tbuckley/cabot-search huggingface dataset:
Total healthcare, treatment, and supportive care costs among metastatic pancreatic cancer (MPC) patients (pts) treated with either nab-paclitaxel/gemcitabine (<i>nab</i>-P+G) or FOLFIRINOX (FFX) in the first-line (1L) setting.
Authors: Brian Ung, Manish Patel, Corey Pelletier, Quanhong Ni
Journal: Journal of Clinical Oncology (2017)

20 Background: The economic burden of MPC is substantial while treatment options are limited. This study compared treatment, supportive care, and total health care costs in MPC pts who initiated nab-P+G or FFX in a large insured US population. Methods: A retrospective study was conducted using claims from the Clinformatics Data Mart Database. Adults who had ≥2 claims for PC, ≥1 claim with a secondary malignancy, completed &gt;1 cycle of nab-P+G or FFX as 1L between 1/1/2013 and 12/31/2015, and had continuous enrollment in health plans for ≥6 months prior to and 3 months following the start of 1L, were selected. Total health care costs and MPC-related treatment costs were measured per patient per month (PPPM) during 1L. Results: 216 MPC pts met selection criteria ( nab-P+G, n=139; FFX, n=77). Pts on nab-P+G were significantly older (mean age: 67.6 vs. 61.4 years; p&lt;0.001) vs. FFX. nab-P+G pts incurred similar total health care costs but less supportive care and treatment administration costs vs. FFX (table). The nab-P+G group had a significantly lower proportion of pts who received peg-filgrastim (13.7% vs. 50.6%; p&lt;0.001); with lower PPPM number of fills (0.11 vs. 0.71; p&lt;0.001), anti-emetics (92.8% vs. 100%; p=0.0154), and hydration procedures (63.3% vs. 98.7%; p=0.0001), but a higher proportion received oral opioids (66.2% vs. 54.5%, p=0.0066) during 1L. Conclusions: Total health care costs were similar. nab-P+G pts had higher chemotherapy drug costs while FFX pts had higher treatment administration and supportive care costs. [Table: see text]
The relative efficacy of neoadjuvant endocrine therapy vs chemotherapy in postmenopausal women with ER- positive breast cancer
Authors: V. F. Semiglazov, V. Semiglazov, V. Ivanov, A. Bozhok, E. Ziltsova, R. Paltuev, G. Dashian, A. Kletzel, E. Topuzov, L. Berstein
Journal: Journal of Clinical Oncology (2004)

519 Background: Neoadjuvant chemotherapy (NACT) or hormonal therapy (HT) is being used increasingly to downstage locally advanced and large operable breast cancer. Following this treatment, inoperable breast cancer often becomes fully resectable, and tumors requiring mastectomy may be successfully removed by breast-conserving surgery (BCS). Patient selection is important to optimize neoadjuvant therapy (NAT), especially in elderly postmenopausal women with co-morbid conditions. Methods: Between March 1998 and March 2003, 121 postmenopausal (PM) women with ER(+) and/or PgR(+) breast cancer (BC) T2N1–2, T3N0–1, T4N0M0 assigned NAT with either CT Dox 60 mg/m2 + Pac 200 mg/m2, every 3 weeks, 4 cycles, n=62 patients (pts), or HT with aromatase inhibitors, anastrazole 1 mg, n = 30 pts, 3 months). The primary endpoint was to compare overall objective response (OR) determined by clinical (palpation) and mammogr. Secondary endpoint was the number of pts who qualified for BCS + radiotherapy (50 Gy for 25 fractions). Results: Table 1. OR rate (clinical and mammogr.) was statistically similar ( p > 0.05 ) in the CT and anastrazole groups. Tendency to more BCS took place in the anastrozol arm that in the CT arm ( 37.9 % vs 20.6 % p=0.054). Local recurrence rate were similar for pts receiving CT or HT (3,2 % and 3,4%, at 34 months median follow up ). In CT arm the most frequent grade III/IV toxicity was alopecia ( 79.3 5 ), neutropenia ( 43.1 %), cardiotoxicity (6.8 %), diarrhea (1.7%). HT was well tolerated. The most commonly adverse events were hot flushes (23.3%), vaginal discharge (6.6%), musculosskeletal disorders (1.7%). Conclusions: NAHT with aromatase inhibitors (anastrazole) is a reasonable alternative to CT for PM women with ER and/or PgR - positive cancer in clinical situation where the low toxicity of the regimen is considered an advantage, for example, for women over 70. No significant financial relationships to disclose.
