tbuckley/cabot-search huggingface dataset:
Epidemiology and survival of lung cancer in a Latin American cohort.
Authors: Rossana Ruiz, Marco Galvez Nino, Zaida Morante Cruz, Fernando Valencia, Cristian Pacheco, Karina Mayra Aliaga Llerena, Mivael Olivera, Natalia Valdivieso, Edgar Amorin, Luis Mas
Journal: Journal of Clinical Oncology (2019)

e13101 Background: Lung cancer epidemiology and survival data is lacking in LA. This information is relevant for understanding regional cancer burden and for designing targeted interventions for cancer control. Methods: Retrospective analysis of lung cancer cases diagnosed at Instituto Nacional de Enfermedades Neoplasicas (INEN) from 2010 to 2014. Data was manually curated from clinical files. Results: 1384 patients were included. Median age at diagnosis was 64 years old (range 20-92) and 51.6% were females. The histologic type was adenocarcinoma, NOS carcinoma, squamous cell carcinoma and small-cell carcinoma in 72.3%, 12.8%, 9.4% and 3.5% of the cases, respectively. The adenocarcinoma/squamous cell carcinoma ratio was 7.7. Among NSCLC cases, most patients presented with advanced disease. Stage III (9.2%) and IV (85.5%) were the most frequent. With a median follow-up of 71.5 months, median overall survival (OS) was 9.2, 7.7 and 8.1 months for adenocarcinoma, NOS carcinoma and squamous carcinoma, respectively. Five-year OS for stage III was 6% and for stage 4, 4%. Detailed results are shown in the table. Conclusions: The epidemiological profile of lung cancer in Peruvian patients is different from that of other countries with a younger age at diagnosis, a preponderance of females over males and an unexpectedly high frequency of adenocarcinomas. This may be in concordance with the low prevalence of tobacco smoking and the high prevalence of EGFR mutations reported for our population as well as with particular exogenous exposures such as biomass fumes from inhouse cooking. The molecular characterization of this cohort of patients is ongoing. [Table: see text]
SAT0243 EFFECTS OF TOFACITINIB SUPPRESSED PULMONARY VASCULAR REMODELING OF ALLERGIC VASCULITIS IN A MURINE MODEL
Authors: Nobuhito Sasaki, Kohei Yamauchi
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> We reported allergic granulomatous vasculitis with eosinophil infiltration in an asthma model of C57BL/6 sensitized with ovalbumin (OVA). TGF-btea and IL-6 are thought to play an important role in fibroblasts proliferation and is critical to vascular remodeling in vasculitis. Tofacitinib inhibits vascular endothelial cells proliferation and canalization. <h3>Objectives:</h3> To elucidate the role of tofacitinib in vascular remodeling of allergic granulomatous vasculitis, we examined the effects of tofacitinib on the vasculitis of the murine model. <h3>Methods:</h3> C57BL/6 mice (6-8 weeks) were sensitized with ovalbumin (OVA) and alum. The positive controls (n=9) were exposed to aerosolized OVA daily for 7 days. The other group of mice (tofacitinib treated mice(n=9)) were administered with tofacitinib (100mg/kg intraperitoneal administration) in parallel with daily exposure to aerosolized OVA for 7 days. On 7th day, bronchoalveolar lavage (BALF) was performed and the lungs were excised for pathological analysis. Cytokines in BALF were measured. <h3>Results:</h3> The total cell number and the number of. Eosinophils in BALF on the 7th day were decreased significantly in the tofacitinib-treated mice compared with those of the control-positive mice. The blood eosinophil counts in the positive control increased after OVA inhalation. The blood eosinophil counts in the tofacitinib treated mice were lower on the than those in the positive control. The concentrations of IL-4, IL-5, IL-6 and TGF-beta in BAL fluids reduced significantly in the tofacitinib treated group. The pathological scores reduced significantly in the tofacitinib treated group compared to the positive control group. Intra luminal infiltration and proliferation of Ki67 positive myofibroblasts, IL-6 positive cell and α-SMA positive cells in pulmonary arteries were reduced dramatically in the tofacitinib treated group compared to the positive control group. <h3>Conclusion:</h3> Tofacitinib suppressed pulmonary vascular remodeling in a murine model of allergic vasculitis with eosinophil infiltration. Tofacitinib is a hopeful therapeutic drug for Eosinophilic granulomatosis with polyangiitis. <h3> Disclosure of Interests:</h3> None declared
