tbuckley/cabot-search huggingface dataset:
Neoadjuvant chemoradiation for locally advanced rectal cancer with fluoropyrimidine alone or intensified with oxaliplatin: A systematic review and meta-analysis.
Authors: Ashlie Nadler, Elizabeth Handorf, Elin R. Sigurdson, Joshua E. Meyer, Crystal Shereen Denlinger, Jeffrey M. Farma
Journal: Journal of Clinical Oncology (2017)

678 Background: Improved outcomes have been demonstrated with the use of neoadjuvant fluoropyrimidine-based chemoradiotherapy and total mesorectal excision for locally advanced rectal cancer. The addition of oxaliplatin in the adjuvant setting has also resulted in improved disease-free survival (DFS). A meta-analysis was performed to evaluate DFS and overall survival (OS) with the addition of oxaliplatin to standard neoadjuvant chemoradiation for locally advanced rectal cancer. Methods: A systematic literature review was performed. Randomized-controlled trials (RCTs) comparing the addition of oxaliplatin in the neoadjuvant setting (oxaliplatin group) to fluoropyrimidine-based chemoradiation (standard group) were included. The primary outcomes were DFS and OS; secondary outcomes were short-term surgical results, morbidity, and mortality. Results were combined using meta-analysis via linear mixed-effects models. Calculations were performed using R. Results: Of 73 studies identified, 4 reported DFS (n=3829) and 3 reported OS (n=2680). There was no difference in DFS between the standard and oxaliplatin groups amongst RCTs [HR 0.90 (0.64-1.26), p=0.5313]. There was no difference in OS [HR 0.93 (0.59-1.47), p=0.9894]. There was no significant heterogeneity between RCTs for primary outcomes. There was also no difference in pathologic complete response rate [OR 0.93 (0.77-1.14), p=0.4923), resection margin (R0) status [OR 1.01 (0.59-1.72), p=0.9846], circumferential resection margin status [OR 0.84 (0.50-1.41), p=0.5079], sphincter saving surgery rate [OR 0.87 (0.74-1.03), p=0.1103], grade 3-4 toxicity [OR 1.60 (0.88-2.92), p=0.1251], and 60-day mortality [OR 1.27 (0.50-3.25), p=0.6148]. There was significant heterogeneity between RCTs for R0 status, circumferential margin status, and grade 3-4 toxicity. Adjuvant treatment varied across studies. Conclusions: There are no short-term or long-term survival benefits with the addition of oxaliplatin to fluoropyrimidine-based chemoradiation in the neoadjuvant setting for locally advanced rectal cancer.
RAS Pathway Mutations As Predictive Biomarker for Treatment Adaptation in Pediatric B-Cell Precursor Acute Lymphoblastic Leukemia
Authors: Isabel S. Jerchel, Alex Q. Hoogkamer, Ingrid M. Ariës, Elisabeth M.P. Steeghs, Judith M. Boer, Nicolle J.M. Besselink, Aurélie Boeree, Cesca van de Ven, Hester A. de Groot-Kruseman, Valerie De Haas, Martin A. Horstmann, Gabriele Escherich, Ronald W. Stam, C. Michel Zwaan, Edwin Cuppen, Marco J. Koudijs, Rob Pieters, Monique L. Den Boer
Journal: Blood (2016)
Cancer survivorship outcomes in immigrants.
