tbuckley/cabot-search huggingface dataset:
Detection of novel genetic aberrations in salivary duct carcinoma (SDC) by SNaPshot analysis.
Authors: L. J. Wirth, V. Nardi, D. Juric, A. K. Cosper, K. Bergethon, V. Scialabba, D. R. Borger, A. J. Iafrate, L. W. Ellisen, D. Deschler, D. Zhao, P. M. Sadow, D. Dias-Santagata
Journal: Journal of Clinical Oncology (2011)

5579 Background: Salivary gland cancers (SGCs) are rare and heterogeneous malignancies, with SDC being one of the more aggressive subtypes. Establishing effective therapy for SGCs is challenging given their rarity and heterogeneity. Cytotoxic chemotherapy has limited efficacy, and of the targeted therapies that have been studied, few objective responses have been seen. It is clear that disease management with targeted agents is most effective when directed by tumor genotype. To address this need, we utilized a clinical test, SNaPshot, designed to detect tumor-specific mutations to help direct treatment of SDC with targeted therapies. Methods: 24 SDC specimens were genotyped. These included 7 patients seen at the Massachusetts General Hospital Cancer Center who were prospectively tested. The SNaPshot assay uses DNA extracted from FFPE tissue and was designed to detect sequence variants in a panel of 14 clinically-relevant cancer genes. FISH was used to detect HER2 gene amplification. Retrospective review of clinical charts and of tumor pathological features was performed. Results: Mutually exclusive genetic aberrations were detected in 13 of 24 (54%) tumors, including 2 mutations in BRAF(8%), 4 mutations in PIK3CA (16%), and 7 cases of HER2 amplification (29%). Prospective clinical testing of 7 SDC identified mutations in 4 tumors, and influenced therapeutic decisions for 3 patients: 1 patient with a BRAF mutation enrolled on a phase I study of GSK1120212 + GSK118436, and experienced a near complete response lasting > 6 months; 1 with a PIK3CA mutation was enrolled on a phase I study of a PI3 kinase inhibitor; and 1 with HER2 amplification received trastuzumab with adjuvant chemoradiotherapy. Given the cohort size, statistical analysis was limited, with no significant correlations being found between genotype and pathologic features or survival. Conclusions: SNaPshot genetic profiling identified novel genetic changes in SDCs, expanded the therapeutic options for patients with this rare tumor, and is changing SDC management at our institution. These findings highlight the importance of using broad genetic profiling to expedite the identification of effective targeted therapies for patients with rare malignancies.
Effect of red blood cell transfusions on patient-reported outcomes in an ambulatory oncology population.
Authors: Lillian Jo-ann Chen, Kimberly D Moeller, Lawrence David Wagman
Journal: Journal of Clinical Oncology (2016)

78 Background: The standard transfusion (Tf) trigger in the hospitalized patient is hemoglobin (Hgb) level driven. Triggers in the ambulatory oncology population are often symptom based. The symptoms of exercise intolerance (EI), fatigue (F), and shortness of breath (SOB) were identified from a hospital quality review. The purpose of this study was to evaluate patient reported symptom (SX) changes following red blood cell (RBC) Tf. Methods: Standardized Tf orders required symptom indication(s) which include EI, F, SOB and Other. After Tf, patients were asked to complete a telephone survey to evaluate symptom changes. Responses were recorded: same, better, or worse. Data collected: # of SX/patient, initial Hgb, days between Tf and survey, cancer diagnosis, # of units Tf, age and gender. Pre and post-Tf changes were calculated. p-values were obtained with binomial distribution, testing that the observed proportion of SX improvement was different from 50%. Results: From 12/2015 to 05/2016, 62 patients had 115 Tf episodes (TfE). M:F 30:32. Avg age: 72, (42-101). Avg Hgb 7.7 (3.4-9.9) Cancer diagnoses: MDS, breast, lung, colon, renal, prostate, gallbladder, rectal, gynecologic, myeloma, lymphoma, leukemia. 106/115 (92%) received 2 units of RBC per TfE. 35/115 (30%) were interviewed on post-TfE day 7 (4-14d). Fatigue (103 of 115, 90%) was the most common SX, Of the 115 TfE : 42/115 (37%) had 1 SX, 30/115 (26%) had 2 SX, 43/115 (37%) had 3 SX. Of the total TfE(155), 82 (71%) resulted in at least 1 SX improvement and in 33 (29%) there was no SX improvement, (p &lt; 0.001). Conclusions: Fatigue, shortness of breath, and total reported symptom changes improved with Tf (statistically significant). The greatest improvement was seen in F followed by SOB. This unique analysis focuses on the ambulatory oncology patient. Reported symptoms can serve as a quality of life endpoint model to develop guidelines for RBC Tf not limited to Hgb levels. [Table: see text]
Managing specialty medication services through a network of specialty pharmacies: A case of oral oncology medications.
Authors: S. Aslam, S. Tschida, L. S. Lal, T. T. Khan, W. H. Shrank, G. R. Bhattarai, J. C. Montague- Clouse, L. N. Newcomer
Journal: Journal of Clinical Oncology (2011)