Long-Term Incidence and Predictors of Significant Hearing Loss Requiring Hearing Assistive Devices Among Childhood Cancer Survivors: A Population-Based Study
Authors: Jason A. Beyea, Cindy Lau, Bonnie Cooke, Stephen Hall, Paul C. Nathan, Sumit Gupta
Journal: Journal of Clinical Oncology (2020)

Hearing loss is a significant late effect among childhood cancer survivors. Recent guidelines note insufficient evidence to quantify its natural history or risk associated with specific exposures. We examined the long-term incidence and predictors of hearing loss requiring hearing amplification devices (HADs) using population-based health care data.In Ontario, Canada, HAD costs are subsidized by the Assistive Devices Program (ADP). Ontario children < 18 years of age at cancer diagnosis between 1987 and 2016 were identified and linked to ADP claims. Cumulative HAD incidence was compared between cases and matched controls. Patient, disease, and treatment predictors of HAD were examined.We identified 11,842 cases and 59,210 controls. Cases were at higher risk for HAD (hazard ratio [HR], 12.8; 95% CI, 9.8 to 16.7; P < .001). The cumulative incidence of HAD among survivors was 2.1% (95% CI, 1.7% to 2.5%) at 20 years and 6.4% (95% CI, 2.8% to 12.1%) at 30 years post-diagnosis. The 30-year incidence was highest in neuroblastoma (10.7%; 95% CI, 3.8% to 21.7%) and hepatoblastoma (16.2%; 95% CI, 8.6% to 26.0%) survivors. Predictors of HAD in multivariable analyses included age 0-4 years at diagnosis (v 5-9 years; HR, 2.2; 95% CI, 1.4-3.3; P < .001). Relative to no cisplatin exposure, patients receiving < 200 mg/m2 were not at greater risk, unlike those receiving higher cumulative doses. Relative to no cranial or facial radiation, those who had received ≤ 32.00 Gy were at no higher risk, unlike those who had received > 32.00 Gy. Carboplatin exposure was not associated with HAD.Childhood cancer survivors are at elevated risk for requiring HAD, which continues to increase between 20 and 30 years after diagnosis. Thresholds of cisplatin and radiation exposure exist, above which risk substantially increases. Prolonged monitoring and trials of otoprotective agents are warranted in high-risk populations.
Which treatment strategies are the most promising for locally advanced resectable human papillomavirus-associated oropharyngeal cancers?
Authors: Tomoya Yokota, Yoshiyuki Iida, Tomoyuki Kamijo, Kotaro Morita, Takashi Mukaigawa, Yukio Nishiya, Noriko Hamaguchi, Satoshi Hamauchi, Sadayuki Kawai, Yusuke Onozawa, Hiromichi Shirasu, Hirofumi Ogawa, Tsuyoshi Onoe, Masahiro Nakagawa, Tetsuro Onitsuka
Journal: Journal of Clinical Oncology (2019)

e17556 Background: The standard of care for oropharyngeal squamous cell carcinoma (OPSCC) is surgical (S) or non-surgical (NS) approach including chemoradiation (CRT). However, CRT is associated with significant long-term toxicity. Human papillomavirus (HPV) status are associated with improved prognosis for patients (pts) with OPSCC. The aim of this study was to explore the most promising treatment strategy with maintaining survival outcomes while improving QOL for locally advanced resectable HPV-positive OPSCC. Methods: A retrospective analysis of 96 pts with locally advanced resectable HPV-positive OPSCC in Shizuoka Cancer Center between 2004 and 2018 was performed. p16 immunohistochemistry was used to determine HPV tumor status. Clinical characteristics, acute and late toxicities, nutritional support, and survival were compared by treatment modalities. In pts who received S, surgical procedure and histological findings of the surgical specimens were additionally compared between pts who underwent upfront surgery (US) and those who did induction chemotherapy followed by surgery (ICT-S). Results: The median age was 62 years, with the majority having tonsil and base of the tongue as primary site. Thirty-six