Relationship of variability in tumor measurement and response assessment.
Authors: Binsheng Zhao, Shing Mirn Lee, Hyun-Ju Lee, Jing Qi, Thorsten Persigehl, Yongqiang Tan, Lawrence H. Schwartz
Journal: Journal of Clinical Oncology (2012)

2541 Background: RECIST is widely used to evaluate anti-cancer therapy efficacy. This study explored variability in reporting tumor change and response to therapy due to both target lesion selection and measurement. Methods: 2256 measurements were performed in CT scans of chest, abdomen and pelvis from 30 patients retrospectively taken from a multicenter Phase II/III colorectal clinical trial. Using RECIST, three radiologists interpreted baseline, 6-wk and 12-wk scans in the following manner: (1) Radiologists independently selected and measured target lesions, (2) one radiologist’s target lesions were re-measured by the other two and (3) one radiologist re-measured the same scans in the above manner at an interval of greater than a month to prevent memory recall. Measurement variability in total tumor burden (TTB) on relative changes at 6-wk and 12-wk from baseline was analyzed for inter- and intra-reader target lesion selection, inter- and intra-reader measurement using Bland-Altman method, and agreements on RECIST categorical responses were assessed by kappa coefficient. Results: When the same target lesions were used, inter- and intra-reader variability in TTB on relative changes at 6-wk and 12-wk from baseline were similar; all had 95% limits of agreement within (-15%, 15%). Kappa coefficients for RECIST were 0.74 (6-wk) and 0.87 (12-wk) for inter-reader and 0.64 (6-wk) and 0.88 (12-wk) for intra-reader to report responses. When radiologists independently selected and measured target lesions, variability in relative changes was within (-17%, 16%) at 6-wk and (-24%, 23%) at 12-wk for inter-reader and (-16%, 16%) at 6-wk and (-14%, 18%) at 12-wk for intra-reader interpretations. Kappa coefficients were 0.66 (6-wk) and 0.75 (12-wk) for inter-reader and 0.63 (6-wk) and 0.80 (12-wk) for intra-reader to report responses. Conclusions: Differences exist in measuring tumor change. The magnitude of change in categorical RECIST response is quantifiable. The largest differences are when radiologists independently select and measure target lesions, the smallest when one radiologist repeats measurements on identical target lesions. The variability may impact the reporting of categorical responses and trial results, especially in a single arm study.
Higher incidence of Simian virus 40 in primary gastric diffuse large B cell lymphoma (DLBCL) than primary nodal disease in Chinese patients, but of no prognostic implication
Authors: R. Liang, S. Y. Ma
Journal: Journal of Clinical Oncology (2004)

6671 Background: Studies have reported the detection of simian polyomavirus SV40 DNA sequence in 10–40% of non-Hodgkin's lymphoma patients and there is compelling evidence that SV40 may contribute to the oncogenesis in human. However, its incidence in Chinese patients, prognostic implication and site predilection are largely unknown. Methods: We analysed the diagnostic histological specimens from 49 Chinese patients with diffuse large B cell lymphoma diagnosed from 1989 to 1996. PCR followed by Southern blot hybridization were performed and SV 40 specific DNA was confirmed by DNA sequencing. Results: Among the 49 patients (M:F=28:21; mean age=58 years, range 22–83), there were 7 cases (14%) positive for SV 40 by PCR and 6 of them were confirmed to be SV 40 specific DNA, giving an incidence of 12%. Primary sites were peripheral lymph node (n=30, 61%), gastric (n=18, 37%) and sternal soft tissue (n=1, 2%). Primary gastric lymphoma had a significantly higher SV40 positivity rate than the nodal disease (5/18, 28% versus 1/30, 3.3%; p=0.02) There was no difference between the SV40 positive and SV 40 negative patients in terms of mean age (51 versus 59), IPI score (2.5 versus 1.9), LDH level (565 versus 675), no. of chemotherapy regimens (6.17 versus 6.3) and first complete remission (CR) rate (67% versus 58%). With a median follow up of 3 years, 31 (63%) patients died (4/6 in SV40 positive versus 27/43 in negative, p=not significant). The overall median survival was 51 months with no difference between SV40 positive and negative cases (53 versus 39 months). Conclusions: SV40 was found at low incidence rate of 12% in Chinese DLBCL patients and it had no prognostic values. However, there was a significant association with gastric lymphoma. Further investigations should be done to study its possible etiological role. No significant financial relationships to disclose.
