tbuckley/cabot-search huggingface dataset:
Impact of systemic therapy sequencing on overall survival for patients with advanced BRAF-mutated melanoma.
Authors: B. Adi Kartolo, Jasna Deluce, Wilma M. Hopman, Linda Liu, Tara D. Baetz, D. Scott Ernst, John Gordon Lenehan
Journal: Journal of Clinical Oncology (2021)

9552 Background: Both immune checkpoint inhibitors (ICI) and BRAF targeted therapy (TT) are effective treatments for patients with advanced BRAF-mutated melanoma. However, the choice of first-line (1L) therapy is at the discretion of treating oncologists without clear guidance from current available data or established guidelines. Utilizing prospectively collected data from the Canadian Melanoma Research Network (CMRN) database, we provide real-world evidence to highlight the impact of sequencing these therapies. Methods: Prospective data from 9 cancer centres in Canada was retrieved from the CMRN database for patients with unresectable/metastatic melanoma, with BRAF targetable subtypes, who received at least one-cycle of 1L palliative-intent ICI or TT, and at least 1-year of follow-up. We categorized patients into 2 groups: 1L BRAF±MEK inhibitors with/without subsequent PD-1±CTLA-4 inhibitors (1L-TT), or vice versa (1L-ICI). The primary study outcome was overall survival (OS). Survival outcomes were analyzed through Kaplan-Meier methods, and multivariable Cox analysis was utilized to account for potential confounders. Results: Our study (N=235) included 152 and 83 patients in 1L-TT and 1L-ICI groups, respectively. Combined BRAF-MEK inhibitors accounted for 59% of the 1L-TT group, whereas single-agent IO accounted for 66% of the 1L-ICI group. There were 93 patients who received second-line (2L) therapy, with a non-significant trend of 1L-TT group receiving more 2L therapy compared to 1L-ICI group (65% vs. 43%, P=0.404). Neither treatment group showed significant differences in median time on 1L therapy (P=0.645) or 2L therapy (P=0.686). The 1L-ICI group was associated with a favourable median overall survival (OS) compared to 1L-TT group (19.3 vs. 10.0 months, P=0.031). Specifically, the ICI only group had the highest median OS, followed by TT-ICI sequence, ICI-TT sequence, and TT only groups respectively (not reached vs. 38.3 vs. 16.9 vs. 6.1 months, P&lt;0.001). However, this OS benefit (HR 0.89, 95% 0.51-1.53, P=0.644) was non-significant upon controlling for confounders such as baseline metastatic sites &gt;2 (HR 2.07, 95%CI 1.24-3.46, P=0.006) and ECOG ≥2 (HR 3.47, 95%CI 2.02-5.97, P&lt;0.001) in multivariable Cox analysis. Conclusions: There was no significant difference in OS between 1L-TT and 1L-IO groups. Rather, OS is driven mostly by the patient’s clinical status and tumour-associated features. Our study provides real-world evidence in an understudied area. Further studies are needed to validate our findings to inform guideline development.[Table: see text]
Relationship between neutrophils/lymphocytes and tumor infiltrating lymphocytes stroma in patients with invasive muscle bladder cancer and the response to treatment.
