tbuckley/cabot-search huggingface dataset:
QLIF-47. HEALTH RELATED QUALITY OF LIFE AND NEUROLOGICAL DETERIORATION FREE SURVIVAL IN INTELLANCE 2/EORTC TRIAL 1410, A RANDOMIZED PHASE II STUDY ON ABT414 IN RECURRENT EGFR AMPLIFIED GLIOBLASTOMA
Authors: Paul Clement, Martin van den Bent, Marica Eoli, Juan Manuel Sepulveda, Annemiek Walenkamp, Jean-Sebastien Frenel, Enrico Franceschi, Michael Weller, Olivier Chinot, Filip de Vos, Nicolas Whenham, Paul Sanghera, Jim Looman, Ho-Jin Lee, Jan-Peter de Geus, Sarah Nuyens, Maarten Spruyt, Thierry Gorlia, Corneel Coens, Vassilis Golfinopoulos
Journal: Neuro-Oncology (2017)

Treatment options for recurrent glioblastoma are limited. 45-50% of glioblastoma show EGFR amplification. ABT-414 is a tumor-specific antibody-drug conjugate (ADC) combining an antibody (ABT-806) targeting a unique conformation of EGFR bound to monomethyl auristatin F (MMAF), a microtubule cytotoxin. We investigated ABT-414 in glioblastoma at 1strecurrence, besides Overall Survival (OS) the study endpoints included Quality of Life (QoL) and Neurological Deterioration Free Survival Analysis (NDFS). EORTC-1410-BTG (NCT02343406) is a randomized open label phase II study. Eligible were patients with a centrally confirmed EGFR amplified glioblastoma with a first recurrence after combined temozolomide chemo-irradiation, occurring ≥ 3 months after the end of radiotherapy, ≥ 18 years, WHO performance status (PS) 0-2, with adequate organ function, and tissue available for central EGFR and MGMT determination. After stratification for region of the world, WHO status and timing of relapse (< 16 weeks or patients were randomized to either a) treatment with ABT-414 1.0 mg/kg every two weeks intravenously alone, or b) the same treatment in combination with temozolomide 150-200 mg/m2 day1-5 every 4 weeks, or c) either lomustine or temozolomide depending of the time of recurrence in relation to the end of temozolomide treatment in 1stline. QoL was assessed using the EORTC QLQ-C30 questionnaire and the QLQ-BN20 Brain Cancer Module. NDFS was assessed by change in WHO Performance Status; the protocol emphasized the collection of WHO PS beyond progression. Primary endpoint of the study is overall survival (OS); QoL and NDFS are both secondary endpoints. Between Mar 10 2015 and July 22 2016a total of 260 patients were randomized. The per protocol required number of 170 events will be observed in June 2017. The database lock is foreseen for August 2017. At the meeting QOL and NDFS analysis will be presented.
Fumaric acid esters in combination with a 6-week course of narrowband ultraviolet B provides an accelerated response compared with fumaric acid esters monotherapy in patients with moderate-to-severe plaque psoriasis: a randomized prospective clinical stud
Authors: S. Tzaneva, A. Geroldinger, H. Trattner, A. Tanew
Journal: British Journal of Dermatology (2017)

BackgroundFumaric acid esters (FAE) are safe and effective in patients with moderate‐to‐severe psoriasis but have a slow onset of action. A short‐term combination with narrowband ultraviolet B (NB‐UVB) may substantially accelerate the therapeutic response in the induction phase of treatment.
Tendances des infections à méningocoque de sérogroupe C en République d'Irlande
Authors: J Fogarty
Journal: Eurosurveillance (1997)

En novembre 1994, un systeme national de surveillance microbiologique des infections a meningocoque a ete mis en place en Republique d'Irlande (RI). Les formulaires de recueil de donnees sont renvoyes et centralises mensuellement, meme si aucun cas n'est survenu ; ils comprennent un ensemble minimum de donnees (nom ; date de naissance ; date et site du prelevement ; serogroupe, serotype et sous-type, si determines ; et statut vital).
IMMU-56. T LYMPHOCYTES FACILITATE BRAIN METASTASIS OF BREAST CANCER BY EXPRESSIONAL IMPRINTING
Authors: Rute Pedrosa, Manuel Valiente, Theo Luider, Reno Debets, Johan Kros, Dana A M Mustafa
Journal: Neuro-Oncology (2017)

