tbuckley/cabot-search huggingface dataset:
The impact of comorbidity on costs and effects of second-line treatment among elderly metastatic colon cancer patients.
Authors: Andinet Woldemichael, Ebere Onukwugha, Zhiyuan Zheng, Nader Hanna, Brian S. Seal, C. Daniel Mullins
Journal: Journal of Clinical Oncology (2014)

536 Background: The Charleston Co-morbidity Index (CCI) was developed as in hospital mortality indicatory and subsequently has been used to both predict and adjust survival differences in cancer patients. We therefore sought to examine how the incremental cost effectiveness of treating elderly metastatic colon cancer (mCC) patients with second-line treatment (Tx2) will vary based upon their baseline CCI. Methods: We identified 2,897 elderly (age 66+) mCC patients who received NCCN recommended first-line treatment (Tx1) between 2003 and 2009 in the SEER-Medicare dataset. Approximately 6% and 1% of patients with missing CCI and outlier costs, respectively, were excluded. We categorized patients by their CCI for 12 months prior to diagnosis into three categories: low (CCI = 0), medium (CCI = 1) and high (CCI = 2+). We calculated 5-years cost-effectiveness of Tx2. Patients enrolled in HMOs, lost part A and/or B, and died of causes other than colon cancer are censored. Costs are inflation adjusted to January 2009 dollars using U.S. Medical Price Index (MPI). We adjusted for censoring using Inverse Probability Weighting (IPW) method and selection bias on observables using Propensity Score Bin Bootstrapping method. Results: Among patients who received Tx1, 56% (n = 1,285) proceeded to receive Tx2. Of those who received Tx2, 67% (n = 864), 23% (n = 289), and 10% (n = 132) have low, medium and high comorbidities, respectively. Compared to those who do not received Tx2, patients who received Tx2 with low, medium, and high baseline comorbidities live 18 (se = 4), 253 (se = 4), and 183 (se = 3) days longer and incur added costs of $66,693 (se = $675), $80,217 (se = $723), and $49,610 (se = $1,136), respectively. The median Incremental Cost-Effectiveness Ratios (ICERs) of Tx2 for patients with low, medium, and high comorbidity are $80,049, $114,693, and $151,627, respectively. Conclusions: Survival benefits from receiving Tx2 vary from an average of 18 days to 253 days and added costs from $49,610 to $80,217 depending on baseline comorbidity levels. The median ICERs associated with Tx2 increase as baseline comorbidity level of patients increase.
An assessment of mid-chemotherapy CT scanning as a predictor of a residual retroperitoneal mass in good prognosis metastatic teratoma of the testis
Authors: S. J. Kirk, S. J. Harland, G. J. Rustin, R. T. Oliver, P. A. Cook, S. P. Stenning
Journal: Journal of Clinical Oncology (2005)

4573 Background: There are 2 widely used approaches to treatment of stage 2 non-seminomatous germ cell tumours of the testis (NSGCT); in the UK, 3 or 4 cycles of chemotherapy (C) are generally followed by surgery in those (∼25%)with residual masses >1cm. In some US centres, intial surgery is followed by 2 cycles of C, with similarly good results (Williams et al, 1987). A critical view of US practice is that 2/3 of pts have unnecessary surgery. A US view of UK practice would be that 25% of pts have excessive C. We assessed whether a mid-C CT scan could predict which pts would require surgery, defined as those likely to have a residual post-C mass ≥ 1cm in maximum transverse diameter (MTD), and might thus be considered for early surgery after 2 cycles of C. Methods: Pts were recruited within MRC/EORTC TE20 (de Wit et al 2001), comparing 3 vs 4 x BEP and a 3 vs 5-day schedule. Pts had histologically proven seminoma (S) or NSGCT and were IGCCCG good prognosis. For this sub-study, pts had a pre-C retroperitoneal (RP) mass ≥ 1cm in MTD. Pts had CT scans at baseline, 4–5 weeks after the start of their 1st cycle of C and then 4 weeks post C to measure the MTD of the largest RP mass. Sensitivity and specificity were used via ROC curve analysis to assess the accuracy of predicting residual masses of <1cm by looking at various cut-offs in both absolute mid-C diameter (D) & pre- to mid-C shrinkage (SH). Results: 77 pts (76 testis 1o, 1 RP 1o). Using MTD at mid-C as a predictor of residual RP mass <1cm gave an optimal cutpoint of 2cm (sens=80%, spec=85%). Investigating SH from pre-C to mid-C as a predictor of residual RP mass <1cm gave an optimal SH of 70% (sens=57%, spec=82%). Combining SH and absolute D did not substantially improve on rules using D alone. Conclusions: This small study suggests a potential role for mid-C CT in selecting certain pts for early surgery. Our results suggest the best predictor of post-C residual mass requiring resection is one where pts with an RP mass >2cm by mid C are recommended to have their mass resected. This means that 80% of pts will be correctly predicted to have a residual RP mass <1cm, and should continue their C and 85% will be correctly predicted to have a residual RP mass ≥ 1 cm and thus require resection. No significant financial relationships to disclose.
