bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chemo-selection as a strategy for organ preservation in patients with T4 laryngeal squamous cell carcinoma
Authors: Worden F. P. , Wolf G. , Eisbruch A. , Lee J. , Bradford C. R. , Chepeha D. , Teknos T. , Prince M. , Hogikyan N. , Tsien C. , Urba S. G. 
Published: March 2020

6005 Background: We previously reported high rates of overall survival (OS) and laryngeal preservation in two sequential phase II trials with stage III/IV laryngeal squamous cell carcinoma patients (pts), who attained a >50% response after 1 cycle of induction chemotherapy, and who were treated with chemoradiation. Since then, all pts were re-staged to correspond with the most recent American Joint Committee on Cancer staging guidelines. Here we report the outcomes of the T4 pts from both studies. Methods: Pts received 1 cycle of cisplatin 100 mg/m2 & 5-FU 1,000 mg/m2/day × 5 days (P+5FU). Pts with > 50% response received chemoradiation with 70 Gy & P 100 mg/m2, days 1, 22, & 43. Pts with ≤ 50% response underwent laryngectomy. Final planned tumor assessment by direct laryngoscopy with biopsy was performed 8 wks after chemoradiation. Pts who were histologic complete responders, received 2 cycles of P+5FU. Pts with residual disease had planned salvage surgery. Results: Thirty-two T4 eligible (cartilage invasion 31, base of tongue involvement 1) pts were enrolled, 23 M; 9 F; median age 56; stage: IVA 31, IVB 1; site: 19 supraglottic, 13 glottic. After 1 cycle induction chemotherapy, 26 pts (81%) had > 50% response & received chemoradiation; 5 (16%) had surgery; & 1 refused surgery. After chemoradiation, 22 pts had a complete histologic response, & 4 pts required immediate salvage larngectomy for residual disease. Of those responding to chemoradiation, 2 pts eventually required salvage laryngectomy. Currently, 17/32 (53%) are alive (15 without disease), 10 are dead of disease, & 5 are dead from other causes. Toxicity: grade 3/4 granulocytopenia 19%, grade 3/4 mucositis 49%. Median time to follow-up is 45 months. The 3 yr overall survival (OS) is 75% (95% CI=55%, 86%), & the 4 yr OS is 70% (95% CI = 50%, 83%). The 3 yr disease-free survival (DFS) is 77% (CI=58%, 88%), & the 4 yr DFS is 72% (CI=52%, 85%). Conclusions: Our results suggest that chemo-selection is an alternative, organ preservation strategy to total laryngectomy for pts with T4 laryngeal squamous cell carcinoma. No significant financial relationships to disclose.
ERCC1 immunohistochemical expression and cancer-specific survival in patients with locally advanced squamous-cell carcinoma of the head and neck treated by cisplatin-based induction chemotherapy
Authors: Mountzios G. , Handra-Luca A. , Hernandez J. , Taranchon E. , Lacau-St Guily J. , Soria J. , Fouret P. 
Published: March 2020

6011 Background: The excision repair cross-complementation group 1 (ERCC1) enzyme is a key element of the nucleotide excision repair (NER) pathway which removes cisplatin-induced DNA adducts and has been associated with resistance to platinum-based chemotherapy. We assessed the correlation of ERCC1 immunohistochemical expression with objective tumor response and cancer-specific survival in patients with locally advanced head and neck squamous-cell carcinoma (HNSCC) treated with cisplatin-based induction chemotherapy (CBIC). Methods: The initial cohort comprised 107 patients who had received CBIC (modified Al Saraf protocol) from 1992 to 1996 for locally advanced HNSCC. P53 mutations had been previously studied. Pre-therapeutic biopsy samples from 96 patients with a known tumor response were available. Two independent observers blinded to clinical annotations evaluated ERCC1 expression using the H-score protocol. The median H-score value was a priori selected as the cutpoint in order to dichotomize ERCC1 expression for statistical analysis. Results: In 68 cases [71%, 95% CI: 61% - 79%] tumors expressed ERCC1 intensively and diffusely. Using the logistic regression method, the 28 patients [29 %, 95% CI:21%-39%] with tumors expressing ERCC1 at lower levels had a four time greater odds of benefiting from an objective response to chemotherapy [OR 4.3, 95% CI: 1.4 - 13.4; p = 0.01]. ERCC1 and p53 status, but not their association, were independent predictors of tumor response. In a Cox proportional hazard model adjusted on well-established prognosticators including age, T, N, M, tumor differentiation and localization, ERCC1 low expression was associated with a lower risk of cancer death [RR 2.13, 95% CI: 1.03 - 4.43; p=0.04], while p53 status had no prognostic value. Conclusions: Patients with ERCC1 negative tumors are more likely to derive a substantial benefit from CBIC, translated to a lower risk for cancer-related death compared to patients with ERCC1 positive tumors. Large prospective trials should evaluate ERCC1 and other critical biomarkers involved in DNA damage repair process as molecular predictors of responsiveness to chemotherapy in patients with HNSCC. No significant financial relationships to disclose.
Final results of a phase II study of erlotinib, docetaxel and cisplatin in patients with recurrent/metastatic head and neck cancer
Authors: Kim E. S. , Kies M. S. , Glisson B. S. , Tsao A. , Ginsberg L. E. , Holsinger F. C. , Burke B. J. , Truong M. , Papadimitrakopoulou V. A. , Lippman S. M. 
Published: March 2020