pts (38%) were current smokers, and 39 (41%) were former smokers. As an initial treatment, 62 (64.6%) and 34 (35.4%) pts underwent S and NS, respectively. Aspiration pneumonia more frequently occurred in NS (41.2%) than in S (8.1%) (p &lt; 0.01). Nutritional support by gastrostomy tube or total parenteral nutrition was required in 20 pts (58.8%) of NS, compared with 15 pts (24.2%) of S (p &lt; 0.01). S showed a trend toward longer overall survival (OS) than NS [HR = 0.204, p = 0.052], while progression free survival (PFS) was comparable between the groups. Of all S, 48 (50.0%) and 14 (14.6%) underwent US and ICT-S, respectively. Transoral surgery was performed in 78.6% of ICT-S, compared with 20.8% of US (p &lt; 0.01). Histological examination of the surgical specimens revealed that positive surgical margins, involvement of ≥ 2 regional lymph nodes, and positive extracapsular extension were present in 7.1, 35.7, and 35.7% of ICT-S, compared with 31.3, 58.3, and 45.8% of US, respectively (N.S.). Pathologic complete response in the primary site and lymph nodes occurred in 43 % of ICT-S. Both OS and PFS was comparable between the groups. Conclusions: Our results suggest the impact of surgical approach on reduced long-term toxicity for HPV-positive OPSCC. ICT followed by surgery might be promising novel treatment strategy.
Vascular endothelial growth factor A (VEGF-A) amplification and long-term response to ramucirumab (ram) in metastatic gastric cancer (mGC): The VERA study.
Authors: Alessandra Raimondi, Patrizia Gasparini, Sara Lonardi, Salvatore Corallo, Lorenzo Fornaro, Maria Maddalena Laterza, Mariantonietta Di Salvatore, Elisa Giommoni, Claudio Lotesoriere, Sabina Murgioni, Serena Saggio, Antonia Martinetti, Monica Niger, Maria Antista, Serenella Pupa, Filippo G. De Braud, Maria Di Bartolomeo, Gabriella Sozzi, Federica Morano, Filippo Pietrantonio
Journal: Journal of Clinical Oncology (2019)

3143 Background: The anti-VEGFR-2 monoclonal antibody ram, alone or with paclitaxel, is a cornerstone of second-line treatment of mGC. Even if about half patients do not benefit from ram, no predictive biomarkers have been identified so far. In TCGA, VEGF-A amplification was found in 7% of cases, almost exclusively in chromosomal instability subtype. We hypothesize that VEGF-A amplification in tumor cells could lead to autocrine/paracrine stimulation of tumor growth beside angiogenesis, potentially identifying a patients’ subgroup with exceptional responses to ram. Methods: VERA was a multicentric, prospective study based on a translational hypothesis. mGC patients were included according to the following criteria: 1) complete (CR) or partial response (PR) to single-agent ram; 2) &gt;6 months PFS to single-agent ram; 3) &gt;10 months PFS to paclitaxel+ram. According to a Fleming single-stage design, hypothesizing a prevalence of VEGF-A amplification of 1% and 15% among all-comers and exceptional responders, 20 exceptional responders were required to reject the null hypothesis of low prevalence of VEGF-A amplification, with alpha- and beta- errors of 0.05 and 0.10, respectively. VEGF-A amplification (defined as &gt;10% tumor cells with ≥10 VEGF-A copies, variably sized signal clusters or a ratio of VEGF-A gene to centromere of ≥2) was centrally assessed through fluorescent in situ hybridization on pre-treatment FFPE tumor tissue. Results: At 7 Italian Centers, we included 20 patients satisfying the 1st (n=1), 2nd (n=2), or 3rd (n=17) criterion. Clinical-pathological features were: M/F, 11/9; median age 63 years; gastric/GEJ, 17/3; intestinal/diffuse, 14/6, HER2+/HER2-, 4/16. Median PFS and overall survival to ram-based treatment were 15.6 and 25.7 months, with best response: CR/PR/SD, 0/10/10. VERA met its primary endpoint, revealing 3/20 (15%) tumors with VEGF-A amplification (1 case presenting big clusters, 1 small clusters and 1 with &gt;10% tumor cells with ≥10 VEGF-A copies). Conclusions: Validation analyses of first- and second-line randomized trials could confirm VEGF-A amplification as a biomarker of long-term response to ram-based treatment in mGC patients, advancing treatment personalization.
