tbuckley/cabot-search huggingface dataset:
Extranodal masses compressing spinal cord in Hodgkin's disease and follicular lymphoma
Authors: W. Jurczak, A. Wywial, A. Zaluska, M. Pasowicz, A. B. Skotnicki
Journal: Journal of Clinical Oncology (2004)

6728 Background: Standard staging procedures in Hodgkin's disease (HD) include full physical examination and imaging studies: usually CT scan of the chest and abdomen. In case of low grade lymphomas (like follicular lymphoma - FL) in advanced clinical stage, they may be even less thorough. Therefore the disease within vertebral column –best visualized by magnetic resonance studies (NMR) –may be missed at diagnosis. Methods/Results: During the last 2 years 3 cases of infiltration of vertebral column (extranodal masses localized within the vertebral canal, compressing but not infiltrating the spinal cord) were diagnosed in over 100 patients treated for HD and FL at that time. In all 3 cases discrete neurological symptoms secondary to spinal cord and/or nerve root compression were present, resulting in further investigations. In a FL patient they were diagnosed at presentation, while in two HD cases they were found 6 and 9 months after completing the first line therapy, being the cause of early relapse (primary resistance?). They were not reported in a routine 3- monthly CT scans performed in purpose to monitor non-progressive residual masses. Radiotherapy –if used in the first line therapy –seems to be a feasible and effective treatment: FL patient is in CR, since IFRT was applied after chemoimmunotherapy (6 cycles of cladribine and cyclophosphamide combined with a standard dose of Rituximab, recycled at day 21); one HD patient treated with 6 cycles of ABVD and Mantle field radiotherapy relapsed evidently below the irradiated field. However both HD cases developed resistance despite second line regimens and high dose chemotherapy supported by autologous stem cell transplant. Conclusions: Therefore we conclude, that HD and FL patients with any neurological signs or symptoms at diagnosis should be considered as likely candidates for NMR imagind studies. No significant financial relationships to disclose.
Improving oral chemotherapy adverse event reporting: Listening to pediatric oncology patients and parents.
Authors: Jessica A. Zerillo, Constance Barysauskas, Paul J. Catalano, Joseph O. Jacobson, Amy Billett
Journal: Journal of Clinical Oncology (2017)

45 Background: Medication-related adverse events and near misses are underreported, particularly in the ambulatory setting. Our aim was to assess pediatric oncology parent and patient-reported oral chemotherapy errors and near misses. Methods: A survey of parent and patient-reported oral chemotherapy errors and near misses over the past month was developed and validated in a subgroup and administered to parents/patients at an academic pediatric hematology-oncology clinic. Parents and patients were included if the patient received any commercially available oral chemotherapy agent within the past month, dispensed by an onsite retail pharmacy, and agreed to participate. Results: Forty-eight of 69 parents and 11 of 17 patients responded (ten from the same household). Fifteen of 59 respondents (25%) reported at least one event, miss, or error (twelve (25%) parents and three (27%) patients). Of five events described by parents and patients of the same household, one was co-reported. Of the errors that occurred in the home, the most common were missed (n=5, 8%) and late (n=3, 5%) doses. Forty-six percent of respondents did not report events to the medical team. Two respondents perceived minor harm as a result of the event. Conclusions: Patients and parents are willing to share information about oral chemotherapy-related adverse events and near misses. Twenty-five percent of respondents noted an oral chemotherapy event, near miss, or error over the preceding month. Importantly, many of these events were unreported to care teams. Missed doses were the most common safety event, and interventions should target this need.[Table: see text]
Different prevalence of <i>BRAF</i> and <i>NRAS</i> somatic mutations in melanomas according to the patients’ origin.
