bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase I trial of hafnium oxide nanoparticles activated by radiotherapy in cisplatin-ineligible locally advanced HNSCC patients.
Authors: Le Tourneau Christophe , Calugaru Valentin , Borcoman Edith , Moreno Victor , Calvo Emiliano , Liem Xavier , Salas Sebastien , Doger Bernard , Choussy Olivier , Lesnik Maria , Mirabel Xavier , Badois Nathalie , Krhili Samar , Blomkvist Josefin , Fakhry Nicolas , Wong-Hee-Kam Stéphanie , Hoffmann Caroline 
Published: May 2020

6573 Background: The standard of care non-surgical approach for locally advanced head and neck squamous cell carcinoma (LA HNSCC) patients (pts) is concurrent chemoradiation with high dose cisplatin or cetuximab in case of contra-indication. Older age is a contra-indication to cisplatin, and cetuximab might not improve survival in older pts. It is therefore urgently needed to develop new treatment options for elderly pts with LA HNSCC. NBTXR3 are hafnium oxide nanoparticles that can enhance the efficacy of radiotherapy (RT) by increasing locally the deposited dose. In this phase I clinical trial we aimed to evaluate the feasibility and safety of NBTXR3 administered as intratumoral (IT) injection prior to RT in LA HNSCC elderly pts. Methods: Pts with stage III-IV LA HNSCC of the oropharynx or oral cavity ineligible for platinum-based chemoradiation received a single IT injection of NBTXR3 into a selected primary tumor and intensity modulated RT (IMRT; 70 Gy/35 fractions/7 weeks) [NCT01946867]. A 3+3 dose escalation design, tested NBTXR3 dose levels equivalent to 5, 10, 15, and 22% of baseline tumor volume, followed by a dose expansion at the Recommended Phase II Dose (RP2D). Primary endpoints included RP2D determination, and early dose limiting toxicities (DLT). NBTXR3 intratumoral bioavailability and anti-tumor activity (RECIST 1.1) were also evaluated. Results: Enrollment was completed at all dose escalation levels: 5% (3 pts), 10% (3 pts), 15% (5 pts), and 22% (8 pts). No early DLT or SAE related to NBTXR3 or injection were observed. The median follow-up from NBTXR3 administration is 7.6 months. One AE (Grade 1) related to NBTXR3 and four AEs (Grade 1-2) related to the injection were observed. RT-related toxicity was as expected with IMRT. CT-scan assessment showed a good dispersion of NBTXR3 throughout the injected tumor and not in surrounding healthy tissues. The RP2D was determined to be 22%. Preliminary efficacy was evaluated in pts who received the intended dose of NBTXR3 and RT. A complete response of the injected lesion was observed in 9/13 (69%) evaluable pts at doses ≥10% (2 unconfirmed) and an overall complete response in 5/13 (38%) evaluable pts at doses ≥10%. Preliminary safety and efficacy data of the dose expansion cohort at the RP2D will also be presented. Conclusions: NBTXR3 activated by RT was well tolerated at all tested doses and demonstrated promising preliminary anti-tumor activity. Recruitment is ongoing in the dose expansion cohort. These results demonstrate that further testing of NBTXR3 in this population is warranted. Clinical trial information: NCT01946867 .
Upfront DPYD genotyping and toxicity associated with fluoropyrimidine-based concurrent chemoradiotherapy for oropharyngeal carcinomas.
Authors: Desilets Antoine , Aubin Francine , Bahig Houda , Ballivy Olivier , Charpentier Danielle , Filion Edith , Jamal Rahima , Lambert Louise , Vadnais Charles , Weng Xiaoduan , Soulieres Denis 
Published: May 2020

