bluuebunny/crossref_metadata_2025 huggingface dataset:
The potential of gemcitabine, cisplatin, and bevacizumab combination therapy for patients with ovarian clear cell carcinoma.
Authors: Ito Kimihiko , Nakagawa Mio , Tashima Lena , Yagi Taro , Odani Chihiro , Ono Hitomi , Okubo Rieko , Shimoji Kanoko , Goto Mayako , Tsuruta Tomohiko , Hori Kensuke
Published: September 2018

e17065

Background: Patients with advanced ovarian clear cell carcinoma (OCC) have poor prognosis, and response rate of chemotherapy for relapsed OCC is less than 10%. The effective standard treatment has not been established yet. The synergic effect between gemcitabine and cisplatin in ovarian cancer patients has been reported. And bevacizumab added on chemotherapy has some evidences of progression-free survival improvement at primary, platinum sensitive relapse and platinum resistant relapse situation than chemotherapy only. Therefore, we conducted a retrospective charts review to examine the safety and efficacy of gemcitabine, cisplatin, and bevacizumab combination (GPB) therapy in OCC patients treated in our hospital. Methods: Intravenous gemcitabine (1,000 mg/m2, day 1, 15), cisplatin (40 mg/m2, day 1, 15), and bevacizumab (15 mg/kg, day 1) were administrated every 28 days. This combination therapy was continued until disease progression or appearance of intolerable toxicity. This retrospective study was approved by our institutional ethics board. Results: Eight patients were treated with this GPB therapy in our institution between April 2013 and August 2015. Six patients received this therapy due to presence of relapse, and 2 patients were administered GPB as post-operative adjuvant therapy. Four patients were not treated with bevacizumab due to their medical conditions. The median treatment cycle was 5.5 (range: 1-15). Six patients were evaluable and their responses were partial response (PR) 1, stable disease (SD) 2, and progressive disease (PD) 3. The overall response rate was 13% and the disease control rate was 50%. Four patients needed dose reduction or treatment delay. Grade 3 adverse events observed were anemia (25%), nausea (13%), and elevation of G-GTP (13%). Conclusions: GPB therapy is feasible and moderately effective for patients with OCC. We are currently conducting the prospective multi-institutional phase II trial (UMIN 000023097) and expect that GPB therapy will be used as the standard treatment regimen for OCC, in future.
Early clinical progression in patients with gynecologic malignancies receiving immunomodulatory antibody therapy.
Authors: Zamarin Dmitriy , Martin Madhuri , Zecca Nicholas , Iasonos Alexia , Zhou Qin , Aghajanian Carol , Sabbatini Paul
Published: September 2018

e17087

Background: The success of immunomodulatory antibodies have led to their increasing investigation in GYN cancers. Many of these patients, however, discontinue the drugs early in treatment due to symptomatic progression, making it challenging to assess clinical benefit and late responses associated with these agents. Here, we describe the clinical characteristics underlying early progression requiring immunotherapy discontinuation in order to better guide patient selection for such trials. Methods: A retrospective analysis was performed on all GYN cancer patients treated with immunomodulatory antibodies at MSKCC between 1/2013 and 6/2016. Patients were defined as early progressors if they had clinical/radiographic disease progression before 12 weeks which required therapy discontinuation. Logistic regression was applied to model the relationship between baseline clinical and radiographic characteristics and early progression. P<0.05 was considered to be statistically significant. Results: A total of 105 patients met the inclusion criteria, with 74 (71%) with ovarian cancer. Therapeutic targets included CTLA-4 (3%), and PD-1/PD-L1 alone and in combination with other targets (97%). Of these, 55 (52%) met the criteria for early progression requiring therapy discontinuation (median therapy duration 7 weeks, range 1.6-12.1). There was an increased risk for early progression in patients with pre-treatment ascites (p=0.005, OR 6.4, 95% CI 1.7-23.7), and with baseline bulky disease, defined by at least one tumor measuring ≥ 5cm, compared to patients with tumors <5cm (p=0.001, OR 4.1, 95% CI 1.7-9.9). Clinical symptoms/deterioration were the reason for early discontinuation in 35 (64%) of the patients, with symptomatic ascites and abdominal pain as the most common complaints. Conclusions: Symptomatic clinical progression of peritoneal disease leading to early discontinuation of immunomodulatory antibody therapy is common in patients with GYN cancers and is associated with increased pre-treatment disease volume. The extent of peritoneal disease should be taken into strong consideration when selecting GYN cancer patients for trials with immunomodulatory antibody therapy.
Alterations in the uterine microbiome in patients with early endometrial cancer: Variations by ethnicity and obesity.
Authors: Clark Leslie Horn , Keku Temitope O , McCoy Nicole Amber , Hawkins Gabrielle , Bae-Jump Victoria Lin , Brewster Wendy R.
Published: September 2018

