bluuebunny/crossref_metadata_2025_split huggingface dataset:
Is docetaxel (D) less efficient than anthracycline-based chemotherapy (A) in triple-negative breast cancer (TNBC) treated in neoadjuvant setting?
Authors: Simon Laurence , Belletier Christine , Rodier Jean-Francois , Weitbruch Delphine , Velten Michel , Wilt Marc , Ghnassia Jean-Pierre , Petit Thierry 
Published: March 2020

e11542 Background: BRCA1 mutation is associated with the TNBC phenotype. Loss of BRCA1, due to genetic mutation or post-genomic inactivation, should confer susceptibility to DNA-damaging agents, such as anthracyclines, but resistance to mitotic-spindle poisons such as taxanes. However, optimal adjuvant systemic therapy for TNBC is difficult to define because of a lack of prospective data in TNBC restricted populations. As our neo-adjuvant regimen changed in 2008 (A followed by D before 2008 then D followed by A from 2008); we were able to compare retrospectively A and D efficacy in matched cohorts of TNBC treated in neo-adjuvant setting. Methods: Group 1 includes 24 patients with TNBC treated between 2005 and 2008 with A followed by D (3x 5FU 500 mg/m², epirubicine 100 mg/m², cyclophosphamide 500 mg/m² followed by 3x docetaxel 100 mg/m²). Group 2 includes 24 patients with TNBC treated in NAS between 2008 and 2011 with D followed by A. Characteristics of group 1 and 2 (median age at diagnosis, tumor grade, Ki67, TNM) were similar. All patients had a core-biopsy before chemotherapy. Chemotherapy response was evaluated by CT scan before 1st cycle, between 3rd and 4th cycle then after the 6th cycle. Surgery was performed 4 weeks after the 6th cycle. Results: In group 1, objective response rate after 3 cycles was 58% (14/24) (RECIST criteria). There was no progression. Complete pathological response rate (no residual invasive and in-situ tumor in breast, no tumor in axillary nodes) was 25%. In group 2, objective response rate after 3 cycles was 25% (6/24). Progression rate was 13% (3/24). Complete pathological response rate was 29%. The objective response rate after the first three cycles was significantly different between group 1 and group 2 (two-sided p-value = 0,039, Fisher exact test). Conclusions: Our retrospective analysis showed that docetaxel was significantly less efficient than anthracycline-based chemotherapy in chemo-naïve TNBC patients. These data should be taken in consideration for clinical practice and further phase III trials design in TNBC.
Prolonged clinical benefit with metronomic capecitabine plus oral vinorelbine as treatment of metastatic breast cancer: Results from a phase II study.
Authors: Orlando Laura , Fedele Palma , Schiavone Paola , Nacci Angelo , Calvani Nicola , Mazzoni Enrica , Quaranta Annamaria , Cinefra Margherita , Cinieri Saverio 
Published: March 2020

e11547 Background: Metronomic chemotherapy regimens have shown efficacy in patients with metastatic breast cancer through antiangiogenic mechanisms. We present preliminary data of a phase II trial of metronomic capecitabine (CAP) in combination with oral vinorelbine (VIN) as treatment of metastatic breast cancer (MBC). Methods: Patients with advanced breast cancer, pretreated or not for metastatic disease, were treated with VIN (60 mg/m2, on days 1 and day 8 of a 21-day cycle) combined with metronomic CAP (1500 mg daily). Primary end-point was overall response rate (ORR), secondary end-point time to progression (TTP), clinical benefit rate (CBR; PR+ CR + prolonged SD for ≥ 24 weeks) and tolerability. Results: A total of 31 patients with histologically confirmed, Her2 negative MBC, have been enrolled, 22 actually valuable for response and toxicity. Median age was 62 years (range 34-75), visceral metastases were present in 18 patients (58%), 11 patients (35%) were pretreated with chemotherapy, most of them with anthracycline and taxanes. Triple negative tumors were 5 (16%). Median number of cycles was 12 (range 4-34). The ORR was 54.5 % (95% CI, 44-63%), with two CR (9 %) and 10 PR (45%). Seven patients had SD, 5 prolonged (23%). The CBR was 77% (95% CI , 71%-84%). Three progressions of disease were observed (14%). Median TTP was 8 months (range 3- 24 +). Median overall survival was 32 months (range, 6-39 + ). The most frequent toxicities were WHO diarrhea grade 1 and neutropenia grade 2. Grade 3 skin toxicity was observed in two patients subsequently found to have DPD enzyme deficiency. No grade 2 alopecia was reported. Conclusions: In this phase II study, the all oral combination of low dose metronomic CAP combined with VIN seems to be very active, confirming data with standard doses, and allows a very long duration of response and treatment. The observed toxicity was mild and manageable. Thus, patients accrual is ongoing to the pre-set target of 66 patients.
Continuous low-irradiance photodynamic therapy (CLIPT) as a novel treatment for cutaneous recurrences of breast cancer.
Authors: Persico Justin , Wazer David E. , Melanson Anne Marie , Rogers Gary S , Graham Roger 
Published: March 2020

