tbuckley/cabot-search huggingface dataset:
Drug-related pneumonitis during everolimus therapy in patients with metastatic breast cancer: Incidence, radiographic findings, and correlation with clinical outcome.
Authors: Chengcheng Gong, Qin Xiao, Xi-Chun Hu, Yajia Gu, Biyun Wang
Journal: Journal of Clinical Oncology (2019)

e12519 Background: Everolimus (EVE) in combination with endocrine therapy are approved for the treatment of HR+/HER2- metastatic breast cancers (MBC) patients. mTOR inhibitor-associated pneumonitis is one of the most worrying and common adverse drug events leading to treatment discontinuation. We investigated the incidence of drug-related pneumonitis (DRP) during EVE therapy in MBC patients and characterize radiographic patterns and clinical impact of pneumonitis. Methods: We retrospectively reviewed the data of MBC patients treated with EVE in Fudan University Shanghai Cancer Center from June 2013 to June 2017, who had baseline and at least one follow-up chest CT available for review (NCT 03730428). Serial chest CT scans were reviewed for abnormalities suspicious for DRP by an independent review of two radiologists. Log rank and Cox proportional hazards regression analysis were used for the time-to-event analysis. Results: DRP was radiographically detected in 45/86 patients (52.3%). Over 80% of DRP occurred in the first 4 months of treatment (cumulative risk 52.3%). Most patients with DRP were asymptomatic (n = 31, 68.9%). Among 14 patients with clinical manifestation, common symptoms included cough, fever and shortness of breath. DRP mostly distributed in bilateral lower lobes. Ground glass opacities and reticular opacities were seen in most of the cases. Elderly patients (OR 1.09, p = 0.002) and patients with baseline pneumonitis (OR 3.96, p = 0.023) are more likely to develop DRP. Patients who developed DRP had significantly longer progression free survival (median 6.8 vs 4.1 months, p = 0.024) and overall survival (OS, median 42.8 vs 21.3 months, p = 0.016). DRP was a predictor of improved OS by multivariate Cox analysis (HR 0.49, 95%CI 0.25-0.97, p = 0.040). Conclusions: DRP was noted in half of the MBC patients treated with EVE. Our preliminary data suggested that DRP would be a predictor for better outcome, which should be further investigated. Given the incidence and outcomes of patients with DRP, close monitoring, prompt diagnoses and appropriate treatment for DRP are critical for the preservation of patients’ quality of life and achievement of maximal treatment outcomes.
How long have we got? The accuracy of physicians’ estimates and scenarios for survival time in 898 women with recurrent ovarian cancer (ROC).
Authors: Felicia Roncolato, Rachel O'Connell, Florence Joly, Anne Lanceley, Felix Hilpert, Aikou Okamoto, Eriko Aotani, Sandro Pignata, Paul P. Donnellan, Amit M. Oza, Elisabeth Avall-Lundqvist, Jonathan S. Berek, Jalid Sehouli, Jonathan A. Ledermann, Dominique Berton-Rigaud, Belinda Emma Kiely, Michael Friedlander, Martin R. Stockler
Journal: Journal of Clinical Oncology (2019)

5549 Background: Predicting, formulating, and communicating prognosis in women with ROC is difficult. Best-case, worst-case, and typical scenarios for survival time based on simple multiples of an individual’s expected survival time (EST) estimated by their oncologist have proven accurate and useful in a range of advanced cancers. We sought the accuracy and prognostic significance of such estimates in the GCIG Symptom Benefit Study: a multinational, prospective cohort study of women with ROC (platinum resistant and potentially platinum sensitive ROC who have had more than 2 lines of chemotherapy). Methods: Oncologists estimated EST at baseline for each woman they recruited to the GCIG Symptom Benefit Study in 11 countries. We hypothesised a priori that oncologists’ estimates of EST would be unbiased (equal proportions [approximately 50%] of women living longer versus shorter than their EST), imprecise ( &lt; 33% living within 0.75 to 1.33 times their EST), and provide accurate scenarios for survival time (approximately 10% dying within ¼ of their EST, 10% living longer than 3 times their EST, and 50% living from half to double their EST). We also hypothesised that oncologists’ estimates of EST would be independently significant predictors of survival in a multivariable Cox model adjusting for prognostic factors established in previous studies. Results: Oncologists’ individualised estimates of EST in 898 women with ROC were unbiased (55% of women lived longer than their EST) and imprecise (23% lived within 0.75 to 1.33 times their EST). Scenarios for survival time based on oncologists’ estimates of EST were remarkably accurate: 7% of women died within ¼ of their EST, 13% lived longer than 3 times their EST, and 53% lived from half to double their EST. The median EST was 12 months (range 3-70), and median observed was 12.7 months. Oncologists’ estimates of EST were independently significant predictors of overall survival (HR 0.96, CI 0.94-0.98, p &lt; 0.0001) in Cox models accounting for previously established prognostic factors. Conclusions: Oncologists’ estimates of EST were unbiased, imprecise, and independently significant predictors of survival time. Best-case, worst-case and typical scenarios based on simple multiples of EST were remarkably accurate, and provide a useful approach for predicting, formulating, and explaining prognosis in women with recurrent ovarian cancer. Clinical trial information: ACTRN: 12607000603415.
Prognostic nutritional index and colorectal cancer deaths: A retrospective cohort study in Chinese patients with locally advanced colorectal cancer.
Authors: Wenling Wang
Journal: Journal of Clinical Oncology (2019)

