This study looked at whether epidermal growth factor receptor inhibition by the monoclonal antibody panitumumab could increase the efficacy of standard chemotherapy in advanced urothelial cancer. Results were disappointing, with higher toxicity and no improvement in efficacy in the combination arm. Background: Epidermal growth factor receptor (EGFR) overexpression is frequent and associated with poor outcome in urothelial carcinoma. EGFR inhibition could improve the antitumor activity of chemotherapy. Patients and Methods: Patients with advanced, treatment-naïve, histologically confirmed advanced urothelial carcinoma and no HRAS or KRAS mutation in the primary tumor received dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (dd-MVAC) without or with the anti-EGFR monoclonal antibody panitumumab (Pmab). A randomized (1:2) phase II design was used with progression-free survival (PFS) as the primary endpoint. Results: Ninety-seven eligible patients were randomized; 96 patients were evaluable for toxicity and 87 for efficacy. The median PFS were 6.8 months (95% confidence interval [CI], 6.3-9.2) for dd-MVAC and 5.7 months (95% CI, 4.6-6.4 months) for dd-MVAC+Pmab. For both immunohistochemical and molecular definition of basal/squamous-like (BASQ) tumors, no difference was observed in objective response rates or PFS between the two arms in BASQ and non-BASQ tumors. Conclusion: dd-MVAC+Pmab was associated with more serious adverse events and no improvement in efficacy outcomes.

Objective: To compare the preferences of older (>= 70 years old) versus younger (<70 years old) cancer patients regarding surrogate designation and decision making. Methods: A cross-sectional survey. Patient characteristics and information about surrogacy and involvement in decision making were collected. Associations between patient characteristics and preferences were examined. Results: The study included 130 patients aged >= 70 years (mean age 80 years) and 102 patients aged <70 years (mean age 55) and. Factors independently associated with surrogate knowledge (66%): younger age, more children living nearby, high income; factors associated with having already designated a surrogate (62%): younger age, decreased number of daily medications; factors associated with designating a surrogate after questionnaire administration (40%): low education, metastasis. Patients requiring an informed consent for any intervention was associated with older age (adjusted OR [aOR](peryear) = 1.04[95% confidence interval 1.00-1.08]), not living alone (aOR =2.52[1.00-6.36]), and having children (aOR = 4.49[1.13-17.81]). Conclusion: All cancer patients, wanted to be fully informed and 72% wanted to be involved in medical decisions. Preferences for decision control vary between age groups, depending on family members' presence and living alone. Practice implications: Sharing complete and clear information should be an important key in the process of cancer patients' care, regardless of patient age. (C) 2018 Elsevier B.V. All rights reserved.

Purpose: Hormone (anti-estrogen) therapy (HT) plays a major role in hormone receptor-positive breast cancer management. The latest guidelines propose to extend the duration of adjuvant treatment from 5 to 10 years. The association between HT and thromboembolic or microvascular complications during breast reconstruction has been investigated. However, while estrogens play a crucial role in wound healing, no study has assessed the impact of tamoxifen or aromatase inhibitors on other postoperative complications, including wound healing complications. This study aimed to assess the impact of HT on surgical outcomes after breast reconstruction. Methods: All patients who underwent breast reconstruction between January 2012 and December 2013 were reviewed. Rates of wound healing complications, prosthesis complications, microvascular thrombosis, flap failures, and venous thromboembolism were retrospectively compared between patients treated and not treated with HT at the time of surgery. Results: A total of 233 operations were performed: 78 free flaps, 12 autologous latissimus dorsi flaps, 47 implants, 42 lipofilling, and 54 secondary symmetrization. At the time of surgery, 38% of patients were treated with HT. Those who received HT experienced significantly more wound healing complications (61% versus 28%; p < 0.001), including fat necrosis (26% versus 8.3%; p < 0.001), infections (15% versus 2.8%; p < 0.001), delayed wound healing (49% versus 13%; p < 0.001), and grade III/IV capsular contracture (55% versus 9.1%; p Z 0.001). No significant difference was observed in the occurrence of microvascular thrombosis and venous thromboembolism. Conclusions: HT seems to be associated with an increased risk of wound healing complications. Currently, there is no guideline on perioperative HT discontinuation. Further investigations are required. (C) 2017 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