6013 Background: Interrupting the epidermal growth factor receptor (EGFR) signaling pathway has shown promise in a variety of cancers and preclinical data has demonstrated possible synergy with platinums and taxanes. Treatment options for recurrent/metastatic HNSCC are limited. A study of cisplatin and docetaxel showed a response rate of 40% and 9.6 month median survival. Erlotinib, an EGFR tyrosine kinase inhibitor, had a 4.3% response rate as single agent in HNSCC. Because of the possible synergy and efficacy, we proposed to study the combination of cisplatin, docetaxel and erlotinib in advanced HNSCC. Methods: Patients (pts) were required to have adequate performance status, measurable disease, no prior EGFR therapy, and may have received prior induction, concomitant or adjuvant chemotherapy, but not for recurrent/metastatic disease. Sites of disease included squamous cell head and neck sites excluding nasopharynx and sinus. Treatment included docetaxel 75 mg/m2 and cisplatin 75 mg/m2 intravenously every 3 weeks and erlotinib 150 mg by mouth daily. All agents were started on day 1. Pts were treated with growth factor support. Results: The trial has completed accrual to 50 pts. 47 pts are available for analysis at this time. Median age is 56 years (range 39–72). ECOG PS is 0, 1, 2 (6, 29, 2 pts). 43 pts are evaluable for efficacy. All responses were confirmed via RECIST. Complete responses have been in observed in 4 pts, partial responses in 25 pts and 12 pts have stable disease for an overall response rate of 67% and disease control rate of 95%. After a follow-up of 19 months, median overall survival was 11 months (8.61, 22.5, 95% CI) and progression free survival was 6.01 months (4.37, 8.25). 6 pts had grade 3/4 febrile neutropenia, 4 pts had grade 3/4 dehydration, 3 pts had grade 3 diarrhea, and 2 pts had grade 3/4 GI bleeding. The most common grade 1–2 toxicities were diarrhea, nausea, and rash. Conclusions: The combination of cisplatin, docetaxel and erlotinib is well tolerated and has very encouraging activity in recurrent/metastatic HNSCC. Tissues are being collected and analyzed for correlative markers including downstream EGFR pathway markers (p-akt, mek, k-ras). Final efficacy and biomarker results will be presented at the annual meeting. No significant financial relationships to disclose.
Correlates and determinants of nuclear epidermal growth factor receptor (EGFR) content in an oropharyngeal cancer tissue microarray
Authors: Psyrri A. , Weinberger P. , Yu Z. , Sasaki C. , Haffty B. , Kowalski D. , Burtness B. 
Published: March 2020