e15160 Background: The nutrition and immune status-based scoring system PNI was originally used to assess the nutritional status and surgical risk of surgical patients before surgery. Subsequent studies have shown that PNI is an important prognostic indicator for some malignant tumors, including hepatocellular carcinoma, pancreatic cancer, laryngeal cancer, renal cell carcinoma and gastric cancer. We speculated that since PNI is associated with the prognosis of other malignancies, is it also relevant in colorectal cancer? In view of the obvious increase in the incidence of colorectal cancer in China, and the clinical progress of colorectal cancer in the entire colorectal cancer accounted for up to 70% and current studies on PNI and local advanced colorectal cancer prognosis association study in Chinese is limited. In the present study, our primary objective was to explore whether PNI evaluated at baseline was independently associated with colorectal cancer deaths after controlling other potential confounders. Methods: Through a retrospective cohort study, we analyzed the clinical data of 400 patients with pathologically confirmed colorectal cancer and radical resection of colorectal cancer from January 2013 to April 2018.The exposure variable was PNI at baseline, the outcome variable was death, and other covariates of this study include: Continuous variables: age, platelet count, tumor markers (CEA, CA199, CA724, CA242).Categorical variables: gender, survival status, tumor location, histological type, degree of differentiation, TNM staging, and postoperative treatment. Results: Fully-adjusted model demonstrated that PNI was not associated with deaths of local advanced colorectal cancer and radical resection of colorectal cancer (HR = 0.88; 95% CI, 0.78-1.00). By applying the cubic spline function to the model, we found that the relationship between PNI and death is nonlinear.Two-piecewise cox model suggested that On the left side of the inflection point (41.35), PNI per 1 change is associated with the 68% decrease of risk of deaths (HR = 0.32; 95% CI, 0.13-0.79), to the right of the inflection point, PNI and death The association is not detected. Conclusions: PNI and deaths are nonlinearity, and within a certain range (PNI = 26-41), PNI is an independent protective factor for death risk.
Direct oral anticoagulants (DOAC) versus warfarin and enoxaparin in ovarian vein thrombosis.
Authors: Fahrettin Covut, Tariq Zuheir Kewan, Oscar Perez, Hassan Awada, Arslan Babar, Bicky Thapa, Abdo S. Haddad, Timothy Peter Spiro, Hamed Daw
Journal: Journal of Clinical Oncology (2019)