6132 Background: Specialty pharmacy programs are increasingly used to improve the quality of outpatient therapy with oral medications for cancer. We evaluated whether use of specialty pharmacy services is associated with improved medication use and reduced overall healthcare costs, as compared to retail pharmacy services, for specific oral oncology medications. Methods: The study is a retrospective claims analysis after the implementation of a specialty pharmacy program. A matched sample of patients assigned to use specialty pharmacies and those who used retail pharmacies for specific oral cancer therapies were compared. Primary outcomes were financial, including overall healthcare costs, outpatient costs, medical costs, and pharmacy costs. Outcomes one year pre- and post-implementation in specialty pharmacy users and retail pharmacy controls were compared with t-tests for continuous variables, chi-square for nominal variables, and logistic regression for matching. Propensity scores were used to adjust for unmeasured confounding in the groups. Results: The final analysis included 464 patients per cohort. The mean total costs per patient was 13% lower in the specialty pharmacy group ($84,105 v $97,196; difference = $-13,092; P = 0.02) in the follow-up period. The mean outpatient hospital costs ($16,777 v $28,629, difference = $-11,852; P < 0.01) were lower in the specialty group by 41%, with an associated significant difference in outpatient hospital visits (15.75 v 19.66, P < 0.01). Patients in the specialty pharmacy group were more adherent to therapy, MPR 0.73 v 0.66, (P < 0.01). A nonsignificant trend of fewer patients started intravenous chemotherapy in the specialty group (7.76% v 12.28%, P = 0.27). Conclusions: Specialty pharmacies appear to improve oral oncology medication adherence and decrease overall healthcare costs, mainly by impacting outpatient hospital utilization.
PSA levels after dexamethasone withdrawal (DW) in castration resistant prostate cancer (CRPC).
Authors: Zafeiris Zafeiriou, Diletta Bianchini, Pasquale Rescigno, Michael Kolinsky, Joaquin Mateo, David Lorente, Raquel Perez Lopez, Anurhada Jayaram, Niven Mehra, Semini Sumanasuriya, Federica Recine, Spyridon Sideris, Adam Sharp, Sophia Wong, Nina Tunariu, Gerhardt Attard, Johann S. De Bono
Journal: Journal of Clinical Oncology (2016)

278 Background: PSA decline (PSAD) in CRPC after withdrawal of antiandrogens and steroid related drugs is well established. DW responses have been anecdotal and not well characterized. In this study we investigated the frequency and magnitude of PSA changes after DW. Methods: We retrospectively identified patients treated in the Royal Marsden for CRPC with D monotherapy. Patients were considered evaluable if they had between DW and their next treatment or radiotherapy an interval of at least 7 days, no other intervention and at least one PSA reading. Patients who received radiotherapy during treatment with D or received D for palliation of symptoms were excluded. The number of patients showing PSAD was recorded together with its percentage change from baseline. Chi-square test was used to compare response rates between different groups and 95% confidence intervals (CI) for the description of frequencies. PSA progression (PSAP) was defined according to Prostate Cancer Working Group 2 criteria. Results: 200 patients were identified who had received D of which 50 were evaluable. During D treatment PSA responses were not available for 5 patients, while 16 (35%, 95%CI [20%-50%]) had a ≥ 50% PSAD which was confirmed a month later with a second reading. For the responders, the median duration of PSA response from initiation of treatment to PSAP was 293 days (range: 219 to 1063). After DW, PSAD was observed in 12 patients (24%, 95% CI [12%,36%]). PSAD ≥ 25%, ≥ 30% and ≥ 50% was observed in 6, 3 and 2 patients respectively (12%, 6% and 4%) and in only one could the ≥ 30% PSAD be confirmed with a second reading a month later. In 5 cases of ≥ 25% PSAD, next treatment was initiated despite a dropping PSA, after 8 to 43 days. In one case only was PSAP reached during DW with a response duration of 53 days from DW to PSAP. The frequency of ≥ 25% PSAW responses was not significantly different between patients with and without prior response to dexamethasone: 6% and 17% respectively, Chi-square test p = 0.29. One patient reported improvement of his urinary symptoms after DW. Conclusions: DW responses are observed in a minority of patients. This phenomenon merits further prospective characterization and needs to be considered in the design of clinical trials.
Whole brain radiotherapy with concurrent erlotinib for brain metastases from non-small cell lung cancer: A phase I study
Authors: J. S. Lind, F. J. Lagerwaard, E. F. Smit, S. Senan
Journal: Journal of Clinical Oncology (2008)