Distinct populations of inflammatory fibroblasts and myofibroblasts in pancreatic cancer
Authors: Daniel Öhlund, Abram Handly-Santana, Giulia Biffi, Ela Elyada, Ana S. Almeida, Mariano Ponz-Sarvise, Vincenzo Corbo, Tobiloba E. Oni, Stephen A. Hearn, Eun Jung Lee, Iok In Christine Chio, Chang-Il Hwang, Hervé Tiriac, Lindsey A. Baker, Dannielle D. Engle, Christine Feig, Anne Kultti, Mikala Egeblad, Douglas T. Fearon, James M. Crawford, Hans Clevers, Youngkyu Park, David A. Tuveson
Journal: The Journal of Experimental Medicine (2017)

Pancreatic stellate cells (PSCs) differentiate into cancer-associated fibroblasts (CAFs) that produce desmoplastic stroma, thereby modulating disease progression and therapeutic response in pancreatic ductal adenocarcinoma (PDA). However, it is unknown whether CAFs uniformly carry out these tasks or if subtypes of CAFs with distinct phenotypes in PDA exist. We identified a CAF subpopulation with elevated expression of α-smooth muscle actin (αSMA) located immediately adjacent to neoplastic cells in mouse and human PDA tissue. We recapitulated this finding in co-cultures of murine PSCs and PDA organoids, and demonstrated that organoid-activated CAFs produced desmoplastic stroma. The co-cultures showed cooperative interactions and revealed another distinct subpopulation of CAFs, located more distantly from neoplastic cells, which lacked elevated αSMA expression and instead secreted IL6 and additional inflammatory mediators. These findings were corroborated in mouse and human PDA tissue, providing direct evidence for CAF heterogeneity in PDA tumor biology with implications for disease etiology and therapeutic development.
Exosomal-miRNA profiles as diagnostic and prognostic biomarkers in head and neck squamous cell carcinoma (HNSCC).
