tbuckley/cabot-search huggingface dataset:
Combining radiotherapy and immunotherapy in the treatment of advanced cancer: A limited meta-analysis.
Authors: Christine Zhou, Jing Zhao, Jianyue Jin, David Munn, Ahmad Albasheer, Feng Ming Kong
Journal: Journal of Clinical Oncology (2014)

3110 Background: A majority of patients with advanced cancer expire from uncontrolled disseminated disease due to lack of effective systemic treatment. Radiation (RT) serves a limited role as palliative therapy. Recently, a unique synergy between RT and immunotherapeutics (IT) has been noted. This study assesses currently published clinical data combining RT and IT (cRIT) to exam the effect of such combination treatment on patient survival and toxicity. Methods: Eligible studies were found through PubMed. Keywords included radiation, radiotherapy, metastasis, advanced cancer, immunotherapy, interleukin, interferon, dendritic cells, and NK cells. Criteria included clinical studies combining any RT and IT in patients with diagnosed advanced disease published since Jan 1, 1999, excluding studies that also combined chemotherapy. Patient survival and toxicity data was captured and analyzed. The primary endpoints included treatment response rates and median survivals. Results: Eleven studies were eligible with a total of 525 patients. Of those patients, 397 received cRIT; 110 and 41 patients received RT or IT alone, respectively. RT methods included conventional radiation, intensely modulated radiation therapy, and stereotactic radiotherapy. IT agents included interleukin 2, interferon α/β, thalidomide, and dendritic cells. Pooled data from seven studies (309 patients) reported response rates of complete response as 21.4% (95% CI 0-49.4%), partial response as 19.5% (95% CI 0-39.9%), stable disease as 19.7% (95% CI 1.7-37.6%), and progressive disease as 30.0% (95% CI 10.7-49.4%). The disease-free survival in cRIT patients was 18.9 (90% CI 1.8-35.9) months and overall survival was 21.7 (95% CI 6.0-37.3) months. Most common toxicities included skin reactions (49.5%), esophagitis (81.2%), anemia (21.8%), anorexia (21.2%), and liver dysfunction (19.1%). Pooled data does not show any significant increase in toxicity level with combined therapy. Conclusions: Based on this limited pooled analysis, cRIT appeared to be effective and safe in certain patients with advanced cancers. Randomized trials are needed to further assess the value of this new treatment modality and the best combination of RT and IT.
Clarifying immunoglobulin gene usage in immunoglobulin light chain amyloidosis by mass spectrometry of amyloid in clinical tissue specimens.
Authors: Taxiarchis Kourelis, Surendra Dasari, Jason D Theis, Marina Ramirez-Alvarado, Paul J Kurtin, Morie A. Gertz, Stephen R Zeldensrust, Ahmet Dogan, Angela Dispenzieri
Journal: Journal of Clinical Oncology (2014)

8605 Background: The goal of this study was to investigate the relative use of light chain variable region genes (LCVG) among patients with systemic (SAL) and localized (LAL) amyloidosis and assess for associations between LCVG and organ tropism. Methods: We evaluated charts from 361 AL patients seen at Mayo who had tissue samples typed using laser dissection mass spectrometry (MS). Results: We identified 240 patients with SAL and 105 with LAL. When compared to LAL, lambda light chain (LC) overall and LV6 in particular were more common in SAL. KV3 and LV2 were overrepresented in LAL. KV1 accounted for 71% of kappa genes in SAL and for 37% in LAL. LV4, KV2 and KV4 were distinctly