e17114

Background: Obesity and race are known to negatively impact clinical outcomes in endometrial cancer (EC). Mounting evidence suggests the gut microbiome may play an important role in the pathogenesis of both obesity and cancer, however, little is known about the microbiome of the malignant uterus. Further, there is known to be microbiome variability by ethnicity in the vagina and gut. Thus, we sought to evaluate the microbiota of ECs and to assess for variations by obesity and race. Methods: Following IRB approval, banked tumor specimens of patients undergoing hysterectomy for management of endometrioid EC were identified. Tumors were analyzed from African-American (AA) and Caucasian (CAU) patients and stratified as obese (BMI ≥ 30kg/m2) or non-obese (BMI < 30kg/m2). The microbiota of the endometrial tumors were characterized by 16S rRNA high throughput sequencing. Descriptive statistics were performed. Results: We evaluated specimens from 11 AA (52%) and 10 CAU (48%). The median age was 68.9 years. Majority of women were postmenopausal (n=17, 81%) and obese (n=14, 66.7%). Tumor grade was evenly distributed with 7 grade 1 (33.3%), 6 grade 2 (28.6%), and 8 grade 3 tumors (38.1%). We found that EC microbiota richness was higher in AA than CAU (p=0.02). When analyzed by race and obesity status, we observed significant differences in EC microbiota composition. The microbiota composition differed between obese AA and obese CAU (p=0.04). In obese subjects the distribution of Proteobacteria was 55% AA vs. 30.7% CAU (p=0.02) while Actinobacteria abundance was 17.8% versus 34.4% (p=0.05) (Table 1). Among CAU, the EC microbiota profile differed between obese and non-obese (p=0.07). At the genus level, the relative abundances of Delftia, Finelgoldia, Geobacillus, Propionibacterium and Pseudomonasvaried by obesity and race. Conclusions: Bacteria exist in the malignant uterus. EC microbiota diversity was greater in tumors of AA versus CAU women, and tumor microbiota profiles were distinct between ECs of obese and lean women. Better understanding of the inter-relationship of obesity and race on the EC microbiota may provide critical insight into the disparate clinical outcomes between AA and CAU women with EC.
TWISTT analysis of open labeled multicentric study of BIOMAb- EGFR [Nimotuzumab] in head and neck cancers with chemotherapy and/or radiotherapy.
Authors: Pawar Dilip , Attili Suresh VS , Sunkavalli Chinnababu
Published: September 2018

e17505

Background: Head and neck Squamous Cell Cancer (HNSCC) have poor prognosis in recurrent and metastatic setting with limited treatment options. The treatment decision are predominantly driven by quality of life (QOL) issues, pharmaco-economics besides the survival and response rates. Present TWISTT analysis was based on the earlier “open labeled multicentric study of Nimotuzumab in head and neck cancers with chemotherapy and/or radiotherapy”, to evaluate the QOL outcomes Methods: The active part study was conducted between Nov 2007 and Jan 2009 followed by long term follow up. Patients received Nimotuzumab w at 200 mg/m2 / week along with RT or chemotherapy Results: A total of 150 patients received therapy, who met the eligibility criteria [ Ref-CTRI/2007/95] Overall adverse event rate is 24% [ 36 subjects who experienced any AE]. Mucosal inflammation [ related to RT] was most frequent AE and three were only 4 [2.7%] serious adverse events [ all of them not related to IP]. Skin rash was not apredictor for the response to BIOMAB and was observed in 1.3%. The median TWISTT score in responding patients was 246 days vs 128 days for non responders. PFS and OS were not presented as the main focus of the study is to report the QOL and TWISTT score. Conclusions: Based on the results of this analysis, Nimotuzumab in combination with chemo +/- radiotherapy appears as an attractive regimen for patients with metastatic HNSCC. Clinical trial information: CTRI/2007/95.
Small cell carcinoma of the head and neck: Incidence and survival trends based on the Surveillance and Epidemiologic and End Results (SEER) analysis.
Authors: Bean Marta , Goodman Michael , Steuer Conor Ernst , Patel Mihir , McDonald Mark William , Higgins Kristin Ann , Owonikoko Taofeek Kunle , Beitler Jonathan Jay , Shin Dong Moon , Saba Nabil F.
Published: September 2018

e17508

Background: Small cell carcinomas of the head and neck (SmCCHN) are rare neoplasms with an unfavorable prognosis. Population based data describing survival and prognostic factors for this malignancy are limited. Methods: Data was obtained from the US National Cancer Institute’s Surveillance, Epidemiology and End Results (SEER) database for the period 1973-2013. Patient and tumor related characteristics for SmCCHN were compared with squamous cell carcinomas (SCC) of the same anatomic sites. Survival for the two groups was compared by constructing Kaplan-Meier curves and Cox proportional hazard models with and without propensity score matching. Cox models results were expressed as hazard ratios (HR) and the corresponding 95% confidence interval (CI). Results: The dataset included 609 SmCCHN and 227943 cases of SCCHN. SCCHN patients with SmCCHN included significantly greater proportions of females and whites. SmCCHN was more likely to originate in the salivary glands and present with more advanced stage and grade. The overall 5 year and 10 year survival estimates were 27% and 18%, respectively. Corresponding values for SCCHN were 46% and 31%. The multivariable analyses adjusting for age, sex, race, marital status, year of diagnosis, stage, grade and receipt of radiation, the HR comparing SmCCHN to SCCHN was 1.53 (95% CI: 1.39-1.68). Elderly, male, black and not married persons had worse prognosis compared to their respective reference groups. Other factors independently associated with lower survival included more advanced stage and tumor grade, and earlier decades of diagnosis. In the propensity score matched analyses the corresponding HR was 1.27 (95% CI: 1.15-1.40). Conclusions: Compared to SCCHN, SmCCHN in addition to carrying a worse survival, is more likely to originate in the salivary glands, present with more advanced stage, and affect females and whites.
Survival and side effects from novel alternative regimen for squamous cell head and neck cancer.
Authors: Bishnoi Rohit , Bejjanki Harini , Bennett Jeffery A , Reisman David , Shah Chintan
Published: September 2018

