bluuebunny/crossref_metadata_2025 huggingface dataset:
Blood biomarker modulation with dasatinib (D) and cetuximab (C) in patients (pts) with advanced solid malignancies
Authors: Egloff A. , Feinstein T. M. , Joyce S. C. , Kelly L. A. , Panelli M. C. , Yang T. , Siegfried J. M. , Grandis J. R. , Argiris A.
Published: August 2020

6034

Background: Src is implicated in the resistance to epidermal growth factor receptor (EGFR) inhibitors. We studied biomarkers in the context of a phase I clinical trial of D, a small molecule inhibitor of several kinases, including Src, and C, a chimeric IgG1 monoclonal anti-EGFR antibody (Esteve et al. ASCO 2008; A14668). Methods: Plasma levels of EGFR, amphiregulin (AR), transforming growth factor-α (TGF-α), COX-2 and hepatocyte growth factor (HGF) were measured using a multiplex enzyme-linked immunosorbant assay (Searchlight TM) at day 0 and day 15. Blood mononuclear cell pSrc/Src levels were measured by Odyssey western blotting at day 0 (no C) and day 15 (with C) prior to and 2, 4, 8 and 24 hours after D. Clinical results were tested for association with biomarkers. The same biomarkers were also measured in plasma collected through an Early Detection Research Network- (EDRN-) sponsored effort from 22 squamous cell carcinoma of the head and neck (SCCHN) pts and 32 cancer-free matched controls. Results: 25 pts had baseline levels, 16 with paired samples. At day 15, EGFR plasma levels significantly decreased (p < 0.001), while AR (p < 0.001) and TGF-α (p < 0.001) significantly increased compared to pretreatment levels. HGF and COX 2 plasma levels did not change with treatment. Pre-daily D pSrc levels on day 0 and day 15 did not differ. pSrc levels decreased from pre-daily D levels by 8 hours post-D at day 0 (p = 0.036, n = 21) and day 15 (p = 0.027, n = 13) and returned to pre-D levels by 24 hours. In 17 pts evaluable for response, only low baseline levels of TGF-α were associated with an increased likelihood of disease control (p = 0.020). Elevated HGF at baseline was seen in treatment pts and SCCHN control pts compared to cancer-free controls (p = 0.006 and p = 0.001, respectively). Otherwise, there was no significant difference in plasma biomarker levels compared to the matched EDRN. Conclusions: D and C significantly decreased plasma levels of EGFR and increased EGFR ligands (AR and TGF-α). Similar data has been shown in vitro, suggesting that C binding to EGFR leads to fewer available receptors for ligand binding. pSrc transiently decreased after D dosing. We will evaluate C plus D and validate these biomarkers in a planned phase II trial in SCCHN.

[Table: see text]
Higher dose per fraction and shorter overall treatment time using intensity-modulated radiation therapy versus conventional radiation therapy with concurrent carboplatin and 5-fluorouracil for locally advanced oropharyngeal carcinoma: A comparison of toxicity and efficacy
Authors: Clavel S. , Nguyen D. , Després P. , Fortin B. , Coulombe G. , Donath D. , Soulières D. , Charpentier D. , Guertin L. , Nguyen-Tan P. F.
Published: August 2020

6038

Background: The aim of this retrospective study was to compare toxicity and efficacy of two different radiotherapy regimens, the first one using intensity-modulated radiation therapy (IMRT) to that of conventional radiotherapy (CRT) in patients treated with concomitant chemotherapy for locally advanced oropharyngeal cancer. Methods: Between January 2000 and December 2007, 249 patients with stage III-IV squamous cell oropharyngeal carcinoma were treated at our institution with definitive concurrent chemoradiation using carboplatin 70 mg/m2/day for four days and 5-fluorouracil 600 mg/m2/day as a continuous infusion every 3 weeks. One hundred patients had 70 Gy in 33 fractions using IMRT (2.12 Gy per day) and 149 received CRT at 70 gy in 35 fractions (2 Gy per day), both administered five times a week. Toxicities were compared using Fisher's exact test. Overall survival (OS), disease-free survival (DFS), and locoregional control (LRC) were estimated using the Kaplan-Meier method and compared with the log-rank test. Results: Median follow-up was 33 months. Three year actuarial rates for OS, DFS, and LRC were 95.4 vs. 75.8% (p < 0.001), 89.3 vs. 71.6% (p < 0.001), and 92.4 vs. 85.3% (p = 0.050) for IMRT and CRT respectively. To minimize the effect of changes in treatment paradigm over time, analyses were performed for patients treated after January 2004 and still showed OS, DFS, and LRC differences. Comparison of toxicities demonstrated that IMRT was associated with fewer dermatitis than CRT (p < 0.01), but caused the same rates of mucositis, weight loss, enteral feeding, hospitalization and death during treatment. There was significantly less xerostomia at 24 and 36 months (p < 0.001) following the end of treatment with IMRT. Conclusions: In this retrospective study, higher dose per fraction and shorter overall treatment time using IMRT given concurrently with chemotherapy when compared to CRT is a safe regimen with better OS, DFS, LRC, and less long term xerostomia. Altered fractionation RT with chemotherapy seems to result in better outcome and future prospective trials are needed to confirm this hypothesis.