Authors: Martin Eduardo Richardet, Maria gimena Ferreira, Martin Paradelo, Luciana Paola Acosta, Matias Molina, Ignacio Magi, Eduardo Richardet
Journal: Journal of Clinical Oncology (2021)

e16513 Background: The bladder cancer is a malignant disease. It has been related to tobacco consumption, fat diet, high body mass index (BMI) and urinary tract infections. As a result of the activation the pro-inflammatory pathways. Neutrophil to lymphocyte radio (NLR) and the infiltrating lymphocytes of the tumor stroma (TILs) have been shown to have a significant prognostic value in different tumors. The primary aim is to analyze the role of TILs and RNL as a predictive factor, in patients with MIBC and objective response rate (ORR). The secondary aim is to evaluate the relationship beteween BMI, tabaquism and ORR, in the same group of pts. Methods: A total of 35 pts with MIBC was included. All pts received neoadjuvant treatment, with cisplatin and gemcitabine. Also, TILs was determined as the percentage of mononuclear inflammatory cells in the total stromal area counted in 5 high-power fields (CGA, X 400), on the invasive front of the tumor. The NLR was obtained before treatment and value of cut-off was 2.6. the evaluation of ORR was calculated used the T-Test and Chi Square test. Results: Of the total of 35 patients. 15 patients obtained complete response (CR), 6 pts partial response (PR), 5 pts stable disease (SD) and 9 pts disease progression (DP). In 21 tumor sample was observed an intense TILS. These patients obtained a better ORR 42.6 % vs 21.7% with low TILs in his tumor samples. The difference was statistically significant (p: 0.001). Regarding NLR, only 9 pts presented response with NLR &gt; 2,6 vs 12 pts with response and RNL &lt; 2.6. The difference was not statistically significant. When analyzing the smoking and response. We could observe response of 69.6% in smoking pts vs Non- smoking the response was 41.7%. Regarding BMI, 21 pts with response of 27% and 14 patient without response 25.9%. But the differences were not significant in any groups. Conclusions: We conclude that the presence of TILS in tumor samples, in patients with MIBC, could be a predictive factor against the response to neoadjuvant treatment. With the other variables, smoking and BMI, we did not observed influence in ORR. We will keep working to obtain a greater number of patients. Then we could have a better analysis and statistical power.
Efficacy of the VEGFR-2 tyrosine kinase inhibitor AZD2171 in human renal carcinoma (Caki-1) cells in vitro and in vivo
Authors: Dietmar Siemann, Sharon Lepler, Chris Pampo
Journal: Cancer Research (2007)

2119  Vascular endothelial growth factor (VEGF) acts as a survival factor for newly-formed vasculature, enhances the permeability of blood vessels and has been implicated as the key factor in the angiogenic process of solid tumors. Thus, interfering with VEGF signaling has become a major strategy to inhibit tumor growth and spread. One approach is to inhibit VEGF receptor-2 (VEGFR-2)-associated tyrosine kinase signaling. The present studies report on the efficacy of AZD2171, an oral, highly potent and selective VEGF signaling inhibitor of VEGFR-1, -2, and -3 tyrosine kinases, in human renal cell carcinoma (Caki-1) cells. In vitro treatment with AZD2171 was found to have a significant impact on endothelial cell (EC) but not renal cell carcinoma proliferation. AZD2171 50-100 nM inhibited the growth of human microvascular endothelial cells (lung) but doses ≤5 μM, had little impact on Caki-1 cell growth. AZD2171 10 nM significantly impaired (by a factor of 2) the number of ECs that migrated into a denuded area over a 48-hour period. An intradermal assay was used to study the effect of AZD2171 treatment on Caki-1 tumor cell-induced angiogenesis in vivo. Nude mice received AZD2171 (3, 6, or 9 mg/kg/day) or vehicle by oral gavage commencing on the day prior to tumor cell inoculation. Caki-1 cells (1 x 105) were injected intradermally at four sites on the ventral surface of each of four mice. Three days post-inoculation, the mice were humanely culled and the skin flap containing the inoculation site was excised and the number of blood vessels induced was counted. Compared with controls, skin flaps from AZD2171-treated mice showed a significant and dose-dependent reduction in the number of blood vessels induced by the tumor cells. The antitumor efficacy of AZD2171 was assessed in mice bearing Caki-1 xenografts. When tumor volume reached ~200 mm3, mice were randomly assigned to receive either no treatment or AZD2171 6 mg/kg/day po for 2 weeks (Mon-Fri). In animals receiving AZD2171, tumors took twice as long to reach five times the starting size compared with untreated controls. These results suggest that inhibition of VEGF signaling with AZD2171 may impair the growth of renal cell carcinoma.