e17515

Background: Toxicity of the standard regimens is a major limitation in treatment of head/neck cancer which impacted about 61,000 persons in 2016 in USA of which 13,000 died. We present data herein with low dose chemotherapy (metronomic) using commonly used drugs Taxols, Platins, 5-Flurouracil and EGFR inhibitors. We achieved equal or better outcomes as compared to standard dosing with minimal side effects (level 3/4). Methods: This is a retrospective study on squamous cell head and neck cancer patients where standard first line therapies were started at ½ normal dosing and was increased until the emergence of side effects and titrated thereafter. Results: Patient population consisted of 32 patients with 87% males and with median age 65.2 years where 59% had recurrent disease, 71% locally advanced and 28% had metastatic disease. Total 270 chemotherapy cycles were delivered among these 32 patients with median of 9 cycles. Median dose for Cispatin was 45mg/m2, Paclitaxol was 80mg/m2, 5-FU was 360mg/m2/day. Cetuximab was used at standard doses. 6 patients who achieved long-term disease control were then placed on immunotherapy with either Nivolumab (median dose of 3mg/kg) or Pembrolizumab (median dose of 2mg/kg) and got median of 7 cyles. Out of 32, 9 patients (28%) achieved complete remission, 3 patients (9%) achieved near-complete remission with more than 95% reduction in tumor size. Overall disease control rate was 68% and overall response rate was 59%. Out of 9 patients who achieved complete remission 5 underwent surgical exploration and 1 went for cryo-ablation and no residual tumor was found. Measuring tumor volume in patients who achieved disease control showed volume reduction of 53%, 62% and 78% in 1st, 2nd and 3rdfollow up surveillance studies at mean interval of 101 , 186 and 331 days showing steady response. Median Progression free survival was 17.8 months and overall survival at 40 months was 54%. Notable high-grade toxicities were generalized fatigue in 12.5% (n = 4), grade 3 neutropenia in 18% (n = 6) and grade 4 neutropenia in 1 patient. Conclusions: These excellent results, low toxicity and subsequent good quality of life encourage patient tailored approach rather than one-size fits all approach.
Clonal repopulation dynamics in recurrent human papillomavirus-associated head and neck cancer.
Authors: Harbison Richard A. , Kubik Mark , Konnick Eric , Faden Daniel , Xu Chang , Pritchard Colin , Rodriguez Cristina P. , Zhang Qing , Delrow Jeffrey J. , Chen Chu , Mendez Eduardo , Duvvuri Umamaheswar
Published: September 2018

e17517

Background: Despite the better prognosis for human papillomavirus (HPV)-associated head and neck cancer (HNC) relative to HPV-negative HNC, 10 to 25% of HPV-associated cases recur within 3 years of completing therapy. We sought to investigate clonal repopulation dynamics in recurrent HPV-related oropharyngeal squamous cell carcinoma (OPSCC). Methods: Deep sequencing ( > 500X) using a CLIA-certified, targeted 262-gene multiplexed assay was performed on DNA extracted from 11 pairs of matched FFPE-preserved primary and subsequent recurrent p16-positive OPSCC samples including two pairs from the University of Washington and nine from the University of Pittsburgh. Results: 82% of patients were male with a median (IQR) age of 62 (15) years. Nine of eleven patients presented with advanced stage disease. Five were initially treated with surgery and concurrent chemoradiation, two with surgery, and four with concurrent chemoradiation. Median (IQR) time to recurrence was 10 (10.5) months. Four patients reported a history of tobacco use. The mean (SD) number of somatic nucleotide variants (SNVs) per tumor was 16.4 (12.2). 42% of SNVs occurred in the primary alone while 28% were unique to recurrences. 28% of SNVs were shared between primary-recurrent pairs. Three patients with distant or regional recurrences had different mutational profiles between the primary and recurrence suggesting repopulation by an early-appearing clone vs sampling error. One patient developed two local recurrences with conserved mutations in addition to de novo mutations in each subsequent recurrence suggesting repopulation by early and late evolving clones. Genes with a substantial functional impact that were frequently mutated in primary tumors include IDH2 and FBXW7. Recurrently mutated genes found in recurrent tumors include TET3, PIK3CA, STK11, and HDAC4. Conclusions: In thistargeted exome sequencing study of matched primary-recurrent OPSCC tumor pairs, we observed clonal repopulation with both transmitted and de novo mutations. Intriguingly, we noted a predilection for mutations involving genes regulating metabolism including IDH2 among primary tumors which has potential implications for precision medicine approaches.
Treatment of radioiodine refractory high-differentiated thyroid cancer with lenvatinib.
Authors: Romanov Ilya , Mudunov Ali , Isaev Pavel , Bychkov Yury , Odzharova Akgul
Published: September 2018

e17518

Background:Long time the patients with high-differentiated thyroid cancer with distant metastases had only one type of treatment. It was radioiodine therapy courses and follow-up. In cases of revealed radioiodine (RAI) refractory process we did not have possibilities for treatment this category of patients. Results of trials DECISION and SELECT gave to oncologist new keys for successful treatment. We present our group of RAI refractory thyroid cancer patients, which was treated by Lenvatinib like routine clinical practice. Methods:We have on treatment 8 patients (3-male, 5-female). Histologically – papillary thyroid carcinoma. Provisions of national clinical recommendations were considered as criteria of a RAI-refractory status. Existence of a symptomatic progression of a tumor was main criterion. Results:Six patients received from 7 to 14 month courses of treatment. All these patients are revealed partial response of the tumor lesions by PET-FDG-CT and the dramatically decrease of thyroglobulin level is noted. Two patients stopped treatment after 1 month of therapy. One patient due to destructive pneumonia, other patient – death due to myocardial infarction. Adverse events not related with Lenvatinib. The adverse events were controllable. We noted the expressed arterial hypertension. Before correction of a dose of a drug increase of arterial pressure more than 160/100 mm Hg is noted. Arterial pressure managed to be corrected the combined scheme of therapy (amlodipin, bisoprolol, hydrochlorthiazide). Correction of a dose of lenvatinib is made at 3 patients to 20 mg daily, 2 patient – 14. Conclusions:Introduction of a lenvatinib clinical practice is very successful. But we noted of important accurate expert selection of patients for treatment after establishment of a condition of a RAI-refractory and revealed really symptomatic progression, adequate correction of the adverse effects (arterial hypertension) and well-timed correction of a dose of a lenvatinib.
Change of three-dimensional DW-MRI for primary tumor and cervical lymph nodes in head and neck cancer during radiotherapy: A phase II prospective study.
Authors: Feng Mei , Lang Jinyi , Wu Fei , Chen Xiaochun , Xu Peng , Huang Yecai , Li Lu , Ren Jing
Published: September 2018