Authors: Giuseppe Palmieri, Amelia Lissia, Antonio Cossu, Paolo Antonio Ascierto, Gerardo Botti, Corrado Caraco, Nicola Mozzillo, Fabrizio Ayala, Annamaria Anniciello, Vincenzo De Giorgi, Daniela Massi, Ignazio Stanganelli, Corrado Rubino, Grazia Palomba, MariaCristina Sini, Antonella Manca, Maria Colombino
Journal: Journal of Clinical Oncology (2013)

e20013 Background: Genetic factors predisposing to melanoma at germline level have been demonstrated to be geographically heterogeneous. We here evaluated the spectrum of NRAS and BRAF mutations at somatic level, in a large subset of melanoma tissues from patients originating from different Italian geographical areas: Sardinia, whose population is genetically homogeneous, and Middle-South Italy, with a genetically heterogeneous population. Methods: Patients were enrolled consecutively between June 2008 and December 2012. Genomic DNA was isolated from tumor tissues [primary melanomas (N=439) and melanoma metastases (N=269)] or melanoma cell lines (N=32). Paired samples of primary melanomas (n=140) and synchronous or asynchronous metastases from the same patients (n=203) were included. The full coding sequences and splice junctions of NRAS (exons 2-3) and BRAF (exon 15) genes were screened for mutations through automated sequencing. Results: BRAF/NRAS mutations were identified in 63% of primary melanomas (48% BRAF; 15% NRAS), 67% melanoma metastases (51% BRAF; 16% NRAS), and 68% melanoma cell lines (56% BRAF; 12% NRAS). A non-significant increase in mutation frequency after progression from primary melanoma was observed. However, distribution of BRAF/NRAS mutations varied between in vivo tumors and melanoma cell lines, suggesting a preponderant role for BRAF activation in highly proliferating cultured melanoma cells. Among paired samples, consistency of BRAF/NRAS mutation patterns between metastatic and primary melanomas ranged from 71% (skin metastases) to about 90% (lymph node and visceral metastases). A significant inverse distribution of BRAF/NRAS mutation rates was observed in our series on the basis of the geographical origin of patients: for BRAF, 58% Sardinian vs. 42% non-Sardinian cases (p=0.045); for NRAS, 2% Sardinian vs. 21% non-Sardinian cases (p&lt;0.001). Conclusions: Our findings provide additional insights into the spectrum and distribution of BRAF/NRAS mutations in melanoma; moreover, they support the hypothesis that differences in patients’ origins and related genetic backgrounds may contribute to even determine the incidence rate of somatic mutations in such cancer genes.
Mesothelin-targeted immunotherapy CRS-207 in combination with standard of care chemotherapy as treatment for malignant pleural mesothelioma (MPM).
Authors: Raffit Hassan, Scott Joseph Antonia, Evan W. Alley, Hedy Lee Kindler, Thierry Jahan, John J. Grous, Somayeh Honarmand, Katherine McDougall, Chan C. Whiting, Nitya Nair, Ed Lemmens, Aimee L. Murphy, Anish Thomas, Dirk G. Brockstedt
Journal: Journal of Clinical Oncology (2015)

7565 Background: MPM is an aggressive disease with poor prognosis and is relatively refractory to currently available therapies. CRS-207 is live-attenuated Listeria monocytogenes engineered to express the tumor-associated antigen mesothelin. Stimulation of potent innate and adaptive immunity by CRS-207 may act synergistically in combination with chemotherapy that alters the tumor environment to be more susceptible to immune-mediated killing. Methods: Eligible patients were chemotherapy-naïve with unresectable MPM, good performance status (ECOG 0 or 1) and adequate organ function. Patients received 2 prime vaccinations with CRS-207 (1 × 109 CFU) 2 weeks apart, followed by 6 cycles of pemetrexed (500 mg/m2) and cisplatin (75 mg/m2) 3 weeks apart and 2 CRS-207 boost vaccinations 3 weeks apart. Subjects were followed every 8 weeks until disease progression. Clinically stable patients received CRS-207 maintenance vaccinations every 8 weeks. Objectives of the study include safety, immunogenicity, objective tumor responses and tumor marker kinetics. Results: Twenty-six subjects (88% male; median age: 69) have been enrolled as of Jan 15 2015. As of Jan 2015, 10/26 were on treatment. Median time on treatment was 7.1 months (range: 1.0-22.5). No treatment-related unexpected toxicities have been observed. The most common adverse events related to CRS-207 were Grades 1/2 infusion-related fever, chills/rigors, hypotension and nausea/vomiting. Of 24 subjects evaluable, 63% (15/24) had confirmed partial response (PR) post CRS-207 and chemotherapy and 29% (7/24) had stable disease (SD). Median duration of response was 4.8 months (range: 3.6-7.2) and PFS was 7.5 months (range: 7.1-8.6) for the first 16 subjects enrolled. Treatment, follow-up, median overall survival and immune response evaluations are ongoing and will be presented at the meeting. Conclusions: CRS-207 can be safely combined with chemotherapy and showed encouraging anti-tumor activity with 63% of subjects having objective tumor responses and 92% disease control. These results are considerably better than those expected with chemotherapy alone and warrant further evaluation. Clinical trial information: NCT01675765.