Impact of low skeletal muscle mass and density on outcomes of locally advanced esophageal cancer patients treated with radical radiotherapy.
Authors: Jiahua Lv, Ningjing Yang, Hongyuan Jia, Long Liang, Lei Wu, Yi Wang, Gang Wan, Qifeng Wang, Tao Li
Journal: Journal of Clinical Oncology (2021)

e16047 Background: Low skeletal muscle mass and density are independent predictors of clinical outcomes in multiple gastrointestinal cancers. However, its effect on the long-term survival of locally advanced esophageal cancer patients undergoing radical radiotherapy is still unclear. Methods: Patients with stage II-III esophageal cancer undergoing radical radiotherapy, enrolled in a observational cohort study, were included. Skeletal muscle mass and density were measured on CT. Patients with high and low skeletal muscle mass and density were compared regarding overall survival (OS). Results: In total, 165 patients (75.8% males, median age 63) were included, from March 2012 to September 2017. Before radiotherapy, 26.7% patients had low skeletal muscle mass and 23.0% patients had low skeletal muscle density. After radiotherapy, 40.6% patients had low skeletal muscle mass and 30.3% patients had low skeletal muscle density.The median OS of high skeletal muscle mass and density group was significantly higher than that of low skeletal muscle mass and density group before radiotherapy (28.7 months vs 28.2 months, p = 0.041; 29.6 months vs 16.9 months, p = 0.025). The median OS of high skeletal muscle mass and density group was also significantly higher than that of low skeletal muscle mass and density group after radiotherapy (30.3 months vs 20.3 months, P = 0.012; 29.6 months vs 17.2 months, p = 0.018). Conclusions: Low skeletal muscle mass and density are associated with long-term outcome in patients undergoing radical radiotherapy. It is suggested that oncologists should pay more attention to the management of muscle mass and density of patients with esophageal cancer undergoing radiotherapy in order to improve their nutritional status and long-term survival.
Comparing adult child and spousal caregiver burden and potential causes.
Authors: Anny Fenton, Nancy Lynn Keating, Katherine A. Ornstein, Erin E. Kent, Kristin Litzelman, Julia H. Rowland, Alexi A. Wright
Journal: Journal of Clinical Oncology (2021)

12127 Background: Adult children caring for a parent with cancer comprise a significant segment of caregivers. Demographic trends indicate this caregiving population will grow as the baby boomer generation ages. Yet little is known about adult child caregivers’ needs and experiences and how they differ from the well-studied spousal caregiver. This knowledge gap may hinder efforts to ameliorate adult children’s caregiver burden and its impact on patients. Methods: We analyzed adult child and spousal/partner caregivers’ surveys from the Cancer Care Outcomes Research and Surveillance consortium, a multi-regional population-based study of approximately 10,000 persons with newly diagnosed colorectal and lung cancer. We used t-tests and a series of multivariate regression models to assess whether adult child and spousal caregivers’ caregiving responsibilities, social/emotional burden, and financial burden (scaled 0-10) differed and examined patient and caregiver characteristics’ mediation of variation in burden. Results: Compared to spouses/partners (N=1029), adult children (N=230) completed similar levels of caregiving tasks but spent less time (14 vs. 24 hours/week; p&lt;0.001). However, adult children experienced higher social/emotional burden (2.9 vs. 2.4; p&lt;0.01). In baseline models controlling for patient clinical factors, caregiving characteristics, and caregiver demographics, adult children’s average social/emotional and financial burdens were statistically higher than spouses/partners. Additional adjustment for caregivers’ childcare responsibilities and employment eliminated social/emotional and financial burden disparities. Additional adjustment to the baseline model for caregiver-patient gender concordance eliminated the social/emotional burden gap. Communication quality was a large and statistically significant predictor of both burdens (p&lt;0.001). Conclusions: Adult children spend less time caregiving than spouses/partners but experience higher caregiving burden. Adult children’s childcare and career responsibilities help explain this increased burden. Gender concordance between caregiver and patient may also contribute to social/emotional burden, adding important context to prior research indicating female caregivers experience the greatest burden. Interventions to improve communication between caregivers and patients have the potential to reduce both adult child and spouses/partners caregiver burden. Adjusted average caregiver burden for adult child and spousal caregivers. [Table: see text]
Association of PIK3CA, PTCH1, FGF6, and NRAS mutations with venous thromboembolism in advanced lung and gastrointestinal cancer.