6580 Background: The combination of carboplatin and 5-fluorouracil (5-FU) is effective when used concurrently with radiotherapy for locoregionally advanced oropharyngeal carcinomas (Calais et al. 1999). DPYD polymorphisms can be associated with an increased risk of severe toxicity to fluoropyrimidines (Deenen et al. 2016). Upfront screening for the DPYD*2A allele is available in the province of Québec, Canada since March 2017. This study aimed to determine the effect of upfront genotyping on grade ≥3 toxicities. Methods: The studied population included all consecutive cases of oropharyngeal carcinomas treated with 5-FU based chemoradiotherapy one year before and after the implementation of upfront DPYD*2A genotyping. All patients were treated at the Centre Hospitalier de l’Université de Montréal (CHUM) between March 2016 and April 2018. Clinical data were extracted from chart review. Extended screening for 3 supplemental at-risk DPYD variants was also retrospectively performed in August 2019. Results: 181 patients were included in the analysis (87 patients before and 94 patients after DPYD*2A screening implementation). 91% of patients (n = 86) were prospectively genotyped for the DPYD*2A allele. Of those screened, 2% (n = 2/87) demonstrated a heterozygous DPYD*2A mutation. Those two patients received cisplatin-based treatment and thus avoided 5-FU toxicities. Extended genotyping of DPYD*2A-negative patients later allowed for the retrospective identification of 6 additional patients with alternative DPYD variants (two c.2846A > T and four c.1236G > A allele mutations). Conclusions: The DPYD*2A, c.2846A > T and c.1236G > A polymorphisms are associated with an increased risk of G3-4 toxicity to 5-FU, as well as higher hospitalization rates. Upfront DPYD genotyping can identify patients in whom fluoropyrimidine-related toxicity should be avoided. This represents an interesting addition in terms of pharmacovigilance. [Table: see text]
A novel multiple-catheter implantation method for advanced head and neck cancer.
Authors: Ohmae Masatoshi , Kato Itsuro , Fujita Yusei , Meshii Noritoshi , Motoki Ayako , Nakazawa Mitsuhiro , Uzawa Narikazu 
Published: May 2020

6582 Background: We previously developed a super-selective intra-arterial chemotherapy (iaCT) approach for head and neck cancer (HNC), by which, an intra-arterial catheter is retrogradely inserted via either the superficial temporal artery (STA) or occipital artery (OA) and connected to a subcutaneous reservoir. As a result, since this approach overcomes the need for frequent fluoroscopy sessions, the infusion frequency can be increased and the therapeutic effectiveness improved. However, since the anticancer effect is limited to the region supplied by the selected blood vessel, it is often difficult to control an advanced HNC by single-catheter iaCT. Subsequently, a novel multiple-catheter implantation method (MCIM) for super-selective iaCT has been developed using, both, the STA and OA. Methods: A total of 21 patients with stage III or IV HNC were enrolled in this study and treated via MCIM for iaCT between 2009 and 2017. The catheters were super-selectively placed in the tumor-feeding arteries after having entered the STA or OA. The first catheter was introduced into one of the target branches. Next, a second catheter was introduced into another target branch. If a third catheter was required, the procedure was repeated. The extra-arterial portions of the catheters were subcutaneously connected to an implanted juxta-mastoidal infusion reservoir. Results: The response rate was 100%; particularly, 20 cases of complete response and 1 of partial response were confirmed. Although the partial responder underwent salvage surgery and two complete responders ultimately died (due to either delayed recurrence or brain metastases), the other 18 patients have been living cancer-free for 2-9 years. Conclusions: The MCIM method allows to expand the infusion region while maintaining the main advantages of super-selective iaCT. As a consequence, due to the lack of need for patient confinement in the catheter room and for frequent fluoroscopy sessions, patients’ mental and physical distress, medical expenses, and treatment time are all ultimately reduced.
ELLA01-1: A study to determine the utility of TP53 mutations as a prognostic biomarker in adenoid cystic carcinoma.
Authors: Metcalf Robert , Mubarak Khaireah , Bola Becky , Rack Samuel , Morgan David , Hussell Tracy , Wallace Andrew , Betts Guy , Harrington Kevin Joseph 
Published: May 2020