Authors: G. Rabinowits, C. G. Taylor, G. H. Kloecker, A. Patel, M. B. Hall, D. D. Taylor
Journal: Journal of Clinical Oncology (2011)

5515^ Background: Predicting individual responses of HNSCC to treatment remain challenging. Better methods of defining HNSCC are needed. Improvements in biomarker research will probably be achieved with sets of various genomic and proteomic markers as provided by microarray technology. In previous work we demonstrated that the pattern of plasma exosomal-miRNA mirrored the miRNA within the tissue. Here we report the potential for blood-borne miRNA to identify HNSCC and to predict outcome. Methods: Plasma samples (1ml) were obtained from patients diagnosed with HNSCC at the time of initial treatment and serial samples were also obtained during clinical follow-up. Circulating exosomes were isolated and total RNA was extracted by a modified Trizol protocol. Small RNA was subsequently isolated using a small RNA isolation kit (SABiosciences). The specific miRNAs within the small RNA were quantitated using a cancer specific qRT-PCR array (SABiosciences) with an Agilent M3005P. The miRNA expression was compared to those expressed in lung cancer on a prior work. Results: Thirty HNSCC patients (19M, 11F), stage II (n=3), III (n=7), IVa (n=20) entered in the study. All but one underwent radiation and a radiosensitizing agent. Fifteen were considered for analysis since at least one follow-up sample was collected post treatment. Patients with HNSCC exhibited miRNA profiles within circulating exosomes that were distinct from normal controls and patients with squamous cell carcinoma (SCC) of the lung. Of the 84 miRNAs analyzed and 12 detected, miR148b and miR222 appeared to be uniquely expressed in HNSCC. miR16 was present in exosomes on patients with SCC. Patients with lung SCC appear to uniquely express miR199a and miR200c. In patients responding to initial therapy, the levels of most exosomal-miRNAs were suppressed; in patients failing to respond, no decrease in the exosomal-miRNAs were observed. Conclusions: miRNA profiles within blood-borne exosomes may have utility in the HNSCC diagnosis, and appear to be useful as disease monitoring. While these findings need to be confirmed in larger studies, determination of miRNA profiles within plasma-derived exosomes will add a new tool to histology directed therapy.
Erlotinib patterns of use and out-of-pocket (OOP) expenses.
Authors: Jonas A. De Souza, Patrick P. Gleason, Catherine I. Starner, Yang P. Qiu
Journal: Journal of Clinical Oncology (2012)

126 Background: Erlotinib is an oral oncology drug FDA-approved for advanced pancreatic and non-small cell lung cancers. Data on its patterns of use, pharmacy dispensing, and patient’s OOP are scarce. Methods: Using integrated medical and pharmaceutical data from 4 Blue Cross Blue Shield plans, we retrospectively identified individuals who received erlotinib between 01/2011 and 06/2011. Their claims were further queried for neoplasm ICD9 codes. A new user was defined as having no erlotinib claims filed in the prior 180 days. All new users were followed for 180 days or until their death/disenrollment (censor date). Excess erlotinib tablets were calculated for individuals with a censor date. The cost of unused tablets was estimated considering the standard 30-day, as well as a hypothetical 15-day drug supply. A gap of 45 days without erlotinib, during the follow-up, was defined as non-persistent to erlotinib therapy. The OOP costs were recorded from their first erlotinib claim. Results: Among 3,357,936 members insured, 125 (40 per million) received erlotinib in the period; 102 members (81.6%) had a lung cancer diagnosis, 18 (14.4%) pancreatic cancer, and 5 (4%) had cancers where erlotinib use is not evidence-based; 31 (24.8%) had a total cumulative supply of less than 30 days suggesting one fill and then discontinuation; 60 patients (48%) were new users in the period, 47 with lung cancer and 12 with pancreatic cancer. Among new users, 27 (45%) died or disenrolled; 18 (30%) of these patients had 211 unused tablets, which amounted to $35,237 or $587 per new user. With a hypothetical 15-day drug supply, there would be 45 unused tablets, totaling $7,515 or $125 per new user. Among the 60 new users, individual OOP on their first claim was &lt; $100 for 38 (63.3%) individuals and &gt; $100 for 22 (36.7%). OOP greater than $100 was associated with a 45-day gap in erlotinib therapy over the 6-month period, p=0.047 (21.0% versus 45.5%). Conclusions: A fourth of patients received erlotinib for less than a month, indicating these patients were either at the end of their lives or had intolerable toxicities. In this cohort, higher OOP costs negatively impacted persistence to therapy. For new users, a care management program with a 15-day drug supply could potentially be a cost-saving approach.
The TRUMPET registry: Assessing clinical outcomes and quality of life in patients with castration-resistant prostate cancer and their caregivers.