Purpose: The coverage of axilla contents by radiation therapy (RT) is an important issue in the new era of minimal axillary surgery based on sentinel lymph node biopsy (SLNB). Data from recent trials demonstrated equivalent survival in breast cancer (BC) patients with 1-2 positive SLNs with or without axillary lymph node dissection (ALND). In a similar context, AMAROS trial showed that complete RT coverage of the axilla is a better option than ALND regarding the risk of arm lymphedema. Our recent data showed that axillary levels are underdosed when only tangential fields (TgFs) are used (Belkacemi et al, Ann Oncol 2013). We aimed to evaluate the dose distribution in the SLNa defined intra operatively by clips placement. This could be a important for patients with SLN involvement who have neither ALND nor RT to the axilla. Materials/Methods: Twenty-five patients have been prospectively included in this study. They had clips placement in the SLNa during the SLNB procedure. Breast dose was ranged between 40 to 50Gy in 15 to 25 fractions. Additional boost to the tumor bed of 10 or 16Gy was delivered in 21 patients. Level I-III and organs at risk were contoured using the RTOG contouring atlas. The SLNa was defined as 1.5 cm in diameter around the clips. Dose-volume-histograms were analyzed regarding the volumes receiving 95% or 50% of the prescribed dose. Percentages overlap between TgFs and SLNa volume were analyzed to define 3 groups: 100% overlap ("suitable group" with SNLa completely included in the TgF), > 50% overlap ("partially suitable group" with SLNa partially included in the TgF) and 0-49% overlap or completely outside the TgFs ("unsuitable group"). Results: The mean dose delivered to levels I, II, III and SLN area were 25, 5, 2 and 33Gy respectively. The volume covered by the 95%-isodose were respectively 2%, 0%, 0% and 4%. The average dose delivered to level I, II, III and SLN area were higher using High TgFs vs STgFs (38 vs 22Gy, p=0.004; 11 vs 3Gy, p=0.019; 5 vs 2Gy, p=0.003; 43 vs 31Gy,p=0.02), respectively. HTgFs covered better 50% of all axilla levels. Boost delivery and initial tumor site did not influence axilla coverage by the TgFs. The SNLa was totally or partially covered in 48% and 28% of patients, respectively. The mean dose delivered to 95% of the SNLa was only 22Gy using STgFs and 33Gy with the HTgFs. Using the STgFs, the SNLa was either totally (n=8/20) or partially (n=6/20) covered by > 50% of dose. Average dose was 46, 34 and 8Gy, respectively in the 3 groups. HTgFs allowed a complete coverage of the SLNa in all patients. Conclusion: In patients undergoing breast conservative therapy, TgFs provide a limited coverage of the SLNa. STgFs allowed total coverage of this area in less than half of the patients. Thus, SLNa should be delineated in patients who have only SLNB procedure. Some of these patients with nodal involvement without additional ALND could benefit from HTgFs irradiation or a better-personalized nodal RT using a dedicated nodal RT technique such that reported in AMAROS trial. The last allow better coverage of the axilla contents than TgFs. Citation Format: Yazid Belkacemi, Veronique Bigorie, Quiong Pan, Romain Bosc, Ryan Bouaita, Frederic Pigneur, Elias Assaf, Hakima Badaoui, Emmanuel Itti, Elie Calitchi. Tangential fields (TgF) breast radiotherapy (RT): Prospective evaluation of the dose distribution in the sentinel lymph node area (SLNa) as determined intra operatively by clip placement [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-15-08.