uncommon, each identified in ≤ 5% of patients in both SAL and LAL. Among patients SAL who had clinical cardiac involvement, only KV3 was underrepresented as compared to patients without clinical cardiac involvement (1% vs 9%, p=0.008). In patients with clinical renal involvement, LV6 was more common (26% vs 9%, p=0.002) and KV3 less common (1% vs 7%, p=0.03).LV6 was also more commonly identified in SAL patients with clinically isolated renal involvement (35% vs.13%, p=0.02). Conclusions: LCVG usage in SAL is different from that of LAL. It is also restricted, with KV1, LV1, LV3 and LV6 accounting for 70% of cases. All patients (N=345) Systemic patients (n-240) Localized (N=105) Systemic (N=240) p Cardiac (n=152) p Renal (n=108) p Kappa 49 (47%) 78 (33%) 0.02 48 (32%) NS 25 (23%) 0.01 Kappa NOS 4 (4%) 1 (0.4%) 0.03 KV1 18 (17%) 55 (23%) NS 38 (25%) NS 19 (18%) NS KV2 1 (1%) 2 (1%) NS 0 NS 1 (1%) NS KV3 21 (20%) 9 (4%) <0.001 2 (1%) 0.008 1 (1%) 0.03 KV4 5 (5%) 11 (5%) NS 8 (5%) NS 3 (3%) NS Lambda 56 (53%) 162 (67%) 0.02 104 (68%) NS 83 (77%) 0.01 Lambda NOS 8 (8%) 31 (13%) 0.09 - - - LV1 13 (12%) 30 (13%) NS 18 (12%) NS 13 (12%) NS LV2 15 (14%) 17 (7%) 0.04 9 (6%) NS 7 (7%) NS LV3 13 (12%) 44 (18%) NS 31 (20%) NS 20 (19%) NS LV4 1 (1%) 1 (0.4%) NS 1 (0.6%) NS 0 NS LV6 6 (6%) 39 (16%) 0.008 23 (15%) NS 28 (26%) 0.002
Pemetrexed monotherapy as salvage treatment in metastatic colorectal cancer patients who failed standard chemotherapy: A phase II single-arm prospective trial.
Authors: Sung Won Lim, Jangho Cho, Jeeyun Lee, Se Hoon Park, Joon Oh Park, Young Suk Park, Ho Yeong Lim, Won Ki Kang, Seung Tae Kim
Journal: Journal of Clinical Oncology (2018)

840 Background: We designed a single-arm, open label phase II study to determine the efficacy and toxicity of pemetrexed monotherapy with vitamin supplement in refractory colorectal (CRC) patients who failed standard treatments, including 5-FU, oxaliplatin, and irinotecan with or without biologic agents. Methods: Patients were treated with pemetrexed 500 mg/m2 on day 1, every 3 weeks, with folic acid and vitamin B12 supplementation. Patients began vitamin supplementation with B12 intramuscular injection (1000 mcg) every 9 weeks starting 1 week before the first pemetrexed dose, and patients received daily oral folic acid (1 mg) starting at least 5 days before the first pemetrexed dose. Treatment was continued until disease progression or intolerable toxicity was observed. Results: Between June 2016 and October 2016, 24 patients were enrolled in this study. One patient withdrew content, leaving a total of 23 patients to be evaluated. The median age of the patients was 54.0 years (range, 23.0 to 67.0), and the median ECOG performance status was 1 (1-2). The median number of previous systemic chemotherapies was 3 (range, 2 to 5). No complete response and no partial response were observed among the patients. Stable disease was observed in 10 patients (43.4%), and 7 patients had a response duration of 2 months or more. The median PFS was 1.6 months (95% CI, 1.1 to 2.0) and the median OS was 9.8 months (95% CI, 5.9 to 13.6). Only one patient experienced treatment-related toxicity of grade 3 or more. Neither hematologic toxicities nor dose reduction due to treatment-related toxicities were observed. There was no treatment-related death. Conclusions: Pemetrexed monotherapy showed moderate disease control and an acceptable toxicity profile as salvage therapy for refractory CRC. Clinical trial information: NCT02588781.
Current quality gaps in rectal cancer pathology reports.