Authors: Phyllis Noemi Butow, Lynley Aldridge, Melanie Bell, Ming Sze, Maurice Eisenbruch, Madeleine King, Michael Jefford, Penelope Schofield, Priya Duggal-Beri, David Goldstein
Journal: Journal of Clinical Oncology (2012)

6111 Background: Immigration is increasing world-wide. Cancer survivorship is now recognised as a period of difficult adjustment for all patients, and possibly more so for immigrants. We explored disparities in quality of life outcomes for immigrant (IM) versus Anglo-Australian (AA) cancer survivors. Methods: In a cross-sectional design, cancer survivors were recruited through the New South Wales, Queensland and Victorian Cancer Registries in Australia. IM participants, their parents and grandparents were born in a country where Chinese, Greek, or Arabic is spoken and spoke one of those languages. AAs were born in Australia and spoke English. All were diagnosed with cancer 1-3 years previously. Questionnaires (completed in preferred language) included the Hospital Anxiety and Depression Scale (anxiety/ depression), FACT-G (quality of life) and Supportive Care Needs Survey (unmet needs). Outcomes were compared between AA and IM groups in adjusted regression models that included age, gender, socio-economic status, education, marital status, religion, time since diagnosis and cancer type (prostate, colorectal, breast and other). Results: There were 599 participants (response rate 41%). Consent was unrelated to demographic and disease variables. AA and IM groups were similar except that immigrants had higher proportions in the low and highly educated groups (p &lt; 0.0001), and higher socioeconomic status (p = 0.0003). In adjusted analyses (see table), IMs had clinically significant higher depression (possible range 0-21), greater unmet information and physical needs, and lower quality of life than AAs. The possible range for the latter three is 0-100. Conclusions: Immigrants experience poorer outcomes in cancer survivorship, even after adjusting for socio-economic, demographic and disease differences. Interventions are required to improve their adjustment after cancer. Results highlight areas of unmet need that might be better addressed by the health system (particularly with regard to provision of information and support. [Table: see text]
Quality of life in poor prognosis patients with locally advanced non-small cell lung cancer (LA-NSCLC) undergoing a phase II study of concurrent cetuximab and definitive thoracic radiotherapy followed by docetaxel and cetuximab.
Authors: Lora Thompson, Martine Extermann, Thomas J. Dilling, Jongphil Kim, Binglin Yue, Craig William Stevens, Scott Antonia, Jhanelle Elaine Gray, Charles C. Williams, Eric B. Haura, Mary Colleen Pinder, Tawee Tanvetyanon, Alberto Chiappori
Journal: Journal of Clinical Oncology (2012)

e17559 Background: A single institution prospective clinical trial was conducted to examine the safety and efficacy of concurrent cetuximab and definitive thoracic radiotherapy followed by docetaxel plus cetuximab. Quality of life (QOL) was assessed as a secondary endpoint. Survival and toxicity data are presented separately. Methods: Eligible pts with unresectable stage IIA or IIIB LA-NSCLC, who also had ECOG PS 2 OR weight loss ≥5% in 3 months OR age &gt;70, completed QOL measures at baseline, after concurrent cetuximab/radiotherapy (recovery), and after docetaxol/cetuximab (consolidation). Scores were calculated for Activities of Daily Living (ADL), Instrumental Activities of Daily Living (IADL), Fatigue Symptom Inventory (FSI) worst fatigue, FSI fatigue interference, and Functional Assessment of Cancer Therapy – Lung Trial Outcome Index (FACT-L TOI). FACT-L TOI assessed physical (e.g., nausea) and functional (e.g., difficulty sleeping) well-being as well as lung cancer specific symptoms (e.g., shortness of breath, cough). Descriptive and t-test results are presented. Results: Pts (N = 27) were primarily male (67%) and non-Hispanic Caucasian (96%) with mean age of 73 years. High attrition between recovery (N = 22) and consolidation (N = 10) occurred. Compared to baseline, pts reported higher levels of worst fatigue (p &lt; .03) and fatigue interference (p = .01) at recovery. There was a decline in IADLs (p = .01) but no significant difference in ADLs or FACT-L TOI. Further examination of FACT subscales revealed declines in physical (p &lt; .0001) and functional (p = .02) well-being but improvement in lung cancer specific symptoms (p &lt; .0001). A similar pattern is found for comparisons between baseline and consolidation (ps &lt; .05). There were no significant differences between recovery and consolidation. Conclusions: Although pts experienced declines in QOL across most domains after concurrent cetuximab and radiotherapy, there was improvement in lung cancer specific symptoms. Pts were also able to maintain their ability to perform ADLs. High attrition after recovery is a notable limitation.
Breast cancer brain metastases: Comprehensive review of tumor extent, histology and treatment on survival.
