tbuckley/cabot-search huggingface dataset:
Asymptomatic distant recurrence detection and survival in early stage breast cancer: A nationally representative study.
Authors: Jessica R. Schumacher, Heather B. Neuman, Ying Zhang, Menggang Yu, David J. Vanness, Yajuan Si, Elizabeth S Burnside, Kathryn Jean Ruddy, Ann H. Partridge, Deborah Schrag, Stephen B. Edge, Elizabeth A Jacobs, Jeffrey Havlena, Amanda B. Francescatti, Patricia Spears, David P Winchester, Daniel P. McKellar, George J. Chang, Benjamin D. Kozower, Caprice Christian Greenberg
Journal: Journal of Clinical Oncology (2017)

6520 Background: Breast cancer follow-up guidelines recommend imaging for distant metastases only in the presence of signs/symptoms. However, data supporting this recommendation predates the current era of improved imaging and targeted therapies based on molecular subtype. The objective was to assess the relationship between mode of distant recurrence detection and survival. Methods: A stage-stratified random sample of Stage II-III breast cancer patients diagnosed in 2006-7 was selected from NCDB records from 1,217 CoC-accredited facilities (10/hospital n = 10,853). Women were categorized by subtype: 1) ER or PR+/HER2-; 2) ER and PR-/Her2- (triple negative); 3) HER2+. Medical records abstracted for 5-years post-surgery supplemented NCDB data and assessed distant recurrence and mode of detection (prompted by signs/symptoms or surveillance imaging), imaging (chest CT, abdomen/pelvis CT/MRI, head CT/MRI, bone scan, PET/CT), death date. The relationship between mode of recurrence detection and days from initial cancer diagnosis to death was assessed using propensity-weighted multivariable Cox proportional hazards regression stratified by subtype. Propensity weights, based on receipt of surveillance systemic imaging, accounted for sociodemographic and tumor/treatment factors. Results: 5-year distant recurrence was 22.3% for triple negative, 14.8% HER2+, and 11.2% for ER or PR+/ HER2- patients. Asymptomatic imaging detected recurrence in 22.9% and signs/symptoms in 77.1%. Patients with asymptomatic as compared to sign/symptom detected recurrences had reduced risk of death in 5 years if triple negative (HR = 0.68, 95% CI = 0.50-0.93) or HER2+ (HR = 0.40, 95% CI = 0.24-0.65) with no significant association for ER or PR+/HER2- (HR = 1.2, 95% CI = 0.88-1.51). This translated to a between-group difference in weighted median survival of 5 months for triple negative and 13 months for HER2+ patients. Conclusions: This is the first nationally representative study to show a survival advantage with asymptomatic detection of distant metastases for patients, with the benefit limited to triple negative and HER2+ disease. Further research to confirm observational findings is warranted.