e17522

Background: DW-MRI become more important, recent study find it help to discriminate metastatic lymph node and distinguish recurrent tumor. However, we still poorly understand the dynamic change of it during treatment, especially for 3D-apparent diffusion coefficient (ADC). It is urgent to study the dynamic change of 3D-ADC for head and neck cancer during radiotherapy, and to investigate the correlation between the ADC change, radiation dose and volume reduction. Methods: 60 head and neck cancer patients treated with image guided IMRT were enrolled. DW-MRI were performed on 3.0T MRI (b = 0, 500, 800 s/mm2) at pre-radiation, the 15th, the 25thand post-radiation. Region of interest was primary tumor (GTV-T) and cervical lymph node (GTV-N). The volumes and the maximum, mean and minimum of 3D-ADC value were automatically measured by MIM software. Pearson analysis was used to assess the correlation between 3D-ADC values, delivered radiation dose and tumor volume reduction. Results: All the patients exhibited the mean 3D-ADC increase in GTV-T (0.64±0.24 x10-3 mm2/s) and GTV-N (0.35±0.09 x10-3 mm2/s), with the mean increased ratios of 0.50±0.20 and 0.44±0.08 between pre- and post-radiation. However, the changes of the maximum and minimum 3D-ADC values for GTV-T and GTV-N had no correlation with delivered dose and volume reduction. The maximum, mean and minimum 3D-ADC changes in spinal cord were almost invisible (≤ 0.04 x10-3 mm2/s). The increased mean ADC had a strong positive correlation with the increased radiation delivered dose for GTV-T and GTV-N respectively (r = 0.977, p= 0.023; r = 0.974 , p= 0.026), and a significantly negative correlation with the volume reduction (r = -0.989, p= 0.011; r = -0.969 , p = 0.031) . Conclusions: The mean 3D-ADC value of primary tumor and cervical lymph node can be increased greatly for head and neck cancer during radiotherapy. It had a strong negative correlation with the volume reduction, and a positive correlation with the increased delivered dose. Dynamic 3D-ADC changes during radiotherapy might be an early indicator to assess the treatment response and helps to make treatment strategy for head and neck cancer.
Gene expression subtypes in early stage oral cavity squamous cell carcinoma and subclinical nodal metastasis.
Authors: Mazul Angela , Zevallos Jose , Wang Lin , Walter Vonn , Hayes David N.
Published: September 2018

e17525

Background: Patients with early stage oral cavity squamous cell carcinoma (OCSCC) without clinical or radiographic evidence of cervical lymphadenopathy present as a therapeutic dilemma. Although studies show a survival advantage with elective neck dissection, about 70% of patients have pathologically negative nodes. In this study, we examine four previously described head and neck squamous cell carcinoma gene expression subtypes [basal (BA), mesenchymal (MS), atypical (AT), and classical (CL)] and subclinical nodal metastasis in early stage, clinically node negative OCSCC. Since the MS subtype is characterized by expression of epithelial to mesenchymal transition (EMT) genes, which is important in the initiation of nodal metastasis, we hypothesize the MS subtype is associated with higher rates of nodal metastasis and worse overall survival. Methods: Using a previously validated integrative genomic analysis, we determined gene expression subtype for T1-T2, clinically node negative OCSCC cases undergoing elective neck dissection from the Cancer Genome Atlas (TCGA) database. We compared rates of pathologically positive lymph nodes and survival in stage by gene expression subtype. Results: We identified 67 T1-T2, clinically N0 cases with pathologic node data. Most of OCSCC cases were BA (N = 24) or MS (N = 26) subtype. Few were either AT (N = 9) or CL (N = 8) subtype. Three of the BA subtype and 11 of the MS subtype tumors were pathologically node positive. MS tumors were 3.38 times (95% Confidence Interval (CI): 1.08-10.69) as likely to have pathologically positive lymph nodes compared to the BA subtype. The MS subtype was associated with worse overall survival (hazard ratio: 2.33, 95% CI 0.79-6.87) compared with the BA subtype. Conclusions: Our findings suggest gene expression subtypes can potentially identify early stage OCSCC patients at higher risk for subclinical nodal metastasis and may reflect high EMT gene expression associated with this phenotype. Gene expression subtype, along with tumor mutation and clinical profiles, could be used to determine the need for neck dissection in early stage OCSCC, and could translate into a reduction in treatment morbidity and length of hospitalization.
Compliance of elderly head and neck squamous cell carcinoma (HNSCC) patients (pts) with concurrent chemoradiotherapy (CRT) in cetuximab versus cisplatin.
Authors: Kazan Eyad , Kleihneny Tiffanie , Sakek Nacera , Thomas Alice , Milian Lucia , Edel Magali
Published: September 2018