Authors: Jennifer A. Crozier, Lauren F. Cornell, Bhupendra Rawal, Edith A. Perez
Journal: Journal of Clinical Oncology (2015)

1059 Background: Breast cancer brain metastases (BCBM) are associated with poor overall survival (OS) and no treatment guidelines exist. Localized treatments include neurosurgery (ns), stereotactic radiosurgery (SRS) and whole brain radiation therapy (WBRT). We studied the association of OS with tumor and patient (pt) characteristics, ns and radiation (rad). Methods: 196BCBM pts who received brain rad from 2009-2013 at three Mayo Clinic sites were retrospectively studied. Data included primary tumor histological subtype: ER+, HER2+, and triple negative (TN). ECOG status at BCBM diagnosis, number of brain lesions, ns and rad treatments were also studied. Results: In single variable analysis (Table), TN status had 1.8 fold (p = 0.004) increased hazard of death compared to ER+, while HER2+ had improved OS (HR 0.6, p = 0.008). Hazard of death in pts with leptomeningeal disease was 2.5 fold higher (p = 0.003) than pts with 1-3 brain lesions. Poor ECOG status was associated with poor OS. Pts who received WBRT and SRS had an improved OS (HR 0.37, p < 0.001) compared to WBRT alone. Combining ns, WBRT and SRS had better OS (HR 0.26, p < 0.001) than WBRT alone. Conclusions: In this large dataset,pts with the best OS had an ECOG score of 0, HER2+ disease, 1-3 brain lesions, and the combination of ns and rad. OS analysis. Variables Single variable analysis HR (95% CI) P-value ER+ 1.0 (Ref) HER2+ 0.61 (0.43, 0.88) 0.008 TN 1.76 (1.20, 2.58) 0.004 Number of BCBM 1- 3 1.0 (Ref) 0 (Leptomeningeal) 2.52 (1.38, 4.58) 0.003 ≥ 4 1.41 (1.03, 1.95) 0.034 ECOG 0 1.0 (Ref) 1 1.53 (1.05, 2.23) 0.028 2 2.93 (1.64, 5.26) < 0.001 3-4 6.79 (3.78, 12.19) < 0.001 NS 0.44 (0.30, 0.63) < 0.001 RAD WBRT 1.0 (Ref) SRS 0.78 (0.51, 1.19) 0.25 WBRT & SRS vs. WBRT as a ref 0.37 (0.26, 0.54) < 0.001 WBRT & SRS vs. SRS as ref 0.48 (0.30, 0.77) 0.002 NS status & RAD combinations No NS, WBRT only (n = 87) 1.0 (Ref) No NS, SRS only (n = 29) 0.67 (0.42, 1.05) 0.082 No NS, WBRT and SRS both (n = 28) 0.32 (0.20, 0.51) < 0.001 NS, WBRT only (n = 18) 0.29 (0.15, 0.57) < 0.001 NS, SRS only (n = 7) 0.48 (0.19, 1.18) 0.11 NS, WBRT and SRS both (n = 27) 0.26 (0.16, 0.42) < 0.001 Ref, reference; HR, hazard ratio; CI, confidence interval. Single variable Cox proportional hazard model was used for P-values.
Anti-PD-L1 Efficacy Can Be Enhanced by Inhibition of Myeloid-Derived Suppressor Cells with a Selective Inhibitor of PI3Kδ/γ
Authors: Ruth J. Davis, Ellen C. Moore, Paul E. Clavijo, Jay Friedman, Harrison Cash, Zhong Chen, Chris Silvin, Carter Van Waes, Clint Allen
Journal: Cancer Research (2017)

Checkpoint inhibitors are relatively inefficacious in head and neck cancers, despite an abundance of genetic alterations and a T-cell-inflamed phenotype. One significant barrier to efficacy may be the recruitment of myeloid-derived suppressor cells (MDSC) into the tumor microenvironment. Here we demonstrate functional inhibition of MDSC with IPI-145, an inhibitor of PI3Kδ and PI3Kγ isoforms, which enhances responses to PD-L1 blockade. Combination therapy induced CD8
Impact of preoperative treatments on the immune microenvironnement of colorectal liver metastases.