No significant financial relationships to disclose.
Comparison of cisplatin (CDDP) and radiation (RT) to cetuximab (C) and RT for locally advanced head and neck cancer (LAHNC): A preliminary analysis
Authors: Koutcher L. , Fury M. , Wolden S. , Zhang Z. , Mo Q. , Zelefsky M. , Kraus D. , Sherman E. , Pfister D. , Lee N.
Published: August 2020

6042

Background: Both concurrent CDDP/RT and C/RT have been shown in randomized trials to yield superior disease control compared to RT alone in LAHNC, but no randomized trial has compared them. We evaluated our center's experience with these regimens. Methods: From 3/1/06 - 4/1/08, 175 patients were retrospectively identified who received definitive treatment for LAHNC with CDDP (planned total dose 100 mg/m2 Q3 weeks X 3) and RT (n = 125) or C (400 mg/m2 load; 250 mg/m2 weekly) and RT (n = 50). Patients who received prior RT, additional systemic therapy, and/or surgery to the primary site were excluded. C was given for the following reasons: auditory 30%, renal 4%, cardiac 2%, performance status 18%, patient choice 16%, neuropathy 4%, unknown 2%, and a combination of factors 24%. The median age: CDDP group 56, 6% >71; C group 66.5, 40% >71. Additional CDDP and C features: male sex, 86 v 78%; stage IV, 70 v 68%; and oropharynx, 78 v 70%. Median RT dose (70 Gy), RT length (46 days), and Karnofsky performance status (KPS) (90%) were the same; alcohol/tobacco use was similar. Results: At a median follow up of 18.7 months, with death without local failure (LF) as a competing risk, the 18 month LF incidence rate was 2.5% in the CDDP group and 43.3% in the C group (p < 0.0001), with the latest event occurring at 16.5 months. The 18 month disease-free survival (DFS) and overall survival (OS) rates were 85.7 v 40.9%, and 96.8 v 73.1%, in favor of CDDP (p < 0.0001 for both). Initially, 21 variables were assessed for significance, and when Cox proportional hazards model was used for multivariate analysis to address prognostic imbalances, treatment with CDDP still predicted for improved LF, DFS, and OS (p < 0.0001 for LF and DFS; p = 0.0017 for OS). For OS analysis, the concordance probability estimates were .67 for using drug choice alone and .80 for using drug choice, T stage, RT dose, and KPS. Conclusions: CDDP/RT and C/RT were used to treat somewhat different populations with LAHNC. The observed superiority of CDDP/RT compared to C/RT in LF, DFS, and OS may reflect patient selection issues. However, preliminary multivariate modeling suggests that CDDP/RT remains the preferred option for fit patients pending further analyses and prospective studies comparing these regimens.

[Table: see text]
Concurrent chemoradiotherapy for locally advanced cervical esophageal carcinoma: A phase II study of oral fluoropyrimidine agents (UFT, S-1) plus cisplatin with radiotherapy
Authors: Iwase H. , Shimada M. , Tsuzuki T. , Hirashima N. , Goto H.
Published: August 2020

6043

Background: Carcinoma of the cervical esophagus is a highly virulent disease. Although surgery is the standard therapy, the results of surgery alone are poor. Oral fluoropyrimidines (UFT, S-1) are useful to treat head and neck cancer and enhance the effectiveness of radiotherapy. We evaluated concurrent chemoradiotherapy using an oral fluoropyrimidine (UFT, S-1) and cisplatin in patients with locally advanced cervical esophageal carcinoma. Methods: Chemoradiotherapy with UFT and cisplatin (R-U-P) consisted of 60Gy of radiotherapy during 6 weeks, with daily UFT (200 mg/m2/day) and a 24-h infusion of cisplatin (70 mg/m2) on Days 8 and 36. Chemoradiotherapy with S-1 and cisplatin (R-S-P) consisted of two courses. One included 30 Gy of radiotherapy over 3 weeks, with daily S-1 (80 mg/m2/day) for 2 weeks and a 24-h infusion of cisplatin (70 mg/m2) on Day 8. The other included chemoradiotherapy after 2 weeks. Responders received at least 2 four-week courses of the chemotherapy. Results: Twenty patients were enrolled: 8 were treated with R-U-P and 12 with R-S-P. Four patients had stage II tumors and 16 had stage III tumors. All patients completed the chemoradiotherapy. The most prominent toxicity was myelosuppression. Grades 3 and 4 leukocytopenia occurred in 5 (25%) and 2 (10%) patients, respectively. Nonhematologic toxicity was moderate: grade 2 nausea/vomiting, pain, oral mucositis, and renal dysfunction occurred in 25%, 25%, 20% and 10% of the patients, respectively. Complete response (CR) was attained in all 4 patients with stage II tumors. In stage III cases, CR, partial response (PR), and response rates were 81%, 13%, and 94%, respectively these reached 75%, 17%, and 92% in the R-U-P group, and 90%, 10%, and 100% in the R-S-P group, respectively. All stage II patients survived. In stage III cases, the one-year survival rate was 75% and the three-year survival rate was 50%. Conclusions: Chemoradiotherapy with an oral fluoropyrimidine (UFT, S-1) plus cisplatin is convenient, tolerable, and effective, and it is a promising nonsurgical management option for patients with locally advanced cervical esophageal carcinoma.

No significant financial relationships to disclose.
First results of induction chemotherapy with cisplatin, docetaxel, and capecitabine for the treatment of nasopharyngeal carcinoma
Authors: Beldjilali Y. , Benhadji K. A. , Boukerche A. , Khellafi H. , Abdelaoui A. , Betkaoui F. , Tourabi Z. K. , Kaïd M. Y. , Djellali L. , Yamouni M.
Published: August 2020