Systematically implementing an electronic platform to improve patient experience measurement in Ontario, Canada.
Authors: Lesley Moody, Suman Dhanju, Sarah Benn, Isabela Olaru, Nadia Sliz, Amy Snow, Sara Khan, Simron Singh
Journal: Journal of Clinical Oncology (2017)

111 Background: Cancer Care Ontario organizes and ensures quality cancer care for 13.5 million residents in Ontario, Canada and is systematically deploying a web-based tool, called Electronic Patient Reported Experience Measures (ePREM), through a touch-screen platform previously deployed within Regional Cancer Centres (RCCs). ePREM has been used to disseminate the first patient reported experience measure (PREM), called Your Voice Matters (YVM). YVM will be collected on all patients in Ontario undergoing cancer treatment in real time, creating the largest known, linkable patient experience dataset. Methods: Implementation feasibility and readiness was assessed across all 14 Regional Cancer Programs through a provincial assessment which informed the phased implementation. Implementation was rooted in a change management framework: clinical and administrative champions, available resources, existing technical environment and competing program priorities. In March 2016 a four-wave implementation was initiated controlling for readiness and centre volumes, with a focus on extensive stakeholder engagement, tool training, launch and operational support. To date, ePREM is fully operational in 10 of 15 RCCs. Results: Provincial deployment was 66% complete in October 2016. By March 2017 full provincial implementation will be complete. Successful implementation has been directly linked to an adaptive design within the implementation and change management framework as a four-wave roll out. Key factors included: multi-faceted communications with centre leadership, and implementation teams. During this initial data stabilization phase, there were 9,266 completed surveys submitted and 10,932 partial survey responses submitted. Conclusions: PREMs are appropriate quality improvement indicators for cancer patients within the treatment phase. ePREMs enables systematic, linkable collection of real time PREMs to improve the patient experience in Ontario and contribute to the planning of new initiatives. Upon full provincial implementation ePREMs will allow for the largest known dataset of PREMs. Successful implementation has been directly linked to an adaptive, four-wave approach.
Association of increased tumor-infiltrating lymphocytes (TILs) with immunomodulatory (IM) triple-negative breast cancer (TNBC) subtype and response to neoadjuvant platinum-based therapy in PrECOG0105.