The appearance of cerebral metastasis usually defines the terminal stage of disease for women suffering from breast cancer. Breast cancer dissemination to brain tumor cells need to take the hurdle of the blood-brain barrier (BBB). To identify specific pathways involved in brain metastasis of breast cancer. We compared the gene expression profiles of estrogen receptor negative primary breast cancer samples of women with metastasized disease, with and without brain involvement. We validated our discovery by IHC, RT-PCR and by using an in vitro BBB model. Additinally, we explored the changes at the protein level cased by T-cells by using liquid chromatography-mass spectrometer (LC-MS). The findings were also validated in vivo by using a mouse model. We found genes related to T cell activation to be prominently associated with the occurrence of brain metastasis. By using an in vitro BBB model breast cancer cells that were co-cultured with T lymphocytes passed the artificial BBB with a 300-600 fold acceleration. Following, we identified 11 differentially expressed proteins in breast cancer cells that were co-cultured with T lymphocytes. After matching these proteins with gene expression profiles of the original patient datasets, we found that some of these genes were upregulated in the samples that were associated with cerebral metastasis, and subsequent silencing in the cancer cells resulted in a 30-70 fold decrease of the passage of the breast cancer cells through the BBB model. In a mouse model, ErbB2-P tumor cells co-cultured with T-cells appeared to develop 6 fold brain metastases than those not co-cultured. Expressional imprinting of breast cancer cells by T lymphocytes accelerate the formation of brain metastases, which is a new insight in the complex interplay of T lymphocytes with cancer cells. This discovery is crucial to open opportunities for preventing the formation of brain metastases.
PUB054 Pathological Discrepancies in the Diagnosis of Thymic Malignancies: The Tallinn-Lyon Experience
Authors: K. Oselin, N. Girard, A. Adamsom, K. Lepik, T. Vanakesa, I. Almre, T. Leismann, L. Chalabreysse
Journal: Journal of Thoracic Oncology (2017)
P2.03-012 Characterization of the Efficacies of Osimertinib and Nazartinib against Cells Expressing Epidermal Growth Factor Receptor Mutations
Authors: K. Masuzawa, H. Yasuda, J. Hamamoto, I. Kawada, K. Naoki, K. Soejima, T. Betsuyaku
Journal: Journal of Thoracic Oncology (2017)
Epidémies de parvovirus B19 dans trois écoles portugaises
Authors: G Gonçalves, A M Correia, P Palminha, H Rebelo de Andrade, A Alves
Journal: Eurosurveillance (2005)