6045

Background: The purpose of this phase II study is to assess a new induction chemotherapy regimen combining cisplatin (P), docetaxel (T), and capecitabine (X) in advanced nasopharyngeal carcinoma. Methods: Previously untreated patients (pts) with histological diagnosed locally advanced nasopharyngeal carcinoma (stages III, IVA, and IVB UICC 2002) received induction chemotherapy associating P 75 mg/m2, T 75 mg/m2, both on day 1 and X 1,000 mg/m2/d days 1–14. Cycles were repeated every 3 weeks. A total of 4 cycles was planned for each patient. Induction chemotherapy was followed by concurrent chemo-radiotherapy: P 75 mg/m2 days 1, 22, 42 and radiotherapy (65–70 Gy) 4 to 6 weeks after the fourth cycle of induction treatment. Primary end point was tumor response of the induction regimen. Pts were evaluated according to RECIST criteria by clinical examination and CT scan of the nasopharynx. Results: 40 pts (26 male and 14 female) were enrolled. Median age was 40 years (range 18–56), ECOG performance status was 0–1 in all pts. 30 pts (75%) had an undifferentiated carcinoma of nasopharyngeal type (UCNT) and 10 pts (25%) a poorly differentiated nasopharyngeal carcinoma. 5 pts had stage III disease, 20 pts stage IVA disease and 15 pts stage IVB. Toxicity and tumor response were assessable in 40 pts. After 160 cycles, grade 3–4 toxicities (NCI-CTC 3.0) were: neutropenia (11 %), anemia (10.5%), nausea and vomiting (28%), diarrhea (8%), mucositis (3%), reversible alopecia (100%), and fatigue (10%). No febrile neutropenia was noted. 2 pts had grade 3 renal toxicity and only one patient had hand-foot syndrome (grade 3). Response rates for the 40 pts were: complete response 48%, partial response 40%, stable disease 4%, and progressive disease 8%. Conclusions: PTX induction chemotherapy resulted on a high response rate with manageable toxicity. Outcome of patients after chemoradiotherapy is awaited to evaluate the effectiveness of this new treatment modality.

No significant financial relationships to disclose.
Phase II study of capecitabine as palliative treatment for patients (p) with squamous head and neck cancer (HNC) with locoregional and/or metastatic relapse after previous platinum-based treatment (PBT): Final results of Spanish Head and Neck Cancer Group (TTCC)
Authors: Martinez-Trufero J. , Isla D. , Adansa J. C. , Irigoyen A. , Hitt R. , Lambea J. , Cruz J. J.
Published: August 2020

6047

Background: PBT is widely used as first line treatment in relapsed and/or metastatic HNC. Therefore, new non-platinum drugs need to be asses as second line treatment options. We proposed this study to evaluate activity and tolerability of capecitabine (X) when used as palliative monotherapy for relapsed HNC p previously treated with PBT. Methods: Forty patients (p) aged 18–75 years, ECOG PS 0–2, with advanced squamous HNC with locoregional and/or metastatic relapse previously treated with PBT and adequate bone marrow, renal and hepatic functions were included. X (1,250 mg/m2 BID) during 14 days was administered every 21 days, for at least 2 cycles. RECIST objective response rate (ORR) was assessed and toxicity following NCI-CTC v2 criteria. Results: Forty patients with median age 58 years old, all of them male, ECOG 0–2 (0:25%/1:70%/2:5%) and with squamous HNC, were analyzed. 34 p had local disease, 9 p regional disease and 19 p distant metastases(12 p lung). Median time since HNC diagnosis was 17.7 months and since disease extension diagnosis, 1.1 months. All p received a total of 169 cycles of X (median 4, range 1–9) and the median relative dose intensity was 91%. 7 p were not evaluable for response, since they do not receive at least 3 cycles ( 3 died, 2p due to toxicity, 2p due to decrease in ECOG PS ). ORR was 22.5 %.The median follow-up time was 5.2 months (alive p: 8.8 months), median TTP was 4.6 months and median OS was 6.2 months. Hematological toxicity G3/4 was reported in 6 p. 2p reported as grade 4 non-hematological toxicity: dysphagia and palmar-plantar erythrodysesthesia; grade III toxicities were: asthenia (4 p), anorexia (1 p), dehydratation (1 p), diarrhea (3 p), dysphagia (3 p) mucositis (4 p), weight loss (1 p), and palmar-plantar erythrodysesthesia (3 p). The most common grade II toxicity was asthenia (8 p). Conclusions: Capecitabine seems to be an active, feasible and well tolerated palliative treatment for advanced HNC patients that have previously received platinum-based schedules.

No significant financial relationships to disclose.
Cetuximab (C) and bevacizumab (B) in patients with recurrent or metastatic head and neck squamous cell carcinoma: An updated report
Authors: Gibson M. K. , Kies M. , Kim S. , Savvides P. , Kotsakis A. , Blumenschein G. , Worden F. , Chen H. , Grandis J. , Argiris A.
Published: August 2020

6049

Background: Epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) represent important therapeutic targets in SCCHN. Cetuximab (C), an IgG1 monoclonal antibody against EGFR, has single agent activity in SCCHN. Upregulation of VEGF has been associated with C resistance, thus, combined targeting may enhance anti-tumor activity. We designed a phase II trial of bevacizumab (B), an anti-VEGF humanized monoclonal antibody, with C to evaluate this hypothesis. Methods: Eligible patients have recurrent or metastatic SCCHN, measurable disease (RESIST), ECOG performance status (PS) 0–2, and no history of bleeding or thrombosis. Up to 1 regimen (without an EGFR inhibitor) for recurrent or metastatic disease and prior chemoradiotherapy with curative intent are allowed. Treatment consists of weekly cetuximab, 250 mg/m2 (after a loading dose 400 mg/m2) and bevacizumab, 15 mg/kg given intravenously every 21 days, until disease progression. The primary endpoint is the objective response rate. Sample size is 45 eligible patients. Specific biomarkers relating to EGFR and VEGFR signaling will be evaluated in tumor tissues and blood samples. Results: 28 patients enrolled (27 eligible). Median age 60 years (range 33–92); male 19; PS 0 (7 pts), PS 1 (18), PS 2 (2). All had prior RT, and 26 had chemotherapy. A median of 4 cycles were given (range, 1–12). Best response in 25 evaluable patients: 5 (20%) PR (1 was uncomfirmed), 14 (56%) SD, and 6 (24%) PD. Progression-free survival was 2.8 months and median overall survival was 8.1 months. Grade (G) 3 adverse events included: hemorrhage (from a benign neck ulcer), 1; hypertension, 2; infection, 2; rash, 2; dysphagia, 4; hypophosphatemia, 1; and fatigue, 1. G 4 AEs: proteinuria, 1. One pt died of aspiration pneumonia, with possible cardiac ischemia of uncertain relationship to study drugs. Conclusions: Preliminary results show that cetuximab and bevacizumab is an active regimen in SCCHN with rare serious toxicities. In particular, our results establish the safety of this bevacizumab-based regimen in regards to bleeding complications in SCCHN. Study accrual continues and biomarker analysis is planned. (Supported by U01 CA099168–01 and P50 CA097190)