Results of the phase 1b study of ABBV-399 (telisotuzumab vedotin; teliso-v) in combination with erlotinib in patients with c-Met+ non-small cell lung cancer by EGFR mutation status.
Authors: D. Ross Camidge, Fabrice Barlesi, Jonathan Wade Goldman, Daniel Morgensztern, Rebecca Suk Heist, Everett E. Vokes, Alexander I. Spira, Eric Angevin, Wu-Chou Su, David S. Hong, John H. Strickler, Monica Motwani, Zhaowen Sun, Apurvasena Parikh, Elysa Noon, Jun Wu, Karen Kelly
Journal: Journal of Clinical Oncology (2019)

3011 Background: Telisotuzumab vedotin (ABBV-399; teliso-v [T]) is a c-Met–targeted antibody and MMAE drug conjugate. Activity of T was shown in late-line c-Met+ non-small cell lung cancer (NSCLC) irrespective of EGFR mutation (M+) status. We present mature data from the T+ erlotinib (E) cohort of a phase 1b study (NCT02099058) by EGFR M+ status. Methods: T was administered at 2.4 mg/kg (dose-escalation phase) or 2.7 mg/kg IV Q3W, and E at 150 mg PO QD/prior tolerated dose in adult patients (pts) with advanced NSCLC. Efficacy-evaluable pts were c-Met+ (central lab IHC H-score ≥150 or local lab MET amplification/Ex 14 skipping) and had ≥1 postbaseline scan or discontinued study. EGFR M+ was defined as del19 or L858R by local lab. PK was assessed. Results: As of Dec 2018, 42 NSCLC pts received T+E; 37 were c-MET+ (36 evaluable; 35 H-score≥150, 1 MET amplified). Median age was 65 years, 25 pts (69%) had ECOG PS 1, 29 (81%) were EGFR M+ (97% had prior EGFR TKI, 55% 3rd-generation TKI, 69% TKI as last prior therapy, and 62% platinum doublet). All-grade (Gr; ≥20%) adverse events (AEs) were dermatitis acneiform (38%), diarrhea (36%), peripheral motor/sensory neuropathy (52%; 7% Gr 3), dyspnea, fatigue, hypoalbuminemia (31% each), decreased appetite, nausea (24% each), asthenia, vomiting (21% each). Gr ≥3 (≥10%) AE: pulmonary embolism (14%). PK of T+E was similar to single-agent T. The table presents efficacy data. Conclusions: These data suggest acceptable safety and promising activity of T+E and support further study in EGFR M+ c-Met+ NSCLC pts for whom frontline EGFR TKI failed. Clinical trial information: NCT02099058. [Table: see text]
Density of CD8+ and CD68+ lymphocyte cell infiltration is associated with clinic outcome in hepatocellular carcinoma.
