bluuebunny/crossref_metadata_2025_split huggingface dataset:
Radiotherapy (RT) potentiation with weekly (q1w) or standard every 3 weeks (q3w) cisplatin chemotherapy (CT) for locally advanced head and neck squamous cell carcinoma (HNSCC).
Authors: Molin Yann , Lavergne Emilie , Pommier Pascal , Racadot Severine , Montbarbon Xavier , Poupart Marc , Zrounba Philippe , Ceruse Philippe , Fayette Jerome 
Published: March 2020

6056 Background: Q3w CT is standard RT potentiation for HNSCC but its toxicity requires to look for new treatment’s modalities. The aim was to explore if q1w CT could be a safe and effective alternative. Methods: Patients (pts) treated by chemoradiation (CT-RT) for a HNSCC were retrospectively included. Study population was first described. Then overall (OS) and progression-free survival since the RT onset were performed. Survival distributions were estimated by Kaplan-Meier method and compared between CT groups using the Log-Rank test. Prognostic effect of CT group was explored using Cox model. Results: 266 pts treated between January 2004 and December 2008 were included: 170 and 96 pts respectively received q1w and q3w CT. At diagnosis, 46% had oropharynx lesions, 20% larynx, 17% hypopharynx and 14% oral cavity. 70% pts experienced surgery, 39% CT induction and a median dose of radiation of 64 Gy without any significant difference between CT groups. However, median age at diagnosis was significantly different between q1w and q3w CT (58 vs 54, p<0.001) as well as alcohol consumption (79% vs 68, p=0.047), stage at diagnosis (30%-60% stage III-IV vs 13% -80%, p=0.003), IMRT use (4% vs 13%, p=0.011) and median weight before RT (66 kg vs71kg, p=0.014). Q3w CT was more toxic than q1w in terms of weight loss (87% vs 75%, p=0.012), renal failure (50% vs 35%, p=0.022), worse CT plan completion (42% vs 66%, p<0.001). Moreover, grade 3/4 toxicities, such as mucositis (34% vs 13%, p<0.001) and dermatitis (7% vs 1%, p=0.012), were more frequent. More pts needed parenteral nutrition (10% vs 2%, p=0.008), analgesics (91% vs 70%, p<0.001), secondary hospitalization (31% vs 8%, p<0.001), RT interruption >= 3 days (8% vs 2%, p=0.037) and had long-term toxicities (24% vs 12%, p=0.014). With a median follow-up of 42 months 95% CI [36.8-48.8], a trend in favour of q3w CT was found:2-years OS of 83% (95% CI [73-90]) vs 74% (95% CI [66-80]), p=0.089. However, after adjustment on prognostic factors CT group was not significantly associated with OS nor with PFS. Conclusions: Q1w RT-CT is safer than q3w and may be as efficient. Follow-up data will be updated to reinforce efficacy results.
Treatment-associated mortality in head and neck cancer: Analysis of phase III trials.
Authors: Shcherba Marina , Viswanathan Shankar , Blakaj Dukagjin , Garg Madhur , Haigentz Missak 
Published: March 2020

6064 Background: Chemoradiotherapy is an accepted standard for patients with locoregionally advanced squamous cell carcinoma of the head and neck (SCCHN). Although acute and long-term toxicities of this approach are known, little is known about early mortality associated with curative-intent treatment. Methods: We reviewed 45 phase III trials of curative-intent radiotherapy in SCCHN published from 2000-2012 for adequate reporting of early mortality defined as deaths during and within 3 months of therapy, regardless of attribution. We estimated pooled proportions of deaths during prescribed therapy using a random effects model of radiotherapy alone (RT), concurrent chemoradiotherapy (CCRT) and induction chemotherapy (IC) regimens. The relative risk of death during CCRT vs. RT and CCRT/IC vs. RT were estimated. Results: Although all trials reported early mortality statistics, definitions had wide variability, and only 34 trials (75%) met adequate reporting characteristics. Ten trials excluded enrolled patients who died prior to initiating therapy. Of studies reporting early mortality statistics, crude frequency of death during prescribed therapy was 2.7% (308/11362). The pooled estimated rates of death observed during RT alone was 1.7% (SE: 0.3, I2=89.2%) from 29 studies, while 2.8% (SE: 0.4, I2=64.9%, 19 studies) and 3.1% (SE: 0.5, I2=53.5%, 9 studies) for CCRT and IC regimens, respectively. The pooled relative risk for death in CCRT compared to RT treatment was 1.08 (95%CI: 0.78, 1.48, p=0.63, I2=0, 15 studies). The relative risk for death in CCRT or IC therapy compared to RT was 1.06 (95%CI: 0.77, 1.45, p=0.72, I2=0, 15 studies). When reported, most early deaths were attributed to infectious complications or cardiovascular events. Conclusions: Early death remains an uncommon but important complication of curative-intent radiotherapy in SCCHN that necessitates consistent reporting. Despite strict eligibility criteria and protocol-defined care, treatment-associated death occurs with all regimens, though no clear increase was observed with CCRT/IC regimens over RT alone. Early mortality should be considered during treatment planning, particularly for patients with considerable comorbidities.