e17553

Background: Cisplatin toxicities substantially increased in elderly patients with head and neck cancer, when it is given as CRT. Bio-radiotherapy using cetuximab could offer a less toxic alternative. The purpose of this retrospective study is to evaluate the compliance of cetuximab versus cisplatin in CRT for HNSCC pts 70 years of age or old pts. Methods: We included over 70 years old patients treated by radio chemotherapy in head and neck cancer. Severity of AE was measured by the percentage of the drug dose reduction. Dose is considered reduced if patient did not receive 200mg/m² in cisplatin group, and if he did not receive the seven planned cycles in cetuximab group. We recalculated the dose reduction percentage including over 65 years old patientes. Results: We enrolled 37 over 70 years pts, middle age 74.5(from 70 to 88). 23 pts were treated by cetximab-RT compared to 14 treated by cisplatin-RT. 30% of pts (7 of 23 pts) in cet-RT group received a dose reduction versus 28% (4 of 14 pts) in cisplatin-RT group. Then, compliance to cetuximab is comparable to cisplatin and dose reduction is close.This finding disclaim a general assumption that cetuximab is better tolerated than cisplatin concurrently to radiotherapy in elderly pts. When we recalculated the dose reduction including also over 65 years old pts, we endrolled 64 pts, dose reduction in cet-RT pts remains about 28% (10 of 35pts) versus only 17% (5 of 29) in cisplatin-RT group. A clear increasing in dose reduction of cisplatin appears once pts passed 70 years old. Finally, we redistributed the 35 cetuximab-RT pts according to period of treatment, the first group included pts treated between 2007 and 2011, dose reduction was 35% (7 of 20patients),the second group included pts treated between 2012 and 2016, dose reduction was only 20% (3 of 15). This supports that good handling of cetuximab's toxicities improves the treatment's compliance. Conclusions: Dose reduction in elderly pts is equal in cetuximab and cisplatin. Dose reduction to cisplatin clearly increases among over 70years old pts. Good handling of cetuximab improves the compliance to treatment
Induction chemotherapy (IC) with EXTREME study regimen for locally advanced head and neck cancer (LAHNC) frail patients.
Authors: Cochin Valérie , De-Mones-Del-Pujol Erwan , Digue Laurence , Garcia-Ramirez Muriel , Dupin Charles , Majoufre-Lefebvre Claire , Daste Amaury
Published: September 2018

e17564

Background: IC with TPF (docetaxel, cisplatin, 5FU) in LAHNC is limited to fit patients (pts). We conducted a retrospective cohort study to evaluate the use of EXTREME regimen (platinum, 5FU, cetuximab) as IC in LAHNC frail pts. Methods: Retrospective analysis of all consecutive pts with unresectable LAHNC treated with EXTREME regimen with or without 5FU as IC from two French centers from 2008 to 2015. We evaluated the rate of realization of the complete sequence (at least 2 cycles of IC and all radiation courses). Tolerance and efficacy, including clinical benefice, median progression free survival (PFS) and median overall survival (OS) were estimated. Results: We included 34 pts with average age of 56 years [46-70] (Table). Patients presented decreased weight (10% in one month or 15% in 6 months): 74% (n=25), pain: 76% (n=26), feeding tube: 82% (n=28), tracheotomy: 15% (n=4), fistula: 15% (n=4) and low albumin <35g/l: 41% (n=14), <25g/l: 12% (n=4). Six pts (17%) not received 5FU (cardiovascular history). Grade 3 toxicities were seen in 50% pts principally due to cisplatin. 5FU dose was decreased in 9% (n=3) and cisplatin switched to carboplatin in 15% (n=4). The sequence was achieved for 76% (n=26) of pts and 80% (n=27) presented clinical response with improvement of symptoms (increased weight: 32%, n=11). Six pts (17%) have a progression disease (PD) under IC, one patient (3%) died during bioradiotherapy (BRT) (stomach perforation) and one (3%) stopped IC after one cycle (infection) but achieved BRT. BRT with cetuximab was used in 85% (n=23) (average of 6 cycles [2-8]). PET-FDG at 3 months showed 9% (n=3) of complete response (CR) and 44% (n=15) of PD. Median PFS and OS were 5.7 and 15.5 months respectively. PD at 3 months was associated with decreased median OS: 21.9 versus 13.6 months, p=0.01. Conclusions: This is the first report of use of the EXTREME regimen as IC. This IC was used in a very frail population and the majority achieved sequence with significant clinical benefice. [Table: see text]
Effect of cabozantinib on bone turnover markers (BTM) and bone metastases (BM) in radioiodine refractory (RAIR)-differentiated thyroid cancer (DTC).
Authors: Konda Bhavana , Knopp Michael V. , Martin Peter R. , Geyer Susan , Cabanillas Maria E. , De Souza Jonas A. , Wirth Lori J. , Menefee Michael E. , Liu Stephen V. , Shah Manisha H.
Published: September 2018

e17580

Background: Cabozantinib is a small molecule multiple-receptor tyrosine kinase inhibitor that primarily targets MET and vascular endothelial growth factor receptor 2 (VEGFR2). We evaluated the effect of cabozantinib on BTM in RAIR DTC. We also assessed the response of BM to cabozantinib using 18F Sodium Fluoride (NaF) PET and radionuclide bone scans. Methods: This prospective analysis was performed as part of a multicenter International Thyroid Oncology Group phase II study of cabozantinibin patients with RAIR DTC who progressed on prior VEGFR-targeted therapy (NCT01811212). BTM [serum C-telopeptide (CTx), osteocalcin, N-telopeptide (NTx), procollagen type 1 (Pc1) and urinary NTx] and NaF PET or Tc-MDP scans were done at baseline and after 8 weeks of therapy. A paired t-test was used between baseline and week 8 BTM. Results: Primary study results were presented elsewhere (Shah, et al. 2015, International Thyroid Congress) showing a response rate of 36% with cabozantinib. Of 25 patients (pts) enrolled, 21 had BM, 10 of whom were on bone-modifying agents (BMA) prior to week 8. Only 2 pts had elevated BTM at baseline. In all pts who had paired BTM, there was a statistically significant decline in all BTM except NTx by week 8 (table). Pts not on BMA also had a significant decline in CTx (p 0.0003), urine NTx (p 0.0300), and Pc1 (p 0.0030) compared to baseline. 19 pts were evaluable for overall response and there was no correlation between BTM and response rate. 6/21 patients underwent paired NaF PET scans and 4/6 had minor reduction in lesion uptake at 8 weeks. Conclusions: Interestingly, most of our patients had normal baseline BTM despite BM. Cabozantinib was associated with a strikingly significant reduction in all BTM (even when BTM were within normal limits at baseline) except NTx by week 8. Minor decreases in bone lesion uptake was noted on NaF PET in 4/6 evaluable patients. Clinical trial information: NCT01811212. [Table: see text]
Morbid mortality associated with total thyroidectomy for differentiated carcinoma in a training institute.
Authors: López Saucedo RaÃºl Alejandro , Rodirguez Roberto , Infante Sergio , Salazar Alejandra , Granados-Garcia Martin
Published: September 2018