Authors: Zaid M. Abdelsattar, Sandra L. Wong, Nancy J. Birkmeyer, Sarah T. Hawley, Reuben Cuison, Robert Wallace Krell, Darrell A. Campbell, Samantha Hendren
Journal: Journal of Clinical Oncology (2014)

6581 Background: High-quality pathology reporting is important for optimal management of rectal cancer (RC). To this end, several quality measures have been clinically validated or endorsed by the National Quality Forum (NQF). In this multi-institutional study, we assess the adherence to these measures and explore pathologists' perspectives. Methods: Seven quality measures (4 NQF endorsed) were assessed for adherence at 10 community and academic hospitals from 2007 to 2012 via trained data abstractor chart review. Measures included documentation of T stage, N stage and histologic grade; ≥12 lymph nodes; measurement of distal and radial margin; and grading of total mesorectal excision (TME) quality. Open-ended phone surveys were conducted with pathologists from six hospitals to identify differences in practice and barriers to improved practice. Results: A total of 333 patients underwent radical RC surgery. Adherence to all measures varied by hospital (Table). For example, only 75% of cases (range by hospital 64-100%) had ≥12 lymph nodes examined and the median number was 15 (range by hospital 13-34). Surveys revealed that pathologists would not find it burdensome to increase requirements for nodes or margin measurements; however, there were greater barriers to TME grading. Although all pathologists aim to retrieve ≥12 nodes, their methods vary and 33% routinely use defatting solutions. TME quality reporting is uncommon. 83% of pathologists were familiar with this measure; however, half of those were not comfortable reporting it to the surgeon. When asked about facilitators of best practices, pathologists emphasized: 1) comprehensive checklists, 2) pathology assistants, and 3) better communication with surgeons. Conclusions: Hospitals vary on the quality of RC pathology reporting, indicating significant room for improvement. Based on pathologist surveys, quality improvement interventions might include peer mentoring of node retrieval methods and strategies for better communication with cancer surgeons. Adherence to pathology quality measures. Quality measure Overall adherence, % Range by hospital, % T stage 94 74 – 100 N stage 93 74 – 100 Grade 78 29 – 100 ≥12 nodes 75 64 – 100 Radial margin 57 11 – 95 Distal margin 89 62 – 100 TME quality 12 0 – 69
Prediction of HNSCC recurrence by using kinetic and volumetric FDG-PET parameters.
Authors: Ronan Abgral, Gerald Valette, Nathalie Keromnes, Philippe Robin, Yves Gobel, Pierre-Yves le Roux, Jean-Philippe Metges, Gilles Robinet, Remi Marianowski, Pierre-Yves Salaun
Journal: Journal of Clinical Oncology (2014)

6081 Background: Head and neck squamous cell carcinoma (HNSCC) are tumors with a high recurrence rate and a poor prognosis. Find pre-treatment indicators for predicting survival of patients is therefore a real challenge. Fluorodesoxyglucose positron emission tomography (FDG-PET) is a functional imaging technique used for initial staging of HNSCC. Its prognostic value has already been demonstrated using SUVmax but no threshold has been established to predict recurrence (4-10 within studies). New quantitative indexes such as volumetric (MTV=metabolic tumoral volume) or kinetic (RI=retention index) parameters have been recently suggested as prognostic factors of HNSCC. The aim of this study was to compare the prognostic interest of these parameters to predict HNSCC recurrence. Methods: Patients referred to our department to perform FDG-PET for HNSCC staging were included. Tumoral RI corresponding to the percentage variation of SUVmax was calculated by using a dual time point method. Tumoral MTV corresponding to the 3D contour around voxels that are equal or greater to 40% of SUVmax was measured by using a semi-automated workflow. ROC analysis was performed to determine best SUVmax, RI and MTV thresholds to predict recurrence. Univariate analysis was performed to test prognostic significance of these parameters. Kaplan–Meier method was used to estimate recurrence free survival (RFS) probabilities. Multivariate analysis using Cox proportional hazard model was performed. Results: Seventy (61M/9F) consecutive patients (62 ± 9yo) were included. ROC analysis revealed SUVmax=7.3 (AUC=0.67), RI=19.5% (AUC=0.76), and MTV=6,7ml (AUC=0.73) as best thresholds to predict recurrence. In univariate, besides age and T stage, SUVmax (p=0.001), RI (p<0.0001) and MTV (p<0.0001) were significantly correlated with RFS. In multivariate, RI (p=0.005) and MTV (p=0.022) persisted as independent predictive parameters of recurrence but not SUVmax (p=0.703). There was no significant correlation between RI and MTV value using a Pearson test (p=0.718). Conclusions: Kinetic and volumetric FDG-PET parameters are independent prognostic factors likely to provide complementary information for predicting recurrence in patients with HNSCC.
Impact of adrenergic and prostanoid inhibitors on outcomes in patients with advanced hepatocellular carcinoma (HCC): A prospective clinical trial.