Significance of myeloid-derived suppressor cells in squamous cell carcinoma of the head and neck.
Authors: Kim Grace G , Zanation Adam M , Taylor Nicholas A , Shores Carol G. , McKinnon Karen P , Serody Jonathan Stuart 
Published: March 2020

6070 Background: Patients with advanced stage squamous cell carcinoma of the head and neck (SCCHN) have less than 50% 5-year survival rate Human papillomavirus (HPV)-associated SCCHN in oropharyngeal sites have shown better prognosis. Little is known about the role of myeloid-derived suppressor cells (MDSCs) in immune suppression or tumor progression in the setting of SCCHN. Our objective is to evaluate the clinical significance of MDSCs in subjects with SCCHN, HPV-positivity, and advanced cancer staging. Methods: Thirty-three subjects with SCCHN and 10 healthy donors were enrolled in this prospective cohort study. Fresh blood was collected at the time of surgical resection of SCCHN in a tertiary academic center between August 2011 and January 2013. Peripheral blood mononuclear cells (PBMCs) were obtained using Ficoll Hypaque. MDSCs were immunophenotyped as CD14-CD33+CD11b+by flow cytometry. HPV status was determined by in situ hybridization Frequencies of MDSCs in blood of different cohorts were evaluated. Results: Thirty-three subjects (ages 34-83 years, 25 males) with SCCHN were enrolled. Increased numbers of CD14-CD33+CD11b+ cells of total leukocytes were found in HPV-associated SCCHN (median 26.6%, n=11) compared to HPV-negative SCCHN (16.3%, n=19). Interestingly, 3 subjects who previously had HPV-positive SCCHN but with no evidence of disease had 6.24% (n=3) CD14-CD33+CD11b+cells of leukocytes which was higher than healthy donors (3.55%, n=10). Subjects with advanced cancer stages (III-IV) had higher levels of MDSCs (26%, n=19) compared to those with a lower grade (I-II, 15.5%, n=11) regardless of HPV status. Three subjects were lost to follow up. Of the remaining subjects, the overall median follow time was 3 months and subjects who were found to have recurrence, regional or local metastasis had higher frequencies of MDSCs in the blood (26.35%, n=4) compared to those with no evidence of disease (18.5%, n=26) at the time of surgery. Conclusions: This study suggests there is an accumulation of MDSCs in peripheral blood of patients with SCCHN, particularly in HPV-associated SCCHN. Further, increased levels of MDSCs in the peripheral blood are related to more advance cancer stage and poor clinical outcomes.
Induction chemotherapy (CT) with docetaxel, cisplatin, and fluorouracil (TPF) followed by concomitant cisplatin plus radiotherapy in locally advanced nasopharyngeal cancer (NPC): Results after 06 years.