e17586

Background: Total thyroidectomy is now a common and relatively safe procedure. In the context of malignant pathology: It optimizes local control, facilitates adjuvant therapy with iodine 131, increases thyroglobulin sensitivity in patient surveillance and improves survival in patients at high risk. The reported morbimortality is related to Transient or definitive hypocalcemia, unilateral or bilateral recurrent laryngeal nerve injury (RLN), postoperative hemorrhage, wound infection, chylous fistula, tracheal injuries or esophageal perforations, cervical sympathetic chain lesions, among others Although death is rare as a result of the procedure and its complications. Methods: The present retrospective, descriptive, observational, cross-sectional, analytical study was performed based on an analysis of the records opened to patients at the National Cancer Institute between November 23, 2012, and January 5, 2015 corresponding to 100 consecutive cases with diagnosis of differentiated thyroid cancer, submitted to at least total thyroidectomy. Results: According with the AJCC 7th edition TNM distribution was: pT1 n = 13, pT2 n = 14, pT3 n = 63, pT4a n = 10, pN1a n = 12, pN1b n = 51, M1 n = 12. In 73 patients, no complications developed, and of the complications presented, 8 patients developed transient hypocalcemia, 19 permanent hypocalcemia, 3 resections of the RLN in a planned manner, 1 accidentally identified intraoperative lesion, 7 unconscious lesions of the RLN, 11 developed dysphonia, 1 Horner's syndrome, 2 Vagus lesions, 2 patients with tracheal or pharyngeal fistula, 1 chylous fistula, 1 transoperative hemorrhage and 1 hematoma. Mortality in one of the patients. Conclusions: Our results translate morbidity and mortality associated with locally advanced tumors, where the only correlation identified were the relationships with the presence of parathyroid glands in the pathology report and the development of hypocalcemia. With the above, we can assure that the best ally of the surgeon is the careful dissection based on a deep knowledge of anatomy, which could reduce the morbidity due to the surgery.
Outcomes and prognostic factors of localized, resected malignant salivary gland tumors: Examining a single institution’s 12-year experience to discover indications for adjuvant chemotherapy.
Authors: Gutschenritter Tyler , Machiorlatti Michael , Vesely Sara , Ahmad Bilal , Razaq Wajeeha , Razaq Mohammad
Published: September 2018

e17587

Background: Survival outcomes remain poor in salivary gland malignancies (SGMs) with multiple poor prognostic factors despite adjuvant radiotherapy. We examined prognostic factors that portended poor survival in resected SGMs to determine possible indications for adjuvant chemoradiotherapy. Methods:Patients who underwent curative resection with or without adjuvant radiotherapy between 2002 and 2014 were identified and retrospective chart review was performed. Bivariate analysis was performed on continuous variables using Analysis of Variance. Chi-Square analysis and Fishers Exact Tests were performed on categorical variables. To evaluate the overall survival (OS) and disease-free survival (DFS), Kaplan-Meier curves and log-rank tests of homogeneity were used. Results: Overall, 99 patients met inclusion criteria. Median follow-up time was 46.8 months. Univariate analysis revealed male sex, smoking history ≥ 10 pack-years, high grade, stage III-IVB, squamous cell histology, and perineural invasion significantly impacted OS and DFS. High-risk histopathology significantly impacted DFS and trended towards poor OS. Positive resection margins trended towards significantly impacting DFS. Multivariate analysis revealed only male sex and perineural invasion significantly impacted OS and DFS. Conclusions: Survival outcomes remain poor for patients with high-grade, late-stage tumors with perineural invasion. Specifically, perineural invasion is a poor prognostic factor regardless of age, histology, stage, and grade. Males and patients with a smoking history ≥ 10 pack-years have worse survival outcomes with male sex being a more influential prognostic factor. Notably, this is the first study to quantify patient’s smoking history in malignant salivary gland tumors and assess the impact of pack-year smoking history on survival outcomes. Given our observed trend, positive resection margins would likely become significant influencer of DFS with larger sample size and longer follow up. Adjuvant chemoradiotherapy should be evaluated in patients with the above-mentioned characteristics.
Second or none: Many patients treated for refractory differentiated thyroid cancer with small molecular kinase inhibitors do not receive a second line of therapy.
Authors: Copher Ronda , Adejoro Oluwakayode , Byfield Stacey DaCosta , DuCharme Mary , Chatterjee Debanjana , Joshi Prashant Ramesh , Desai Avinash , Baig Mahadi Ali
Published: September 2018