Authors: Shaveta Vinayak, Robert James Gray, Sylvia Adams, Kristin C. Jensen, Judith Manola, Anosheh Afghahi, Lori J. Goldstein, James M. Ford, Sunil S. Badve, Melinda L. Telli
Journal: Journal of Clinical Oncology (2014)

1000^ Background: Increased TILs are prognostic and predictive of therapy response in TNBC. PrECOG 0105, a neoadjuvant trial of carboplatin, gemcitabine and iniparib, enrolled 80 pts with clinical stage I-IIIA TN or BRCA1/2 mutation-associated BC. This correlative study was designed to assess the association of pre-therapy TILs in PrECOG 0105 with pathologic response, germline BRCA1/2 genotype & gene expression profiles, including TNBC subtypes. Methods: Evaluable pts had TNBC and completed at least 4 of 6 planned cycles of therapy. H and E stained tumor sections from pre-therapy biopsies were evaluated by a central pathologist for density of stromal (sTILs) and intratumoral (iTILs) lymphocytes. Pathologic response was assessed by the residual cancer burden (RCB) index. All patients had comprehensive BRCA1/2 genotyping. TNBC subtypes were derived from Affymetrix U133 plus 2.0 arrays. Results: 70 pts were included in this analysis. Median age = 47 yrs, median T size = 3.2 cm, 20% BRCA1/2 mutant & 48% node positive. 76% of tumors had at least 10% sTILs (range 10-80%) & 31% at least 10% iTILs (range 10-40%). Lymphocyte-predominant BC (LPBC), defined as ≥50% sTILs, was seen in 13%. pCR rate was highest (56%) in LPBC, though not significantly different from the non-LPBC group (38%, p=0.47). sTILs were significantly associated with TNBC subtype; median sTIL = 40% in the IM subtype, 15% in BL1, 20% in BL2, 10% in LAR, 0% in M, and 10% in MSL (p=0.0005). iTILs were also significantly associated with TNBC subtypes (p=0.0003); iTIL>0 for 10/14 (71%) in IM subtype, 1/7 (14%) in BL1, and 0 in others. Association with BRCA1/2 mutation status was not significant. In a multivariate model, each 10% increase in iTILs (OR 2.62 [95% CI 1.08 – 6.35]; p=0.03), but not sTILs (OR 1.17 [95% CI 0.87 – 1.58];p=0.28) was independently associated with pCR (RCB=0). However, both sTILs (p=0.02) and iTILs (p=0.009) were significantly associated with continuous RCB value. Conclusions: Both sTILs and iTILs are predictive of response to platinum-based neoadjuvant therapy and are significantly associated with TNBC subtypes, with the highest frequency in the IM subtype. Clinical trial information: NCT00813956.
ZD6474, a novel antiangiogenic agent, in combination with docetaxel in patients with NSCLC: Results of the run-in phase of a two-part, randomized phase II study
Authors: J. V. Heymach, R.-P. Dong, I. Dimery, C. Wheeler, P. Fidias, C. Lu, B. Johnson, R. Herbst
Journal: Journal of Clinical Oncology (2004)

3051 Background: ZD6474 is a novel, orally available VEGFR-2 TKI that also has activity against EGFR. Objective tumor responses in NSCLC patients (pts) were observed during Phase I evaluation. In this Phase II trial of ZD6474 plus docetaxel (doc), the safety, efficacy, and possible pharmacokinetic (PK) interaction of the combination were assessed. Methods: Eligibility included locally advanced or metastatic NSCLC after failure of 1st line platinum-based chemotherapy, WHO status of 0 or 1, and no significant hematologic or cardiac abnormalities. In the open-label Part 1 phase, pts received doc (75 mg/m2 every 21 days, i.v.) plus ZD6474 (100 mg once daily, p.o.). If no dose-limiting toxicity occurred by week 4, the next cohort received ZD6474 300 mg. Results: At completion of this phase, 15 pts with a WHO status of 0 (N=6) or 1 (N=9) received the ZD6474/doc combination (100 mg N=4, 300 mg N=11). Pts received a median of 4 cycles of doc (range 1–11) and 12 weeks' ZD6474 (range 2–29). Preliminary evaluation in pts who continued to receive ZD6474/doc for ≥ 3 cycles revealed the most common AE to be rash (CTC grade 3 in 6 of 9 pts), classified as acneiform or desquamation, with a photosensitivity component in all affected patients. The rash was reversible, and was manageable by dose interruption followed by a dose reduction. Other AEs such as GI complaints (nausea/vomiting) and laboratory abnormalities also occurred, (CTC grade 1 or 2). Seven pts experienced CTC Grade 3 or 4 myelosuppression thought to be related to doc treatment. Preliminary PK assessment shows that ZD6474 did not appear to affect exposure to doc, with any changes observed being similar to the intra-patient variability for doc alone. No marked effect on the exposure to ZD6474 was seen when administered with doc, with maximal changes of ±20% compared with ZD6474 alone. Conclusions: This phase has confirmed that the combination of ZD6474 and doc is not associated with significant changes in exposure to either drug and the toxicities are manageable. The double-blind, randomized phase comparing doc/placebo with the doc/ZD6474 (100 or 300 mg) combination is ongoing. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca AstraZeneca AstraZeneca
Sensitivity rate of ultrasound (US)-guided fine-needle aspiration cytology (FNAC) using the Berlin morphology criteria for lymph node metastases to reduce the need for surgical sentinel node (SN) staging in melanoma.