No significant financial relationships to disclose.
Phase II study of pemetrexed (P) and gemcitabine (G) in patients with advanced head and neck cancer (SCCHN)
Authors: Mehra R. , Sherman E. , Ruth K. , Litwin S. , Sylvester J. , Tuttle H. , Burtness B. , Cohen R. B. , Langer C.
Published: August 2020

6052

Background: Unresectable/metastatic squamous cell cancer of the head and neck (SCCHN) has a poor prognosis despite standard therapy with cisplatin. Given the substantial toxicities of cisplatin and its widespread use in combination with RT in LA- SCCHN, we investigated an alternative regimen of gemcitabine (G) and pemetrexed (P). A phase II study of pemetrexed in SCCHN had a response rate (RR) of 26.5%. A phase I study of the P and G combination showed the doses and schedule below to be feasible. Methods: Eligibility stipulated measurable, incurable, unresectable recurrent/metastatic SCCHN; Karnofsky PS of > 60%, and adequate bone marrow, renal and hepatic function. One prior therapy for recurrent disease was allowed. Patients were treated with P 500 mg/m2 and G 1,500 mg/m2 every 2 weeks. Each cycle was 28 days. Primary endpoint was RR. Secondary endpoints included overall survival and toxicity. Patients were re-imaged every 2 cycles. In a 2-step design, 16 patients were to be accrued during stage 1, and 16 were projected for stage 2. If 1 or fewer responses were observed during the first stage, then the trial was to be stopped and the regimen deemed insufficiently active. Results: 17 patients were enrolled in stage 1. Median age was 64 years (range, 49–82); 10 males; 13 smokers (including 4 current smokers). 15 patients previously received definitive therapy with surgery and/or chemo-RT, and 9 had prior systemic therapy for recurrent/metastatic disease. Median number of cycles administered was 2 (range, <1 to 10). Reasons for treatment discontinuation included progressive disease in 15 patients and decreased PS in 1. Grade 3 toxicities included neutropenia (1), anemia (3), thrombocytopenia (1), dysphagia (11), fatigue (4), hypertension (4), and hyperglycemia (4). 1 pt had grade 4 anemia. Best response: 1 confirmed PR, 1 unconfirmed PR, 3 SD, 10 PD, 2 not evaluable. 7 patients received subsequent treatment. Estimated median overall survival is 5.5 months. Conclusions: The combination of P and G for advanced HNSCC was well tolerated, but its clinical efficacy was marginal in an unselected population. Due to early stopping rules, the study was closed to accrual after stage 1 for lack of efficacy. Further study of this regimen should be considered in patients enriched for TS and RRM1 status.

[Table: see text]
A phase II study examining the feasibility of long-term and low-dose oral capecitabine in newly diagnosed head and neck squamous cell carcinoma after surgery, radiation, and/or chemotherapy
Authors: Sukari A. , Mulrenan H. , Almhanna K. , Kafri Z. , Kim H. , Ensley J. , Kucuk O. , Yoo G.
Published: August 2020

6053

Background: In advanced head and neck squamous cell carcinoma (HNSCC), the five-year survival rate is less than 40%. Although the efficacy and tolerability of continuous IV 5-Fluorouracil (5FU) therapy has been established in HNSCC, the feasibility and tolerability of long-term therapy of oral capecitabine has not been established in HNSCC. Our primary objective is to assess the feasibility of treating patients with squamous cell carcinoma of the head and neck (HNSCC) with adjuvant Capecitabine after undergone definitive treatment. The secondary objectives are to estimate time to recurrence, local-regional control and survival rates along with incidence of second primary tumors. Methods: Eligible patients with newly diagnosed locally advanced HNSCC received capecitabine 1,000 mg orally once daily for one year, after undergone definitive treatment. Patients’ compliance with oral capecitabine as will as the side effects profile was evaluated on monthly basis over the first 12 months. Feasibility, survival, progression and progression free survival were measured over 36 months. Results: Thirty five patients were enrolled in the study. 17 patients had stage IV b, 7 had stage III, and 5 had unknown primary HNSCC. All but one took at least 60% of dispensed tablets. Twenty six patients completed at least 7 months of capecitabine. Sixteen patients completed at least 10 month of capecitabine. Two years overall survival rate was 97%. Three years progression free survival was 86%. Conclusions: Adjuvant capecitabine in locally advanced HNSCC is a feasible approach with minimum side effects. A favorable 3-year progression-free survival was found as compare to historical results. We recommend a randomized phase III trail to examine the effect of one year of adjuvant capecitabine versus placebo in locally advanced HNSCC after definitive treatment.