e17589

Background: Describe the treatment patterns of patients initiated on NCCN-recommended small molecular kinase inhibitors (SMKIs) for radioiodine-refractory differentiated thyroid cancer (DTC) approved in the United States. Methods: A large national US claims database was used to identify adult patients diagnosed with thyroid cancer (≥2 non-DX medical claims, ≥ 30 days apart) from 1/1/2006 - 6/30/2016 (study period) with claims for SMKIs from 1/1/2010 - 5/31/2016. Continuous enrollment required participation in a commercial or Medicare Advantage health plan ≥3 months before and ≥1 month following index date (date of first pharmacy claim for SMKI). Line of therapy (LOT) periods were defined by receipt and timing of SMKIs. Patient follow up was earliest disenrollment, death or end of the study period. Patient characteristics and SMKI treatment patterns were described. Results: A total of 217 DTC patients were identified; 63% commercially insured and 37% Medicare Advantage. Almost half were male (48%); mean age was 61.2 years (standard deviation SD 12.5 years) and mean follow-up period was 499 days (SD 414 days). In the study period, 35% (n = 77) of patients had ≥2 LOTs and 18% (n = 39) had ≥3 LOTs. Mean treatment duration was 5.4 months (SD 6.7 mos) for LOT1, 4.9 months (SD 3.8 mos) for LOT2, and 4.2 months (SD 4.9 mo) for LOT3. During the full study period, the most used regimens were Sorafenib for both LOT1 (37%) and LOT2 (25%), pazopanib (18%) and sunitinib (18%) in LOT3. Also, in the study period, 33 patients had sorafenib in LOT1 of which 16 were treated with sorafenib again (48%) in LOT2. Post FDA approval in 2015, Lenvatinib became the predominant first-line regimen (47%, n = 29) during study period. Across all first line therapies, for those patients with ≥12 months of follow-up, 53% (n = 60) initiated LOT2. Conclusions: Sorafenib was the most common first line of therapy for DTC, with Lenvatinib adoption increasing as first-line therapy since the drug’s approval in 2015. Depending on the period evaluated, almost half to 2/3 of patients are not receiving a second line of treatment, efficacious and patient appropriate therapy is of importance in treating this rare cancer.
US-guided percutaneous radiofrequency versus microwave ablation for benign thyroid nodules: A prospective multicenter study.
Authors: Cheng Zhigang
Published: September 2018

e17593

Background: To evaluate the clinical outcomes between radiofrequency ablation (RFA) and microwave ablation (MWA) in treating benign thyroid nodules (BTNs) with a prospective multicenter study. Methods: The prospective multicenter study achieved the registration of Chinese Clinical Trial Registry (Number: ChiCTR-ONRC-13003087). From January of 2013 to December of 2015, the total number of 1,252 patients with 1351 benign thyroid nodules (BTNs) at eight participating institutions was enrolled in the multicenter study. The ablation devices were applied in the study including RFA system of VIVA RF generator (VIVA RF generator, STARmed, Goyang, Korea) and MWA system of KY-2000 2450MHz microwave system (KY-2000, Kangyou Medical, Nanjing, China). All the procedures of RFA or MWA were performed under ultrasound (US) guidance in each center. Results: The number of target nodules treated by RFA and MWA were 687 in 649 cases and 664 in 603 cases, respectively. For the estimation of efficacy, the mean maximal diameter reduction ratios (MDRRs) of RFA vs. MWA groups at the 3rd, 6th, 12th month and last follow-up were 36.4±17.3% vs. 36.0±23.0% (p = 0.765), 54.1±22.7% vs. 49.3±28.0% (p = 0.005), 64.5±22.1% vs. 57.9±40.1% (p = 0.008) and 65.5±26.0% vs. 58.2±33.5% (p = 0.028), respectively. The mean volume reduction ratios (VRRs) of RFA vs. MWA groups at the 3rd, 6th, 12th month and last follow-up were 67.6±20.3% vs. 64.4±43.5% (p = 0.143), 84.1±13.5% vs. 78.4±48.2% (p = 0.016), 89.6±20.0% vs. 82.5±49.7% (p = 0.035) and 91.3±12.6% vs. 81.1±70.4% (p = 0.045), respectively. For the estimation of safety, for all the complications and side effects encountered at the peri-ablation and follow-up period in two groups, the major, minor complication and side effect rates of RFA vs. MWA group were all no statistical significances with 4.78% vs. 6.63% (p = 0.156), 2.00% vs. 2.49% (p = 0.562) and 4.93% and 4.64% (p = 0.812), respectively. Conclusions: As a conclusion of the prospective multicenter study, both RFA and MWA under US guidance percutaneously are safe and effective techniques for selected patients with BTNs. Larger MDRR and VRR can be achieved in RFA group than the ones in MWA group at 6-month and later follow-up. Clinical trial information: ChiCTR-ONRC-13003087.
Improving lung cancer diagnosis at a large urban minority-based medical center: Where can we do better?
Authors: Su Christopher , Chau Vincent , Bhargava Amit , Shah Chirag D , Ohri Nitin , Gucalp Rasim A. , Packer Stuart H. , Perez-Soler Roman , Halmos Balazs , Cheng Haiying
Published: September 2018