6022 Background: We have previously reported nuclear localization of EGFR protein in oropharyngeal cancer tissue. Nuclear EGFR levels were inversely correlated with survival and response to radiotherapy. Here, we sought to identify determinants and correlates of nuclear EGFR content. Methods: We analyzed an oropharyngeal cancer tissue microarray for expression of key molecules of EGFR signaling cascade utilizing an automated image analysis technique (AQUA) scored on a scale of 0–255 which permits protein quantitation and subcellular localization. Patients with OSCC treated with radiotherapy (RT) or surgery and RT were eligible. Data were analyzed using Pearson correlations and multiple linear regression with robust standard errors. Results: Of the 95 tumors included in this study, 72 (75%) had sufficient tissue for analysis of nuclear EGFR. Nuclear EGFR levels were associated with membranous/cytoplasmic EGFR levels (rho=0.85, p<0.01), nuclear ERK2 (rho=0.34, p=0.01), tumor cyclin D1 (rho=−0.25, p=0.06) and the proliferation markers Ki-67 (rho=0.24,p=0.06) and PCNA (rho=0.38, p<0.01). Nuclear phosphorylated-Akt, PTEN, p53 levels did not correlate with nuclear EGFR level. In multivariable analysis, only PCNA retained its significant association (p=0.01). Conclusions: Our results are consistent with the preclinical model of translocation of membranous EGFR to the nucleus acting as a transcriptional factor and fostering cell proliferation. Nuclear EGFR may constitute a mechanism of resistance to current EGFR-targeted therapies. No significant financial relationships to disclose.
Final results following exclusive chemotherapy for selected patients with squamous cell carcinoma of the laryngopharynx
Authors: Holsinger C. , Bassot V. , Brasnu D. , Laccourreye O. 
Published: March 2020

6039 Purpose: To determine the long-term oncologic outcomes for patients with squamous cell carcinoma (SCC) of the laryngopharynx treated with exclusive chemotherapy after complete clinical response to induction chemotherapy. Materials and Methods: After platin-based induction chemotherapy, selected patients with a complete clinical and histologic response were treated exclusively with additional chemotherapy and observed closely. The rates of overall survival, disease control, and organ preservation were calculated. Results: Survival at 1- and 5-years was 94.5% and 60.2%, respectively. Main causes of death were metachronous second primaries (27) and intercurrent disease (23) than local recurrence (10), distant metastasis, (9) and nodal recurrence (4). The 1-, 3- and 5- year Kaplan-Meier local control estimates were 73.5%, 53.3%, and 50.3%, respectively. No variable was associated with local recurrence using a multivariate analysis. Salvage treatment resulted in an observed final 85.6% local control rate and varied from 96% in patients with glottic cancer to 71% in patients with tumor originating from other locations. Overall, this treatment approach was well-tolerated: 30 patients (20%) experienced grade 3 toxicity; two patients (1.4%) had grade 4 toxicity events. Overall, chemotherapy allowed for successful modulation of local therapy in 66% of patients (96/146). Conclusions: For selected patients, exclusive chemotherapy does not significantly impact survival and maintains function in a majority of patients. Most remarkable, platin-based chemotherapy permitted us to modulate and to diminish the extent of local therapy. Future work should be directed to identify markers of response and resistance to identify which patients are best suited for this approach. No significant financial relationships to disclose.
Swallowing function after intensity modulated radiotherapy (IMRT) and chemotherapy for head and neck cancer
Authors: Caglar H. B. , Allen A. M. , Burke E. , Posner M. , Haddad R. , Norris C. , Annino D. , Wirth L. , Tishler R. 
Published: March 2020

6046 Background: To evaluate the swallowing function of patients treated with intensity modulated radiation therapy (IMRT) + chemotherapy (CT) for HNSCC. Methods: Patients completing RT between 9/04 and 8/06 at the DFCI/BWH were evaluated with IRB approval. All patients had formal swallowing evaluation following the completion of therapy; patients with swallowing difficulty underwent video swallow and both stricture and aspiration were scored. Variables examined for correlation with swallowing pathology were: age, race, gender, smoking and alcohol history, primary site, LVI, PNI, RT intention (primary, postop) and use of induction CT. All variables were analyzed via two-sided t-test. Results: 96 patients were evaluated. Median follow-up 10 mos. 75% of the pts were given definitive RT and 25% received postop RT. 72% stage IV, 24% stage III. Primary sites: oropharynx-43, hypopharynx/larynx-17, oral cavity-13, nasopharynx-11, maxillary sinus-2 and unknown primary-10 pts. All pts received once daily IMRT. 9 pts received RT alone, 28 pts received sequential induction and concurrent (CT) and 59 pts received concurrent CT. 31 pts (32%) had some aspiration after therapy; 36 pts (37%) had evidence of a stricture following RT. All but 5 patients had percutaneous endoscopic gastrostomy placed prophylactically RT. Smoking history was the only significant factor found on univariate analysis to correlate with stricture (p=0.05) but not aspiration. Induction CT was not a significant factor in causing aspiration or stricture. 22 of the strictures (71%) resolved after dilation. RT doses to swallowing structures are under evaluation and will be presented. Conclusions: Aspiration and stricture are common side effects after radical treatment with IMRT and CT for HNSCC. Smoking has a significant negative impact on functional outcome. No significant financial relationships to disclose.
Why do women get mastectomy? Results from a population-based study
Authors: Morrow M. , Hamilton A. S. , Katz S. J. 
Published: March 2020