Authors: Kerboua Esma , Bouzid Kamel 
Published: March 2020

6075 Background: In squamous cell carcinoma of head and neck cancer, TPF induction CT improved survival over cisplatin plus fluorouracil (Posner MR: NEJM, vol357, Oct 2007). The main objective of this study is to evaluate the activity and safety of TPF in patients (pts) with locally advanced NPC followed by concomitant cisplatin plus radiotherapy (cCTRT). Methods: Pts with undifferentiated NPC were enrolled from December 2006–December 2012 and received 3 cycles of TPF (docetaxel 75 mg/m2 and cisplatin 75/m2 day 1, plus fluorouracil 750 mg/m2 days 1–5, every 4 wks) with G-CSF days 1–5 post CT. CT was followed by cCTRT with cisplatin 40 mg/m2/wk and radiotherapy (65–70 Gy) starting 4–6 wks after the third cycle of CT. The primary endpoint was overall response rate (ORR) after induction CT and after cCTRT. Secondary end points were safety, disease free survival (DFS), and overall survival (OS). Results: 42 pts have been enrolled (26 M/16 F). UICC 1997 classification: n=9 stage II, n=10 stage III, n=23 stage IV. Median age is 37 yrs (range 18–64). Evocative clinical signs are cervical nodes n=20, rhinologic n=13, otologic n=5, and neurologic n=4. All pts were evaluated for safety and 38 for response.TPF well tolerated with main toxicities grade 3–4 (WHO) were neutropenia 36%, thrombocytopenia 32%, anemia 18%, diarrhea 6%, and mucositis 18%. Four pt died from sepsis that was probably treatment-related. ORR was 90% with an 71.4% (n=27) complete response (CR) rate, 23.6% (n=9) partial response (PR), and 5.2% (n=2) stable disease. No pts progressed after induction CT. Main toxicity during cCTRT was neutropenia grade 3–4 in 9%, mucositis grade 3 in 45% and grade 4 in 4%. Late toxicities were xerostomia grade 3 in 50%. At treatment completion, CR and PR rates were 79% and 20%; 2 pts had stable disease. At a median follow up of 72 months (range 7–72), 8% of pts have shown recurrence or progressive disease. DFS and OS rates at 72 months were 65% and 70%, respectively. Conclusions: TPF followed by cCTRT appears to be an active and feasible regimen with a manageable safety profile and may be a promising therapeutic option for pts with high stage NPC.
Specific detection of Epstein-Barr virus microRNAs in plasma samples from nasopharyngeal carcinoma patients: Correlation with tumor mass assessed by MRI.
Authors: Ferrand francois-Regis , Gatolliat charles-Henry , Bidault Francois , Verillaud Benjamin , Gelin Aurore , Jimenez-Pailhes anne-Sophie , Amiel Corinne , Guigay Joel , Busson Pierre 
Published: March 2020

6079 Background: Epstein-Barr virus (EBV) microRNAs of the BART family can be detected in the plasma of at least a fraction of nasopharyngeal carcinoma (NPC) patients. Our aim was to investigate the specificity of plasma BART detection in NPC patients and the correlation with viral DNA load and/or clinical characteristics. Methods: Hsa miR484 and 4 miR-BARTs (ebv-miR BART 2-5p, 5, 9 and 18) were assessed by RT-PCR following RNA extraction in 37 plasma samples including 20 NPC, 8 non-NPC head and neck squamous cell carcinoma (SCC) patients and 9 healthy EBV carriers. EBV DNA copy numbers (viral load) were measured in the same samples. To explore correlations of BART concentrations with tumor mass, MRI-based volume analysis was designed and performed on a subset of 13 patients with non metastatic NPC. In addition, longitudinal variations of BART concentrations were studied in 9 NPC patients for whom we had sequential plasma samples. Results: The cellular hsa miR-484 was detected in all plasma samples with a slightly higher average concentration in plasma samples from NPC and SCC patients. On the other hand, the miR-BARTs were undetectable or at a very low level in samples from SCC patients and healthy carriers contrasting with a high level in most NPC patients. There was an overall positive correlation between EBVDNA copy numbers and plasma concentrations of each miR-BART. However substantial amounts of plasmatic miR-BARTs were observed in several patients for whom no plasma EBV DNA was detected.Their concentration was apparently not correlated to the initial tumor volume but their longitudinal variations were parallel with clinical evolution in all but one case. Conclusions: To a large extent, detection of plasma miR-BART-2-5p, 5, 9, and 18 is specific of NPC patients. Their concentration does not seem to correlate with tumor mass, at least in localized NPC patients. In a fraction of patients without initial detection of plasma EBV DNA, the kinetics of plasma BARTs may provide informations on early tumor response under treatment and may have prognostic value.