No significant financial relationships to disclose.
UAB 0210: A phase I/II trial of induction chemotherapy followed by concomitant docetaxel/radiotherapy with subcutaneous amifostine for advanced squamous cell carcinoma of the head and neck (SCCHN)
Authors: Nabell L. M. , Peters G. , Meredith R. , Carroll W. , Bonner J. , Ove R. , Spencer S.
Published: August 2020

6061

Background: Attempts to improve the outcome of locally advanced SCCHN have generally added chemotherapy to radiation, though the optimal manner of integration has been controversial. To impact distant and local control, we utilized neoadjuvant chemotherapy followed by concomitant boost radiation (CBR) with docetaxel as a radiosensitizer. To improve cytoprotection, subcutaneous amifostine was added during radiotherapy. Methods: From April 2003-March 2007 46 patients with stage III or IV newly diagnosed SCCHN were enrolled (30 Caucasian, 16 African-American). Treatment consisted of 3 cycles of neoadjuvant chemotherapy with cisplatin 75 mg/m2 and docetaxel 75 mg/m2 intravenously at 21 day intervals followed by CBR and concurrent dose-escalated weekly docetaxel starting at 20 mg/m2. Standard 2D radiotherapy was used in the majority of patients. Subcutaneous amifostine was administered at 500 mg during each day of radiation. Results: 39 patients were evaluable. The neoadjuvant chemotherapy was well tolerated by the majority of patients and appeared effective; no patient had progressive disease while on therapy. Three patients required a change to carboplatin due to toxicity. Weekly docetaxel during all weeks of CBR was not tolerable due to severe mucositis and the phase I component defined the MTD of concurrent docetaxel as 20 mg/m2 for 4 cycles during CBR. 4 patients (10%) had persistent disease at completion of treatment. Amifostine administration was well tolerated though 4 patients required discontinuation of the drug. The majority of recurrences have been localized at the primary site (6 patients). 3 patients developed isolated pulmonary metastasis. Only 2 patients remain PEG dependent with median follow-up of 24 months. Conclusions: Induction chemotherapy using cisplatin and docetaxel is feasible and easy to administer in the outpatient setting; those patients who had a major radiographic and clinical response did particularly well in follow-up. Weekly docetaxel can be safely and effectively administered during CBR with good local control. Amifostine can be safely administered via the subcutaneous route; the benefit in locally advanced patients is difficult to assess.

No significant financial relationships to disclose.
Prophylactic fluconazole treatment of mucositis in radiotherapy of head and neck cancer patients
Authors: Demiroz C. , Ozkan L. , Karadag O.
Published: August 2020

6062

Background: The aim of the study is to evaluate the preventive role of antifungal fluconazole prophylaxis on mucositis in head and neck cancer patients treated with radiotherapy. Methods: We evaluated 43 head and neck cancer patients treated with radiotherapy with/without chemotherapy. The patients were randomized to two groups: twenty patients (group A) received fluconazole when micotic infections appeared; 23 patients (group B) received fluconazole 200 mg once a week starting from the sixth irradiation session throughout the treatment.The two groups were similar in terms of patients and radiotherapy characteristics. Oral mucositis was recorded according to EORTC/RTOG criteria. Results: The usage of fluconazole 200 mg once a week was well tolerated and no early and late toxicity was observed. Mucositis was appeared in both groups on the third week of radiotherapy. Grade 3 mucositis developed at eight of the patients in group A (40%), three of the patients in group B (13%) and the result was statistically significant (p = 0.044). While grade 3 mucositis was observed the second/third week in group A, it was also observed in group B on third/fourth week in group B (p = 0.043). Conclusions: Weekly fluconazole prophylaxis showed a significant effect on the grade 3 mucositis and improved radiotherapy results.

No significant financial relationships to disclose.
Oral cavity squamous cell carcinoma in patients aged 80 or older: Risk factors, treatment, and outcome
Authors: Ortholan C. , Bensadoun R. , Italiano A. , Teman S. , Dassonville O. , Benezery K. , Lusinchi A. , Thariat J. , Auperin A. , Bourhis J.
Published: August 2020

6064

Background: We have recently reported a large series of patients aged ≥ 80 years showing that in this population about half of head and neck squamous cell carcinomas (SCC) are located in the oral cavity. There are no specific data on this cancer location outcome in elderly patients. Therefore, we report here the experience of two French cancer centers in the treatment of oral cavity SCC in patients aged ≥ 80 years. Methods: Two hundred sixty patients aged ≥ 80 years with a primary oral cavity SCC were included in this retrospective analysis. Results: Sex ratio was near to 1. The risk factor distribution was significantly different between men and women: tobacco/alcohol consumption (66.3% vs 15.8%, p < 0.001), history of leukoplakia/lichen planus/oral traumatism (10.8% vs 55.3%, p = 0.002). Two hundred patients received a loco regional (LR) treatment with a curative intent (surgery and/or radiotherapy), 29 with a palliative intent and 31 did not receive a LR treatment. Curative treatments were delivered according to the institution policy in 56 patients (28%).The median disease specific survival (DSS) was 16.9 months. In multivariate analysis, independent prognostic factors were stage (HR = 0.45 [0.29–0.69], p < 0.001), and curative intent of treatment (HR = 0.28 [0.17–0.45], p < 0.001). Median overall survival (OS) was 13.9 months. In multivariate analysis, the independent prognostic factors for OS were age (HR = 0.63 [0.33–0.76], p < 0.001), stage (HR = 0.61 [0.40–0.91], p = 0,016), and curative intent of treatment (HR = 0.41 [0.23–0.71], p < 0.001. In patients treated with a curative intent, the standard treatment was not associated with improved overall survival or disease specific survival as compared with those treated with an adapted treatment. However, prophylactic lymph node treatment in early stage cancer decreased the rate of nodal recurrence from 38% to 6% (p = 0.01). Conclusions: This study emphasizes the need for prospective evaluation of standard and adapted schedules in elderly patients with oral cavity cancer.