Platelet bio-nanobubbles as microvascular recanalization nanoformulation for acute ischemic stroke lesion theranostics
Authors: Mingxi Li, Yang Liu, Jinpeng Chen, Taotao Liu, Zhuxiao Gu, Jianqiong Zhang, Xiaochun Gu, Gaojun Teng, Fang Yang, Ning Gu
Journal: Theranostics (2018)

Since the expected therapeutic results of ischemic stroke are strictly time dependent, early and accurate diagnosis as well as short intervals between diagnosis and treatment are key factors for the survival of stroke patients. In this study, we fabricated platelet (PLT) membrane-derived biomimetic nanobubbles (PNBs) for timely perfusion intervention and ultrasound imaging of acute ischemic stroke. Methods: The PNBs are fabricated by sonication-assisted reassembly of repeatedly freeze-thawed live platelet-derived PLT membrane vesicles (PMVs). The TEM, SEM, EDS and DLS were used to analyze the morphology and physicochemical properties of PNBs. The HPLC and LC-MS/MS were applied to confirm the lipid and protein compositions of PNBs. The in vitro macrophage uptake and platelet aggregation of PNBs were designed to examine the immune escape and thrombotic response characteristics. Furthermore, based on a photothrombotic ischemic stroke mouse model, the biodistribution, stroke microvascular network change, as well as cerebral blood flow of PNBs were studied by using near-infrared fluorescence imaging, multimodal optical imaging, and full-field laser perfusion imager. Finally, we assessed the brain ultrasound imaging of PNBs with a high-resolution micro-imaging system using both B-mode and contrast mode. Results: The natural lipid and protein components isolated from PLT membrane endow the PNBs with accurate lesion-targeting ability. The preferentially accumulated PNBs exhibit microvascular bio-remodeling ability of the stroke lesion, which is critical for recanalization of the obstructed vessels to protect the neural cells around the ischemic region of the stroke. Furthermore, with the increased accumulation of PNBs clusters in the lesion, PNBs in the lesion can be monitored by real-time contrast-enhanced ultrasound imaging to indicate the severity and dynamic development of the stroke. Conclusions: In summary, platelet membrane-based nanobubbles for targeting acute ischemic lesions were developed as microvascular recanalization nanoformulation for acute ischemic stroke lesion theranostics. This biomimetic PNBs theranostic strategy will be valuable for ischemic stroke patients in the future.
Anti-PD-1 in patients with advanced malignancies and baseline organ dysfunction.
Authors: Bridgette A Kanz, Megan Lynn Hames Pollack, Zeynep Eroglu, Romany Anne Nilanthi Johnpulle, Leora Horn, Suthee Rapisuwon, Robert Martin Conry, Jeffrey Alan Sosman, Igor Puzanov, Douglas Buckner Johnson
Journal: Journal of Clinical Oncology (2016)

e14539 Background: Anti-PD-1 (aPD1) is increasingly used in various advanced malignancies. Patients (pts) with baseline organ dysfunction are largely excluded from clinical trials. Therefore it is unclear whether aPD1 is safe or effective in this setting. Further, these pts are often not candidates for other anti-cancer therapies, highlighting their need for active treatment options. Methods: We assessed pts from multiple centers with various advanced cancers and baseline organ dysfunction who received aPD1. Organ dysfunction was defined as cardiac (left ventricular ejection fraction ≤45%), renal (creatinine ≥2mg/dL or GFR ≤30ml/min) or hepatic dysfunction (evidence of cirrhosis on imaging or AST, ALT or bilirubin ≥3x ULN). We assessed for worsening baseline organ dysfunction or immune related adverse events (irAEs) as well as response rate (RR), progression free survival (PFS) and overall survival (OS). Results: We identified 24 pts with renal cell carcinoma (8), melanoma (8), non-small cell lung cancer (3), small cell lung cancer (2) and urothelial bladder cancer (3) who received nivolumab or pembrolizumab. All patients had multiple comorbidities; specific baseline organ dysfunction is listed in the table below. Worsening organ dysfunction requiring hospitalization or dose delays occurred in 4 patients (17%) although in most cases this was thought not-drug related and resolved with supportive care. Grade 3 irAEs occurred in 2 pts (8%; hepatitis and colitis). PFS was not reached in 12 of 19 pts with evaluable responses (63%). Of these, 3 (25%) experienced partial response and 9 (75%) had temporary or ongoing stable disease lasting ≥12 weeks. Updated safety/efficacy data will be presented. Conclusions: In our experience, aPD1 agents were associated with tolerable irAEs and infrequent worsening of organ dysfunction. Further, objective responses and prolonged PFS were observed in a number of pts. Baseline Features (n=24) N (%) Median age, years (range) 69 (47-85) Male 21 (88) ≥2 prior therapies 17 (71) Renal dysfunction 10 (42) Hepatic dysfunction 3 (13) Cardiac dysfunction 5 (21) 2 organ dysfunctions 6 (25) Received nivolumab 16 (67)
Response to crizotinib in advanced ALK-rearranged NSCLCs with different variants and abundance of ALK-fusion alleles.