Recent Research in Psychosomatics
Authors: R.A. Pierloot, A.H. Crisp, E. Ringel, I. Cermak, P.E. Sifneos, S. Grochmal, M. Damasiewicz, A. Pachalski, R. Kertész, A.E. Meyer, Hilka Otte, Marie-E. Houben, Roland A Pierloot, J.P. Watson, R.C.B. Aitken, H. Freyberger, P.-B. Schneider, Ed. de Perrot, J.C. Nemiah, L. Ectors, Chase P. Kimball, J.J. Groen, A.H. Crisp, R.G. Priest, Trevor Silverstone, Ph. Pinkerton, H. Musaph, Myron A. Hofer, Hitoshi Ishikawa, M. Haber, D. Luminet, Chase P. Kimball, J. Válek, E. Kuhn, R. Karstens, K. Köhle, D. Ohlmeier, S. Weidlich, H. van Dijl, F.H. Olthuis, R. Berg-Larsen, P. Hahn, R. Leisner, W. Schüffel, Cornelia Schaumburg, K. Köhle, C. Simons, R. Penrose, P. Storey, T. von Uexküll, H. Weiner, M. Dongier, N. Koninckx, W. Knopp, S. Black, J.C. Nemiah, P.E. Sifneos, A.H. Crisp, E. Stonehill, G.W. Fenton, Fay Fransella, A.H. Crisp, J.J. Groen, A. Welner, D. Ben Ishay, Elisabeth Richter-Heinrich, B. Heine, P. Sainsbury, J. Hambling, J. Bastiaans, G.F.M. Russell, C.J. Beardwood, P.J.V. Beumont, M. Rotmann, D. Becker
Journal: Psychotherapy and Psychosomatics (1970)
Phase II study evaluating the effect of concomitant ramucirumab (IMC-1121B; RAM) on the pharmacokinetics (PK) of paclitaxel (PTX) and the PK of RAM as monotherapy in patients (pts) with advanced malignant solid tumors.
Authors: Laura Quan Man Chow, David C. Smith, Antoinette R. Tan, Crystal Shereen Denlinger, Ding Wang, Dale Randall Shepard, Archana Chaudhary, Yong Lin, Minori Koshiji
Journal: Journal of Clinical Oncology (2014)

e13554 Background: This study evaluated the effect of RAM on the PK of PTX (Part A) and the PK of RAM as monotherapy (Part B). Methods: Key eligibility criteria included pts aged ≥18 years with metastatic or locally advanced, malignant solid tumors that were resistant to standard therapy or for which no standard therapy was available, and an Eastern Cooperative Oncology Group performance status of 0-2. Pts received RAM 8 mg/kg and PTX 80 mg/m2. Parts A and B were conducted in different cohorts of patients. In Part A, cycle 1, PTX was given on day 1 of a 2-week cycle; in cycle 2, RAM was given on days 1 and 15, and PTX on days 1, 8, and 15 of a 4-week cycle. In Part B, RAM 8 mg/kg monotherapy was administered on day 1 of one 3-week cycle. Blood was drawn immediately before and at regular intervals after infusions for cycles 1 and 2 to determine serum concentrations of PTX and RAM. All patients who completed cycle 1, day 1 and cycle 2, day 1 in Part A, and cycle 1, day 1 in Part B, were included in the drug-drug interaction analysis. Results: PK parameters were assessed in 20 pts in Part A and in a different cohort of 16 pts in Part B. Coadministration of RAM had no effect on dose-normalized AUC(0-∞) and Cmaxof PTX, with ratios (Part A cycle 2 vs. cycle 1) of geometric LS means at 1.09 (90% CI: 0.93, 1.29) and 0.97 (90% CI; 0.83, 1.13), respectively. Similar RAM PK parameters were observed for Part A and Part B. The most frequent treatment-emergent adverse events (TEAEs) related to any study drug in Part A were fatigue (10 pts, 41.7%), anemia (7 pts, 29.2%; 1 patient grade ≥3), epistaxis (7 pts, 29.2%), alopecia (5 pts, 20.8%) and hypertension, nausea, and neutropenia (4 pts each, 16.7%; 1 pt grade ≥3 hypertension, 3 pts grade ≥3 neutropenia). In Part B, the most common TEAEs related to any study drug were epistaxis (4 pts, 25.0%) and headache, hyperglycemia, nausea, and stomatitis (2 pts each, 12.5%). Conclusions: Coadministration of RAM has no effect on the PK of PTX and coadministration of PTX had no effect on the PK of RAM. The incidence and severity of TEAEs were consistent with the known safety profiles of PTX and RAM. Clinical trial information: NCT01515306.