Authors: Satish Maharaj, Shruti Bhandari, Xiaoyong Wu, Anuja Abhyankar, Daniel Zetter, Shesh Rai, Adam Rojan, Jason Alan Chesney, Vivek R. Sharma
Journal: Journal of Clinical Oncology (2021)

e15087 Background: Venous thromboembolism (VTE) in patients with gastrointestinal (GI) and non‐small cell lung cancer (NSCLC) is common and increases morbidity and mortality. In advanced GI and NSCLC, molecular subtyping has increased use of next-generation sequencing (NGS). The association between tumor mutation profile and VTE risk remains undetermined. Methods: We conducted a retrospective cohort study of consecutive GI/NSCLC patients from 2014-2019 with NGS and follow‐up at Brown Cancer Center. The NGS platform detected substitutions, indels, copy number alterations and select rearrangements in 324 genes. Patients with thrombophilia, anticoagulation use or &gt;1 malignancy were excluded. VTE was defined as deep vein thrombosis, pulmonary embolism or visceral vein thrombosis within 6 months prior to diagnosis or any time after. For statistical analysis SAS 9.5 was used with significance at alpha=0.05. Multinomial logistic regression was performed, in which the log odds of VTE was modeled as a linear combination of the genes. Odds ratios and 95% confidence intervals for VTE were generated. Results: A total of 364 patients were reviewed; after exclusions 326 patients were included comprising Stage III/IV NSCLC (58%), metastatic colorectal (33%) and other metastatic GI cancers - gastric, duodenal, esophageal, pancreatic and cholangiocarcinoma (9%). Approximately half (53%) were males with mean age of 59.1 yrs and 76.4% current/former smokers. There was a low level of microsatellite instability (0.9%). VTE occurred in 75 patients (23%) during a mean follow‐up of 24.5 months. Only 1 patient had surgery within 90 days prior to VTE. Of 248 genes mutated in the VTE group, 9 were more prevalent compared to those without VTE (Table). Statistical analysis showed PIK3CA, PTCH1, FGF6, and NRAS mutations significantly increased odds of VTE, with PIK3CA the most prevalent of these (Table). Conclusions: Patients with PIK3CA, PTCH1, FGF6 and NRAS mutations had significantly higher VTE risk. These tumor mutations and associated pathways may provide novel insight into risk stratification, prevention and targeted treatment of VTE in cancer. [Table: see text]
Circulating tumor cell-driven use of neoadjuvant chemotherapy in patients with muscle-invasive bladder cancer.