Authors: Gouri Shankar Bhattacharyya, Shailesh Arjun Bondarde, Ghanashyam Biswas, K Govind Babu, Debasis Dutta, Newell F. Bascomb, Hemant Malhotra
Journal: Journal of Clinical Oncology (2014)

e15148 Background: Increasing evidence from preclinical studies and retrospective studies suggests that adrenergic and prostaglandin signaling are important in control of tumorigenesis. Data presented to date in humans have been primarily from retrospective studies. The data presented here will include the first data on the use of Sorafenib (S) with (Arm A) or without propranolol (P) and etodolac (E) (Arm B) in the treatment of patients with advanced HCC. Methods: Patients with inoperable advanced and/or metastatic HCC (Child-Pugh A or B7), ECOG status 0–1 were eligible for this randomized investigator initiated trial. Patients received P + E daily; P was administered at breakfast and at 3 PM to reach a heart rate of between 60 and 70 BPM (mean of 40 mg per day); E was administered 300 mg at breakfast and 300 mg in the evening. After one week S was administered at 400 mg per day, which was increased to 800 mg per day after an additional week. The primary endpoint was overall survival. Results: From 2004 to 2011, 36 patients were enrolled: median age, 54.6 years; 74% male; BMI, 23.0; C-reactive protein (CRP), 69.3; cirrhosis (8.8%), fibrosis (50%), hepatitis C positive (85%). Characteristics were well balanced in both arms. Median duration and dose intensity of S with P+E was higher than in S arm alone. Main severe (grade 3–4) toxicity (arm A/B) consist of hand foot skin reaction (HFSR) (grade 3–4:45.5%/0%). For evaluable patients (N = 34), median overall survival was 9 vs 16 months for Arms A vs B, respectively. Magnitude of change in select biomarkers (albumin, ferritin, AFP, bilirubin, CRP, VEGF, IL-6, heart rate) was substantially different between arm A and arm B, but none of the biomarkers were found to be predictive of response in this small population. Conclusions: S with P plus E was feasible and well tolerated in HCC. This trial showed a significant improvement in its primary endpoint of overall survival with substantial reduction in the primary toxicity of (HFSR). A similar study is currently underway in the United States, clinical trial information NCT 01265576. Further study of this treatment is warranted.
Results from Ongoing Phase 1/2 Clinical Trial of Tagraxofusp (SL-401) in Patients with Relapsed/Refractory Chronic Myelomonocytic Leukemia (CMML)
Authors: Mrinal M. Patnaik, Haris Ali, Vikas Gupta, Gary J. Schiller, Sangmin Lee, Abdulraheem Yacoub, Moshe Talpaz, Megan Sardone, Halyna Wysowskyj, Shay Shemesh, Janice Chen, Arturo Olguin, Christopher Brooks, Vanessa Dunn, Animesh Pardanani, Ayalew Tefferi, Srdan Verstovsek, Joseph David Khoury, Naveen Pemmaraju
Journal: Blood (2018)
Association of adjuvant chemotherapy with improved survival after esophagectomy without induction therapy for node-positive adenocarinoma.