Authors: Haibei Xin, Huan Chen, Lihong Wu, Yanhui Chen, Hongli Luo, Henghui Zhang, Nan Li
Journal: Journal of Clinical Oncology (2019)

e15612 Background: The achievements of immune checkpoint blockade strengthen the concept that tumor outgrowth and development are comprehensively regulated by immune system. The aim of the study was to explorer whether distinct infiltrated immune cell features differentially affect clinical outcome in hepatocellular carcinoma (HCC). Methods: We obtained respectable stage II HCC specimens, along with adjacent para-tumor tissues from 221 patients who underwent surgical resection at Eastern Hepatobiliary Surgery Hospital, (in Shanghai, China) from 2015 through April 2018. CD8+ and CD68+ tumor-infiltrating lymphocytes (TILs) in the cancer area (CA) and stroma area (SA), as well as PD-1/PD-L1 expression, were analyzed by multiple immunohistochemistry. Results: The density of CD8+ TILs were significantly associated with gender, tumor size, and cirrhosis; while the density of CD68+ TILs were associated with copies of HBV DNA and anti-viral treatment. Multivariate Cox regression analysis revealed that high densities of CD8+ TILs and low densities of CD68+/CD8+ ratios independently predicted better outcomes. Of note, a prognostic signature combining clinic features [portal vein tumor thrombus (PVTT) and tumor size (TS)] and CD8+ TILs densities discriminated HCC patients into four subtypes with increasing risk of mortality: PVTT-negative/TS-small/CD8-high (6.8% of cases), PVTT-negative/TS-small/CD8-low (45.7%), PVTT-negative/TS-large (34.4%) and PVTT-positive (13.1%). Further association studies suggested that the four subgroups correlated with gender, tumor envelope, microvascular invasion (MVI), and SA-PD1 expression. Similarly, a prognostic signature combining PVTT, TS and CD68+/CD8+ ratios discriminated HCC patients into four subtypes with increasing risk of recurrence. Conclusions: Combined immune features including CD8+ and CD68+ lymphocyte infiltration and clinic characteristics are useful prognostic biomarkers for HCC patients.
A phase III, randomized, open-label, multicenter, global study of efficacy and safety of durvalumab in combination with gemcitabine plus cisplatin for neoadjuvant treatment followed by durvalumab alone for adjuvant treatment in muscle-invasive bladder cancer (NIAGARA).
Authors: Thomas Powles, Joshua J Meeks, Matt D. Galsky, Michiel Simon Van Der Heijden, Hiroyuki Nishiyama, Hikmat A Al-Ahmadie, Erik T. Goluboff, Stephan Hois, Sarah E. Donegan, Vanessa Williams, Feng Xiao, James WF Catto
Journal: Journal of Clinical Oncology (2021)

TPS505 Background: Management of muscle-invasive bladder cancer (MIBC) includes both surgery and systemic therapy. Neoadjuvant cisplatin-based combination chemotherapy has demonstrated improved pathologic complete response (pCR), event-free survival (EFS), and overall survival (OS) compared with radical cystectomy alone. Yet at least half of patients will still experience recurrence and will progress to metastatic disease. Durvalumab (anti–PD-L1 antibody) combined with gemcitabine + cisplatin, administered as either neoadjuvant or adjuvant treatment, may increase the rate of pathologic response and prolong long-term survival. This approach will be evaluated in this study in patients with MIBC identified for curable intent, as reflected in the NCCN guidelines. Methods: NIAGARA (NCT03732677) is a phase III, randomized, open-label, multicenter, international trial that will enroll ~1050 patients with MIBC who, prior to radical cystectomy, will be randomized (1:1) to durvalumab and gemcitabine + cisplatin (Arm 1) or gemcitabine + cisplatin (Arm 2). Following radical cystectomy, patients in Arm 1 will receive durvalumab monotherapy for 8 cycles (8 months) while patients in Arm 2 will receive no adjuvant treatment. Eligible patients are aged ≥18 years with resectable MIBC (clinical stage T2-T4aN0/1M0) with urothelial histology eligible for a radical cystectomy. Patients with pure non-transitional cell variant histologies and any small cell histology are not eligible. A tumor tissue sample for biomarker analysis is mandatory as PD-L1 expression is a stratification factor. Primary endpoints are pCR and EFS in patients with adequate renal function. Secondary and exploratory endpoints include proportion of patients who achieve pathologic response &lt; stage II (stages Ta, T1, and carcinoma in situ) at the time of cystectomy following neoadjuvant treatment, EFS at 24 months, metastasis-free survival, efficacy of Arm 1 vs Arm 2 at radical cystectomy and proportion of patients who undergo cystectomy, OS rate at 5 years, safety, patient-reported outcomes, and pharmacokinetics. Immunogenicity and biomarkers are exploratory endpoints. Enrollment opened in Dec 2018. Clinical trial information: NCT03732677.
Accelerated partial breast irradiation (APBI) using intensity modulated radiation therapy (IMRT) in stage 0-II breast cancer: A preliminary report of 57 cases.