6585 Background: TP53 mutations are reported in 5% of patients with adenoid cystic carcinoma (ACC). Whilst TP53 mutations are associated with adverse clinical outcomes across multiple tumour types, their prognostic significance in ACC is unknown. We sought to determine the utility of TP53 mutations as a prognostic biomarker in a prospective cohort of ACC patients. Methods: From April 2017 to September 2019, 146 patients with ACC were prospectively recruited to an ethically approved study. DNA was extracted from archival FFPE samples and underwent targeted next generation sequencing (Qiagen GeneRead DNAseq Targeted Panel V2 n = 134; Foundation Medicine; n = 12). Clinical, pathological and outcome data were collected on all patients and Kaplan-Meier survival analysis was performed to test for survival differences between TP53 mutated and wild-type ACC. Results: 146 ACC patients (mean age 48 years, range 16-79) underwent DNA extraction and next generation sequencing for TP53 mutations. The primary site was major salivary gland in 47% and minor salivary gland in 48% (other 5%). Analysis was successful in 122/146 patients (84%). Recurrent or metastatic disease was present in 94% (115/122) at study entry. TP53 alterations were identified in 9% (11/122), most frequently within the DNA binding domain (9/11). Non-pulmonary visceral metastases were seen more frequently in TP53 wild-type than in TP53 mutated ACC (44% vs. 10%; p = 0.042), and other clinical parameters were balanced between groups. During follow-up from diagnosis (median follow up 6.6 years), death occurred in 45% of patients with TP53 mutation and in 23% with TP53 wild-type ACC (p = ns). In TP53 mutated ACC, median overall survival was significantly shorter (5.3 vs. 16.3 years), and 10-year survival rate significantly lower (42% vs. 82%) than TP53 wild-type ACC (log-rank p = 0.013). Conclusions: In this cohort of patients with ACC, TP53 mutations were seen with a higher frequency than previously reported. This may be explained by the high frequency of recurrent or metastatic disease at study entry. TP53 mutation was associated with a statistically significant reduction in overall survival in patients with recurrent and metastatic ACC. These findings suggest that stratifying by TP53 status may be of clinical value to inform follow-up strategy in addition to established clinical, pathological and genomic biomarkers.
Radioiodine (RAI) in combination with durvalumab for recurrent/metastatic thyroid cancers.
Authors: Burman Bharat , Sherman Eric Jeffrey , Kriplani Anuja , Michel Loren S. , Dunn Lara , Fetten James Vincent , Warner Elizabeth , Grewal Ravinder K , Sabra Mona , Tuttle R. Michael , Boucai Laura , Fish Stephanie , Haque Sofia , Ostrovnaya Irina , Ghossein Ronald A , Knauf Jeffrey , Pfister David G. , Fagin James A , Ho Alan Loh 
Published: May 2020

6587 Background: Immune checkpoint blockade (ICB) has limited efficacy for radioiodine-refractory thyroid cancer. The high incidence of autoimmune thyroid disease and ICB-induced hypothyroidism suggests that loss of T cell tolerance to thyroid protein epitopes is common and can be activated by ICB to induce immune responses. We hypothesize that RAI can enhance presentation of thyroid protein immunogens and putative neoantigens in thyroid cancers to amplify the effectiveness of ICB. We studied the safety and efficacy of RAI plus the anti-PD-L1 agent durvalumab (durva) in recurrent/metastatic (R/M) patients (pts). Methods: Pts. had at least one RAI-avid tumor on the most recent RAI scan or one tumor on FDG PET with an SUVmax < 10. RECIST measurable disease was required. Any number of prior therapies was allowed. Pts were treated with durva 1500 mg IV every 4 weeks with recombinant human TSH (rhTSH)-stimulated RAI (100 mCi) administered in Cycle 1. Treatment beyond progression was allowed. The primary objective was to assess safety. Durva related dose limiting toxicities (DLTs) were monitored for 6 weeks after the first dose. Since no durva DLTs were observed in the first 6 pts, per protocol rules the trial accrued 11 pts total. Secondary objectives were assessing best overall response (BOR) per RECIST and progression-free survival (PFS). Results: 11 pts (7 female) were enrolled. Eight had prior drug therapy. No DLTs or > Grade 3 durva related adverse events (AEs) were observed. The most common non-laboratory AEs (regardless of attribution) were cough (7), hypertension (7), pain (6), edema (5), and fatigue/nausea/diarrhea/arthralgia/dry skin/dyspnea/edema (4 each). As of 2/6/20, 2 had partial response, 7 stable disease, and 2 progression of disease as BOR. Six pts had tumor regression. Four pts received treatment for > 6 months. Six are still on treatment. Analyses of research biopsies (bxs) (8 had pre-treatment bxs, 6 had an additional on-treatment bx) will be presented. Conclusions: Durva plus RAI is safe and well tolerated. The preliminary efficacy signal in this small cohort is promising. Understanding how RAI plus PD-L1 targeting impacts the tumor immune microenvironment may guide how RAI should be evaluated in future ICB trials. Clinical trial information: NCT03215095 .
Relationships among skeletal muscle, symptom burden, health care use, and survival in hospitalized patients with advanced cancer.
Authors: Azoba Chinenye C. , Van Seventer Emily E. , Marquardt Jan Peter , Troschel Amelie S. , Best Till D. , Horick Nora K. , Newcomb Richard , Roeland Eric , Rosenthal Michael Hayden , Bridge Cristopher P. , Greer Joseph A. , El-Jawahri Areej , Temel Jennifer S. , Fintelmann Florian J. , Nipp Ryan David 
Published: May 2020