Authors: Frederic Bibeau, Hugo Gil, Florence Castan, Magalie Pedot, François Quenet, Marc Ychou, Florence Boissière-Michot, Fabien Gaire, Vaios Karanikas, Michael Cannarile, Solange Romagnoli, Véronique Charrier
Journal: Journal of Clinical Oncology (2014)

3631 Background: An adaptive CD8+/CD45+ immune response, is considered as a favorable prognostic factor in primary colorectal cancer (CRC). FoxP3+regulatory T lymphocytes (Ly) inhibit this response. Such data are lacking in CRC liver metastases (LM), notably after preoperative treatments. We aim to analyze this subject. Methods: 105 CRC LM were selected as follows: chemotherapy alone (CT, n= 29), CT + anti-VEGF (bevacizumab) (n= 27), CT + anti-EGFR (cetuximab) (n= 20), surgery alone (control group, n= 29). LM were treated in first-line. Histologic response was assessed according to the Tumor Regression Grade (major response: MR, partial response: PR, no response: NR). Immune microenvironnement was evaluated as follows: intratumoral (IT), peritumoral (PT) , classified as minor or major and assessed by immunohistochemistry to characterize: i)T Ly: CD8+ (cytotoxic) , CD 45+ (memory), Tbet+ (T helper 1), FoxP3+ (regulators) ii) macrophages: CD68+, CD163+. Results: A major immune infiltrate was more frequently associated with LM showing MR vs PR vs NR, with the following markers and locations: CD8+ (IT; p = 0.003), CD45+ (IT; p = 0.011), Tbet+ (PT; p= 0.015), CD 68(IT; p= 0.050), CD163 (PT, IT; p = 0.002, p = 0.023). Conversely, a major FoxP3+ IT infiltrate was more frequently associated with LM displaying NR vs PR vs MR (p = 0.033). Moreover, a major immune infiltrate was more frequently associated with treated LM than with untreated LM as folows: CD8+ (IT; p = 0.012), TBet+ (PT, IT; p = 0.015 p= 0.023), CD 68 (IT; p = 0.048), CD163 (IT; p = 0.012). Among treated LM, a major PT CD45 infiltrate was more frequently associated with CT+anti-EGFR than other treatments (p = 0.036), and a major IT CD45 infiltrate was more frequently associated with CT+anti-EGFR and chemotherapy alone than CT+anti-VEGF ( p = 0.022). Conclusions: Pre-operative treatments have an impact on CRC LM immune microenvironnement. Treated CRC LM with histologic response harbor a CD8+/CD45+ adaptive immune response, a stimulated T helper 1 pathway and a down regulation of Treg lymphocytes. The use of therapies targeting the immune microenvironnement can be suggested as an option in LM CRC. The prognostic impact of these results will be determined and presented.
Increased utilization of advanced imaging technology and its economic impact for patients diagnosed with bladder cancer in the United States.
Authors: Christopher David Kosarek, Jinhai Huo, Jacques G. Baillargeon, Yong-Fang Kuo, Justin Edwin Fang, Cameron Ghaffary, Preston Kerr, Simon P. Kim, Eduardo Orihuela, Douglas S. Tyler, Sharon Hermes Giordano, Stephen J. Freedland, Ashish M. Kamat, Stephen Bentley Williams
Journal: Journal of Clinical Oncology (2017)

368 Background: This study examined utilization patterns and predictors for use of positron emission tomography-computed tomography (PET/CT), magnetic resonance imaging (MRI), and computed tomography (CT) among Medicare beneficiaries diagnosed with bladder cancer. Methods: We used the Surveillance, Epidemiology and End Results (SEER)-Medicare linked databases to analyze claims data for 36,855 patients aged 60-90 years diagnosed with bladder cancer from 2004 to 2011. The Cochran-Armitage test for trend was used to determine whether significant changes in the proportion of patients receiving advanced imaging after cancer diagnosis occurred during the time interval; trends in the usage of the imaging modality types were assessed. Multivariable logistic regression modeling was conducted to analyze potential demographic and clinical predictors associated with receipt of advanced imaging. The costs of imaging were measured using Medicare payments. Results: While the overall trend of imaging use remained essentially unchanged over the study period, there was a significant decrease in the proportion of patients who received conventional imaging modalities (MRI and CT; P &lt; .05) and a significant increase in the proportion of patients receiving the more advanced imaging modality (PET/CT; P &lt; .0001). On multivariable analysis, receipt of PET/CT was significantly higher in female patients, Non-Hispanics, residents in West Census region, patients with higher grade tumors, those diagnosed with advanced stage disease, hydronephrosis, and those that received radical cystectomy and chemotherapy. In the cost analysis, the estimated national excess medical spending for advanced imaging was $6.1 million. Conclusions: The sharp increase of advanced imaging (PET/CT) and substantial costs associated with this rapid adoption as we have documented suggests that further efforts should be made to evaluate the clinical and economic benefits of PET/CT imaging and to elucidate its appropriateness of use among bladder cancer patients.