Authors: Paul J Speicher, Brian R Englum, Asvin M Ganapathi, Mark W. Onaitis, Thomas A. D'Amico, Mark F. Berry
Journal: Journal of Clinical Oncology (2014)

4077 Background: Adjuvant therapy is recommended when patients undergo esophagectomy without induction therapy for node-positive (pN+) adenocarcinoma, but some patients may not receive adjuvant treatment due to complications related to surgery (CRS). This study investigated adjuvant chemotherapy (AC) use in this clinical setting using the National Cancer Database (NCDB). Methods: In the NCDB, 2,442 patients from 2003-2011 who underwent R0 esophagectomy without induction therapy for pN+ adenocarcinoma of the middle or lower esophagus and survived at least 30 days were reviewed. Predictors of AC were identified with multivariable logistic regression. The impact of AC on survival was estimated using Kaplan-Meier and Cox proportional hazards methods. Results: AC was given to 874 of 2,442 (35.8%) patients; 618 (70.7%) AC patients received radiation. Older age (AOR 0.58/decade, p<.001), longer travel distance (AOR 0.78/100 miles, p=.03) and CRS (AOR 0.45, p<.001) predicted that AC was not used. Patients given AC had better 5-year survival than patients not given AC (24.2% vs 14.3%, p<.001), and AC use predicted improved survival in multivariate analysis (HR 0.67, p=0.008, Table). Receiving radiation in addition to AC did not improve survival (p=0.3). Although CRS was associated with worse survival, patients who had CRS but received AC had superior survival compared to patients who did not have CRS or get AC (p=.016). Conclusions: AC is associated with significantly improved survival but used in a minority of patients treated with esophagectomy without induction therapy for pN+ esophageal adenocarinoma. CRS lower the chance of getting AC and predict worse long-term survival, but even patients with CRS had improved survival when given AC. Predictors of long-term mortality. Predictor HR Upper 95% CI Lower 95% CI P Adjuvant chemotherapy 0.67 0.49 0.9 0.008 Age (per decade) 1.1 0.97 1.2 0.13 Female sex 0.9 0.5 1.5 0.7 Race (ref = White) Black 2.2 0.8 5.9 0.14 Other 8.1 1.1 60.1 0.04 Charlson score 1.2 0.9 1.4 0.2 Pathologic T stage 1.6 1.3 1.9 < 0.001 Facility volume 0.6 0.3 1.1 0.077 CRS 1.5 1.1 2.1 0.012
Optimizing donor selection for public cord blood banking in Korea.
Authors: Jung Lim Lee, Su Yeon Kim, Tai Gyu Kim
Journal: Journal of Clinical Oncology (2014)

7040 Background: It is well recognized that TNC and CD34 define a superior Cord blood unit (CBU). According to “the Law of Korean CB Banking and Research”, only 40% of collected CBUs meet the criteria. To improve a rate of banking, we analyzed the characteristics of CBUs and assessed predictive factors for numbers of TNC and CD34+ in collected CBUs. Methods: This study examined 5,065 UCB (2,943 at the Catholic Hematopoietic Stem Cell Bank and 2,122 at the Daegu Fatima Hospital Public Umbilical Cord Bank) collected at two hospitals from Oct 2003 to Jan 2014. The variables were collected from retrospective records at the time of donation. The associations between TNC, CD34+ and variables including maternal age (MA), gestational age (GA), fetal body weight (FBW), time from collection to processing (T) and collecting volume (CV) were analyzed by logistic regression. Results: In our study cohort (n=5,064), the median values of TNC, numbers of CD34, MA, GA, FBW, T and CV were 9.02×108/unit, 2.0×106/unit, 32.0 years, 277 days, 3,320g, 18 hours and 80.0ml respectively. In univariate analysis, variables that were associated with high TNC (TNC>9.02×108/unit) included MA (MA≤32years) [OR 1.32 (95% CI 1.17-1.48 p<0.001)], normal delivery [OR 2.30 (95% CI 1.97-2.66 p<0.001)], GA (GA>277 days) [OR 1.20 (95% CI 1.07-1.34 p=0.002)], female gender [OR 1.27 (95% CI 1.13-1.43 p<0.001)], FBW (FBW>3320) [OR 1.37 (95% CI 1.23-1.53 p<0.001)] and CV (CV>80ml) [OR 2.40 (95% CI 2.15-2.69 p<0.001)]. Variables that were associated with high CD34 (CD34>2.0×106/unit) included MA [OR 0.85 (95% CI 0.76-0.95 P=0.005)], normal delivery [OR 1.33 (95% CI 1.15-1.53 p<0.001), GA [OR 1.20 (95% CI 1.07-1.34 P=0.002)], FBW [OR 1.41 (95% CI 1.27-1.58 p<0.001)] and CV [OR 1.42 (95% CI 1.28-1.60 p<0.001)] In multivariate analysis of TNC, CV>80ml [OR 2.84] was the best predictor of followed by normal delivery [OR 2.33], FBW [OR 1.52], female gender [OR 1.36], MA [OR 1.25] and T [OR 1.25]. Conclusions: M/D characteristics were associated with normal delivery which is the best predictor for TNC and CD34+ followed by CV for TNC and BW for CD34+ in collected Korean CBUs. These associations could be used to prioritize donations, collections, optimizing and financial modeling in Korean CB banks.