Authors: Jianming Ying, Yan Li, Tongtong Zhang, Wenbin Li, Pu-Yuan Xing, Jing Zhang, Li Junling
Journal: Journal of Clinical Oncology (2017)

e20651 Background: Anaplastic lymphoma kinase ( ALK) rearrangements are present in approximately 5% of non-small-cell lung cancers (NSCLCs). NSCLCs with ALK-rearrangement can be effectively treated with crizotinib. However, magnitude and duration of responses are found to be heterogeneous. This study explored the clinical efficacy of crizotinib in different ALK variants and abundance levels using next-generation sequencing (NGS). Methods: Among 89 ALK-rearrangement patients treated with crizotinib, 47 patients were identified with tumor specimens that could be evaluated by NGS. We retrospectively evaluated the clinical efficacy of crizotinib in different ALK variants and the abundance of ALK-fusion alleles. Results: The median PFS of the 89 ALK-rearrangement patients was 14.1 months (95%CI: 11.27-18.43 months). Among the 47 patients with NGS results, the most frequent variants were variant 3a/b (29.79%, 14/47), variant 1 (25.53%, 12/47) and variant 2 (14.89%, 7/47). Rare EML4- ALK variants were detected in 6 cases (12.77%). Other new fusion partners were detected in 8 cases (17.02%). Patients with EML4- ALK variant 2 appeared to have longer PFS than other EML4- ALK variants with a borderline p value. Patients were categorized into three groups based on the abundance of ALK-fusion alleles: low-abundance group ( &lt; 35%), middle-abundance group (≥35% and &lt; 55%), and high-abundance group (55%). Middle-abundance group had a better PFS than both low-abundance group and high-abundance group (P = 0.01). After adjusting for other baseline characteristics, abundance levels of ALK-positive alleles and ALKvariant type were identified as important factors for predicting clinical efficacy of crizotinib. Conclusions: Our results indicate prolonged PFS in patients with EML4- ALK variant 2 versus other EML4- ALK patients. The abundance of ALK-fusion alleles also correlated with the extent of benefit from crizotinib treatment.
SWOG S1206: A dose-finding study of veliparib (ABT-888) added to chemoradiotherapy (CRT) with carboplatin (C) and paclitaxel (P) for unresectable stage III non-small cell lung cancer (NSCLC).
Authors: Mihaela C. Cristea, Jieling Miao, Athanassios Argiris, Allen M. Chen, Megan Eileen Daly, Roy H. Decker, Linda L. Garland, Ding Wang, Marianna Koczywas, James Moon, Karen Kelly, David R. Gandara
Journal: Journal of Clinical Oncology (2016)

8537 Background: Preclinical studies of the PARP inhibitor velaparib (V) demonstrated synergistic effects when combined with various cytotoxic agents and radiation (RT). S1206 is a phase I trial of V given concurrently with standard CRT in stage III NSCLC. Methods: Newly diagnosed pts with unresectable stage III NSCLC, performance status 0–1 and adequate organ function were eligible. A standard 3+3 design was used with 3 V dose levels, 40 mg, 80 mg and 120 mg orally, twice a day. Pts received weekly C (AUC 2) and P (45 mg/m2) during concurrent thoracic RT (2 Gy fractions/day, total dose 60 Gy) and V throughout RT duration. Pts without progression received 2 cycles (every 21 days) of consolidation C (AUC 6), P (200 mg/m2) and V 80 mg twice daily on days 1-7 of each cycle. Dose-limiting toxicity (DLT) was assessed during the first 9 weeks of treatment. Results: From January 2013 to December 2015, a total of 21 pts were enrolled of whom15 (6/8 at 40 mg cohort, 6/7 at 80 mg, 3/6 at 120 mg) are evaluable for DLT. Three pts. at the 120 mg dose level are currently in the DLT evaluation period. Fifteen pts were enrolled to V dose levels 40 mg and 80 mg (median age 67, male 60%, stg. IIIA 67%, stg IIIB 33%, ECOG 0 47%, non-squamous histology 60%). Two pts developed a DLT: grade (G) 3 esophagitis with dysphagia (at the 40 mg cohort) and G 3 esophagitis with dehydration (at 80 mg). Other G 3/4 AEs during CRT, on the 40 mg and 80 mg cohorts, not meeting DLT definition included: neutropenia (6 pts), leukopenia (5 pts) and esophagitis less than 7 days duration (3 pts). One pt had G 3 neutropenic fever during CRT (DLT included G 4 neutropenic fever). One treatment-related death due to sepsis occurred after consolidation chemotherapy. Conclusions: V in combination with CRT with weekly C and P is well tolerated with expected toxicities that relate to the backbone CRT regimen. At completion of this phase I trial a randomized phase II trial comparing CRT with or without V will be initiated. Clinical trial information: NCT01386385. Support: NIH/NCI grants CA32102, CA38926, CA180888 and CA180819 Clinical trial information: NCT01386385.