e14698 Background: Ovarian vein thrombosis (OVT) is a rare condition that is commonly associated with malignancy. Efficacy and safety profile of DOAC in OVT has not been compared with warfarin and low-molecular-weight-heparin in the literature. Methods: We reviewed patients who were diagnosed with OVT between 11/2012 and 1/2018 and had follow-up imaging with computed tomography to assess resolution of thrombus. The outcomes of interests were thrombus resolution, recurrent thromboembolic events, and 1-year cumulative incidence of clinically significant bleeding events. Cumulative incidence was calculated with death and discontinuation of therapeutic anticoagulation as competing risks. Results: We identified 36 patients, 17 (47%) had right, 14 (39%) had left, and 5 (14%) had bilateral OVT. Median age and body mass index at diagnosis were 47 (range: 25 - 86) and 28 (range: 19 – 43), respectively. At least one predisposing factor was identified for 32 (92%) patients, 16 (44%) had underlying active malignancy. Overall, 27 (75%) patients achieved complete or partial recanalization at follow up CT after median of 4 months (range: 1 – 13) from initiation of anticoagulation. Ten (28%) and 11 (31%) patients were treated with DOAC and warfarin after median of 3 and 2 days of anticoagulation with unfractionated heparin or enoxaparin, and follow up CT after median of 6 and 4 months showed complete/partial recanalization rates of 70% and 55%, respectively (p = 0.47). Whereas, 15 patients received enoxaparin and follow up CT after median of 3 months showed that 93% of patients achieved complete/partial recanalization (p = 0.12 between DOAC vs enoxaparin cohorts). Recurrent thromboembolic event has not occurred in any patient during median follow-up of 14 months (range: 3 – 71). One-year cumulative incidence of clinically significant any bleeding for DOAC cohort versus warfarin and enoxaparin cohorts was 10% (95% CI: 9 – 28) versus 18% (95% CI: 12 – 41), p = 0.64, and 25% (95% CI: 4 – 46), p = 0.42, respectively. Conclusions: Apixaban and rivaroxaban showed similar risk-benefit ratio as warfarin and enoxaparin, hence, they can be considered as alternatives for OVT patients.
MDNA109: Effect of an interleukin-2 superkine on CD8 T-cell properties in the tumor microenvironment.
Authors: Moutih Rafei, Shafique Fidai, Rosemina Merchant, Fahar Merchant
Journal: Journal of Clinical Oncology (2019)

e14220 Background: Proleukin (a cysteine-modified variant of interleukin (IL)-2) is the only common-γc cytokine approved for the treatment of metastatic melanoma and renal cell carcinoma. Its therapeutic use is however hampered by its short half-life and severe toxicity. At low doses, Proleukin administration leads to preferential activation of regulatory T cells (Tregs) due to their expression of the high affinity trimeric IL-2 receptor (IL-2R) consisting of CD25, CD122 and CD132 instead of cytotoxic CD8 T cells expressing the intermediate affinity IL-2R (CD122 and CD132). Methods: To bypass these limitations, we evaluated engineered variants of IL-2 (MDNA109 superkine) exhibiting enhanced affinity towards CD122 including their long-acting and bispecific superkine fusions. This approach allows preferential activation of CD8 T cells while displaying reduced adverse effects in vivo. Results: Both Biacore analysis and signaling studies on human peripheral blood mononuclear cells confirmed enhanced binding of MDNA109 to CD122 and STAT5 activation, respectively. When tested in vivo, MDNA109 co-administration with the immune-checkpoint blockers anti-programmed cell death (PD)-1 or anti-cytotoxic T-Lymphocyte-Associated Protein (CTLA)4 cured mice with pre-established MC38 or CT26 colon cancers respectively. In addition, bi-weekly administration of the long-acting MDNA109-Fc fusion led to similar therapeutic outcomes in the B16F10 model when compared to MDNA109 administered daily. Finally, in vitro and in-vivo results using (a) MDNA109 muteins with completely impaired CD25 binding activity and (b) novel bispecific superkine fusions consisting of MDNA109 and a dual IL-4/IL-13 super-antagonist capable of selective CD8 T-cell activation while mitigating the suppressive functions of myeloid-derived suppressor cells and tumor-associated macrophages will be presented. Conclusions: Altogether, these data demonstrate that both MDNA109 and MDNA109-Fc are therapeutically superior to Proleukin. Furthermore, use of MDNA109-based strategies will not only ensure complete abrogation of adverse effects, but will in addition eliminate immunosuppression caused by both Tregs and myeloid cells.
Post-treatment clinical status of patients with cervical cancer.
Authors: Polina A. Kruze, Ekaterina V. Verenikina, Vera P. Nikitina, Anna A. Cherkasova, Olga G. Selezneva, Yuriy A. Poryvaev, Natalia V. Chernikova, Tatiana G. Chalabova, Ivan S. Nikitin, Anna P. Menshenina, Oksana E. Zhenilo, Meri L. Adamyan
Journal: Journal of Clinical Oncology (2019)