Survival in metastatic Ewing sarcoma (EWS) and rhabdomyosarcoma (RMS) following consolidation immunotherapy with autologous lymphocyte infusion, dendritic cell vaccines ± CYT107 (rhIL-7).
Authors: Crystal Mackall, Kristin Baird, Donna B Bernstein, Bradford J Wood, Seth M. Steinberg, Stephanie Beq, Therese Croughs, Marianna Sabatino, Dave Stroncek, Melinda S. Merchant
Journal: Journal of Clinical Oncology (2013)

10013 Background: Higher lymphocyte levels correlate with better survival in a variety of cancers, but it remains unclear whether there is a causal relationship between immune function and survival in cancer patients. A pilot study in high-risk pediatric sarcomas was undertaken to determine if a regimen designed to enhance immune reconstitution following standard cytotoxic therapy could improve survival. Methods: Forty-four patients (median 16 yrs, range 5-33) enrolled following a diagnosis of metastatic or late recurrent pediatric sarcoma, and underwent apheresis to collect mononuclear cells and tumor biopsy to generate tumor lysate, then received standard therapy at their home institution. After standard therapy, 29 patients received immunotherapy, comprising a single infusion of autologous lymphocytes depleted of CD4 + CD25 + regulatory T cells, plus dendritic cell vaccines pulsed with autologous tumor lysate and keyhole limpet hemocyanin (KLH, Q14d x 6). After the first 5 patients, CYT107 (rhIL-7, 20 mcg/kg SQ Q14d x 4) was added to the regimen. Intensive biologic analyses measured global and regulatory T cell immune reconstitution and vaccine responses. Results: This outpatient regimen was well tolerated with toxicities limited to rash, low-grade fever and mild constitutional symptoms. CYT107 dramatically enhanced global immune reconstitution and diminished regulatory T cell frequency. All patients developed immune responses to KLH and 31% developed immune responses to tumor lysate. Intent-to-treat analysis of all patients enrolled shows 56% 5-yr OS, with immunotherapy recipients having a 64% 5-yr OS (median f/u 30 mos, range 23-65). Intent-to-treat analysis of the subset of patients enrolled at the time of a new diagnosis of metastatic EWS or RMS shows 83% 5-yr OS and 54% 5-yr EFS (n=13, median f/u 35 mos, range 24-63), which is superior to previous outcomes reported for this population. Conclusions: A low intensity immunotherapy regimen focused on enhancing immune reconstitution following standard therapy may diminish recurrence in newly diagnosed metastatic EWS and RMS. Clinical trial information: NCT00923351.
The role of VEGFR-2 expression in outcomes and survival of patients with peritoneal carcinomatosis from appendiceal cancer.