605 Background: Persistently high rates of mastectomy (M) use for breast cancer have motivated lingering concerns about over-treatment. Yet, little information exists about the etiology of current rates of M. Methods: 2,030 women with non- metastatic breast cancer diagnosed from August 2005 to May 2006 and reported to the LA County SEER registry were identified and mailed a survey shortly after receipt of surgical treatment. Latina and African American women were over-sampled. Survey data were merged to SEER data. We report results on a 50% respondent sample (n=736) which will be updated based on a final respondent sample of 1400 patients (projected response rate, 72%). Results: M was ultimately performed in 279 women (37.9%): 47.3% (n=132) received initial M based on surgeon recommendation and most (80.8%) reported a clinical contraindication to breast conserving surgery (BCS); 69 patients (24.7%) chose M despite a surgeon recommendation for BCS or no recommendation favoring either procedure; and 28.0% (n=78) received M after initial attempts at BCS. This latter group included 16 of 22 patients who attempted BCS in spite of a surgeon recommendation for M. The failure rate of BCS in patients thought to be candidates for the procedure was 12.6%. One quarter of patients who received an initial recommendation for M sought a second opinion, and 80.6% reported concordance in recommendation for M between their first and second surgeons. Conclusions: Receipt of M in this large population sample was the result of clinical contraindications to BCS and, to a lesser extent, patient preference. The infrequent discordance in surgical opinions about the need for M and infrequent conversion to M in patients selected for BCS suggest that surgeons have accepted BCS and recognize standard contraindications to the procedure. Initiatives to improve surgical treatment decision-making should focus on patient perspectives about risk and benefits of surgical options and clinicopathologic features predictive of the success of re-excision after initial attempt at BCS. [Table: see text] No significant financial relationships to disclose.
Influence of the vascular endothelial growth factor-A (VEGF-A) 936C>T germinal polymorphism on tumoral VEGF-A expression in head and neck cancer patients (HNCP)
Authors: Etienne-Grimaldi M. , Formento J. L. , Francoual M. , Pagès G. , Onesto C. , Chamorey E. , Dassonville O. , Poissonnet G. , Milano G. 
Published: March 2020

6050 Background: VEGF-A is a potent inducer of endothelial cell growth and tumor neo-vascularisation. We previously reported that tumoral VEGF-A expression is linked to overall survival in HNCP (Onesto et al. Br J Cancer 2006). The present purpose was to extend this study by analyzing VEGF-A gene polymorphisms since functional VEGF-A polymorphisms associated with serum VEGF-A and risk of cancer have been described. Methods: VEGF-A polymorphisms in position (relative to translation initiation) −2578C>A (promoter region), − 1498T>C (promoter region), −634G>C (5’UTR) and 936C>T (3’UTR) were analyzed (PCR-RFLP) in tumoral genomic DNA from 49 Caucasian HNCP (34 men, 15 women; 16 T1-T2, 33 T3-T4; 31% N0). Tumoral VEGF-A expression was measured with an ELISA kit. Results: Genotype distributions agreed with those predicted by the Hardy-Weinberg equilibrium. A linkage disequilibrium was observed between −2578C>A and −634G>C (p<0.001) as well as between −2578C>A and −1498T>C (p<0.001). Of note, tumoral VEGF-A expression was influenced by the 936C>T polymorphism, with a median at 540 pg/mg in CT+TT patients (N = 5) versus 940 pg/mg in CC patients (N = 44) (p = 0.064). VEGF-A expression was not related to any other polymorphisms. None of the analyzed polymorphisms was linked to node involvement or to tumor size. Unlike tumoral VEGF-A expression, the analyzed genotypes were not related to patient survival. Conclusions: In addition to the known influence of tumor hypoxia, the present data suggest that the 936C>T polymorphism can modulate tumoral VEGF expression, with the presence of the T allele associated with decreased VEGF-A expression. Determination of this germinal polymorphism may thus provide an easily accessible test that deserves further investigation as a potential factor to aid anti-angiogenic treatment selection. No significant financial relationships to disclose.
Lack of effect of palifermin on the anti-tumor activity of cisplatin, cetuximab or panitumumab in the FaDu human head and neck carcinoma model
Authors: Borges L. , Brake R. , Radinsky R. , Starnes C. 
Published: March 2020