Patient-reported symptoms following IMRT alone for oropharynx cancer: A survivorship study.
Authors: Gary Brandon Gunn, Clifton David Fuller, Adam S. Garden, Steven J. Frank, William H. Morrison, Beth Michelle Beadle, Jack Phan, Tito R. Mendoza, Ehab Y. Hanna, K. Kian Ang, Charles S. Cleeland, David Ira Rosenthal
Journal: Journal of Clinical Oncology (2012)

5561 Background: Patients (pts) with favorable oropharynx cancer (OPC) are often treated with single modality RT with excellent disease control. We present the pattern of pt-reported symptoms in OPC survivors treated with IMRT alone. This will represent a benchmark for later comparison to pts treated with other modalities (e.g., proton therapy, transoral surgery). Methods: Pts eligible for this cross-sectional questionnaire-based study had OPC treated with IMRT (no systemic therapy), in remission &gt;18 mos, completed the MD Anderson Symptom Inventory – Head and Neck Module (MDASI-HN). Clinical data were tabulated and analyzed using non-parametric statistics. Results: 89 pts participated. OPC sub-site was tonsil in 58, base of tongue (BOT) in 30, and soft palate in 1 pt. 65% were TX/1, 28% T2, and 7% T3/4, while 53% were NX/1 with 47% N2. Mean RT dose was 66 Gy (SD±2.5). Median age was 54 years (SD±11). Mean follow-up at MDASI-HN was 74 months (SD±15). Mean MDASI-HN symptom rating (0 to 10 scale) was 1.3 (95% CI 0.97-1.6), with no significant difference by OPC sub-site. No single MDASI-HN items showed significant difference in the percentage of pts with moderate to severe (M/S) reports by OPC site, thou dry mouth approached significance (p=0.054), 53% in BOT vs. 32% for tonsil. Overall, 14% of pts were entirely symptom free (i.e. “0” across all 22 symptom items), 33% reported only mild symptoms, 23% only moderate symptoms, and 31% reported any symptom as severe . The top 7 symptoms were dry mouth, swallowing, sleep, taste, fatigue, distress, and teeth and these were reported at M/S levels by 39%, 24%, 19%, 17%, 16%, 14%, and 10% of pts, respectively. For those with any M/S symptom, the median number of symptoms reported at M/S levels was 3. 1/89 pts had a feeding tube at the time of MDASI-HN completion. Conclusions: The late symptom burden for long-term OPC survivors following IMRT alone was low, with nearly half of pts with only minimal symptoms across all items. Considering other endpoints (e.g. disease control, acute toxicity, second malignancies, and functional measures), future treatment strategies should seek to match or exceed these results. Future RT symptom prevention/reduction strategies should focus on the top symptoms identified here.