19122 Background: Whole brain radiotherapy (WBRT), the standard treatment for multiple brain metastases from NSCLC, results in a median survival of 4 months with approximately 50% of patients dying from intracranial progression. We performed a two-phase dose-escalation phase I trial (NCT00536861), evaluating the safety of WBRT with concurrent and maintenance erlotinib. Methods: Pts with untreated brain metastases from pathologically confirmed NSCLC were eligible. Erlotinib (cohort 1: 100mg/day; cohort 2: 150mg/day) was started 1 week prior to, and continued during, WBRT (30 Gy/10 fractions). Maintenance erlotinib (150mg/day) was continued until unacceptable toxicity or disease progression. Serial neuro-imaging was performed at 3-monthly intervals. The primary study end-point was toxicity. Secondary end-points were survival and time to disease progression. Results: 13 pts were enrolled between May 2006-Dec 2007. Two pts withdrew prior to WBRT due to rapid clinical progression and 11 pts (M:F 6:5, median age 65 years) completed WBRT. Median duration of erlotinib treatment was 78 days (range 38–523). No treatment-related toxicity ≥ grade 3 was observed in cohort 1 (4 pts). In cohort 2 (7 pts) grade ≥ 3 toxicity consisted of grade 3 acneiform rash (n=1); grade 3 fatigue (n=1); fatal interstitial lung disease (n=1). No treatment-related neurotoxicity was observed. Median overall survival was 130 days (range 42–557), with 3 pts alive at the time of analysis. Five pts developed an acneiform rash, including all 3 pts surviving > 150 days. Median time till disease progression was 96 days (range 38–523), which was located exclusively extracranially (n=6). No clinical intracranial progression was observed. In the 6 pts with follow-up neuro-imaging, the intracranial response was PR in 4 and SD in 2. Four pts without disease progression had died at the time of analysis: erlotinib- induced interstitial lung disease (n=1); COPD exacerbation (n=1); pulmonary embolism (n=1); congestive cardiac failure (n=1). Conclusions: WBRT (30 Gy/10 fractions) with concurrent erlotinib (150mg/day) is well tolerated in patients with brain metastases from NSCLC. The absence of clinical intracranial progression warrants further study of concurrent erlotinib and WBRT. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Roche, the Netherlands
Phase II study of cetuximab in combination with modified FOLFIRI in patients with advanced gastric cancer who failed first-line chemotherapy (EFFI study).
Authors: J. Li, X. Liu, B. Y. Wang, W. J. Guo, J. L. Yin, X. D. Zhu, J. Zhang, T. Liu
Journal: Journal of Clinical Oncology (2010)