L’article suivant decrit l’etude d’epidemies d’episodes d’exantheme aigu chez des enfants de trois ecoles de la ville de Braga, Portugal. Les analyses de laboratoire, effectuees pour cinq cas, ont montre que la maladie n’etait pas liee a une infection par le virus de la rougeole ou de la rubeole, et ont confirme l’infection par parvovirus B19. Quarante-et-un enfants ont ete touches : 12 en maternelle, 17 a l’ecole secondaire et 12 a l’ecole primaire. Seul un membre du personnel, travaillant a l’ecole maternelle, a ete contamine. Huit cas ont ete identifies parmi les contacts familiaux ; deux d’entre eux etaient des freres, l’un en maternelle et l’autre a l’ecole secondaire ou l’epidemie est survenue apres celle de la maternelle. Les valeurs estimees du taux de reproduction de base R0 etaient tres faibles et l’existence de cas infectieux asymptomatiques est probable. Les autorites sanitaires locales ont publie des documents ecrits et rencontre les membres du personnel et les parents. Les etablissements de soins primaires ainsi que le service d’obstetrique de l’hopital local ont egalement ete informes. L’objectif de l’elimination de la rougeole au Portugal etant proche, comme dans toute l’Europe, avec des couvertures vaccinales tres elevees, il est tres possible qu’une proportion importante d’exanthemes non vesiculaires seront dus a des infections par B19. Cela devrait etre pris en compte dans la mise en place et la conduite des activites de surveillance, dans le contexte des programmes d’elimination de la rougeole et de la rubeole.
Rechallenge in GIST progressing to imatinib, sunitinib and regorafenib: An Italian survey
Authors: B. Vincenzi, M. Nannini, G. Grignani, E. Fumagalli, S. Gasperoni, L. D'Ambrosio, G. Badalamenti, A.P. Dei Tos, L. Incorvaia, P. Casali, D. Santini, G. Tonini, M. Stellato, G. Catania, M. Spalato Ceruso, M.A. Pantaleo
Journal: Annals of Oncology (2017)
P1.01-019 ALK+ Non-Small Cell Lung Cancer Treated with First Line Crizotinib: Patient Characteristics, Treatment Patterns, and Survival
Authors: C. Martín, A. Cardona, O. Arrieta, O. Castillo-Fernandez, G. Oblitas, L. Corrales, L. Lupinacci, M.A. Pérez, L. Rojas, L. González, L. Chirinos, C. Ortíz, M. Lema, C. Vargas, C. Puparelli, H. Carranza, J. Otero, L. Ramirez-Tirado
Journal: Journal of Thoracic Oncology (2017)
P3.01-082 Surgical Rebiopsy in Advanced Non-Small Cell Lung Cancer Resistant to Previous Chemotherapy
Authors: S. Shin, J.H. Cho, H.K. Kim, Y.S. Choi, J. Kim, J.I. Zo, K. Park, M. Ahn, J.S. Ahn, J. Sun, S. Lee, Y.M. Shim
Journal: Journal of Thoracic Oncology (2017)
P1.01-022 Prediction of Central Nervous System Progression During Crizotinib Treatment in ALK+ NSCLC Among Hispanics
Authors: A. Ruiz Patino, C. Martin, A. Cardona, O. Arrieta, O. Castillo-Fernandez, G. Oblitas, L. Corrales, L. Lupinacci, M.A. Pérez, L. Rojas, L. González, L. Chirinos, C. Ortiz, M. Lema, C. Vargas, C. Puparelli, H. Carranza, J. Otero, Z. Zatarain-Barron
Journal: Journal of Thoracic Oncology (2017)
NTOX-11. DISEASE OUTCOMES, TOXICITY PROFILES, AND HEALTH-RELATED QUALITY OF LIFE IN PATIENTS WITH RECURRENT GLIOBLASTOMA RECEIVING INTRA-ARTERIAL CARBOPLATIN SALVAGE THERAPY
Authors: Anna Babcock, Meghan Hultman, Patricia Bruns, Katheryn Gilliland, Amy Schrecengost, John Trusheim, Nilanjana Banerji
Journal: Neuro-Oncology (2017)

Glioblastoma (GBM) remains the most aggressive entity of primary brain tumors with a reported median survival of 14.6 months, despite maximal therapy. While the paradigm developed by Stupp et. al. is considered to be standard care treatment for primary GBM, there is no consensus regarding optimal treatment regimens at disease relapse. We describe here our experience with local disease control, overall survival (OS), toxicity profiles, and patient reported Health-Related Quality of Life (HR-QOL) of an intra-arterial (IA) carboplatin-based treatment for recurrent high-grade gliomas in combination with intravenous bevacizumab. Patients ≥18 years-of-age with recurrent GBM were treated with 400 mg/m2IA carboplatin every 4 weeks and10 mg/kg bevacizumab every 2 weeks at Abbott Northwestern Hospital’s neuro-oncology program. Patients were followed for treatment related adverse events, progression-free survival (PFS), and OS. HR-QOL scores were measured at specific time-points with EORTC QLQ-30 & BN-20 questionnaires. Twenty-three patients with a median age of 52 (33-66) years were included in the final cohort. Median PFS was 7 (3-10) months and OS was 26 (16-36) months. Number of surgical resections (1 vs. ≥2) were significantly associated with OS (p=0.02) and MGMT-promoter methylation associated with better prognosis (22 vs. 26 months). Headaches (n=10) were the most prevalent neurological complications. Seven patients had focal seizures and 3 had generalized seizures. Nausea was reported by 15 patients and fatigue by 16 patients. Grade 4 thrombocytopenia was observed in 4 patients. Three patients had strokes, 2 of which were deemed related to the IA procedure. Prior to treatment failure, longitudinal global-QOL was maintained in most of the patients. IA carboplatin with avastin provides an adequate option for salvage therapy in GBM with encouraging survival outcomes in a carefully selected group of patients. Until disease progression, no significant unfavorable effects on HR-QOL was noted with this therapy.
Survival with docetaxel plus capecitabine comparing with vinorelbine plus capecitabine followed by capecitabine maintenance treatment as first-line therapy in patients with advanced breast cancer: A phase III randomized clinical trial.
Authors: Binghe Xu, Jiayu Wang, Qing Li, Pin Zhang, Peng Yuan, Fei Ma, Ruigang Cai, Ying Fan, Yang Luo, Qiao LI
Journal: Journal of Clinical Oncology (2014)