The Long-HER study: Clinical and molecular analysis of advanced HER2+ breast cancer treated with trastuzumab and associated to long-term survival.
Authors: Espinosa Enrique , Gámez-Pozo Angelo , Perez Carrion Ramon Maria , Manso Luis , Crespo Carmen , Mendiola Cesar , Alvarez Isabel , Margeli Mireia , Bayo Juan L. , Gonzalez Xavier , Santaballa Ana , Ciruelos Eva , Cabrera Miguel Angel , Anton Antonio , Catalan Gustavo , Álvarez Gallego José Valero , Miramon Jose , Lopez Vacas Rocio , Zamora Pilar 
Published: March 2020

608 Background: Some patients with advanced HER2+ breast cancer survive in the long-term after receiving trastuzumab-based therapy. Long-HER study was an observational, multicenter study that compared long-term survivors and a control group from the clinical and molecular point of view. Methods: Patients with metastatic HER2+ breast cancer that had been treated with trastuzumab-based therapy and had an objective response or stable disease for at least 3 years were included. A control group having a progression in the first year of therapy was selected for comparison (similar first-line therapy). A microarray platform was used to assess whole genome expression analysis in paraffin-embedded samples. Differential expression, ontology and analysis of metabolic pathways were performed. Results: 103 patients were registered, 71 of who had a long-term complete remission. Only 5 of these patients had received trastuzumab in the adjuvant setting: this was the only clinical factor associated to long-term survival. The molecular study included 35 Long-HER and 18 control samples. Gene expression ontology revealed alterations in HIF, apoptosis, and EGF, PI3K and p53 pathways. The PI3K pathway was mostly related with a poor response to therapy. Conclusions: trastuzumab-based therapy achieves long-term survival in a selected group of women with advanced HER2-positive breast cancer. Whole genome analysis comparing such a group with a control group found some alterations that may predict early progression to trastuzumab.
Long-term disease control of ≥2 years achieved with cabozantinib in subjects with metastatic medullary thyroid carcinoma on a phase I study.
Authors: Cohen Ezra E.W. , Hong David S. , Pfister David G. , Salgia Ravi , Burtness Barbara , Cohen Roger B. , Ball Douglas Wilmot , Mehra Ranee , Mangeshkar Milan , Yaron Yifah , Bentzien Frauke , Kurzrock Razelle 
Published: March 2020

6090 Background: Metastatic medullary thyroid cancer (MTC) carries a median survival of about two years (Modigliani et al. 1998; Roman et al. 2006). Cabozantinib inhibits three primary pathways implicated in MTC pathogenesis and progression: MET, vascular endothelial growth factor receptor-2 (VEGFR2), and RET. A phase I study was initiated in September 2005 in patients (pts) with advanced solid tumors. Methods: 85 pts, including 37 with MTC were enrolled to evaluate safety, pharmacokinetics, and to determine maximum-tolerated dose (MTD). Once the MTD of 140 mg freebase (equivalent to 175 mg malate salt) was determined, 20 metastatic or locally advanced MTC pts were enrolled in an MTD expansion cohort. 10/37 MTC pts achieved a confirmed partial response (cPR) (Kurzock et al. 2011). We report here on long-term disease control (DC), defined as cPR or progression-free at ≥ 24 months (m), in the MTC cohort. Results: After a minimum follow-up period of 52 m, 11 of 37 pts (30%) experienced DC, and have remained progression-free for > 24 m. Time from diagnosis and time since development of metastatic disease was similar in patients with (11) or without (26) long term DC. As of 04 Dec 2012, 5 of these 11 pts remain on treatment for a median time of 55 m (53-73m). A best response of cPR was associated with long-term benefit: 4/5 pts continuing on treatment achieved cPR, one achieved SD. The adverse event profile of cabozantinib was generally predictable and adverse events were managed with symptomatic treatment and dose modifications. The median final dose for pts with long-term DC was 60 mg (range 20-140), with a median number of dose reductions of 2 (range 0E4). Reasons for dose reductions in two or more pts experiencing long-term DC included diarrhea (7), palmar-plantar erythrodysaesthesia syndrome/rash (6), mucositis/stomatitis (3), anorexia (3), nausea (2), and vomiting (2). Conclusions: Treatment with cabozantinib demonstrates long-term DC in a cohort of pts with metastatic MTC. Cabozantinib offers an important new treatment option for patients with progressive, metastatic MTC. Clinical trial information: NCT00215605.