e18017

Background: Lung cancer diagnosis is a complex process with barriers to care which are more apparent in underserved communities. We examined factors affecting lung cancer diagnosis in an underserved urban community, including demographics, lung cancer screening, and survival outcomes. Methods: All new lung cancer diagnoses with confirmed pathology at an urban academic medical center in 2015 were identified. Retrospective chart review was conducted and time from initial abnormal imaging to tissue sampling was calculated. Analyses were performed with χ2, ANOVA, linear regression, and log-rank tests. Results: In 2015, 229 patients were diagnosed with lung cancer. 36 patients (16%) expired or were referred to hospice due to clinical deterioration without treatment. 162 patients (71%) were ultimately started on therapy. Patients were predominantly Black (38%), Hispanic (30%), underserved (mean per capita income $21729), and enrolled in Medicare or Medicaid (83%). Only 62% of the patients had a PCP at time of diagnosis. Most presented at an advanced stage (63% III or IV) and 88% were former/current smokers. 78 patients (48%) were eligible for low-dose CT screening but only 9 (12%) completed screening. Screening completion was correlated with established PCP (p = 0.012). Time from abnormal imaging to biopsy was 31±40 days without significant difference across age, gender, race, ethnicity, income, insurance, and primary language. Cancers diagnosed in the inpatient vs. outpatient setting were found at a more advanced stage (p = 0.002) and had lower survival (p < 0.001). Hispanics had better survival (p = 0.008) despite lower per capita income and higher incidence of smoking. Conclusions: There was no significant difference in imaging to biopsy time across major demographic factors and they are unlikely to be a source of poor outcomes. However, the advanced stage and poor prognosis of cancers detected in the inpatient setting, proportion of patients who expired or were referred to hospice immediately after presentation, and disparity between screening eligible and completed patients underscores the critical importance of increasing lung cancer screening and establishment of primary care.
Racial disparities in NCI Cancer Center (NCI-CC) care for multiple myeloma (MM).
Authors: Fiala Mark A , Ailawadhi Sikander , Schroeder Mark A. , Stockerl-Goldstein Keith , Vij Ravi , Wildes Tanya Marya
Published: September 2018

e18061

Background: Despite a favorable genetic profile, African-Americans (AAs) with mm have poorer outcomes secondary to inferior treatment. NCI-CCs provide the highest-quality of care and attendance has been associated with better outcomes in many cancers. AAs have greater access to NCI-CCs proximally; however, they attend these facilities at lower rates than their white peers. The impact of attendance at NCI-CCs on mediating racial disparities in mm outcomes has not been reported on to date. Methods: We reviewed cases of mm the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database from 2000-2011 who were enrolled in Medicare Part A and B > 1 year prior to diagnosis, excluding cases enrolled prior to age 65 and those where mm diagnosis occurred post-mortem. Any center designated a NCI-clinical or -comprehensive center in 2002, 2005, or 2010 was considered a NCI-CC; attendance was defined as 2 or more claims on separate dates (MEDPAR and Outpatient files) from a NCI-CC in the 12 months following mm diagnosis. Logistic regression was performed to determine if race was associated with attendance, Cox regression to determine the association of attendance with survival. Results: 21,843 cases were analyzed; the median age was 77 years; 80% were white, 15% AA/Black. Overall NCI-CC attendance was low, only 11% of the population. Compared to white patients, black patients had a 13% decreased odds (aOR 0.87, 95% CI 0.75-0.99) of NCI-CC attendance after controlling for age, gender, socioeconomic status, geographic, and overall health variables. Attendance was associated with a 28% decrease risk for death (aHR 0.72, 95% CI 0.68-0.76), but had little impact on black-white outcome disparities. Black patients had a 9% increase in risk (aHR 1.09, 95% CI 1.04-1.13) after controlling for NCI-CC attendance. Conclusions: Black patients with mm have lower NCI-CC attendance. This may be related to referral bias and/or patient declining referral. NCI-CC attendance was associated with superior outcomes; however, controlling for attendance did not mediate black-white outcome disparities suggesting that racial treatment disparities pervade beyond access to NCI-CCs.
Disparities in cancer outcomes across age, sex, and race/ethnicity among pancreatic cancer patients.
Authors: Tramontano Angela , Nipp Ryan David , Kong Chung Yin , Pandharipande Pari , Dowling Emily , Schrag Deborah , Hur Chin
Published: September 2018

e18071

Background: Age, sex, and racial/ethnic disparities exist for several malignancies, but these relationships are understudied in pancreatic adenocarcinoma (PDAC). We used the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database to determine whether these disparities persist in survival and treatment after adjusting for demographic, clinical, and treatment characteristics. Methods: Our study includes PDAC patients (pts) diagnosed from 1992-2011 in the SEER-Medicare database. We used Cox regression models to compare survival across age, sex, and race/ethnicity, stratified by non-metastatic and metastatic cancer. We used logistic regression to compare differences in chemotherapy, radiation, and surgery receipt across age, sex, and race/ethnicity. We adjusted for marital status, urban location, socioeconomic factors, SEER region, comorbidities, cancer stage, lymph node status, tumor location, tumor grade, diagnosis year, and chemotherapy, radiation, and/or surgery receipt. Results: Of 20,896 PDAC pts (median diagnosis age = 75 years; 56% female), 84% were White, 9% Black, 5% Asian, and 2% Hispanic; 53% had metastatic cancer. Among non-metastatic pts, adjusted Cox regression demonstrated that older pts had worse survival compared with younger pts (HR: ≥1.1 for all ages [reference = 66-69 years vs. 70-74, 75-79, 80-84, 85+], p < 0.01 for all); we found no survival differences between sexes. Black (HR: 1.1, p = 0.01) and Hispanic (HR: 1.2, p < 0.01) pts had worse survival compared to White pts. Among metastatic cancer pts, adjusted Cox regression demonstrated that older pts (HR: 1.1 for age 85+ [reference = 66-69 years], p < 0.01) had worse survival than younger pts, and males (HR: 1.1, p < 0.01) had worse survival than females. There were no racial/ethnic differences. There were disparities in treatment received; older age and minority race/ethnicity were associated with lower likelihood of receiving chemotherapy, radiation, and/or surgery. Conclusions: Age, sex, and racial/ethnic disparities in survival outcomes and treatment received exist for PDAC pts; these disparities persist after adjusting for differences in demographic, clinical, and treatment characteristics.