Authors: Christiane A. Voit, Alexander Christopher Jonathan Van Akkooi, Saskia Gooskens, Petra Siegel, Gregor Schaefer-Hesterberg, Alfred Schoengen, Joachim Roewert-Huber, Wolfram Sterry, Alexander M. Eggermont
Journal: Journal of Clinical Oncology (2012)

8535 Background: US-guided-FNAC prior to surgical SN staging is emerging as a possible cost-effective addition to the staging of melanoma patients (pts). Formerly, sensitivity (sens) rates of lymph node US in melanoma were disappointing (20–40%). The introduction of the Berlin Morphology Criteria has significantly improved sens rates for US-FNAC (J Clin Oncol 2010;28(5):847-52). The aim of the current study was to report on 1000 patients the sens, specificity (spec), positive (PPV) and negative (NPV) predictive value rates of US-FNAC from our prospective database with prolonged follow-up. Methods: Since 2001, &gt;1000 stage I / II consecutive melanoma pts have undergone US-FNAC prior to SN. All patients underwent lymphoscintigraphy. Peripheral Perfusion (PP), Loss of Central Echoes (LCE), Balloon Shaped (BS) were the Berlin Morphology Criteria which were registered. FNAC was performed in case of presence of any of these factors. SN tumor burden was measured according to the Rotterdam Criteria. All patients underwent SN or LND in case of positive FNAC. Results: Mean/median Breslow thickness was 2.56 / 1.57 mm (0.2 – 44 mm).Mean/median follow-up was 39 / 32 months (0 – 115). Ulceration was present in 24 %. SN positivity rates were 20 % (202 / 1000). Sens was 51 %. Spec, PPV and NPV were 99%, 91% and 89%. Sensitivity was highest for T4 tumors (77%). PP, LCE, BS had sens of 69%, 24%, 25%. SN tumor burden &gt; 1 mm in largest diameter according to the Rotterdam Criteria was identified by US-FNAC in 86%. Threshold for positive FNAC was 0.4 mm in maximum diameter. Conclusions: The new criterion of Periferal Perfusion is of key importance to achieve the high sensitivity of US-FNAC according to the Berlin Morphology Criteria (J Clin Oncol 2010; 28:847-852) to identify lymph node metastases. Especially for T4 patients and in patients with advanced SN tumor burden it can reduce significantly the need for surgical SN staging. The EORTC Melanoma Group will launch the prospective validation study, USE FNAC, in 2012.