6060 Background: The FaDu human pharyngeal carcinoma cell line expresses the receptors for both KGF and EGF. Palifermin is a recombinant form of human KGF. The objective of this study was to determine whether the combination of palifermin with cisplatin and the EGFR inhibitors cetuximab or panitumumab interferes with the anti-tumor activities of these agents in the FaDu head and neck xenograft model. Methods: FaDu tumor cells were implanted subcutaneously in CD1 nude mice. For the combination of palifermin with cetuximab and cisplatin, treatment began on day 9 and for the combination of palifermin with panitumumab and cisplatin, treatment began on day 10. The primary endpoint was the measure of tumor volume. Results: There was no statistically significant difference in tumor volume between the control arm and palifermin alone (p = 0.9993, 0.9831). Neither was there a statistically significant difference between the combination of palifermin, cisplatin and cetuximab compared to the combination of cisplatin and cetuximab (p = 0.7730). Similarly, there was no significant difference between the combination of palifermin, cisplatin and panitumumab compared to the combination of cisplatin and panitumumab (p = 0.9739). Conclusions: In drug combination settings, the addition of palifermin did not affect the therapeutic efficacy of cisplatin, cetuximab or panitumumab in any of the two- or three-way drug combinations. When used alone, palifermin did not promote the growth of the FaDu human xenograft despite the fact that these tumors express KGFR. The lack of interference of palifermin with the anti-tumor activity of cisplatin and the anti-EGFR target therapeutics suggests it is appropriate to move forward clinically investigating the use of palifermin in solid tumor settings in which these therapeutic modalities are used. No significant financial relationships to disclose.
Low-dose gemcitabine and radiation alternated to cisplatin/5fu in stage IV squamous cell carcinoma of the head and neck (HN- SCC): A phase II trial
Authors: Benasso M. , Vigo V. , Bacigalupo A. , Ponzanelli A. , Marcenaro M. 
Published: March 2020

6062 Background: At the National Institute for Cancer Research of Genoa, Italy, we conducted two consecutive phase II single-institution trials testing the addition of gemcitabine into an alternating chemo-radiation (CT/RT) regimen that is considered standard of care in our Institute for patients (pts) with loco-regional advanced HN-SCC (NEJM, 327:1115,1992). In the former trial (ALT-G trial; 47 pts) high dose gemcitabine was administered with cisplatin and RT (Annals of Oncology, 15:646,2004). Methods: In the present trial (ALT-g trial) 3 courses of cisplatin, 20 mg/m2/day and 5-fluorouracil, 200 mg/m2/day, days 1–5 (weeks 1, 4, 7) alternated to 3 courses of standard RT (weeks 2–3, 5–6, 8–9) up to 60 Gy and gemcitabine, 40 mg/m2 on monday of each week of RT, were administered to 47 pts with stage IV (42 pts) or relapsed after surgery (5 pts), unresectable SCC of the oral cavity (11 pts), oropharynx (11 pts) hypopharynx-larynx (24 pts). None had previously received CT or RT. Results: Seven pts (15%) did not complete the planned treatment. Four of them died due to pulmonary embolism (2 pts), fulminant pneumonia (1 pt) or uncertain causes (1 pt). Main grade 3–4 other than local toxicities were: neutropenia (11%), neutropenia with fever (6%), thrombocytopenia (30%), anemia (17% grade 3). 27 pts reached a CR (57%). 7 PRs were rendered disease-free by surgery mainly on the neck (final CR rate: 72%). At a median follow-up of 37 months, 3-yr results and acute local toxicity are compared with those from ALT-G trial and from our data-base of pts treated with alternating cisplatin/5-FU and RT without gemcitabine (ALT): Conclusions: In conclusion, the addition of low-dose gemcitabine into a consolidated cisplatin/5FU and RT alternating program may improve the outcomes with an acceptable increase in acute severe mucositis. No significant financial relationships to disclose. [Table: see text]