7006 Background: Loss of skeletal muscle mass (quantity) is common in patients with advanced cancer, but little is known about muscle density (quality). Hospitalized patients with advanced cancer are a highly symptomatic population at risk for the adverse effects of muscle loss. Thus, we sought to describe associations between muscle mass and density, symptom burden, health care use, and survival in these patients. Methods: We prospectively enrolled hospitalized patients with advanced cancer from 9/2014-4/2017. Upon admission, patients reported their physical (Edmonton Symptom Assessment System [ESAS]) and psychological (Patient Health Questionnaire 4 [PHQ4]) symptoms. We used computed tomography (CT) scans performed per routine care ≤45 days prior to enrollment to evaluate muscle mass and density at the level of the third lumbar vertebral body. We categorized patients as sarcopenic using validated sex specific cutoffs. We used regression models to examine associations between muscle mass and density and patients’ symptom burden, health care use, and survival. Results: Of 1,121 patients enrolled, 677 had evaluable CT scan data (mean age = 62.86±12.95 years; 51.1% female). The most common cancer types were gastrointestinal (36.8%) and lung (16.7%) cancer. Most met criteria for sarcopenia (64.0%). Older age and female sex were associated with lower muscle mass (age: B = -0.16, p < .01; female: B = -6.89, p < .01) and density (age: B = -0.33, p < 0.01; female: B = -1.66, p = .01), while higher BMI was associated with higher muscle mass (B = 0.58, p < .01) and lower muscle density (B = -0.61, p < .01). Higher muscle mass was significantly associated with improved survival (HR = 0.97, p < .01), but not with symptom burden or health care use. Higher muscle density was significantly associated with lower ESAS physical (B = -0.17, p = .02), ESAS total (B = -0.29, p < .01), PHQ4 depression (B = -0.03, p < .01) and PHQ4 anxiety (B = -0.03, p < .01) symptoms. Higher muscle density was also associated with decreased hospital length of stay (B = -0.07, p < .01), risk of readmission or death in 90 days (OR = 0.97, p < .01), and improved survival (HR = 0.97, p < .01). Conclusions: Most hospitalized patients with advanced cancer have muscle loss consistent with sarcopenia. We found that muscle mass (quantity) correlated with survival, whereas muscle density (quality) was associated with patients’ symptoms, health care use, and survival. These findings underscore the added importance of assessing muscle quality when seeking to address the adverse effects of muscle loss in oncology.
Survival outcomes among older adults (OA) receiving second-line therapy for metastatic CRC (mCRC): 5,289 patients (pts) from the ARCAD Clinical Trials Program.
Authors: McCleary Nadine Jackson , Harmsen William S. , VanCutsem Eric , Sobrero Alberto F. , Goldberg Richard M. , Tabernero Josep , Seymour Matt , Saltz Leonard B. , Giantonio Bruce J. , Dirk Arnold , Rothenberg Mace L. , Koopman Miriam , Schmoll Hans-Joachim , Pitot Henry C. , Hoff Paulo Marcelo , Falcone Alfredo , De Gramont Aimery , Shi Qian 
Published: May 2020

7009 Background: Survival outcomes of 2nd line mCRC therapy for OA are poorly understood. We evaluated the rates and survival outcomes of 2nd line therapy among OA age 70+ compared to younger adults (YA) age < 70 following progression on 1st line clinical trials. Methods: Associations between clinical characteristics of pts with available treatment data after progression on 10 of 23 1st line ARCAD trials, time to initial progression (TTiP) and 2nd line therapy were evaluated. Time to progression (TTP) and overall survival (OS) were compared between OA and YA enrolled on 2nd line trials by Cox regression, adjusting for age, sex, ECOG PS, number of metastatic sites, presence of metastasis in lung/liver/peritoneum. Results: Sixteen percent of 1st line ARCAD trial participants were age 70+ (n = 870). Data for 2nd line therapy was available for 60.6% pts (3206/5289). Each additional decade of life was associated with 11% lower odds of receiving 2nd line therapy in multivariate analysis (p = 0.0117). OA participating in 2nd line trials (7.9% age 75+ of 7921) experience similar TTP and OS to YA (mTTP: 5.1 vs. 5.2mos; mOS 11.6 vs 12.4mos, respectively). Conclusions: We did not observe a statistical difference in survival outcomes by age following 2nd line mCRC therapy. Further study is needed to examine unmeasured comorbidity and use of geriatric assessment to select OA likely to benefit from 2nd line therapy. [Table: see text]
Saving the best to the last: Can we wait for second-line?
Authors: Barak Renana , Wolf Ido 
Published: May 2020