1049 Background: Docetaxel/capecitabine (TX) is one of the standard regimens recommended by NCCN for metastatic breast cancer treatment. There are few clinical studies directly comparing TX and navelbine/capecitabine (NX), followed by capecitabine maintenance treatment, especially in advanced breast cancer patients previously treated with taxane in adjuvant setting. This study aimed to compare the efficacy and safety of TX and NX medications followed by capecitabine maintenance for patients with metastatic breast cancer. Methods: A total of 206 patients with advanced metastatic breast cancer were randomly assigned into TX (n=104) and NX (n=102) treatment groups, both with capecitabine maintenance medication. The primary endpoint was progression-free survival (PFS) and secondary endpoints included overall survival (OS), response rate (RR), duration of response (DOR) as well as safety. Results: The TX group achieved longer median PFS than the NX group (8.4 months vs. 7.1 months; p = 0.0026, HR = 1.65) and had better median DOR (7.8 months vs. 6.6 months, p = 0.0451). In the TX group 48 (46.2%) and in the NX group 42 (41.2%) patients attained maintenance medication. The OS period of the TX group was longer than in NX patients (35.3 months vs. 19.8 months), but without statistical significance. Patients ≥40 years of age, postmenopausal and with visceral metastases were more likely to benefit from a TX regimen in terms of PFS and OS, whereas hormone and positive HER2 receptor and history of taxane treatments did not affect PFS and OS differences between TX and NX patients. The tumor response rates were 55.3% in the TX vs. 54.9% in the NX group. In the TX group hand-foot syndrome occurred more frequently than in the NX group (47% vs. 16.7%, p < 0.0001), but frequencies of other minor adverse effects were similar in both groups. Conclusions: A TX regimen for advanced breast cancer followed by capecitabine maintenance medication led to longer PFS and DOR than a NX regimen even for patients who were previously treated with taxane in (neo) adjuvant settings. Clinical trial information: NCT01126138.
CMET-33. A SYSTEMATIC REVIEW REVEALS LOCATION SPECIFIC TOXICITY RATES AFTER SRS FOR BRAINSTEM METASTASES
Authors: Ajay Patel, Tuo Dong, Shaheryar Ansari, Aaron Cohen-Gadol, Gordon Watson, James Miller, Tim Lautenschlaeger
Journal: Neuro-Oncology (2017)

Although stereotactic radiosurgery (SRS) is an effective modality in the treatment of brainstem metastases (BSM), radiation induced toxicity remains a critical concern. To better understand how severe or life-threatening toxicity is affected by the location of lesions treated in the brainstem, a systematic review of all available studies on PubMed reporting SRS treatment for BSM was performed. Twenty-seven retrospective studies investigating SRS to BSM were found. Reports included SRS delivered via Gamma Knife, Linear accelerators, and Cyber Knife. There was a total of 1992 SRS treated metastases in 1844 patients. The percentage of BSM in the pons was 62.7%, 22.6% in the midbrain, 9.4% in the midbrain, and the others were comprised of junctions among the substructures of the brainstem. The median margin dose ranged between 13–18 Gy. The number of patients receiving WBRT either before or after ranged from 6.5% - 96.4% (mean 49.8 ± 20.0%). The median tumor volume ranged from 0.1–2.8cc. Local control rate at 12 months varied from 74–100%(mean 86.5% ± 6.2%). Overall survival varied from 3.9–12 months. The rates of grade 3 or greater toxicity, based on the Common Terminology Criteria for Adverse Events varied from 0–9.5%(mean 3.6% ± 3.0%). Overall, the median time to toxicity after SRS was 3 months with 90% of toxicities occurring before 9 months. A total of 1072 cases had toxicity and location data available. The rates of toxicity associated with treatments for metastases in the pons, midbrain, and medulla regions were 3.1% (8/254), 2.8% (19/692), and 0% (0/113), respectively. A χ2 analysis demonstrated the p-value to be 0.06 and 0.07 when comparing the rate of toxicity in the medulla to that in the midbrain and pons, respectively. This raises the question if there is less toxicity in the medulla from SRS to BSM.
L'action de l'Europe face à la résistance aux antibiotiques
Authors: M J Struelens
Journal: Eurosurveillance (2004)