Authors: Scott C Flanders, Daniel W. Lin, Lawrence Ivan Karsh, Daniel H. Shevrin, Neal D. Shore, James Thomas Symanowski, David I. Quinn, Gretchen Otermat, Kathryn Starzyk, Bruce Brown, Peter St. John Francis, Elaine Karol Wong, Jun Wu, Samuel D Wilson, David F. Penson
Journal: Journal of Clinical Oncology (2016)

241 Background: Patient care in castration-resistant prostate cancer (CRPC) is complex, with varying treatment patterns due to differences in therapies, patient characteristics, and physician practices. The impact of such patterns on clinical outcomes and quality of life (QoL) represent a contemporary medical issue. This study aims to improve the understanding of clinical outcomes and QoL of patients with CRPC and their caregivers. Methods: TRUMPET is a prospective, observational, multi-center study of patients with CRPC in the United States. Approximately 2000 patients and their caregivers (if eligible) will be enrolled over 24 months from IRB-approved urology and oncology sites. Eligible patients with CRPC include those with life expectancy of ≥ 6 months initiating the first active course of anti-cancer treatment for M0 or M1. A 48-month observation period will follow the last patient enrolled. Primary objectives are to describe longitudinal patterns of care, disease assessment methods, treatment decisions, treatment settings, physician referral patterns, and CRPC patient characteristics associated with these. Patient-reported health-related QoL (HRQoL) instruments will assess the effects of CRPC and its management on patient perception of key aspects of HRQoL. The following will be administered at baseline and follow-up: SF-12v2 Health Survey, Functional Assessment of Cancer Therapy–Prostate, Brief Pain Inventory-Short Form, and Memorial Anxiety Scale for Prostate Cancer (prostate-specific antigen anxiety subscale). In a patient sub-study, work productivity and treatment satisfaction will be described using the Work Productivity and Activity Impairment (WPAI) Questionnaire: Specific Health Problem and Service Satisfaction Scale for Cancer Care. Caregiver QoL and productivity will be captured with the Caregiver Quality of Life Index–Cancer and the Caregiver-modified WPAI Questionnaire. Results: As of August 21, 2015, 60 sites were active, with 63 patients and 39 caregivers enrolled. Conclusions: Outcomes from the TRUMPET study will describe treatment patterns, QoL, and health care resources associated with patient management in CRPC. Clinical trial information: NCT02380274.
Clinical response to neoadjuvant therapy to predict success of adjuvant chemotherapy for esophageal adenocarcinoma.
Authors: Vernissia Tam, Craig M. Hooker, Daniela Molena, Alicia Hulbert, Beverly Lee, Lawrence Kleinberg, Stephen C. Yang, Arlene A. Forastiere, Malcolm Brock
Journal: Journal of Clinical Oncology (2014)

137 Background: Evidence informing current guidelines advising postoperative chemotherapy following trimodality therapy for esophageal cancer are limited. Our objective was to identify patients with locally advanced esophageal adenocarcinoma treated with trimodality therapy who may benefit from adjuvant chemotherapy. Methods: A single institution retrospective study was performed in 308 patients with esophageal adenocarcinoma who underwent neoadjuvant chemoradiation followed by surgery between 1989-2012. Kaplan-Meier analysis compared postoperative survival by clinical response to trimodality therapy and the use of adjuvant chemotherapy. Cox proportional hazards regression models estimated the association of adjuvant chemotherapy with survival. Results: After trimodality treatment, 93 out of 308 patients(30%) received adjuvant chemotherapy. Partial response to trimodality treatment was observed in 150(48%) patients; 50 of whom received adjuvant therapy. The median survival for partial responders who received adjuvant therapy vs. those receiving trimodality therapy alone was 53.2 vs. 27.6 months, respectively (p=0.047). Patients with complete response or no response to trimodality therapy showed no difference in median survival with the addition of adjuvant chemotherapy. Univariate Cox regression revealed a 26% decrease in relative hazard for long-term survival amongst patients who received adjuvant chemotherapy compared to no adjuvant therapy (HR=0.74, 95% CI 0.55-0.98). This association remained stable after adjusting for clinical response to trimodality therapy, age, and ASA score (aHR=0.75, 95% CI 0.55-1.01). Conclusions: Adjuvant therapy for patients with locally advanced esophageal adenocarcinoma was associated with a 26% decrease in relative hazard for mortality compared to trimodality treatment alone. Long-term survival following adjuvant therapy was dependent on initial response to trimodality therapy. Partial responders may benefit most from adjuvant chemotherapy.