Authors: Rufus J. Mark, Valerie Gorman, Steven McCullough
Journal: Journal of Clinical Oncology (2019)

e12068 Background: Randomized trials in Stage 0-II breast cancer have proven that APBI given via HDR implant in 5 days is equivalent to whole breast External Radiation Therapy (XRT) given in 5-6 weeks in regard to breast tumor local recurrence (LR). However, complications have been significant. Recently APBI using non-invasive IMRT given in 5 fractions has been shown in another randomized trial to be equivalent to XRT in 6 weeks, with respect to LR. IMRT was superior in regard to acute effects, late effects, and cosmesis. In the randomized clinical trial of APBI IMRT, the Clinical Target Volume (CTV) was defined by the injection of individual fiducial markers bordering the surgical cavity. At our institution, we have used the Biozorb fiducial system to localize the CTV for IMRT. We sought to confirm the APBI IMRT results with this simpler less labor intensive fiducial placement system. Methods: Between 2017 and 2019, 57 patients have undergone IMRT targeted to a Biozorb defined CTV with the walls of the surgical cavity sewn to the Biozorb device. Eligible patients were older than age 40, had tumor sizes ≤ 3 cm, negative surgical margins, and negative sentinel node dissections. IMRT dose was 30 Gy given in 5 fractions. Dose Constraints were as follows : V-30 Gy &lt; 105%, Ipsilateral Breast V-15 Gy &lt; 50%, Ipsilateral Lung V-10 Gy &lt; 20%, Contralateral Lung V-5 Gy &lt; 10%, Heart V-3 Gy &lt; 20%, Contralateral Breast Dmax &lt; 2 Gy and Skin Dmax &lt; 27 Gy. The Planning Target Volume (PTV) ranged from 27 to 355 cc with a median of 80 cc. PTV = CTV + 1-2 cm. Results: Follow-up ranged from 1-14 months with a median of 7 months. LR has been 0% (0/57). There were no skin reactions. One patient developed pain around the Biozorb site. This resolved within 2 days on a short course of steroids. Cosmetic results as rated by the Surgeon, Radiation Oncologist, and Nurse, were rated excellent in 100% (57/57) of cases. Conclusions: Non-invasive APBI with IMRT targeted to Biozorb has resulted in LR, complications, and cosmetic results which compare favorably to invasive APBI given with HDR implant. At last follow-up, there have been no LR, skin reactions, or complications. Cosmesis has been excellent in 100% of patients.
Melanoma nodal management in Ontario following ASCO/SSO guidelines.
Authors: Steven Latosinsky, Salimah Shariff, Britney Allen
Journal: Journal of Clinical Oncology (2019)

e21054 Background:Methods:Results: Conclusions:The American Society of Clinical Oncology and Society of Surgical Oncology (ASCO/SSO) published a joint guideline in 2012 regarding indications for sentinel lymph node biopsy (SLNB) in cutaneous melanoma. The guideline supported completion lymph node dissection (CLND) for all patients with a positive SLNB. We examined the rates and predictors of SLNB and CLND for melanoma patients in Ontario (population 13.6 million) following guideline publication. Methods: We used the Ontario Cancer Registry (OCR) to identify cutaneous melanoma patients diagnosed in 2013. Patient records were linked to prospectively maintained health administrative databases to obtain details for each patient including surgical procedures. Results: We identified 3298 melanoma patients from Ontario in 2013 of which 1,973 (59.8%) could be analyzed. The majority, 1,227 (62.2%) had a local excision alone, while 746 (37.8%) had a SLNB. SLNB was performed on T1, T2, T3 and T4 primary melanomas in 13.9%, 67.8%, 62.6% and 47.2% of cases respectively. Receipt of a SLNB was positively associated with a younger age (&lt; 80), higher T stage, and non-head and neck primary in multivariate analysis. Of the patients who received a SLNB 136 (18.2%) were found to be node positive. A CLND was performed in 82 (60.3%) of these patients. Conclusions: In Ontario only two-thirds of intermediate thickness melanomas (T2, T3) received a SLNB as recommended by the ASCO/SSO guidelines. Utilization was lower for head and neck patients and higher for younger (&lt; 80 years) patients. Use of CLND for positive SLNB was also low relative to the guidelines.