Long‐term outcomes of entecavir monotherapy for chronic hepatitis B after liver transplantation: Results up to 8 years
Authors: James Fung, Tiffany Wong, Kenneth Chok, Albert Chan, Tan‐To Cheung, Jeff Wing‐Chiu Dai, Sui‐ling Sin, Ka‐Wing Ma, Kelvin Ng, Kevin Tak‐Pan Ng, Wai‐Kay Seto, Ching‐Lung Lai, Man‐Fung Yuen, Chung‐Mau Lo
Journal: Hepatology (2017)

Long-term antiviral prophylaxis is required to prevent hepatitis B recurrence for patients with chronic hepatitis B after liver transplantation. We determined the long-term outcome of 265 consecutive chronic hepatitis B liver transplant recipients treated with entecavir monotherapy without hepatitis B immune globulin. Viral serology, viral load, and liver biochemistry were performed at regular intervals during follow-up. The median duration of follow-up was 59 months. The cumulative rates of hepatitis B surface antigen (HBsAg) seroclearance were 90% and 95% at 1 and 5 years, respectively. At 1, 3, 5, and 8 years, 85%, 88%, 87.0%, and 92% were negative for HBsAg, respectively, and 95%, 99%, 100%, and 100% had undetectable hepatitis B virus (HBV) DNA, respectively. Fourteen patients remained persistently positive for HBsAg, all of whom had undetectable HBV DNA. There was no significant difference in liver stiffness for those who remained HBsAg-positive compared to those who achieved HBsAg seroclearance (5.5 versus 5.2 kPa, respectively; P = 0.52). The overall 9-year survival was 85%. There were 37 deaths during the follow-up period, of which none were due to hepatitis B recurrence.Long-term entecavir monotherapy is highly effective at preventing HBV reactivation after liver transplantation for chronic hepatitis B, with a durable HBsAg seroclearance rate of 92%, an undetectable HBV DNA rate of 100% at 8 years, and excellent long-term survival of 85% at 9 years. (Hepatology 2017;66:1036-1044).
Safety and activity of ziv-aflibercept in combination with irinotecan, 5-fluorouracil, and leucovorin (FOLFIRI) in patients with colorectal cancer previously treated with irinotecan: Results from a phase 1 study.
Authors: Eric Van Cutsem, David Khayat, Chris Verslype, Bertrand Billemont, Sabine Tejpar, Jean-Baptiste Meric, Pankaj Bhargava, Karen Soussan-Lazard, Sylvie Assadourian, Michael L. Andria, Solenn Le-Guennec, Olivier Rixe
Journal: Journal of Clinical Oncology (2014)

e14510 Background: In a phase 1 study investigating ziv-aflibercept (Z, known as aflibercept outside the United States) with FOLFIRI, an analysis was performed to evaluate safety and activity in colorectal cancer (CRC) patients previously treated with irinotecan (I). Methods: The first part of the study was an open-label, dose-escalation stage in which patients with advanced solid tumors received Z at doses of 2, 4, 5, or 6 mg/kg on day 1, followed by FOLFIRI q2wks. The second part of the study was an expansion stage at the recommended dose of Z (4 mg/kg). This analysis is limited to CRC patients previously treated with I and receiving a dose of Z ≥4 mg/kg in either part of the study. Results: Of the 61 patients in the overall study with a planned dose of Z ≥4 mg/kg, 37 CRC patients previously treated with I received an actual dose of Z ≥4 mg/kg (56.8% men; mean age 57.6 years; 94.6% with ECOG performance status 0-1). Table shows response rates for the prior I efficacy population (n=36) and overall study efficacy population (n=58); 91.9% of patients had at least 1 grade 3/4 adverse event (AE) compared with 93.4% in the overall study population. Percentages of patients with grade 3/4 hypertension, neutropenia, fatigue, stomatitis, diarrhea, and proteinuria in the prior I group were 43.2%, 37.8%, 29.7%, 16.2%, 16.2%, and 10.8% vs 37.7%, 44.3%, 31.1%, 16.4%, 16.4%, and 16.4% in the overall study population, respectively (percentages for neutropenia and proteinuria are based only on AEs rather than laboratory data). Conclusions: In this study, more than half of patients receiving Z ≥4 mg/kg had previously received I. FOLFIRI + Z following previous exposure to I in patients with CRC appeared to be safe and showed antitumor activity in this small cohort. Clinical trial information: 2004-001059-12. Best overall response, n (%) Overall study population* n=58 CRC patients previously treated with I* n=36 Partial response 12 (20.7) 4 (11.1) Stable disease 36 (62.1) 25 (69.4) Stable disease >3 months 30 (51.7) 21 (58.3) *Patients receiving Z ≥4 mg/kg.