Survival and prognostic factors of radioiodine refractory pulmonary metastatic differentiated thyroid carcinoma (DTC).
Authors: Wassermann Johanna , Bernier Marie-Odile , Spano Jean-Philippe , Lepoutre-Lussey Charlotte , Simon Jean-Marc , Ménégaux Fabrice , Hoang Catherine , Aurengo André , Leenhardt Laurence 
Published: March 2020

6093 Background: The challenging key point of management of radioiodine refractory DTC patients is to define those who could benefit from experimental drugs in clinical trials. Methods: We reviewed clinical and pathological data of patients with refractory pulmonary metastatic DTC treated in our center from 1990 to 2011. Survival was estimated with the method of Kaplan-Meier. Associated prognostic factors were studied in Cox model based analyses. Results: Among 167 pulmonary metastatic DTC, 46% (n=76) met a criterion of radioiodine refractory disease: at least one metastases without I131 uptake: 61% (n=46); progressive disease despite I131: 22% (n=17) and absence of complete response despite a cumulated dose >600mCi: 17% (n=13). There were 63% of female (n=48) and the median age was 64 years (range 18-87). The initial treatment was total thyroidectomy in 92% (n=70), lymph node dissection in 71%, (n=54) and radioiodine therapy in 100% of patients. Pathological features were papillary histology in 61% (n=46), follicular histology in 29% (n=22) and poor differentiated histology in 10% (n=8). pT stage was 1ab, 2, 3, and 4 in 11%, 13%, 63% and 13% respectively, pN stage after lymph node dissection was 0, 1a and 1b in 33%, 7% and 60% respectively. Metastasis were present at diagnosis in 45% (n=34) of cases. The refractory feature was established at the time of diagnosis and in the follow-up in 18% and 82% of cases respectively. When the disease was considered as refractory, the median overall survival was 5.5 years. The refractory feature at the initial diagnosis was the only independent prognostic factor correlated with poor survival (p<0.001). Conclusions: Patients who are considered as radioiodine refractory at the initial diagnosis of DTC have poor prognosis and should be considered for clinical trials in case of progression.
Safety of trastuzumab in HER2-positive primary breast cancer in Japan: Initial safety report for the large-scale cohort study (JBCRG C-01).
