg/kg) and intravenous pertuzumab (840 mg loading dose in the first cycle and then at 420 mg) and intramuscular fulvestrant (500 mg) every 4 weeks for four cycles. The coprimary endpoints were change from baseline in Ki67 expression at surgery and pathological complete response. Results: Between January, 2020, and June, 2023, we enrolled 12 patients. At baseline, geometric mean Ki67 expression was 42·9 and 12·1 at time of surgery (n=8; p=0·013). A clinical objective response immediately before surgery was achieved by 10 of 12 patients. At surgery, eight patients had a pathological complete response in breast and axillary nodes. The most frequent grade 3 adverse events was diarrhea (n=4), and stomatitis. No grade 4 or serious adverse events were recorded in the study and there were no deaths. Conclusions: The combination of fulvestrant, trastuzumab, and pertuzumab had a effect on the expression of Ki67 and pCR at surgery. Triple targeting of ER, HER2, could be an effective chemotherapy-free treatment strategy for older patiens. Further clinical testing and additional molecular characterisation is necessary.
Clinical determinants of survival in patients with stage II-III pancreatic cancer.
Authors: Haruka Itakura, Qinmei Xu, Diego Toesca, Lucas Vitzthum, Arash Jamalian, Emil Schueler, Emel Alkim, J Richelcyn Baclay, Daniel Tandel Chang, George A. Fisher
Journal: Journal of Clinical Oncology (2024)

56 Background: We sought to identify the clinical determinants of overall survival (OS) in patients diagnosed with stage II-III pancreatic cancer not undergoing surgery. We curated a relatively homogenous cohort of patients who did not undergo surgical resection, but instead underwent chemotherapy in sequence with stereotactic body radiation therapy (SBRT) to examine the features that differentiated those with poor OS. Methods: In a retrospective study, we examined a cohort of 259 patients with stage II-III pancreatic cancer who underwent chemotherapy in sequence with SBRT without surgery at a single institution (Stanford Health Care). We conducted both univariate and multivariate Cox regression analyses to assess the relationships between OS and individual clinical and tumoral variables, including: age, sex, stage, Karnofsky performance status (KPS), body mass index, vessel involvement, tumor location, and biological equivalent dose [BED] of SBRT as potential determinants. Results: The study cohort consisted of 136 men (52.5%) and 123 women (47.5%) with a median age of 69 (range 38-94). Tumor histology was predominantly ductal adenocarcinoma (n=249, 96.1%), with tumor sites of involvement spanning: uncinate (n=35, 13.5%), head (n=160, 61.8%), body (n=59, 22.8%), and tail (n=5,1.9%). More patients had stage III (n=171, 66%) than stage II (n=88, 34%) disease, and their tumor resectability by NCCN criteria were rated as: unresectable (n=145, 56%), borderline (n=28, 10.8%), resectable (n=11, 4.2%), or unrecorded (n=75, 29%). Tumor progression was observed in local (n=71, 27.4%), regional (n=29, 11.2%), and distant (n=150, 57.9%) sites during the median follow up period of 17 months (range 15-18 months) from diagnosis and 12 months (10-13 months) from SBRT. Death (n=213, 82.2%) during this period was more common than survival (n=46, 17.8%). In univariate analyses, clinical features impacting OS included: KPS (hazard ratio [HR] 0.14, p=0.007); male sex (HR 1.44, p=0.01), pancreatic head tumors (HR 1.44, p=0.011), BED (HR 1.33, p=0.035), and age (HR 1.013, p=0.044). In the multivariate analysis, which incorporated only features significant in the univariate analyses, tumor location at the pancreatic head (HR 1.412, p=0.021) and male sex (HR 1.360, p=0.03) conferred the highest risks for poor OS, with BED bordering on significance (p=0.059) (Table). Conclusions: Among patients with stage II-III pancreatic cancer who underwent chemotherapy in sequence with SBRT, but not surgery, the most significant clinical determinants of poor OS were location of the tumor in the pancreatic head and male sex. Prioritizing additional disease monitoring and alternative therapies for this subset of patients at higher risk of poor survival may be warranted. [Table: see text]
Prognostic value and therapeutic response of neutrophil-to-lymphocyte ratio in penile cancer.
Authors: Xingliang Tan, Yiqi Yu, Hang Li, Weicheng Wu, Juexiao Chen, Zhiming Wu, Kai Yao
Journal: Journal of Clinical Oncology (2024)