4107 Background: This multicenter, nonrandomized phase II study was launched to evaluate the efficacy and safety of cetuximab in combination with modified FOLFIRI as second-line treatment for advanced gastric cancer patients. Methods: Inclusion criteria were: 18-70 years, ECOG PS ≤ 1, histologically confirmed adenocarcinoma of stomach and failure to first-line therapy. C225 was given at an initial dose of 400 mg/m2, followed by weekly infusions of 250 mg/m2. On day 2 of each 14-day period, patients received CPT-11 at a dose of 180 mg/m2; CF at a dose of 200 mg/m2; and 5-Fu as a bolus of 400 mg/m2 and then 2,400 mg/m2 by continuous infusion for 46 hours. Treatment was continued until disease progression, unacceptable toxic effects, or withdrawal of consent. The study was carried out according to the Gehan's two- stage phase II trial design, the planned sample size was 55. The primary endpoint was TTP. Secondary endpoints included RR, OS and AEs. Results: Sixty-one patients were enrolled: 34 males (56%), 27 females (44%); median age was 52 years (range 26-69). 7 patients discontinued without tumor assessment within first cycle of treatment: 1 patient for obstructive jaundice, 3 patients for unacceptable grade 4 febrile neutropenia, 3 patients for intestinal obstruction, and 5 patients are too early to evaluate. 56 patients were evaluable for safety and 49 patients were evaluable for efficacy evaluation. The median TTP was 4.9 months (95% CI: 3.9-5.9 months). Objective responses (RECIST) were: 1 (2.0%) CR, 16 (32.7%) PR, 17 (34.7%) CR + PR, 25 (51.0%) SD, 7 (14.3%) PD. The median OS was 8.1 months (95% CI: 7.2-9.0 months). Grade 3-4 toxicity (CTC v3.0) was 62.5% neutropenia (12.5% febrile neutropenia), 26.8% anemia, 5.4% thrombocytopenia, 8.9% asthenia, 5.4% vomiting, 3.6% diarrhea, 3.6 % fatigue, 1.8% elevated transaminase and 1.8% allergic reaction. Skin reactions ≥ 2 was observed in 42.9%. Conclusions: The combination of cetuximab and FOLFIRI was well-tolerated and appears to be active (85.7% of disease control rate) as second-line treatment for advanced gastric cancer patients. Further analysis of this study will allow more detailed assessment of this combination treatment. No significant financial relationships to disclose.
Phase I trial of sorafenib with concurrent radiotherapy (RT) in patients with invasive bladder cancer treated with bladder-sparing intent: A Spanish Oncology Genitourinary Group study.
Authors: Juan Martin Liberal, José Pablo Maroto, Begoña Mellado, Ferran Ferrer, Gemma Sancho, Angels Rovirosa, Francesc Vigues, Joan Palou, Maria Jose Ribal, Joaquim Bellmunt, Xavier Garcia del Muro
Journal: Journal of Clinical Oncology (2012)

270 Background: Preclinical studies suggest enhanced radiation-induced cell death when VEGFR inhibitor therapies are combined with RT. Methods: Patients with localized muscle invasive urothelial carcinoma of the bladder in clinical stage T2-3 N0 M0, who were not eligible or rejected radical cystectomy, ECOG PS 0-2, and adequate hematological, renal and hepatic function, were enrolled in this phase I study to assess safety and identify the dose limiting toxicity (DLT), maximum tolerated dose (MTD) and recommended dose (RD) of sorafenib and RT. A 3+3 dose escalation design with cohorts of 3-6 patients was used. Treatment consisted of TUR, followed by normofractionated (2 Gy/day) external-beam RT with high-energy photons, 46 Gy to minor pelvis and 66 Gy to bladder, combined with sorafenib given po continuously. Sorafenib was started two weeks before RT and was administered for 12 weeks, finishing 4 weeks after RT. Dose levels 1, 2 and 3 corresponded to sorafenib 200 mg qd, 200 mg bid and 800 mg bid. Pathological response was assessed by post-treatment TUR. Results: Ten patients were included: median age 71 years (44-84); gender 7M: 3F. Patients were treated at 3 dose levels, the MTD was reached at level 3 and the RD was: sorafenib 200 mg bid with RT. Two DLTs occurred, both at the third dose level: diarrhea grade 3 and digestive bleeding grade 3 with secondary anemia and hemodynamic angor in a patient with previous small bowel angiodysplasia. The most frequent toxicity was diarrhea. Other grade 1-2 toxicities included rash, fatigue, hand-foot syndrome, hypertension, dysuria and urinary frequency. One patient developed late radiation cystitis. Pathological complete response was achieved in 8 of 9 patients evaluated. Salvage cystectomy has been performed in one patient due to recurrent superficial bladder tumor. After a median follow up of 30 months, 6 patients remain disease-free with intact bladder. Conclusions: The combination of sorafenib and RT appears to be feasible and safe allowing long-term bladder preservation in selected patients. A phase II study to assess the activity of this promising combination is warranted.
Simple oral therapy with capecitabine (CAPE) and cyclophosphamide (CPA) for metastatic breast cancer (MBC).
Authors: A. F. Schott, D. Lew, W. E. Barlow, K. S. Albain, H. K. Chew, J. L. Wade, K. S. Lanier, H. M. Linden, G. N. Hortobagyi, R. B. Livingston
Journal: Journal of Clinical Oncology (2010)