High incidence of brain metastases at the time of death in women with metastatic breast cancer treated with trastuzumab
Authors: A. Herrero, R. Grandez, T. Puertolas, V. Alonso Orduña, J. Martinez Trufero, R. Pazo Cid, A. Artal, J. Lao, A. Ruiz de Lobera, A. Anton Torres
Journal: Journal of Clinical Oncology (2004)

765 Introduction: Since Trastuzumab was introduced for the treatment of over-expressing HER 2 metastatic breast cancer a high incidence of patients (P) who developed CNS metastases have been reported. Methods: We retrospectively studied all the P with metastatic breast cancer treated at our hospital with T in order to assess the incidence of CNS metastases at the time of death. From January/99 to April/02, 42 P, all of them HER 2+++ (Dako's Herceptest or FISH +) were treated. Results: Median follow-up from starting T was 12 months (3–48). Response rate: Complete responses 7P (16,6%), Partial 13P (31%), Stable 9P (21,4%) and Progressive disease 13P (31%). By the time of analysis, 21P had died, all of them from progressive disease. 12P of them had CNS metastases diagnosed before death (57%): 4P were diagnosed prior to T and 8P during T treatment. In 6 of these cases CNS was the only site of progressive disease. Median time from beginning T and SNC metastases diagnosis was 7 months and median time from SNC involvement and death was 2 months. Conclusions: Incidence of SNC metastasis detected in women with metastatic breast cancer treated with T is very high by the time of death and this involvement is a dismal prognosis indicator. Prophylactic strategies should be investigated to avoid SNC progression, especially if a patient achieve an objective response with trastuzumab. No significant financial relationships to disclose.
Final report of an open-label phase II trial of bevacizumab plus docetaxel and gemcitabine in metastatic, previously untreated nonsquamous non-small cell lung cancer (NSCLC).
Authors: Nathan A. Pennell, Sujith R. Kalmadi, Marc A. Shapiro, Hamed Daw, Cristina P. Rodriguez, Abdo S. Haddad, Tara Rich, Julia Samsa, Paul Elson, Patrick C. Ma, Afshin Dowlati
Journal: Journal of Clinical Oncology (2012)

e18046 Background: Platinum and non-platinum doublet chemotherapy has similar efficacy in advanced NSCLC patients (pts). Bevacizumab (B) improves outcomes when added to platinum doublets, but its safety and efficacy in combination with non-platinum doublets is unknown. This study was designed to test the combination of B, docetaxel (D), and gemcitabine (G) in first-line treatment of advanced NSCLC. Methods: Pts with metastatic, non-squamous NSCLC, PS 0-1, and measurable disease by RECIST were enrolled in this open-label, single arm phase II trial. Pts received D (75 mg/m 2 ) on d1, G (900 mg/m 2 ) on d1 &amp; 8, and B (15 mg/kg) on d1 every 21d for up to 6 cycles, followed by B maintenance until progression or 12 mos total. Pts received growth factor d9. CT scans were performed every 6 wks. The primary endpoint was 1-yr progression-free survival (PFS), with secondary endpoints of safety, objective response rate (ORR), overall PFS, and overall survival (OS). Pts with tumor cavitation, untreated brain metastases, and hemoptysis were excluded. Planned enrollment was 46. Results: 13 pts were enrolled from 12/2009 to 4/2011. Pt characteristics: Median age 63 (35-69), 85% male, PS 0 (38%), PS 1 (62%). The median # of cycles of chemotherapy was 6 (1-6), median # cycles of B was 4 (1-15), with 2 pts coming off study prior to the first evaluation (1 grade 5 encephalopathy, 1 grade 4 febrile neutropenia). 5 pts (38%) had chemo dose reduction and 4 (31%) discontinued treatment for toxicity. 3 pts (23%) discontinued B prior to progression, 2 for tumor cavitation and 1 for grade 1 hemoptysis. The grade 3-5 non-hematologic toxicity rate was 69%, with 6 pts (46%) hospitalized with pneumonitis/pneumonia felt possibly related to study drugs. At this point enrollment was halted for safety concerns. The 1-yr PFS was 8%, and the median PFS was 6.9 mos (95% CI 2.0-NYR). 11 pts were evaluable for response, and 6 pts had partial responses for an ORR of 55%. The median OS was NYR with median follow up of 10.9 mos. Conclusions: The combination of B, D, and G was not tolerable at the doses and schedule used in this study. A formal phase I trial is needed if this combination is to be investigated further.