7013 Background: A common perception of some oncologists is that the vast majority of their patients with metastatic disease will receive 2nd line treatment upon progression. Therefore, “saving” good treatment options for the future may be acceptable. We aimed to examine whether this perception correlates with real-life. Methods: Using an oncology electronic database, consisting of >27,000 patients treated at our institution, we selected consecutive patients with metastatic or locally advanced lung, colon, pancreatic, bile duct and gastric cancers who started standard 1st line, consisting of at least doublet therapy. We then assessed the correlation between proceeding to 2nd line therapy and demographic and clinical variables, including age, gender, initial BMI, hemoglobin, WBC, creatinine, glucose, calcium, as well as survival. Results: A total of 553 patients met the inclusion criteria. Their median age was 66 and 317 were men. Their diagnoses were colon (197), lung (129), pancreas (101), bile duct (71) and gastric (55) cancers. Only 59% received at least one course of 2nd line treatment (61.9% colon, 65.1% lung, 66.3% pancreas, 35.2% bile duct and 54.5% gastric). Probability of reaching 2nd line treatment was associated with disease site (P=0.0002) as well as with age, with patients who received 2nd line being 2.5 years younger compared to those who did not (65 vs. 67.5 years, P=0.008). No other factor, including gender, BMI or standard laboratory values at presentation could predict chances of proceeding to 2nd line, for either the whole group or by primary cancer origin. Survival of patients not starting 2nd line was also significantly shorter across all tumor types. Conclusions: These real-life data indicate that only 60% of patients starting standard doublet or triplet treatment for advanced cancers will commence 2nd line therapy; and this cannot be reliably predicted in advance using standard clinical and laboratory characteristics. Our data challenge the practice of saving good treatment options for subsequent lines, and call for the development of tools enabling prediction of response and tolerance to treatment, pursuing for better patient selection and patient-tailored therapy.
The potential cost-effectiveness of a risk-based pancreatic cancer screening strategy in new-onset diabetes.
Authors: Schwartz Naomi RM , Matrisian Lynn McCormick , Shrader Eva , Feng Ziding , Chari Suresh , Roth Joshua A. 
Published: May 2020

7017 Background: There are no established methods for pancreatic cancer (PC) screening, but the National Cancer Institute and the Pancreatic Cancer Action Network (PanCAN) are investigating risk-based screening strategies in new-onset diabetes (NOD)—a group with elevated PC risk. Preliminary estimates of the cost-effectiveness of these strategies can provide insights about potential value and inform supplemental data collection. Using data from the Enriching New-Onset Diabetes for Pancreatic Cancer (ENDPAC) risk model validation study, we assessed the potential value of CT screening for PC in those determined to be at elevated PC risk, as is being done in a planned PanCAN Early Detection Initiative (EDI) trial. Methods: We created an integrated decision tree and Markov state-transition model to assess the cost-effectiveness of screening those age ≥50 and with NOD for PC using CT imaging vs. no screening. PC prevalence, sensitivity, and specificity were derived from the ENDPAC validation study. PC stage distribution in the no screening strategy and PC survival were derived from SEER. Background mortality for diabetics, screening and cancer care expenditure, and health state utilities were derived from the literature. The base case assumed 40% of screen-detected PC cases were resectable, and a threshold analysis explored the fraction required for screening to be <$100,000 per QALY gained. Life years (LYs), quality-adjusted life years (QALYs), and costs were tracked over a lifetime horizon and discounted at 3% per year. Results are presented in 2019 USD, and we took a U.S. payer perspective. Results: In the base case, screening resulted in 0.0055 more LYs, 0.0045 more QALYs, and $305 in additional expenditure for a cost per QALY gained of $68,059 (Table). Among PC cases, screening resulted in 0.67 more LYs, 0.55 more QALYs, and $22,691 in additional expenditure. In probabilistic analyses, screening resulted in a cost per QALY gained of <$50,000 and <$100,000 in 34% and 99% of simulations, respectively. In the threshold analysis, >25% of screen-detected cases needed to be resectable for the cost per QALY gained with screening to be <$100,000. Conclusions: We found that risk-based pancreatic cancer screening in NOD is likely to be cost-effective in the U.S. if even a modest fraction (>25%) of screen-detected cases are resectable. Future studies should reassess the value of this intervention once PanCAN EDI data become available. [Table: see text]