A phase IIb trial of docetaxel concurrent with radiotherapy plus hormotherapy versus radio hormonotherapy in high-risk localized prostate cancer (QRT SOGUG trial): Preliminary report for design, tolerance, and toxicity.
Authors: Joan Carles, Enrique Gallardo Diaz, Montserrat Domenech, Albert Font, Joaquim Bellmunt, Begoña Mellado, Cristina Suárez, Teresa Bonfill, M Isabel Saez, Marta Guix, Maria Jose Mendez, Pablo Maroto, Teresa de Portugal, Mariona Figols, Raquel Luque, Ramon Aldabo, Rafael Morales, Marta Bonet, Xavier Maldonado, Palmira Foro
Journal: Journal of Clinical Oncology (2015)

15 Background: Docetaxel improves survival in patients (pts) with metastatic hormonosensitive prostate cancer (PC) and castration-resistant prostate cancer. The objective of this phase IIb trial was to assess the activity of low dose docetaxel concurrent with radiotherapy plus standard hormonal treatment in pts with high risk localized CaP. Methods: High-risk localized CaP was defined by ≥ 1 of the following criteria: T3-T4, Gleason score (GS) ≥ 8, PSA &gt; 20 ng/mL, pN+. Pts were randomly assigned to either arm A (LH-RH analogs every 3 months for 3 years and radiotherapy 73.8 Gy [1.8 Gy x 41 fractions] or 74 Gy [2Gy x 37 fractions]) or arm B (LH-RH analogs every 3 months for 3 years, radiotherapy and concurrent weekly docetaxel at 20 mg/m 2 for 9 weeks). Chemotherapy was started one week before of radiotherapy. Primary endpoint was PSA relapse according to the Phoenix definition. The planned number of pts was 130 to detect a 15% difference with a power of 80% and an alpha of 0.05 (two-sided). Results: From 12/2008 to 9/2012, 130 pts were accrued (Arm A: 64, Arm B: 66). Median age was 68 years (61-73). Patients had T3-T4 (82.6%), GS ≥ 8 (76.3%), PSA &gt; 20 ng/mL (26.9%) and pN+ (18.9%). All characteristics were well-balanced between arms. Median dose of radiotherapy was 74 Gy (72–74.8) in arm A, and 73.8 Gy ( 72-75.6) in arm B. 75.7% of pts received the planned 9 treatments of docetaxel and median number of cycles delivered per patient was 9. After a median follow-up of 29.6 months (9.6-40.2), most common grade 1/2 toxicities (arm A and arm B) were: cystitis ( 12.5% vs 8.3%), diarrhea (35.9% vs 70%), proctitis (12.5% vs 13.3%), rectal tenesmus (3.1% vs 23.3%), asthenia (23.4% vs 61.6%) and dysuria ( 28.1% vs 30.0%). Toxicity G3/G4 diarrhea was reported in 8.3% of pts in arm B and 0% in arm A. G3/G4 lymphopenia occurred less often in arm A than in arm B (3.1% vs 23.3%). %). There was no toxicity-related death. Conclusions: The QRT SOGUG phase IIb trial met its accrual target and shows that concurrent weekly docetaxel can be administered with standard doses of radiotherapy and without increasing toxicity profile. Clinical trial information: 2008-003554-14.
The role of EGFR mutation status in patients with stage III non-squamous non-small cell lung cancer treated with chemoradiotherapy.