No significant financial relationships to disclose.
Neurocognitive outcomes of head and neck chemoradiotherapy: A pilot study
Authors: Gan H. K. , Bernstein L. J. , Brown J. , Ringash J. , Vakilha M. , Wang L. , O'Sullivan B. , Waldron J. , Chen E. X. , Siu L. L.
Published: August 2020

6068

Background: Evidence suggests cancer-related treatments affect cognition. To our knowledge, no studies have systematically investigated cognitive impairment in head and neck cancer (HNC) patients (pts). We assessed ten relapse-free HNC pts after curative-intent radiotherapy (RT), half of whom received cisplatin (Cp). Methods: Pts completed a 2-hr battery of tests/questionnaires assessing objective cognitive function (CF), subjective CF, quality of life and affect. Objective measures of CF were transformed to Z-scores (mean=0, standard deviation=1) using age normative data. A negative value for the Difference Score (DS=Z-score minus IQ score) in each tested domain indicates cognitive deterioration as IQ is a pre-morbid estimate of pts’ CF. A Global Deficit Score (GDS) was obtained by averaging the DS of all tested CF domains. Results: Pt demographics were: M:F=8:2; mean age=58 yrs(range 47–66); mean smoking pack yrs=15(0–45); mean drinks/week=7(0–25); mean IQ Z-score=+1.2(-1.0 to +2.0), mean school yrs=15 (6–18) and mean time post treatment=20 mo(9–41). All pts completed the battery within 2 hr. Nine participants appeared to have impaired CF based on negative DS and GDS scores ( Table 1 ). Exploratory univariate analyses showed trends that higher RT dose and Cp use were associated with increased impairment but cytokines, anemia, hormonal status and affective state were not. Conclusions: This feasibility study suggests cancer-related treatment affects cognition in HNC survivors. A longitudinal study is underway.

[Table: see text]

No significant financial relationships to disclose.
Correlation of body mass index with toxicity and survival in locoregionally advanced head and neck cancer patients treated with induction chemotherapy and concurrent chemoradiotherapy
Authors: Jain A. K. , Salama J. K. , Stenson K. M. , Blair E. , Cohen E. E. , Witt M. , Haraf D. J. , Vokes E. E.
Published: August 2020

6074

Background: Concurrent chemoradiotherapy (CRT) offers high functional organ preservation rates for locoregionally advanced head and neck cancer (LRAHNC) patients, but is associated with significant acute and chronic speech and swallowing toxicity. Recently, body mass index (BMI) has been suggested as a predictor of head and neck cancer patient outcome. In this analysis we sought to determine the impact of BMI on survival and toxicity outcomes in LRAHNC patients treated with CRT. Methods: 220 LRAHNC patients were treated on a multiinstitutional protocol consisting of induction carboplatin and paclitaxel followed by CRT. CRT was delivered for 4–5 cycles; each 14-day cycle consisted of 5 days concurrent paclitaxel, continuous infusion 5-FU, hydroxyurea, and 1.5 Gy twice daily radiation followed by 9 days without any treatment. Each patient's pre-treatment BMI was classified as overweight (BMI >= 25) or non-overweight (BMI < 25). As an independent variable, BMI was analyzed as a predictor of IndCT or CRT toxicity, locoregional control, and overall survival. BMI was analyzed as categorical variable, and also a continuous variable in a multivariate proportional hazards model. Results: There was no association between BMI and IndCT toxicity. During CRT overweight patients had significantly lower rates (24/103 vs 42/112) of grade 3 or higher neutropenia (p = 0.027), mucositis (p = 0.05), dermatitis (p = 0.028) and higher rates of anorexia (p = 0.05). Overweight patients had 12% long term PEG tube rate, compared to 34% of non-overweight patients (p < 0.001). On pooled survival analysis, patients with BMI > 25 had significantly better overall survival outcomes (mean 81.2 months, 95% CI 75.1–87.3 months) than patients with BMI < 25 (median 58.2 months; mean 56.5 months, 95% CI 49.6–63.3 months) (log-rank p < 0.001). Conclusions: Our data suggest patients with pre-treatment BMI > 25 experience lower rates of toxicity commonly associated with chemoradiation, and have a significantly better prognosis than patients with BMI < 25. Although the mechanism of BMI as an independent predictor of outcomes is unclear, we are continuing to explore mechanisms underlying this association.

No significant financial relationships to disclose.
Adjuvant radiotherapy use in a population-based sample of breast cancer patients
Authors: Jagsi R. , Abrahamse P. , Griggs J. J. , Katz S. J.
Published: August 2020

617

Background: Previous studies have suggested underutilization and socioeconomic disparities in use of adjuvant radiotherapy (RT) among patients with breast cancer. However, these studies used registry data which may be incomplete. Methods: We evaluated data from 2260 survey respondents with nonmetastatic breast cancer, aged 20–79 years, diagnosed from June 2005-February 2007 in Detroit and Los Angeles and reported to SEER registries (72% response rate). Survey responses regarding treatment and sociodemographic factors were merged to SEER data. Rates of RT receipt were based on patient report. Patients were divided into 3 populations: DCIS pts undergoing breast conservation (BCS), invasive pts undergoing BCS, and invasive pts undergoing mastectomy. These were then stratified based on recurrence risk in the absence of RT (3 groups based on tumor size and grade for DCIS pts, 2 groups separating pts over 70 with Stage I, ER+ tumors from others undergoing BCS for invasive disease, and 3 groups based on tumor size and nodal status for those undergoing mastectomy for invasive disease). Results: Among 306 pts undergoing BCS for DCIS, 85.6% received RT (77.9% of pts at low recurrence risk, 84.8% at intermediate risk, and 95.8% at high risk). Among 1018 pts undergoing BCS for invasive disease, 93.6% received RT (83.6% of low-risk patients and 94.9% of others). Among 661 pts undergoing mastectomy for invasive disease, 39.3% received RT (81.5% of pts at high-risk, 44.5% at intermediate-risk, and 12.1% at low risk). In separate multivariate logistic regression models including risk grouping and sociodemographic variables for each population, there were no significant associations between RT receipt and race, education, or income. Among pts receiving RT, delay was reported by 15.9% of the DCIS group, 19.5% of those treated for invasive disease after BCS, and 27.4% of those treated for invasive disease after mastectomy. Conclusions: RT use is high after BCS with little evidence of socioeconomic disparities. But lower than optimal rates after mastectomy even among patients with high expected benefit suggest lingering barriers to effective treatment in these patients. Less RT use in patients with lower expected benefit suggests that legitimate clinical uncertainty influences decision-making.