Dans ce numero, Wolfgang Witte et ses collegues decrivent l'emergence en 2002, en Allemagne, de cas d'infections a Staphylococcus aureus resistants a la methicilline communautaires (co-SARM) produisant la leucocidine de Panton-Valentine. Leur article montre la rapide dissemination geographique a travers l'Europe de ce variant extremement virulent d'un vieux pathogene.
Do Published Data in Trials Assessing Cancer Drugs Reflect the Real Picture of Efficacy and Safety?
Authors: Jia-Wei Lv, Yu-Pei Chen, Guan-Qun Zhou, Xu Liu, Ying Guo, Yan-Ping Mao, Jun Ma, Ying Sun
Journal: Journal of the National Comprehensive Cancer Network (2017)

Background: The reporting quality of publications is of vital importance to ensure accurate evidence dissemination. This study aimed to compare the consistency of results reporting between the ClinicalTrials.gov results database and the respective matching publications. Methods: We identified 323 phase III/IV cancer drug trials with a randomized controlled design and searched PubMed for publications in a 50% random sample (n=160). Data were extracted independently from ClinicalTrials.gov and publications. A scoring system was applied to determine characteristics associated with reporting quality. Results: Of 117 reviewed trials with publications, result reporting was significantly more complete in ClinicalTrials.gov for efficacy measurement (92.3% vs 90.6%), serious adverse events (SAEs; 100% vs 43.6%), and other adverse events (OAEs; 100% vs 62.4%). For trials with both posted and published results for design information (n=117), efficacy measurements (n=98), SAEs (n=51), and OAEs (n=73), discrepancies were found in 16 (13.7%), 38 (38.8%), 26 (51.0%), and 54 (74.0%) trials, respectively. Overreporting of treatment effects (7 trials) and alteration of primary end points favoring statistically significant outcomes (11 trials) were the major discrepancies in efficacy reporting; incomplete (66 trials) and underreporting (20 trials) of SAEs were the predominant issues in benefit/risk reporting. Median quality score was 21 (range, 14–28). Trials that had parallel assignment, were phase IV, had primary funding by industry, were completed after 2009, and had earlier results posted possessed better reporting quality. Conclusions: Although most trials showed reasonable completeness and consistency, some discrepancies are prevalent and persistent, jeopardizing evidence-based decision-making. Our findings highlight the need to consult results systematically from both ClinicalTrials.gov and publications.
P3.01-055 The Usefulness of Liquid Biopsy for ctDNA in Patients with EGFR-Mutant NSCLC During and After Treatment with EGFR-TKIs
Authors: T. Yokoyama, G. Naka, H. Ishida, K. Kishi, Y. Ohashi, H. Kunitoh
Journal: Journal of Thoracic Oncology (2017)
P2.03-011 Correlation and Problems of Re-Biopsy and Liquid Biopsy for Detecting T790M Mutation
Authors: K. Komiya, T. Nakamura, M. Hayase, H. Hirakawa, S. Ogusu, T. Abe, C. Nakashima, K. Takahashi, Y. Takeda, S. Kimura, N. Sueoka-Aragane
Journal: Journal of Thoracic Oncology (2017)
P3.07-006 Pemetrexed Exerts Intratumor Immunomodulatory Effects and Enhances Efficacy of Immune Checkpoint Blockade in MC38 Syngeneic Mouse Tumor Model
Authors: R. Novosiadly, D. Schaer, Z. Lu, N. Amaladas, S. Luo, A. Capen, C. Meyer, J. Manro, G. Donoho, T. Doman, G. Hall, T. Smeal, M. Kalos, S. Geeganage
Journal: Journal of Thoracic Oncology (2017)
PDTM-09. KCNA1 IS A MOLECULAR TARGET OF A NOVEL SET OF microRNAs THAT DRIVE PEDIATRIC GBM INVASION
Authors: Lin Qi, Yulun Huang, Hua Mao, Mari Kogiso, Xiumei Zhao, Yuchen Du, Holly Lindsay, Patricia Baxter, Jack Su, Chris Man, Laszlo Perlaky, Xiao-Nan Li
Journal: Neuro-Oncology (2017)