116 Background: Chronic inflammation mediated by poor genital hygiene is a well-recognized pathogenic trigger for penile squamous cell carcinoma (PSCC). The neutrophil-to-lymphocyte ratio (NLR) is a simple and reproducible factor reflecting the systemic inflammatory response and has been reported as an unfavorable indicator in PSCC. However, previous studies limited by small sample sizes, confounding prognostic features and without high-quality evidence to demonstrate the clinical significance of the NLR. Methods: A large cohort of 582 penile cancer patients who underwent radical inguinal lymphadenectomy with definitive pN stages were enrolled in this study. Univariate and multivariate Cox regression analyses were performed to investigate prognostic factors and inflammation-related markers in PSCC patients. More importantly, the propensity score matching (PSM) method was used to minimize the prognostic confounding clinicopathological features. Immunofluorescence was further used to investigate the correlation between tumor-infiltrating neutrophils, CD8 + T cells and the NLR. Results: According to the ROC curve, the optimal cutoff value for the NLR was 3.0, and 226 (38.8%) PSCC patients had a high NLR. Survival analyses indicated that advanced pT, pN, pathological grade, lymphovascular invasion, high NLR, C-reactive protein (≥ 2.2 mg/L) and serum amyloid A (≥ 11.3 mg/L) were associated with poor PFS and CSS. After PSM to eliminate interference from clinical factors, pN and the NLR were found to be independent prognostic indicators in PSCC patients (both p&lt;0.001). Cox multivariate regression analysis revealed that the HR for PFS was 1.64 (1.15–2.34) in the high NLR group and 1.56 (1.04–2.34) in the high NLR group (p=0.006 and 0.030, respectively). PSCC patients with high NLRs experienced shorter PFS after receiving cisplatin-based chemotherapy (p=0.037) and PD-1 immunotherapy (p=0.020). In addition, we found that the infiltration of tumor-associated neutrophils (CD66 + ) and the CD8 + T-cell ratio were positively correlated with the NLR. The development and formation of neutrophil extracellular traps (NETs) might contribute to chemoresistance and tumor progression in high-NLR PSCC patients. Conclusions: In this study, we demonstrated that the NLR is an effective, simple and independent prognostic indicator for PSCC. The NLR holds promise as a powerful tool to guide decision-making in clinical practice. [Table: see text]
Association of peripheral edema with immune checkpoint inhibitors: A systematic review.
Authors: Kazuya Tsuchiya, Evelyn Elias, Mako Koseki, Jonathan Estaris, Fnu Chesta, Kensuke Takaoka, Yoshito Nishimura, Nicholas Cole Rohs, Yu Fujiwara
Journal: Journal of Clinical Oncology (2024)

187 Background: Immune checkpoint inhibitors (ICIs) are widely used to treat patients with cancer but immune-related adverse events occasionally disrupt treatments and affect their quality of life. Peripheral edema from ICI therapy appears rare but can occur due to increased peripheral vascular permeability. Thus, we aimed to report the incidence and outcomes of peripheral edema from ICIs. Methods: Medline, Embase, and Web of Science were searched to identify phase 3 randomized controlled trials (RCTs) reporting the incidence of peripheral edema in patients treated with ICIs. We calculated the incident rate of peripheral edema based on treatment patterns (monotherapy and combination therapy) and ICI subtypes (PD-1, PD-L1, and CTLA-4 inhibitors). We also performed a systematic review to identify articles reporting treatment outcomes of peripheral edema from ICIs. Results: Overall, 60 RCTs comprising 22,590 patients were identified for the incidence analysis. Treatment-related peripheral edema (Grade 1-5) occurred in 2.8% from ICI monotherapy (n = 195/6969; PD-1 inhibitors: 2.2% [n = 104/4694], PD-L1: 3.7% [n = 58/1557], CTLA-4: 4.6% [n = 33/718]), 5.0% (n = 112/2257) from ICI with chemotherapy, and 8.7% (n = 205/2349) from ICI with molecular-targeted therapy. Grade 3-5 treatment-related peripheral edema occurred in 0.3% of patients treated with ICI monotherapy (Table). For treatment outcomes of peripheral edema, a systematic review identified 19 studies (17 case reports/series,1 phase 1/2 clinical trial, 1 pharmacovigilance study) comprising 40 patients with immune-related peripheral edema. In total, 82.5% (n = 33/40) of cases received glucocorticoid treatment, and 55.0% (n = 22/40) required a high dose (≥ 1 mg/kg/day) of prednisone. ICI was discontinued in 77.5% (n = 31/40) due to peripheral edema (permanent discontinuation in 35% [n = 14/40]). Conclusions: Peripheral edema occasionally occurs in patients treated with ICIs but its occurrence often requires glucocorticoid administration, which may impact cancer treatment outcomes. [Table: see text]