No significant financial relationships to disclose.
Correlation of SPARC, ER, PR, and HER2 tumor with progression-free survival from a phase II neoadjuvant trial of gemcitabine, epirubicin, and nab-paclitaxel
Authors: Inhorn R. C. , Daniel B. , Daniel D. , Naot Y. , Zubkus J. , Lane C. , Trieu V. , Knauer D. , Desai N. , Yardley D. A.
Published: August 2020

618

Background: Neoadjuvant combinations of gemcitabine (G), anthracyclines and taxanes have demonstrated substantial activity with pCR rates of 20–25%. Secreted protein acidic rich in cysteine (SPARC) is an albumin binding protein that mediates intratumoral accumulation of nab-paclitaxel (nab-P) via a SPARC-albumin binding activity and is a poor prognostic factor for survival. This study was designed to evaluate the feasibility and safety of a biweekly schedule of neoadjuvant nab paclitaxel (nab-P) with G and epirubicin (E) with SPARC tumor assessments performed in consenting patients (pts). Methods: Eligibility: Clinical T1c-T4d and/or N0–3, M0 breast cancer (T1N0M0 excluded), normal LVEF. ER/PR/HER-2 obtained for all pts. Treatment: neoadjuvant G 2,000 mg/m2, E 50 mg/m2, and nab-P 175 mg/m2 q14 days x 6 cycles followed by surgery. Post operative therapy: G 2,000 mg/m2 and nab-P 220 mg/m2 q14 days x 4 cycles. Myeloid growth factors were mandated with all cycles. Two different antibody reagents were used to probe for SPARC expression of tumoral SPARC and stromal SPARC; level 3 immunohistochemical (IHC) SPARC staining was considered positive. Results: 123 pts enrolled. Pathologic responses are available for 112 pts with 11 unevaluable. 82 pts consented to SPARC tumor testing. Median age 51 (29–72). Median tumor size 4.5 cm. 42% ER-/PR -. 55% clinical T3/T4 and 66% node positive. Pathologic complete responses (pCR) were noted in 22 pts (18%) with PRs in 84 pts (68%), and 6 SD (5%). SPARC IHC staining was available in 77 tumor samples; SPARC positivity was noted in 89% of evaluated tumors achieving pCR. Triple negative, ER negative or PR negative tumors were associated with worse PFS. SPARC + tumors showed a trend to improved PFS that was strongly associated with tumoral SPARC but not stromal SPARC. Conclusions: Dose dense neoadjuvant G, E, and nab-P is active and well tolerated with a favorable pCR rate of 20%. ER neg, PR neg, and triple negative tumors were associated with worse PFS. Despite literature reports of SPARC positivity associated with poor prognosis, SPARC+ tumors in this study showed a high concordance with tumor response and a trend to improved PFS with tumoral SPARC.

[Table: see text]
Neoadjuvant platinum-based chemotherapy (CT) for triple-negative locally advanced breast cancer (LABC): Retrospective analysis of 125 patients
Authors: Leone J. P. , Guardiola V. , Venkatraman A. , Pegram M. D. , Welsh C. , Silva O. , Larrieux R. , Franchesci D. , Gomez C. , Hurley J.
Published: August 2020

625

Background: Triple-negative breast cancer (TNBC), defined by lack of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2, accounts for 15–20% of all breast cancers and is associated with poor prognosis. There is no consensus regarding optimal CT for treatment of such patients. Preclinical data suggests TNBC may be sensitive to platinums because of deficiencies in BRCA-associated DNA repair. The aim of this study was to evaluate pathologic complete response (pCR) and overall survival (OS) in patients with TNBC treated with neoadjuvant platinum-based CT. Methods: We identified 674 patients with LABC who received neoadjuvant CT between January 1999 and June 2008 at University of Miami. Of these, 125 (18.5%) had histopathologic confirmation of TNBC. All patients received neoadjuvant platinum salts + docetaxel. 76 (61%) also received neoadjuvant AC, while 42 (34%) received adjuvant AC. pCR was defined as no residual invasive disease in breast and axilla. OS was calculated according to Kaplan-Meier. Results: Demographics: median age 50 (28–86 years). 60% premenopausal. TNM stage distribution: T1 0.9%, T2 5.2%, T3 53.4%, T4 40.5%, N0 25.0%, N1 36.2%, N2 35.4%, N3 3.4%, M0 100%, inflammatory 11%, median tumor size = 9.5 cm. Follow up duration ranged from 0.3 to 8.9 years. pCR was observed in 42 of 125 patients (34%; 95% CI 26–43%). Among patients receiving neoadjuvant AC, 30 of 76 (40%; 95% CI 28–51%) had pCR, while amongst those receiving adjuvant AC, 12 of 42 (29%, 95% CI 16–45%) had pCR at the time of definitive surgery. Patients achieving pCR had significantly higher OS (5-yr rate = 73% in pCR, vs. 49% in non-pCR; p < 0.001). OS in TNBC patients receiving cisplatin/docetaxel was significantly superior to those receiving carboplatin/docetaxel (11 mortality events out of 78 patients receiving cisplatin based CT vs 24 out of 47 receiving carboplatin based CT logrank p = 0.001). Conclusions: To date, this is the largest single institution cohort of locally advanced TNBC uniformly treated with platinum+docetaxel-based CT regimens. Platinum/docetaxel-based neoadjuvant CT provided high rates of pCR and excellent OS for women with locally advanced TNBC.