e17007 Background: Extended hysterectomy with fixation of preserved ovaries to the round ligaments of the uterus and subsequent transposition of the gonads from the irradiation area have already become a routine procedure in the treatment of cervical cancer in young women in order to avoid castration syndrome. The aim of the study was to analyze clinical characteristics of patients with cervical cancer 10 years after treatment. Methods: Clinical and hormonal status of 216 patients with stage Ib cervical cancer after complex treatment was studied. The majority of women (160 patients, 74%) remained fertile at the time of the study, and 56 patients (26%) were peri- and postmenopausal (from 46-55 years). The presence or absence of climacteric symptoms was assessed by a questionnaire; functional ovarian insufficiency (FNU) was determined as mild, moderate, and severe. Plasma levels of steroid and gonadotropic hormones were evaluated by radioimmunoassay. Results: Analysis of menopausal complaints according to questionnaires showed that the symptoms increased with the age of patients. Only 8 patients of the reproductive age reported hot flashes (Table 1). In this group of patients, levels of sex and gonadotropic hormones were common for this age. Patients aged 45-50 years reported also dry skin and mucous membranes, dyspareunia and dysuric disorders, which indicated perimenopause. And in postmenopause, urogenital disorders were very persistent. This group included patients treated 6 and 10 years ago. Conclusions: Thus, the function of preserved ovaries "faded away" independently according to the age, providing a smooth transition to menopause and optimal medical and social rehabilitation of patients.[Table: see text]
Immunotherapy efficacy and patients' age: A systematic review and meta-analysis.
Authors: Jianchun Duan, Longgang Cui, Zhengyi Zhao, Guoqiang Wang, Shiqing Chen, Yuezong Bai, Shangli Cai, Lei Xiong, Xiaochen Zhao, Zhijie Wang, Jie Wang
Journal: Journal of Clinical Oncology (2019)

e14168 Background: Immunotherapy has revolutionized the treatment of cancer, however, little is known about the effect of patients’ age on the efficacy of immune checkpoint inhibitors. We did a systematic review and meta-analysis to assess the heterogeneity of immune checkpoint inhibitor efficacy between young and elder patients in pan cancer. Methods: We systematically searched PubMed, Cochrane library, and Embase from January 2000 to November 2018 for randomized controlled trials that had available hazard ratios (HRs) for death according to patients’ age. We also reviewed abstracts and presentations from all major conference proceedings. Retrospective studies and trials that compared anti-PD-1/PD-L1 with other immunotherapies were excluded. The primary outcome was the difference in overall survival (OS). We calculated the pooled overall survival HR and 95% CI in young and elder patients using a random-effects model. Results: A total of 3365 publications were retrieved through initial literature search, 19 randomized controlled trials involving 12276 patients with solid tumors were included for this meta-analysis. PD-1 inhibitors exhibited significantly improved OS over PD-L1 inhibitors in younger patient population (HR 0.67, 95% CI 0.53-0.85), while no differences have been observed in elder population (HR 0.89, 95% CI 0.70-1.13). Subgroup analysis showed that PD-L1 inhibitors plus chemotherapies led to significantly improved overall survival (OS) in elder population (&gt; = 65 years old) over that in younger population (&lt; 65 years old) (HR 1.29, 95% CI 1.01-1.64). However, the opposite tendency was observed with PD-1 inhibitors plus chemotherapies, showing that the younger population obtained better OS benefit compared to the elder population (HR 0.69, 95% CI 0.47-1.01). Conclusions: In general, PD-1 inhibitors exhibited better clinical performance for survival outcome over PD-L1 inhibitors in younger patients. When combined with chemotherapies, PD-1 inhibitors and PD-L1 inhibitors showed distinct efficacy tendency across different age groups, indicating that age should be taken into account when making decisions about treatment strategies. Future studies and explorations of the underlying mechanisms are needed for the further optimization of treatment strategies in clinical practice.
The interplay of adiposity, metabolic factors, and tumor infiltrating lymphocytes in an East Asian breast cancer cohort.
Authors: I Chun Chen, Chun-Wei Kuo, Tsu-Hsin Hsueh, Yen-Shen Lu, Ching-Hung Lin
Journal: Journal of Clinical Oncology (2019)