e17664 Background: Because of weak solubility in water, many cytotoxics are dissolved in ethanol. FDA recently raised alert noticing that patients could be intoxicated after their treatments. The main alcohol-containing chemotherapy drugs are gemcitabine (Gem), paclitaxel (Pac) and docetaxel (Doc). We explored prospectively blood alcohol levels in pts treated with Gem, Pac or Doc. Methods: Alcohol concentration was determined by peripheral blood sample before chemotherapy infusion (T0), at the end (T1) and 30 min later (T2) in three different prospective cohorts (Gem, Pac, Doc) in a single institution. Bioelectrical impedance analysis was performed to estimate fluid volume in order to calculate theoretical alcohol level. Clinical impact was evaluated through psychometric tests (Zazzo attention test, Stroop test) before and at the end of chemotherapy infusion. Results: 60 consecutive patients were included in our study (M/F 29/31) (Gem n = 21, Pac n = 19, Doc n = 21). Median age was 63.8 yrs (35-88). Median Gem infusion duration (ID) was 100 minutes. Median alcohol administration was 20.5 g (11.6-26). T0 alcohol concentration was 0 g/l, T1 0.32 g/l (0.1-0.65), T2 0.17g/l (0.1-0.4).Median Pac ID was 96 minutes. Median alcohol administration was 9.5 g (6.9-10.5). T0 alcohol concentration was 0 g/l, T1 0.1 g/l, T2 0.1 g/l. Median Doc ID was 90 minutes. Median alcohol administration was 2.8 g (1.8-4). T0 alcohol concentration was 0 g/l, T1 0.1 g/l, T2 0.1 g/l. Concerning Zazzo test, a significant decrease in attention abilities were shown after gemcitabine infusion, compared with taxanes (p = .001). Conclusions: Patients should be clearly informed concerning alcohol infusion during chemotherapy, and that abilities may be impaired. They should be monitored during 1 hour after gemcitabine infusion before leaving care unit.

Randomized trials have established that patients with limited involvement of sentinel lymph node (SLN) do not require axillary lymph node dissection (ALND). The similar outcome in patients with ≤2 positive SLN with or without additional ALND is attributed, in part, to tangential fields (TgF) RT. We evaluated the dose distribution in the SLN biopsy area (SLNBa) as determined intraoperatively by clips placement for radiotherapy (RT) optimization.

Background: Current first-line cisplatin-based combination chemotherapy regimens provide interesting response rates but limited impact on survival for patients with metastatic transitional cell carcinoma of the urothelium. Such results leave a significant patient population in need of salvage therapy. Patients and Methods: As the epidermal growth factor receptors 1 and 2 (EGFR and HER2) are frequently overexpressed in urothelial carcinoma, we explored the feasibility of a combination of paclitaxel (80 mg/m(2)/week) and lapatinib (1,500 mg orally daily) for six patients who were treated after failure of first-line platinum-based chemotherapy. Results: Only one out of six patients was able to receive the full doses during the first six weeks of treatment, while grade 2 or 3 diarrhea events required lapatinib dose reduction (one patient) or discontinuation (five patients), despite loperamide support. Conclusion: This combination is not recommended for this population of patients.

Background: To evaluate the efficacy and toxicity of irinotecan and oxaliplatin plus 5-fluorouracil (FU) and leucovorin (FOLFIRINOX) as second-line therapy in metastatic pancreatic adenocarcinoma (MPA). Patients and Methods: We retrospectively analyzed the medical records of 27 patients with MPA treated with FOLFIRINOX as second-line therapy between January 2003 and November 2009 in our hospital. The recommended schedule was oxaliplatin 85 mg/m2 on day 1 + irinotecan 180 mg/m2 on day 1 + leucovorin 400 mg/m2 on day 1 followed by FU 400 mg/m2 as a bolus on day 1 and 2,400 mg/m2 as 46-hour continuous infusion biweekly. Results: The median age of the 27 patients (13 males and 14 females) was 63 years (45–83). All patients had progressive disease after first-line chemotherapy by gemcitabine. A total of 167 cycles were administered, with a median number of 6 cycles (1–29) per patient. One toxic death occurred (sepsis). Tolerance of treatment was acceptable, and the relative dose density delivered per patient was 92.8% for oxaliplatin, 89.1% for irinotecan and 96.4% for FU. Grade 3–4 neutropenia occurred in 55.6% of the patients, including 1 febrile neutropenia. The other toxicities were manageable. Regarding efficacy, 22 of the 27 patients were evaluable (WHO and RECIST criteria). Five patients had partial responses and 12 stable disease, resulting in an overall disease control rate of 63%. Median time to progression was 5.4 months (0.7–25.48), and median event-free survival was 3 months (0.5–24.9). Median overall survival was 8.5 months (0–26). A clinical benefit was reported for 55% of the patients. Conclusions: These results confirmed the good safety profile and the efficacy of the FOLFIRINOX regimen as second-line treatment of MPA.