No significant financial relationships to disclose.
Intraoperative radiotherapy (IORT) as a boost during breast conserving surgery (BCS) using low kV X-rays: The first 5 years of experience with a novel approach
Authors: Wenz F. K. , Welzel G. , Blank E. , Hermann B. , Steil V. , Suetterlin M. , Kraus-Tiefenbacher U.
Published: August 2020

626

Background: Recently, the concept of IORT during BCS has been introduced using linear accelerators, brachytherapy or dedicated mobile IORT devices generating fast electrons or low energy X-rays. Here, we report the first 5 years of a single center experience after introduction of a novel approach to deliver IORT as a tumor bed boost during BCS for breast cancer. Methods: 155 breast cancers in 154 women (median age 63 yrs, range 30 - 83 yrs, T1/T2 = 110/45, N0/N+ = 104/51) were treated between February 2002 and December 2007 at the University Medical Center Mannheim/University of Heidelberg, in whom IORT as tumor bed boost was applied using 50 kV X rays (20 Gy, INTRABEAM, Carl Zeiss Oberkochen, additional OR time about 45 - 60 min) followed by 46 - 50 Gy external beam whole breast radiotherapy (EBRT). Chemotherapy was given before EBRT. The median interval between BCS+IORT and EBRT was 10 wks. Median follow-up was 34 mon (max 79.6 mon, 1 pt lost to f/u). Overall survival (OS), local relapse free survival (LRFS) and disease free survival (DFS) were calculated at 5 yrs using the Kaplan Meier method. 81 patients were evaluated at 3 yr f/u for normal tissue effects using the LENT SOMA scoring system. Results: Ten patients have died, 2 pts suffered from in breast relapse and 8 pts developed distant metastases yielding a 5yr OS of 87.0%, a 5yr LRFS of 98.4% and a 5 yr DFS of 73.9%. Grade 3 fibroses of the tumor bed were detected in 6% of the patients after 3 yrs. Skin toxicity was mild (teleangiectases and hyperpigmentations in 6% each). Conclusions: IORT as a tumor bed boost using the INTRABEAM system yields low recurrence and toxicity rates when followed by external beam whole breast radiotherapy.

[Table: see text]
The final results of the United Kingdom sentinel node training program: New Start
Authors: Mansel R. E. , McNeill F.
Published: August 2020

629

Background: Formal introduction of new surgicaltechniques is rare, but the rate of technological advances in cancer surgery mandates that surgeons in current practice will need to learn new techniques in an enviroment less rigorous than residency programs. The rapid introduction of sentinel node biopsy in breast cancer is a classic exemplar of the problematic issues around quality assurance and patient safety in new technology. In the UK this technique was introduced in a unique formal program –The New Start training program –which utilised educational methods with a mandatory quality assurance system for each individual surgical team prior to routine introduction of the technique in practice. Methods: Every hospital had to submit the breast team to a formal program consisting of a theory training day followed by in house supervised training for the first 5 cases in the operating room in their instituition.Surgical teams performed 5 directly supervised procedures followed by 25 further audited cases with data being submitted centrally. All sentinel procedures were combination isotope/blue dye, (Nanocoll 99 Tm and a blue dye (Patent Blue V- laboratoires Guerbert Paris, France). In order to be approved each team had to achieve a localisation rate of at least 90% and a false negative rate of less than 10%. Results: The program has now trained 242 surgeons performing a total of 6341 audited sentinel node validation procedures. The localisation rate was 99% and the false negative rate was <8%. The median number of sentinel nodes was 2 and in 54% of the node positive patients, the sentinel node was the only positive node. Preoperative scintigraphy showed hotspots in 83% of patients. Blue dye reactions in this large dataset were lower than quoted in the literature, (<1% of patients), suggesting over-reporting in smaller trials. There was short learning curve for false negativity falling to <4% after 40 audited cases. Failure to find a sentinel node correlated strongly with a higher rate of histological node positivity. Conclusions: This major national training program with in house practical training has shown a high localisation rate and a shortened learning curve for false negative cases, and has demonstrated the value of a formal training program, which can form the template for the introduction of new surgical techniques.

No significant financial relationships to disclose.
Survival advantage by neoadjuvant radiochemotherapy in locally advanced noninflammatory breast cancer
Authors: Roth S. L.
Published: August 2020

638

Background: The impact of timing of radiochemotherapy (RCT) relative to surgery has been assessed in terms of ten year survival rate for locally advanced or surgically in terms of breast conserving surgery or simple mastectomy unfavourable, noninflammatory breast cancers (LABC). Methods: A total of 644 women were included in the retrospective study from 1991–1998. Chemotherapy was applied in 166 as neoadjuvant, in 236 simultaneously and in 113 as adjuvant. 119 patients received no chemotherapy. 40% of the patients received four courses of epirubicin/ cyclophosphamide, 26% concurrent mitoxantrone, 5% three cycles of CMF, 3% six cycles of CMF and 15% had no chemotherapy. 315 patients with locally advanced breast cancer (LABC) received neoadjuvant and 329 adjuvant RCT. Preoperative radiotherapy consisted of 50 Gy to the breast and the supra/infraclavicular lymph nodes with a 10 Gy electron or interstitial boost. The mean time interval between the end of radiotherapy and the surgery was 27 weeks (6–89 weeks). Results: Breast conservation was possible in 48% in the preoperative arm and in 52% in the postoperative arm. The rate of pT0 after neoadjuvant RCT was 38% (120/315) and the pCR in breast and axilla 30% (95/315). The ten year survival in the neoadjuvant group (n = 315) compared favourably 68.6% vs. 65% in case of the adjuvant group (n = 329; p = 0.21) in spite of more advanced disease. Patients with cT1- (n = 3) and cT2- (n = 97) categories had a significantly 13.6% better ten year survival rate after neoadjuvant RCT (85.76% vs. 72.19%) compared to cT1- (n = 1) and cT2- (n = 180) after adjuvant RCT (p = 0.0026). Conclusions: This study compares, retrospectively, neoadjuvant RCT vs. adjuvant RCT in LABC. Preoperative RCT achieved a pT0-rate of 38% and a prolonged ten year survival to a degree of 13.6% statistically significant in patients with cT2- category breast cancer compared to adjuvant RCT.

No significant financial relationships to disclose.