e14207 Background: Breast cancer is rapidly emerging in East Asian countries in recent 2 decades. Unlike western countries in which obesity are quite prevalent and contributes to BC patients, the body mass index (BMI) of BC patients in East Asian countries are usually normal to no more than overweight. In our previous study, we noticed a 30% incidence of crown-like structure of breast (CLS-B) in our BC patients. Despite a lower BMI in this East Asian cohort than the US cohort, the body fat percentage (BF%) is significantly higher in the East Asian The roles of tumor infiltrating lymphocytes (TILs) in BC are inconslusive in different disease contexts. This study aims to decipher the interplay of adiposity, metabolic factors, and TILs in a BC cohort from an East Asian country. Methods: Breast cancer patients from National Taiwan University Hospital were prospectively enrolled into the protocol. Clinicopathologic factors were collected from electronic medical records. Fasting serum collected prior to surgery was used to quantify metabolic factors, including lipid and glucose profiles. Adiposity, including BF% and BMI were quantified by bioimpedance analysis method prior to surgery. Immunohistochemical staining from formalin-fixed, paraffin-embedded BC tumor samples were done to profile TILs by pathologist. CLS-B was stained and interpreted by pathologists. The correlation of TILs with different clinicopathologic factors, adiposity, or relapse-free survival (RFS) were analyzed. Results: 72 BC patients were included in this analysis. The density of CLS-B positively correlates with tumor infiltrating lymphocyte (TIL) percentage ( p = .042), higher BF% correlates with higher regulatory T cells ( p = .026) and tumor associated macrophages (TAM, p = .010), high glucose level is associated with higher CD56 ( p = .040) and higher TAMs ( p &lt; 0.0001). Higher BMI is also associated with higher TAMs ( p= .005). In multivariate analysis, TAMx M2 macrophage is an independent predictor for RFS. Higher TAM level is associated with shorter RFS. Conclusions: Higher TAMs are associated with metabolic alterations such as higher adiposity, higher glucose level, and higher BMI. This result suggests a potential interplay between higher TAMs, altered metabolic factors, and worse RFS.
Trends in the use of proton beam therapy among newly diagnosed cancer patients in the United States.
Authors: Leticia Maciel Nogueira, Jason A. Efstathiou, Helmneh M. Sineshaw, K Robin Yabroff, Ahmedin Jemal
Journal: Journal of Clinical Oncology (2019)

6551 Background: Proton Beam Therapy (PBT) is a potentially superior radiotherapy technology for tumors with complex anatomy surrounded by sensitive tissues and for childhood cancers where sparing surrounding normal tissue is better achieved than with photon radiotherapy. The first conditions for payment of PBT claims went into effect in 2009. In 2014, the American Society of Radiation Oncology categorized PBT clinical indications into Group 1, for which health insurance coverage is recommended, and Group 2, for which coverage is recommended only if additional requirements are met. Methods: We evaluated 21,920 newly diagnosed patients in the National Cancer Database (NCDB) who received PBT between 2004 and 2016. Joinpoint analyses were used to evaluate the Annual Percent Change (APC) in the number and characteristics of patients treated with PBT. Results: The number of patients treated with PBT in NCDB facilities increased from 1,114 in 2004 to 3,173 in 2016 (APC = 8.78, p &lt; .001), due mainly to increases in Group 1 cancers after 2010 (from 271 patients in 2010 to 1,124 in 2016, APC = 26.4, p &lt; .001). The number of Group 2 patients treated with PBT increased slower (from 937 in 2004 to 2,049 in 2016, APC = 6.1, p &lt; .05). Breast and prostate cancers were most common, although trends varied substantially by cancer site. Between 2010 and 2016, receipt of PBT increased for breast cancer patients from 40 in 2010 to 405 in 2016 (APC = 48.5, p &lt; .001), but decreased for prostate cancer patients from 1,205 in 2011 to 680 in 2016 (APC = -14.06, p &lt; .001). While most of Group 1 patients had private insurance coverage (59.3% of patients treated in 2016), Medicare was the most common primary insurance type among Group 2 patients (50% of patients treated in 2016). Conclusions: The number of newly diagnosed cancer patients treated with PBT has increased between 2004 to 2016 in the US, with a sharp increase for cancers with clinical indications for health insurance coverage since 2010. While most of these patients have private insurance coverage, the steady increase in the number of patients being treated with PBT for cancers with additional requirements for health insurance coverage is primarily in those with Medicare coverage.