Clinicopathologic characteristics of patients (pts) with large-cell neuroendocrine carcinoma of the lung (LCNCL).
Authors: Michael Vaslamatzis, Apostolos Laskarakis, Th Argyrakos, Nektarios Alevizopoulos, Ch Zoublios, Kalliopi Athanassiadi
Journal: Journal of Clinical Oncology (2014)

e19163 Background: LCNCL is a newly recognized clinicopathologic entity, characterized by the cell morphology and the immunohistochemical evidence of neuroendocrine markers. The optimal treatment for LCNCL is not yet established. The aim of our study was to describe the clinicopathologic findings, the outcome and treatment toxicity in LCNCL pts. Methods: Nineteen patients, smokers (>40 pack/y), with LCNCL, among 385 (5%) with small cell lung cancer (SCLC), were admitted & treated consecutively in our Unit between 1/1996–12/2013. Patients’ characteristics are shown in the Table. The presenting symptoms, at the diagnosis were cough±haemoptysis±fever, dyspnoea, SVC syndrome, bone pain±subcutaneous nodules and chest pain in 5 (26%), 4(21%), 3 (16%) 2 (10.5%) and 2 (10.5%) pts, while 3 (16%) absolutely asymptomatic, were diagnosed during routine check-up. Paraneoplastic tetraplegy, and myopathy had 1(5%) & 1(5%) pts. Six (31.5%) pts underwent curative surgery (4 lobectomy, 2 pneumonectomy), while the diagnosis in the other pts was established by biopsy of the enlargement cervical lymph node in 2 (10.5%), liver biopsy in 1 (5%) and during bronchoscopy in 16 (84.5%) pts. The 12 pts stage IV had, at presentation, metastases in: liver, bones, adrenals, CNS, lung and breast in 6 (50%), 6 (50%) 3 (16%), 2 (10.5%), 2 (10.5%) and 1(5%) cases, respectively. Results: One (5%) pt, pT2N2 IIIA underwent left upper lobectomy and then was only followed-up. He is still alive, 145+ mö. Eighteen (95%) received CDDP + VP-16 ± mediastinal ± cranial RT. Gr III + IV, febrile leukopenia, thrombocytopenia and anaemia had 4, 2 and 1 pts. In m f-u of 10 (1+ - 145+) mö, 17 pts died. The mPFS and mOS for stages ≤IIIA vs IIIb + IV was 8.5 vs 2 and 17.25 vs 6 mö. Conclusions: In pts with LCNCL, the prognosis was poor and the disease seems to be chemorefractory. Radical surgery may be the only curative procedure. No of pts 19 Median (m) age 64 (33-76) y M/F 14/5 ECOG 0 3 (16%) 1 10 (52.5%) 2 2 (10.5%) 3 4 (21%) 4 0 (0%) Histology Pure LCNCL 17 (89.5%) Mixed LCNCL-SCLC 2 (10.5%) cStage Ib 1 (5%) IIa 1 (5%) IIb 1 (5%) IIIA 3 (16%) IIIB 1 (5%) IV 12 (64%) Ki67 60% (40-90%) NSE(+) 19 (100%) TTF1(+) 18 (95%) Chromogranine± Synaptophysine(+) 18 (95%) CK7(+) 19 (100%) CD56(+) 19 (100%) Morphology Large cell
Safety and Early Oncologic Outcomes of Lung Resection in Patients with Isolated Pulmonary Recurrent Prostate Cancer: A Single-center Experience
Authors: Paola Ciriaco, Alberto Briganti, Annalisa Bernabei, Giorgio Gandaglia, Angelo Carretta, Cristina Viola, Francesco Montorsi, Giampiero Negri
Journal: European Urology (2019)
Atomic-Level Dissection of the Polyclonal Immune Response to the Human Platelet Alloantigen, HPA-1a (PlA1)
Authors: Huiying Zhi, Maria Therese Ahlen, Aye Myat Myat Thinn, Hartmut Weiler, Brian R. Curtis, Bjorn Skogen, Jieqing Zhu, Peter Newman
Journal: Blood (2018)