Authors: Nick Beije, Ingeborg Elisabeth de Kruijff, Joep de Jong, Sjoerd O. Klaver, Peter de Vries, Rens Jacobs, Diederik Meindert Somford, Ed te Slaa, Toine van der Heijden, Johannes Alfred Witjes, Laurent Fossion, Egbert Boeve, John van der Hoeven, Harm H.E. van Melick, Carl J Wijburg, John W.M. Martens, Ronald De Wit, Jaco Kraan, Stefan Sleijfer, Joost L. Boormans
Journal: Journal of Clinical Oncology (2021)

4523 Background: International guidelines for the treatment of non-metastatic muscle-invasive bladder cancer (MIBC) recommend neoadjuvant chemotherapy (NAC), which, however, is underutilized in practice. We hypothesized that the absence of circulating tumour cells (CTCs), an established prognostic marker in MIBC, may identify patients with such a favourable prognosis that NAC may be withheld. Methods: The CirGuidance study included adults with clinical stage T2-T4aN0-N1M0 muscle-invasive urothelial carcinoma of the bladder who were fit to undergo radical cystectomy. CTCs were enumerated using the CellSearch system. CTC-negative patients (no CTCs detectable) underwent radical surgery without NAC; CTC-positive patients (≥1 detectable CTCs) were advised to receive NAC followed by radical surgery, but NAC could be withheld at the discretion of the treating physician. The primary endpoint was the two-year overall survival (OS) in the CTC-negative group, analysed in the intention-to-treat population. The prespecified criterion for trial success was a two-year OS of minimally 75% (95% confidence interval (CI) ±5%) in the CTC-negative group. Results: Of 315 patients screened for eligibility, 273 were enrolled in the study. The median age was 69 years; the median follow-up was 36 months. The two-year OS in the CTC-negative group was 69.5% (n = 203; 95% CI 62.6%-75.5%); in the CTC-positive group it was 58.2% (n = 70; 95% CI 45.5%-68.9%). CTC-positive patients had a higher rate of cancer-related mortality (hazard ratio (HR) 1.61, 95% CI 1.05-2.45, p = 0.03) and disease relapse (HR 1.87, 95% CI 1.28-2.73, p = 0.001) than CTC-negative patients. Explorative analyses suggested that CTC-positive patients who had received NAC (n = 22) survived longer than CTC-positive patients who had not (n = 48), with a two-year OS of 74.8% (95%CI 49.5%-88.8%) versus 52.0% (95% CI 37.2%-65.0%), respectively. Conclusions: The two-year OS in the CTC-negative group did not meet the prespecified criterion for trial success. However, given the trial population’s advanced age and high rate of non-cancer related mortality, the benefit of NAC is likely to be limited in CTC-negative MIBC patients. CTC enumeration at the moment of diagnosis could aid in the decision to prescribe neoadjuvant chemotherapy for a muscle-invasive bladder cancer patient as a criterion in addition to clinical characteristics. Clinical trial information: NL3954.
Joven y Fuerte (J&amp;F): Multidisciplinary distance care program in Mexico for young women with breast cancer (YWBC) during the COVID-19 pandemic.
Authors: Lucero Labra, Andrea Guerra-Anlen, C. Lizette Galvez, Juan Torres, Alan Fonseca, Cynthia Villarreal-Garza, Jose Maria De Arrigunaga, Fernanda Mesa-Chavez, Jose R Espinosa Fernandez, Milagros Perez-Quintanilla, Enrique Bargallo-Rocha, Paula Cabrera-Galeana, Alejandra Platas, Alejandro Mohar Betancourt, Marlid Cruz-Ramos
Journal: Journal of Clinical Oncology (2021)

e13536 Background: The COVID-19 Pandemic represents unprecedented new challenges for healthcare systems, care programs and especially for vulnerable populations like oncologic patients. The J&amp;F Program, developed at the National Cancer Institute (INCan) in Mexico City, provides multidisciplinary care and navigation support for YWBC patients. During the first months of 2020, the whole mexican healthcare system, including the INCan and programs like J&amp;F had to undergo structural adjustments to offer distance care attention (DCA) and face the Pandemic challenges. Methods: From March to September 2020, 196 patients received DCA (phone and video calls, text messages and virtual workshops), which addressed navigation, unmet psychological needs, psychoeducation, oncology and sexual support provided by different healthcare professionals (oncologists, psychologists, sexual specialists). Seventy agreed to participate in this study (intervention group, IG). Forty-three recently diagnosed breast cancer patients could not be contacted by the Program (control group, CG). The patients from the IG completed the emotional distress thermometer and were interviewed about stressors, coping strategies during the Pandemic, and satisfaction with the multidisciplinary support given by the J&amp;F Program. We compared thestandard care given within the institutional facilities and the multidisciplinary support provided virtually by J&amp;F Program for YWBC during the COVID-19 Pandemic regarding their perceived stressors and emotional distress. Results: The CG had more concerns about oncology treatments and their side effects (nausea p = 0.031, fever p = 0.007, anorexia p = 0.006) than the IG. Emotional distress was present in 77% and 86% in the IG and the CG respectively. The IG received significant navigation guidance and multidisciplinary support with the J&amp;F Program’s DCA strategy during the Pandemic than the CG (p &lt; 0.01 and p = 0.019). The J&amp;F Program's psychological care significantly helped YWBC manage their distress (p = 0.001); 70% of the IG patients considered that the support given by the J&amp;F Program dealt with the COVID-19 Pandemic challenges successfully (p &lt; 0.01). Conclusions: DCA by theJ&amp;F Program showed feasibility and benefit in the COVID-19 Pandemic context for YWBC. These findings suggest that multidisciplinary care could be preserved by combining care provision physically and virtually depending on patients' resources or unmet needs.