Glioblastoma (GBM) is the most malignant brain tumor that occurs in both adults and children. Diffuse invasion into normal brain tissue is one of the major features that makes GBM particularly difficult to treat. While direct comparison of matched invasive (GBMINV) and tumor core (GBMTC) cells would facilitate the discovery of molecular drivers of GBM invasion, GBMINV cells are extremely difficult to obtain from patients. To overcome this barrier, 6 patient derived orthotopic xenograft (PDOX) mouse models of pediatric GBM were utilized to isolate GBMTC and GBMINV cells. Global profiling of 768 human microRNA using a real-time PCR-based Taqman system identified 23 microRNAs were upregulated in the GBMINV cells as compared with the matching GBMTC cells. Functional validation was performed by lentivirus-mediated silencing of miR-126, miR-487b and miR-369-5p, the top three overexpressed microRNA in the GBMINV cells. Compared with the control cells, silencing of miR-126, miR-487b or miR-369-5p in GBMINV cells resulted in significant inhibition of cell migration in vitro (without affecting tumor proliferation) (P<0.05), and the blocking of in vivo invasion. The depth of invasive fronts was remarkably decreased (P<0.05) in mouse brains. Whole genome gene expression profiling from the same pairs of GBMINV and GBMTC cells identified a subset of genes regulated by miR-126 (n=74), miR-487b (n=46) and miR-369-5p (n=2) that occurred in at least 4 of the 6 pairs. Surprisingly, KCNA1 was the only gene that was co-regulated by all three miRNAs and significantly over-expressed in the GBMINV cells (p=0.033). Targeting KCNA1 by specific inhibitor ADW1 and Agi suppressed GBMINV cell invasion in vitro without affecting tumor proliferation. In conclusion, our strategy of utilizing functionally validated matching pairs of GBMINV and GBMTC cells has identified KCNA1 as the molecular target of a novel set of microRNAs (miR-126, miR-487b and miR369-5p) that drive GBM invasion.
RARE-31. DUAL BRAF/MEK THERAPY FOR PATIENTS WITH BRAF V600E-MUTATED TUMORS: DRAMATIC CLINICAL AND RADIOGRAPHIC RESPONSES AND A REDUCTION IN CUTANEOUS TOXICITY
Authors: Aaron Bernstein, Oliver Mrowczynski, Amrit Khalsa, Sandra Ryan, Catherine Chung, Michael Glantz
Journal: Neuro-Oncology (2017)

The BRAF V600E mutation is a common oncogenic driver present in a variety of primary brain tumors including pleomorphic xanthoastrocytoma (66%), pilocytic astrocytoma (9%), primary and secondary glioblastoma (2% and 6%), giant cell glioblastoma (7%), ganglioglioma (18%) and papillary craniophyaryngioma (90%). Dabrafenib, a selective oral inhibitor of several mutated forms of BRAF kinase, and trametinib, a reversible inhibitor of MEK1 and MEK2 activation and activity, target two different kinases in the RAS/RAF/MEK/ERK pathway. Both are approved for treatment of metastatic melanoma. Cutaneous lesions including squamous cell carcinoma are common debrafenib-associated toxicities. We treated three BRAF V600E-positive patients, one with a pilocytic astrocytoma, one with a papillary craniopharyngioma, and one with a ganglioglioma with this combination regimen. Patients initiated therapy with single-agent dabrafenib (150 mg every 12 hours). Trametinib (2 mg nightly) was added 7-14 days later. The patient with the pilocytic astrocytoma experienced a near-complete radiographic and complete clinical response after 6 weeks of therapy. Substantial partial responses (by RANO criteria) were observed in the other two patients. The patient with the craniopharyngioma developed dramatic, diffuse verrucal keratosis within two weeks of starting dabrafenib. This completely resolved within two weeks of adding trametinib. Dual BRAF/MEK inhibitor therapy represents an exciting therapy for patients with BRAF V600E-mutated primary brain tumors. In addition to greater efficacy than single-agent dabrafinib (documented in melanoma), this combination has the potential to reduce some distressing BRAF inhibitor-related adverse events, including some cutaneous toxicities.