Authors: Yamamoto Naohito , Yamashiro Hiroyasu , Iwata Hiroji , Masuda Norikazu , Ohtani Shoichiro , Takahashi Masato , Yamazaki Kosuke , Kato Makoto , Ohno Shinji , Kuroi Katsumasa , Yamagami Kazuhiko , Morimoto Takashi , Hasegawa Yoshie , Takano Toshimi , Kadoya Takayuki , Hosoda Mitsuchika , Abe Hajime , Morita Satoshi , Yasuno Shinji , Toi Masakazu 
Published: March 2020

613 Background: The global randomized trials with trastuzumab (H) shows increased cardiotoxicity in patients (pts) with HER2 positive early breast cancer (BC). Safety in Japanese has not been fully evaluated. We evaluated the safety, especially focused on cardiotoxicity, of H adjuvant (adj) therapy in an observational study in Japan (UMIN000002737). Methods: Pts with histopathologically confirmed HER2 positive invasive BC were registered. Women with stage I-IIIC disease who received H as neo-adj and/or adj therapy were eligible. Mean LVEF at 3, 6, 9 and 18 months (M) was evaluated. The time points represent examination on day 60-120, 150-210, 240-330 and 455-635, respectively. Results: A total of 2024 pts were registered from 56 institutes between July 2009 and June 2011. Data of 1875 pts were collected and finalized by September 2012, and 1800 of them were analyzed for safety. The median follow-up was 35 M. The mean age was 54.5 years. Elderly pts ≥60 years were 32.7%. Treatments after surgery were: concurrent chemotherapy (CT) and H in 20.1%, sequential CT and H in 43.5% and H monotherapy in 35.9%. Adverse events (AEs) associated with H were reported in 350 pts (19.4%) and grade (G) 3/4 AEs in 12 pts (0.7%). G 3/4 cardiotoxicity was reported in 7 pts (dysfunction, 4pts; angina, 1 pt; myocardial infarction, 1 pt and heart failure, 1 pt). The mean LVEF at the baseline was 69.4%. Mean LVEF at 3, 6, 9 and 18M were 66.9%, 66.3%, 65.3% and 66.3%, respectively. Compared to the baseline, LVEF decreased with significant difference at all time points (p<0.0001). LVEF decrease ≥10% occurred in 177 pts (during H treatment,130 and after H treatment, 47). Follow-up data were available in 66 pts: 34 pts recovered to the baseline. Mean time to recover was 262 days. The univariate analysis showed using anthracycline (odds ratio 2.312, p=0.003) was the only risk factor for cardiotoxicity. However, elderly, radiation concurrent/sequential treatment with CT and H had no impact. Conclusions: From our study, we found the AE profiles of H were consistent with previously known AEs. We found using anthracycline was the risk factor for cardiotoxicity at the moment. We should carefully follow pts and watch long-term safety. Clinical trial information: 000002737.
Cardiac toxicity in breast cancer patients treated with dual HER2 blockade: A meta-analysis of randomized evidence.
Authors: Valachis Antonis , Nearchou Andreas Demetrios , Polyzos Nikolaos P. , Lind Pehr 
Published: March 2020

624 Background: The dual antiHER2 blockade has been shown promising results in patients with HER2-positive breast cancer. Whether this treatment strategy jeopardizes the risk for cardiac adverse events is unclear. We conducted a meta-analysis of randomized trials to investigate the risk of cardiac adverse events when a combination of anti-HER2 therapies is used. Methods: We searched Medline, the Cochrane library, as long as the electronic abstract databases of the major international congresses’ proceedings to identify randomized trials that evaluated the administration of anti-HER2 monotherapy (lapatinib or trastuzumab or pertuzumab) versus anti-HER2 combination therapy with or without chemotherapy in breast cancer. Study outcomes were the congestive heart failure (CHF) grade >/= 3 and left ventricular ejection fraction (LVEF) decline < 50% or more than 10% from baseline. We calculated pooled odds ratios (ORs) and 95% Confidence Intervals (CI) with the Peto method. Results: Six trials were considered eligible. Overall incidence results for CHF in the combined antiHER2 therapy and the antiHER2 monotherapy were 0.88 % (95% CI: 0.47% - 1.64%) and 1.49 % (95% CI: 0.98% - 2.23%). The incidence of LVEF decline was 3.1 % (95% CI: 2.2% – 4.4%) and 2.9% (95% CI: 2.1% - 4.1%) respectively. The OR of CHF was 0.58 (95% CI: 0.26-1.27, p-value= 0.17) while the OR of LVEF decline was 0.88 (95% CI: 0.53-1.48, p-value= 0.64). In subgroup analyses, there were no significant differences in CHF or LVEF decline among different treatment settings or types of antiHER2 therapy. Conclusions: This meta-analysis offers substantial randomized evidence from trials with well-defined cardiac evaluations that a dual anti-HER2 therapeutic approach does not increase the risk for cardiac toxicity.