1006 Background: There is continued interest in oral agents for the treatment of MBC as many patients (pts) prefer oral, home-based therapy to IV clinic-based regimens. The SWOG evaluated a simple oral combination cytotoxic regimen for MBC in a phase II trial, S0430. There is a dual scientific basis for combining CAPE with CPA. 1) CAPE is converted to 5-FU in tumors, utilizing the enzyme thymidine phosphorylase (TP). Preclinical and clinical studies show that TP in tumors is increased by CPA. 2) Metronomic regimens may inhibit angiogenesis by continuously exposing the tumor endothelial cells to cytotoxic drug. Methods: Eligible pts had MBC, 0-2 prior chemo regimens, and if ER+ had progressed on endocrine therapy in the metastatic setting. Pts had RECIST- measurable disease or CA 15-3/CA 27-29 > 2X ULN. Pts received CPA 100 mg po qd days 1-14 and CAPE 1,500 mg po bid days 8-21, cycles repeated every 21d. Doses were not adjusted for BSA. Results: 112 pts enrolled between 8/15/2005 and 9/1/2007. 16 were ineligible. Toxicity (tox) was mild, with no treatment-related deaths. Grade 4 tox included thrombosis/embolism (1 pt). Grade 3 tox included HFS (7 pts), fatigue, diarrhea, and dehydration (2 pts each). RECIST RR (80 pts), and PFS, OS (96 pts) are listed in the Table, in context with recently reported trials of other CAPE combinations. Conclusions: This therapy did not meet prespecified criteria of interest, a 42% RR. However, RR and PFS of CAPE/CPA compare favorably with CAPE monotherapy or combination therapy with bevacizumab or sorafenib, especially given more highly pretreated and ER- pts in S0430. If either becomes standard Rx with CAPE, we believe that a randomized trial comparing these to the SWOG regimen is warranted, as the toxicity and cost of CPA is lower. RIBBON-1 RIBBON-2 SOLTI S0430 CAPE combinator Placebo/bevacizumab Placebo/bevacizumab Placebo/sorafenib Cyclophosphamide # of pts 206/409 47/97 114/115 96 Prior regimens 0 100% E 54%/43% 54% 1 E 100% 45%/57% 32% 2 E E E 13% Receptors ER or PR + NR NR 68%/77% 59% ER- NR NR 29%/17% 41% HER2 + E E E 6% RECIST RR 23.6%/35.4% NR 30.7%/38.3% 36% (95% CI 26-48%) PFS (mo.) 5.7 /8.6 4.1/6.9 4.1/6.4 5.9 (95% CI 3.9-8.0) OS (mo.) 21.2/29.0 NR NR 19.6 (95% CI 13.5-21.9) Abbreviations: E, excluded; NR, not reported. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech, Roche Roche Genentech, Roche
Prediction of clinical outcome in stage II and III colon cancer by a common gene variant in AXIN2.
Authors: Joanna Szkandera, Gudrun Absenger, Melanie Weissmueller, Martin Pichler, Michael Stotz, Sigurd Lax, Gerhard Leitner, Martin Asslaber, Wilfried Renner, Armin Gerger
Journal: Journal of Clinical Oncology (2013)

387 Background: Recent evidence suggests that the Wnt and Notch signaling pathways are involved in colon cancer progression and tumor recurrence. There is substantial germline genetic variability in these pathways, including single nucleotide polymorphisms (SNPs). SNPs may alter transcription, translation or splicing, thereby causing inter-individual differences in a patient’s tumor recurrence capacity and chemoresistance. We hypothesized that SNPs analyzed in a comprehensive panel of Wnt and Notch pathway genes predict clinical outcome in patients with colon cancer. Methods: A total of 815 patients with stage II and III colon cancer treated at the Medical University of Graz were included in this retrospective study. FFPE tissue specimens from normal tissue adjacent to the tumor samples were available from 599 patients. 18 SNPs in Wnt and Notch pathway genes (SFRP, DKK2, DKK3, Axin2, APC, MYC, TCF7L2 and NOTCH-2) were determined by 5’-exonuclease assay (TaqMan). The primary endpoint of the study was disease-free survival (DFS). Results: The homozygous mutant variant of AXIN2 rs2240308 G&gt;A was associated with a significantly increased median DFS (HR 0.638, 95% CI 0.432-0.942, p=0.024) in univariate analysis. Patients carrying at least one G allele in AXIN2 rs2240308 G&gt;A showed a median DFS of 114 months. In contrast, patients with homozygous A/A showed a median DFS of 133 months. After Cox proportional hazards model adjustment for known prognostic markers this result remained significant (HR 0.671, 95% CI 0.453-0.992, p=0.046). Conclusions: To the best of our knowledge, this is the first study identifying a common genetic variant in AXIN2 as an independent prognostic marker in stage II and III colon cancer. Larger prospective trials are warranted to confirm these findings.