Authors: F. Li, G. y. Zhu, X. N. Li, R. Yu, A. Shi, L. Yin
Journal: Journal of Clinical Oncology (2011)

7032 Background: The presence of epidermal growth factor receptor (EGFR) mutations is predictive of a better response to EGFR-TKIs and initial chemotherapy in advanced non squamous non-small cell lung cancer (NSCLC). We reviewed EGFR mutation status in patients with non-squamous NSCLC, and then analyzed the association between the EGFR mutations and the outcome of combination chemoradiotherapy in stage III non-squamous NSCLC. Methods: Patients with stage III non-squamous NSCLC who had identified EGFR mutation status were retrospectively analyzed, 87 patients of those were evaluated response to combination chemoradiotherapy and 2 years survival rate, and128 patients of those could be evaluated response to initial chemotherapy. Results: The objective response rate to combination chemoradiotherapy was 84.6% (33/39) in patients with mutation-positive EGFR, significantly higher than 56.3% (27/48) in those with mutation-negative EGFR (P=0.004). By comparing the images of pre- and post-thoracic radiotherapy, the response rate to thoracic radiotherapy with or without concurrent chemotherapy was 79.5% (31/39) in patients with mutation-positive EGFR and 50% (24/48) in those with mutation-negative EGFR. The overall response rate to initial chemotherapy was 34.5% (19/55) in patients with mutation-positive EGFR, as compared 21.9% (16/73) in those with mutation-negative EGFR. Two years survival rate was 53.8% in patients with mutation-positive EGFR and 50% in those with mutation-negative EGFR. There was no difference in overall survival for patients with mutation-positive EGFR compared with those with mutation-negative EGFR. Conclusions: EGFR mutation-positive status can predict better response to combination chemoradiotherapy, but do not associate with overall survival in patients with stage III non-squamous NSCLC.
Clinical Significance of CD21 Co-Expressed with LFA-1 in Non-Hodgkin’s B-Cell Lymphoma.
Authors: Kazushi Tanimoto, Yoshihiro Yakushijin, Hiroshi Fujiwara, Masaki Otsuka, Koichi Ohshima, Atsuro Sugita, Akira Sakai, Takaaki Hato, Hitoshi Hasegawa, Masaki Yasukawa
Journal: Blood (2008)
Feasibility of dignity therapy in patients with stage IV colorectal cancer receiving chemotherapy.
Authors: Maxwell Thomas Vergo, Halla Sayed Nimeiri, Mary Frances Mulcahy, Jamie H. Von Roenn, Al Bowen Benson, Linda Emanuel
Journal: Journal of Clinical Oncology (2012)

671 Background: Dignity Therapy (DT) is a structured psychotherapeutic interview which allows people to create a permanent document to validate their existence and leave a legacy. It focuses on life review, meaningful relationships, and words of comfort to loved ones. In terminal patients no longer receiving chemotherapy, this intervention improved the majority of patients’ sense of dignity, purpose, and meaning, and also reduced depression and self reported suffering (Chochinov, J Clin Oncol, 2005). This study evaluates the feasibility of DT in patients receiving active chemotherapy. Methods: Outpatients ≥ 18 years of age with metastatic colorectal cancer recently starting second line chemotherapy were recruited. DT was administered, the interview transcribed, and the transcription edited into a proof version. This version was read to the patient and given to them after it was finalized. Main outcome was feasibility as measured by enrollment rate, discontinuation rate, and satisfaction after completing therapy. Other secondary measures included assessments for terminal illness acknowledgement (TIA), symptoms, peacefulness, quality of life, and finally preferences in a hypothetical end-of-life scenario. Results: Overall, there has been a 91% enrollment rate (10 out of 11 approached), 0% discontinuation, and a 100% rate of being satisfied or very satisfied (7 patients). 3 patients were removed due to non-compliance, sedation, or lost data. Of those who completed therapy, &gt; 70% felt it was helpful or very helpful and strongly or very strongly felt it increased their sense of dignity, purpose, and meaning as well as the potential to help their family in the future. Symptoms remained stable over time. Exploratory endpoints included a 33% increase in TIA (p=0.23), no increase in peacefulness (p=0.44), less aggressive goals of care (p=0.28), and decreased distress. Conclusions: DT is a highly satisfying and meaningful intervention for advanced colorectal cancer patients receiving chemotherapy. Given its feasibility, an ongoing randomized wait-list control study should help answer if DT effects TIA, end-of-life goals of care, or distress levels in this population. Funding: ACS-IRG 93-037-15.