Authors: Armando Sardi, William Andres Jimenez, Jennifer Francis, Ryan Macdonald, Kimberly Studeman, Carol Ann Nieroda, Juan Camilo Falla
Journal: Journal of Clinical Oncology (2013)

e15123 Background: Vascular endothelial growth factor receptor 2 (VEGFR-2) is considered a prognostic factor and treatment target for metastatic colorectal and ovarian cancer. Peritoneal Carcinomatosis (PC) from appendiceal cancer is a rare malignancy, treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), for which tumor histology, completeness of cytoreduction (CC), and lymph node (LN) status are predictors of survival. We hypothesize that high VEGFR-2 expression is a negative prognostic factor for survival in patients with PC from appendiceal cancer. Methods: A retrospective study of a prospective database was conducted in 127 patients with PC from appendiceal cancer who underwent CRS/HIPEC. Surgical specimens from a total of 59 patients were tested to identify “high” vs. “low” VEGFR-2 expression. Patients were divided into 2 groups: high VEGFR-2 expressers and low VEGFR-2 expressers. Patients’ outcomes and survival were analyzed. Results: There were 26 males and 33 females. Mean age was 51 years. Mean follow up of high and low expressers was 25.1 and 26.6, respectively (p = 0.806). At follow up, 33 (70%) of high expressers were alive and 14 (30%) deceased, while 11 (92%) of low expressers were alive and 1 (8%) deceased. Overall recurrence, use of bevacizumab, CC score, PCI, and LN status showed no differences between high and low expressers and did not correlate with survival or outcome. OS for high expressers was 90.5%, 59.8, and 47.1% at 1-, 3-, 5-years (p = 0.133) respectively, while OS for low expressers was 91.7% at 1-, 3-, and 5-years. Conclusions: There is a trend toward better outcomes and survival in patients with PC from appendiceal cancer who have low expression of VEGFR-2 compared to high expression. However, follow up is short and a larger number of patients is needed to confirm this trend and possibly correlate a high expression of VEGFR-2 to poorer outcomes and decreased survival in PC of appendiceal origin.
The role of AURKA in liposarcoma.
Authors: Chueh-Chuan Yen, Wei-Ming Chen, Paul Chih-Hsueh Chen, Hung-Ta Hondar Wu, Cheng-Ying Shiau, Tain-Hsiung Chen, Chien-Lin Liu, Ta-Chung Chao, Cheng-Hwai Tzeng, Wayne Yen-Hwa Chang, Hong-Jen Chiou, Jonathan A. Fletcher
Journal: Journal of Clinical Oncology (2015)

e21512 Background: Liposarcoma (LPS) is one of the most frequently found soft tissue sarcoma (STS). Among them, well-differentiated (WD) and dedifferentiated (DD) LPS are two the most common subtypes. WD and DD LPS shared similar genomic changes with 12q13-15 amplification. MDM2 and CDK4 are two candidate genes with this region. WD LPS can remain stable for a long period of time. However, DD LPS usually run a rapidly deteriorated clinical course. Chemotherapy is not so effective in LPS, and currently there is no available target agents against this deadly disease. Methods: In this study, we re-analyzed published microarray datasets of WD and DD LPS in order to identify potential biomarkers or targets in DD LPS. Also we explored the potential of newly found genes as treatment target in LPS cell lines. Results: By comparing the top 50 genes that over-expressed in DD LPS of two sets of data, 12 overlapping genes were identified, including NUSAP1, MELK, AURKA, BAG2, CKS2, KIF11, TOP2A, RACGAP1, ASPM, RRM2, RAI14 and UBE2S. AURKA (aurora kinase A) was selected for further studies. We found that AURKA is a potential biomarker in predicting poor prognosis in LPS. MLN8237, a well-known AURKA inhibitor, was found to exert cytotoxic effect on LPS cells by inducing apoptosis and cell cycle G2/M arrest. MLN8237 also work synergistically with paclitaxel against LPS cell lines. MLN8237 also induced cellular senescence in LPS cell lines. Conclusions: We identified AURKA as a poor prognostic marker for LPS, and could serve as a treatment target in LPS.