Effect of follow-up appointments and admission unit on readmissions in patient with cancer on chemotherapy: A tertiary center experience.
Authors: Zaid Abdel Rahman, Joyce Philip, Omar Mohtadi, Pushpinderdeep Singh Kahlon, Vijaya Donthireddy
Journal: Journal of Clinical Oncology (2017)

e18239 Background: Readmissions are a huge burden on patients and organizations, especially in light of the newly emerging bundled payment systems. Many interventions have been proposed to reduce readmissions, including admitting patients to a cancer-specific unit (CSU) and scheduling follow-up appointments after discharge. Methods: We conducted a retrospective cohort study to identify the effect of admission unit and follow-up appointments on readmissions within 30 days among cancer patients receiving outpatient chemotherapy. We included unplanned admissions between July and October 2016 at Henry Ford Hospital. Results: There were 232 inpatient admissions. Of those, 73 (31%) were readmitted. The number of admissions to the CSU was 100 (43%) compared to 132 admissions (57%) to other general practice units (GPUs). Mean length of stay was 5.8 (1-29) days and 3.8 (1-30) days, respectively. Most common malignancies were hematological (27% and 22%) and gastrointestinal (26% and 19%). The most common reasons for admissions were infections (29% and 28%) and pain management (19% and 12%). Of patients who were admitted to the CSU, 24 (24%) were readmitted compared to 49 (37%) for other GPUs, OR 0.53 (95% CI:0.3-0.95, p = 0.033). Readmission rates were also calculated based on the type of appointment scheduled within 30 days of discharge (Primary care (PCP) and oncology, PCP only, Oncology only and neither). Odds ratios of readmission were calculated for the last three categories in comparison to having both appointments. Of admissions that had both appointments, 15 (23%) had a readmission within 30 days. Of admissions that had oncology only appointments, 39 (33%) had a readmission; OR 1.6 (95% CI: 0.8 to 3.3, p = 0.15). Of admissions that had a PCP only appointment, 6 (42%) had a readmission; OR 2.5 (95% CI: 0.7 to 8.3, p = 0.13) and of admissions that had neither appointments, 12 (57%) had a readmission; OR 4.4 (95% CI 1.6 to 12.6, p = 0.0049). Conclusions: Care for cancer patients is challenging as they carry a high risk of readmission, admitting cancer patients to cancer-specific units significantly reduces that risk. Having no follow-up appointments carries a high risk of readmission.
Histopathology correlation between depth of invasion and cervical lymph node metastasis in post operative patients of carcinoma buccal mucosa and tongue.