Prevalence and risk factors for self-reported sexual dysfunction in Hispanic female breast cancer survivors 0-3 years post-cancer treatment: Results of a single-center retrospective study.
Authors: Rosalind Guest, Noah Zanville, Lisellet Morin, Muni Rubens, M. Beatriz Currier
Journal: Journal of Clinical Oncology (2021)

e24039 Background: Improvements in breast cancer screening and treatment have improved survival for many women in the U.S. However, side-effects associated with cancer treatment remain a serious issue for survivors. It is estimated that up to half or more of female breast cancer survivors (BSC) report unwanted changes in sexual function following cancer treatment. Studies have also suggested that both younger BCS and Hispanic women may be at higher risk for developing sexual dysfunction following treatment. However, women of Hispanic origin remain highly underrepresented in research on sexual dysfunction, despite being one of the fastest growing racial/ethnic populations in the U.S. The purpose of this study was to compare the prevalence and risk factors for sexual dysfunction between Hispanic and non-Hispanic BCS during the first-three years post-cancer treatment. Methods: Data for this single-center, non-randomized, retrospective study came from a database of self-reported symptom data collected as part of routine clinical practice in our institution’s Survivorship Clinic. Results: Over a 2.8-year period between Apr. 2017 and Dec. 2019, a total 815 female BCS were evaluated for sexual dysfunction. Nearly two-thirds (63.0%) of BCS identified as Hispanic, and 37.0% (n = 302) of BCS identified as non-Hispanic. Mean age of the sample was 58.4 ± 11.7 (range: 24.2–91.8). Results found that approximately a quarter (25.8%) of BCS reported “vaginal dryness, discharge, or pain with intercourse” at their initial survivorship visit. Rates of sexual dysfunction were nearly identical between Hispanic and Non-Hispanic BCS (25.7% vs. 25.8%; p = 0.975). Consistent with previous studies, BCS who reported sexual dysfunction tended to be younger, on average (53.7±10.5 years vs. 60.0 ±11.6 years; p = 0.002) and more likely to have been diagnosed with Stage 2 or 3 cancer (p = 0.038) than BCS not reporting sexual dysfunction. Multivariate logistic regression models using age, race, stage of cancer, chemotherapy, radiation type, and hormone therapy as predictors confirmed this association between younger age and likelihood of sexual dysfunction, showing that for every one-year younger BCS were at their initial survivorship visit, the odds of reporting sexual dysfunction at the initial survivorship visit increased by approximately 6.5% (OR: 0.943, 95% CI: 0.927-0.96; p &lt; .0001). Conclusions: Results suggest that signs/symptoms such as vaginal dryness, discharge, or pain with intercourse are common for both Hispanic and non-Hispanic BCS following treatment, affecting as many as one in four BCS. Results also show that symptoms are prevalent among younger BCS. Together, results underscore the need for clinicians to be prepared to assess and manage sexual dysfunction, especially in younger BCS.