Patients (pts) with stage IV, non-metastatic advanced head and neck squamous cell carcinoma (HNSCC) submitted to concurrent chemoradiotherapy (CCR) present with manageable toxicity
Authors: G. Castro, I. M. L. Snitcovsky, E. M. M. S. Gebrim, M. D. E. Diz, W. Nadalin, M. H. H. Federico
Journal: Journal of Clinical Oncology (2004)

8228 Background: Although meta-analysis and phase III trials have shown CCR improves survival in unresectable HNSCC, critical issues are aggressive toxicity management and pt selection. Methods: In this phase IV trial, previously untreated pts with locoregionally advanced, unresectable, HNSCC received 70 Gy, 200 cGy/d concurrent with cisplatin 100 mg/m2 on days 1, 22 and 43. Eligibility criteria included a histological proof of SCC, from oral cavity, oropharynx, hypopharynx, larynx or paranasal sinus; stage III/IV, M0 (AJCC, 2002); age 18–70 yrs; ECOG-PS 0–2; adequate organ function; measurable disease; assigned informed consent. Endpoints were survival, response rate (RR), toxicity and clinical benefit. Toxicity was graded according to the NCI-CTC v. 2.0 and tumor response by RECIST criteria. Pain (rate 0–10) and nutritional status were evaluated before and after treatment. Results: To date, 18 pts entered the trial, median age 54.5 yrs (37–68); 15 male; 16 PS1 and 1 PS2; 15 pts were able to eat orally; median body-mass index 19.7 kg/m2 (13.8–27.3); primary site: oropharynx (10 pts), oral cavity (6), larynx (2); TNM: T3N1 (1 pt), T3N3 (1), T4N1 (5), T4N2 (5), T4N3 (6). Mean albumin level: 3.9±0.5 g/L (2.7–5.1). Mean hemoglobin level: 12.2±1.5 g/dL (9.6–13.9). 11 pts completed radiation therapy (median time 64 d); median number of chemotherapy cycles: 2. Tumor response in 8 evaluable pts was: 1 CR, 3 PR, 1 SD and 3 PD (RR 50%). 16 pts presented grade 3/4 toxicity: nausea/vomiting (3 pts), dysphagia (8), mucositis (6), dermatitis (5), anemia (4) and leucopenia (5). 9 pts required feeding tubes and red cell transfusion was done in 8 pts in order to maintain Hb level above 10 g/dL. Mean weight loss was 3.8±4.1 kg (95%CI 1.0–6.6, p=0.012; paired t-test). Pain score decreased by 3±3 after treatment (95%CI 1–5, p=0.007; paired t-test). 3 pts died, 2 from disease progression. Conclusions: With aggressive nutritional and transfusional support, toxicity was manageable with an overall 50% RR to CCR in this trial. CCR is a feasible treatment strategy in this group of pts of locoregionally advanced HNSCC. No significant financial relationships to disclose.
Triple probe FISH approach for detecting EML4-ALK gene rearrangement in Chinese patients with NSCLC.
Authors: Weimin Mao, Mark Han, Zhiqiang Ling, Wenyong Sun, Gu Zhang, Hongshan Dong, Yingzi Zhang
Journal: Journal of Clinical Oncology (2012)

e21080 Background: The echinoderm microtubule-associated protein like 4-anaplastic lymphoma kinase (EML4-ALK) fusion represents a novel target for the therapy of a subset of non-small cell lung cancer (NSCLC). ALK rearrangement has been found in approximately 1.6–11.6% of NSCLC in unselected patient populations, but the frequency also varied when different diagnostic approach was used. We, for the first time, investigated frequency of EML4-ALK rearrangement in unselected Chinese patients with NSCLC using recent developed fluorescence in situ hybridization (FISH) triple color break-apart probe. Methods: One hundred-thirty one FFPE specimens from NSCLC patients were collected for the investigation. Fusion between 3’ portion of ALK gene and the 5’ portion of EML4 gene was detected using FISH tri-check probe (ZytoVision, Germany). Positive cells were defined as having any signal A ( distance more than two-time the ALK signal size) or signal B ( distance between one- and two-time the ALK signal size plus EML4 translocation signal) or any isolated ALK 3’ signal. Total 100 nuclei for each specimen were counted. Specimen was as classified as EML4-ALK rearrangement when the proportion of positive cells was over 15%. ALK/EML4 signals over 6 in over 10% nuclei were classified as gene amplification. Results: Of 131 specimens, frequency of ALK rearrangement was 10.7% (14/131) when positive cells were counted by signal A and isolated ALK 3’ signal (dual color). Frequency of EML4-ALK rearrangement was 13.0% (17/131) when positive cells were counted by signal A, B and isolated ALK 3’ signal (triple color), in which 21% (17/14) more cases were classified as EML4-ALK rearrangement comparing dual color enumeration. ALK and EML4 amplification were observed in 2.3% (3/131) specimens, respectively, in which two were co-amplified and none of them had EML4-ALK rearrangement. Conclusions: Present result showed that frequency of EML4-ALK rearrangement in unselected Chinese patients with NSCLC was 13.0% determined by FISH tri-check probe. This study suggested that counting both ALK inversion and EML4 translocation may contribute to defining EML4-ALK positive cells.