Authors: Dipti Rani Samanta, Surendra Nath Senapati, Ashish Upadhyaya
Journal: Journal of Clinical Oncology (2016)

e17542 Background: Many histopathologic parameters in head and neck squamous cell carcinoma have been identified as predictive factors for lymph node metastasis. Few studies have highlighted the depth of invasion with pathological lymph node metastasis. No definite treatment protocol has been defined with respect to depth of invasion This study is taken up to correlate between depth of invasion and lymph node metastasis in post operative cases of carcinoma buccal mucosa and tongue. Methods: Retrospectively the histopathology report of cases of operated carcinoma buccal mucosa and tongue respectively from August 2014 to December 2015 were reviewed. Total 82 cases were retrieved. All the patients had adequate neck dissection. The depth of invasion and lymph node involvement were analysed using SPSS v. 21. Results: Among 82 patients, there were 59 cases of Carcinoma Buccal Mucosa and 23 cases of Carcinoma Tongue. The overall cervical metastatic rate was 55.93% (n = 33/59) in Carcinoma Buccal Mucosa and 69.56% (n = 16/23) in Carcinoma Tongue. Upto 8 mm depth of invasion in case of Carcinoma Buccal Mucosa there is 37.5%(n = 6/16) involvement of cervical lymph nodes, whereas from depth of invasion more than 8 mm nodal metastasis is 62.79%(n = 27/43) of cases. While in Carcinoma Tongue upto 6 mm depth of invasion lymph node metastasis is seen in 50% (n = 2/4) cases and above 6 mm depth of invasion it is seen in73.68%(n = 14/19) cases. Conclusions: With increasing depth of invasion,the frequency and number of lymph node involvement increases in both Carcinoma Buccal Mucosa and Carcinoma Tongue. At 8 mm and 6 mm depth of invasion lymph node involvement increases significantly in Carcinoma Buccal Mucosa and Tongue respectively. Elective neck therapy should be considered at 8 mm and 6 mm of depth of invasion in Carcinoma Buccal Mucosa and Carcinoma Tongue.
Patient With Unexplained Weight Loss, Anorexia, and Back Pain
Authors: Sachinder Hans, Robert J. Acho
Journal: JAMA Surgery (2018)

A 74-year-old man presented with a 3-month history of weight loss, anorexia, and back pain. Physical examination revealed poor dental hygiene and findings in the lower extremity suggestive of postthrombotic syndrome. What is your diagnosis?
Quality-adjusted time without symptoms or toxicity (Q-TWiST) of nanoliposomal irinotecan (nal-IRI; MM-398) plus 5-fluorouracil and leucovorin (5-FU/LV) vs 5-FU/LV alone in metastatic pancreatic adenocarcinoma (mPAC) patients (pts) previously treated with gemcitabine-based therapy.
Authors: Uwe Pelzer, Jean-Frédéric Blanc, Davide Melisi, Antonio Cubillo, Daniel D. Von Hoff, Andrea Wang-Gillam, Li-Tzong Chen, Jens T. Siveke, Yin Wan, Caitlyn T. Solem, Marc Botteman, Yoojung Yang, Floris de Jong, Richard Hubner
Journal: Journal of Clinical Oncology (2016)

e15732 Background: nal-IRI is a nanoliposomal formulation of irinotecan. In the primary analysis of the pivotal NAPOLI-1 Phase-3 trial, nal-IRI+5-FU/LV significantly improved median overall survival (OS, primary endpoint; 6.1 vs 4.2 months, HR = 0.67, P = 0.012) and progression-free survival (PFS; 3.1 vs 1.5 months, HR = 0.56, P = 0.0001) vs 5-FU/LV alone in mPAC pts previously treated with gemcitabine-based therapy. This analysis evaluates between-treatment differences in quality-adjusted survival using a Q-TWiST approach. Methods: Total survival in NAPOLI-1 intent-to-treat cohort over 12 months was partitioned into time with adverse event grade ≥ 3 toxicity (TOX), time in relapse after disease progression (REL), and time without symptoms or adverse event grade ≥ 3 toxicity (TWiST). Mean Q-TWiST was calculated by multiplying time spent in each health state by its respective utility. In the base-case, the utility for TOX (uTOX), REL (uREL) and TWIST (uTWiST) were set to 0.5, 0.5 and 1.0. Nonparametric bootstrapped 95% CIs were derived. The relative Q-TWiST gain of nal-IRI+5-FU/LV vs mean OS for 5-FU/LV was calculated. Threshold analyses varied uTOX and uTWiST between 0.0 and 1.0. Scenario analysis was conducted using per-protocol (PP) population. Results: Nal-IRI+5-FU/LV (n = 117) vs 5-FU/LV (n = 119) pts had significantly more time in TWiST (mean 3.4 vs 2.4 months) and TOX (1.0 vs 0.3 month) but similar time in REL (2.5 vs 2.7 months). In the base-case, nal-IRI+5-FU/LV pts had a 1.3 months (95% CI: 0.4–2.1; 5.1 vs 3.9) greater Q-TWiST (range threshold analyses: 0.9–1.6 months), with a relative Q-TWiST gain of 24% (range threshold analyses: 17%-31%). In the PP population, Q-TWiST was also significantly superior in MM-398+5-FU/LV pts (Q-TWiST gain = 1.8 months; 95% CI: 0.7–3.0). Conclusions: Within NAPOLI-1, combination of nal-IRI+5-FU/LV resulted in statistically significant and clinically important gains in quality-adjusted survival vs 5-FU/LV alone, confirming the clinical outcome benefit of nal-IRI+5-FU/LV in mPAC. Clinical trial information: NCT01494506.
Retrospective study of the safety of administering pegfilgrastim on the same day of 5- Fluorouracil pump disconnect.
Authors: Nikita Patel, Christina Wu, Amber Draper, Jennifer Ann LaFollette, Edith Brutcher, Bassel F. El-Rayes, Olatunji B. Alese, Walid Labib Shaib, Mehmet Akce, Zhengjia Chen, Chaejin Kim
Journal: Journal of Clinical Oncology (2018)

e16190 Background: Pegfilgrastim (Pg), a long-acting G-CSF used to prevent neutropenia, is not indicated for administration within 24 hrs of completion of chemotherapy. The safety of administering Pg in gastrointestinal (GI) cancer chemotherapy regimens containing continuous infusion of fluorouracil (5-FU) on the day of completion of 5-FU has not been adequately studied. Despite absence of safety data, many institutions dose Pg on the final day of 5-FU administration after pump disconnection for patient convenience. Methods: An IRB-approved multi-institution retrospective analysis of patients with GI malignancy receiving 5-FU based chemotherapy who received Pg on the day of 5-FU pump disconnect was conducted. A total of 300 patients were reviewed from January 2010-May 2017. The primary end point was to determine the incidence of grade 3-4 neutropenia and febrile neutropenia (FN) when Pg was administered on the same day of 5-FU pump disconnect. The secondary endpoint was to determine rate of dose reductions and treatment delays. Results: Patient demographic data is in Table 1. Of the 300 patients, 45% were male and 55% were female with a median age of 61 years (range 33-82). There were 3 events of grade 3 neutropenia, 2 events of grade 4 neutropenia, and 2 events of FN. Treatment delay due to neutropenia occurred 3 times. Based on this data, the risk of a patient developing grade 3 neutropenia was 0.010 (95% CI 0.002-0.029) and grade 4 neutropenia was 0.007 (95% CI 0.001-0.024). The risk of FN was 0.007 (95% CI 0.001-0.024). The risks of treatment delay or treatment reduction were 0.013 (95% CI 0.004-0.034) and 0.010 (95% CI 0.002-0.029), respectively. Conclusions: Due to the low risk of grade 3-4 neutropenia, FN, as well as dose delays and/or reduction, Pg can be safely administered on the day of 5-FU pump disconnect. Table 1: Patient demographics Demographics n (%) Cancer Pancreas 181 (60.33%) Colorectal 75 (25%) Gastroesophageal 16 (5.33%) Other GI 28 (9.33%) Stage Stage II or III 69 (23%) Stage IV 231 (77%)