e14584 Background: The safety profile and efficacy of the Folfirinox regimen as first-line chemotherapy in metastatic pancreatic cancer (MPC) was previously reported in a phase II study (Conroy, J Clin Oncol, 2005:1228). We retrospectively studied the feasability and the efficacy of this regimen as second-line therapy in our institution. Methods: Twenty-seven patients (pts) with MPC were treated by Folfirinox between January 2003 and November 2009. The recommended schedule was oxaliplatin 85 mg/m2 d1 + irinotecan 180 mg/m2 d1 + LV 400 mg/m2 d1 followed by 5-FU 400 mg/m2 bolus d1 and 2,400 mg/m2 46h continuous infusion biweekly. Results: Pts characteristics: M/F = 13/14; median age = 63 years (45-83). Ten had a complete resection of primary tumor, 6 had a adjuvant chemotherpy by gemcitibine, and 4 had an adjuvant radiotherapy concomittant with capecitabine. All patients had a progressive disease after first-line chemotherapy by gemcitabine. Safety: A total of 167 cycles were delivered, with a median number of 6 cycles (1-29) per patient. One toxic death occurred (sepsis). Tolerance was excellent with a good respect of the dose density (Ox: 92.8%, Ir: 89.1%, 5-FU: 96.4%). Grade (G) 3-4 neutropenia occurred in 55.6% of pts, including 1 febrile neutropenia. 44.5% of patients received G-CSF. Other relevant toxicities were: G3-4 thrombopenia (14.8%), G3-4 fatigue (29.6%), G3-4 nausea- vomiting (18.5% pts), G3-4 diarrhea (11% pts) and G3 neuropathy (3.7% pts). Efficacy: 17 of 22 pts were evaluable (WHO and RECIST criterias). 5 PR and 12 SD were observed. Median PFS was 5.4 months. (0.7- 25.48) and median EFS was 3 months (0.5-24.9). Median overall survival was 8.5 months (0-26). Conclusions: These results confirmed the good safety profile and the efficacy of Folfirinox regimen in the treatement of MPC, which merits to be assessed in a phase III trial. No significant financial relationships to disclose.

PURPOSE:To investigate a potential link between telomere length, chromosomal instability, and the advent of a second cancer (SC) in patients with Hodgkin's lymphoma (HL), who are known to be at risk for SCs. This study was premised on the finding that telomere dysfunction and DNA repair pathways were related to many pathologic conditions. METHODS AND MATERIALS:Three cohorts of patients with HL were studied: 73 who were prospectively followed >5 years after diagnosis (prospective HL cohort), 28 who developed a SC (SC HL cohort), and 18 long-term survivors with no evidence of disease or complication since their initial treatment (NED HL cohort). Telomere length was analyzed by a telomeric restriction fragment assay in peripheral blood lymphocytes. Thirty healthy donors and 70 patients with a newly diagnosed solid tumor were the control population. RESULTS:Compared with controls, patients from the prospective HL cohort, before any treatment, showed age-independent shorter telomeres (mean, 8.3 vs. 11.7 kb in healthy donors; <6 kb in 18% in HL patients), increased spontaneous chromosomal abnormalities, and increased in vitro radiation sensitivity (p < 10(-4) each). After treatment, telomere shortening was associated with cytogenetic profiles characterized by the persistence of complex chromosomal rearrangement and clonal aberrations. Moreover, the two cases of SC in the prospective HL patients had short telomeres and CCR initially. In addition, the SC HL cohort was characterized by markedly short telomeres (6.6 vs. 9.7 kb in the NED HL cohort), the presence of complex chromosome rearrangements, and increased in vitro radiation sensitivity. CONCLUSIONS:An intimate relationship between pre-treatment telomere shortening, chromosomal instability, radiation sensitivity and occurrence of SC was found in HL patients.