e11548 Background: Photodynamic therapy (PDT) has been used for the treatment of many malignancies. This binary therapy involves the administration of a photosensitizer followed by exposure to light. Treatment toxicity has historically limited the use of PDT. Our study aimed to assess whether a novel approach, termed continuous low irradiance photodynamic therapy (CLIPT), would result in enhanced efficacy with reduced toxicity. Preclinical data suggest decreased toxicity and increased cell death by apoptosis with CLIPT. Methods: Breast cancer patients with chest wall progression were eligible for our study. No systemic anti-cancer therapy within 30 days and no radiation to the target site within 60 days of enrollment was allowed. All patients received porfirmer sodium intravenous 0.8mg/kg at time 0 and returned at time 48 hours for light exposure. A wavelength of 630nm was delivered continuously over 24 hours by a Diomed laser via a flexible light patch. An area of uninvolved normal skin was used as a control. Post-treatment biopsy was performed to assess for apoptosis by TUNEL assay. Results: Eight breast cancer patients were enrolled in our study. The initial dose of light was 100J/cm2 and was given to subjects 1 and 2 but resulted in partial-thickness ulceration of the epidermis. Subjects 3-8 received light at 50J/cm2 and experienced erythema at the intervention site, with no ulceration observed. All patients reported mild pain at the treatment site and 6 required short-term narcotic analgesia. Five of the 8 patients showed evidence of response, and no patients had progression of treated lesions. Four of 7 biopsy specimens showed evidence of apoptosis on TUNEL assay. Conclusions: CLIPT may prove to be a valuable option for treatment of breast cancer chest wall recurrence. The dose-limiting toxicity was skin ulceration and the maximum tolerated dose (MTD) was determined to be 50J/cm2/24h. A 50% response rate was seen in patients treated at the MTD, with apoptosis seen on post-treatment biopsy specimens. Further investigation of CLIPT as a therapeutic modality is warranted.
Which is your choice? Neoadjuvant doxorubicin hydrochloride and doxetaxel (AD) versus doxorubicin hydrochloride, cyclophosphamide, and paclitaxel (AC-T) in locally advanced breast cancer.
Authors: Kang Seok Yun , Choi Jin-Hyuk , Kim Ku Sang 
Published: March 2020

e11559 Background: It is well known that neoadjuvnat chemotherapy is acceptable for women with locally advanced breast cancer. However, it is not achieving consensus that what kind of regimen is most effective and tolerable, although lots of regimens and dosages were clinically used. Methods: We compared the patients who were received adriamycine and doxetaxel (AD) and adriamycin, cyclophosphamide followed by paclitaxel (AC-T) as neoadjuvant chemotherapy and then received operation from 1 January 2006 to 30 September 2011. The group of AD regimen was scheduled for 3 cycles of AD (50mg/m2 and 75mg/m2, respectively) with 3 weeks interval and then completes resection. The group of AC-T was scheduled for 4 cycles of AC regimen (50mg/m2 and 500mg/m2, respectively) and then 4 cycles of paclitaxel(175mg/m2) with 3 weeks interval and then completes resection. Results: The patients who were enrolled in this study were totally 78(AD and AC-T were equally 38.) The significant differences of patients’ characteristics between two groups were not observed. However, the significant differences were identified in hematologic toxicity including neutropenia more than grade 3 p<0.001), neutropenic fever p<0.001), dose reduction rate due to hematologic toxicity (p=0.012) and chemotherapy induced anemia (p=0.012)), although chemotherapy induced thrombocytopenia (p=1.0) was not different between two groups. No differences were identified in non-hematologic toxicity including hepatic toxicity, gastrointestinal toxicity and peripheral neuropathy. The response of chemotherapy was no difference between two groups, which was estimated by conversion rate of breast conserving surgery, clinical response of chemotherapy (p=0.148), clinically downstaging rate (p=0.464) and pathologic complete response rate (p=1.0). There is no factor to predicting pathologic complete response or conversion to breast conservation in this study. Conclusions: The neoadjuvant AC-T regimen is more tolerable with similar clinical outcome compared to AD regimen.
Significance of chromosome 17 polysomy in breast cancer.
Authors: Galamaga Robert W. , Mariani Rachel , Almanaseer Imad , Bitran Jacob D. 
Published: March 2020

e12002 Background: Human epidermal growth factor receptor 2 (HER-2) overexpression occurs in up to 30% of breast cancers and has been associated with poor clinical outcomes that have improved with advances in HER-2 directed therapy. The HER-2 gene resides on the long arm of chromosome 17 and amplification is typically assessed via immunohistochemistry or fluorescence in situ hybridization (FISH); HER-2 is interpreted as amplified, non-amplified, or equivocal. The effect and clinical impact of chromosome 17 polysomy in specimens interpreted as HER-2 non-amplified has not been well-established in breast cancer patients. This subgroup may represent a unique set of patients who may benefit from HER-2 directed therapy given the increase in HER-2 gene copy number. If tumors with polysomy 17 share biologic similarities with those positive for HER-2 amplification this may significantly influence the approach to treating these patients. In a single institution study we reviewed all breast cancer cases diagnosed in 2008 which were reported as HER-2 equivocal or non-amplified via FISH and with chromosome 17 polysomy in order to extrapolate disease-free and overall survival data within this subset. Methods: HER-2 expression via FISH from patients diagnosed with breast cancer in 2008 was reviewed. In those patients with equivocal or non-amplified HER-2 expression we selected those with chromosome 17 polysomy defined as a chromosome 17 centromere copy number of > 3 per tumor cell. A total of 9 patients were identified. Results: The median age was 74 (36-88). Median tumor size was 1.6 cm (0.7-4.9) and 8 patients (88%) had both estrogen and progesterone positive tumors. Stage distribution was as follows: stage IA: 4 (44%); stage IIA: 2 (22%); stage IIB: 2 (22%) and stage IIIA: 1 (11%). The actuarial 3 year disease free survival was 67%. Conclusions: Breast cancers with equivocal or non-amplified HER-2 expression with chromosome 17 polysomy represent a unique subset of tumors with a biology that is not well-understood. Previously published studies have yielded conflicting results regarding the prognostic significance of this genotype. Our study reflects a three year survival of 67% which suggests that these patients represent an aggressive subset.
Comparison of real prognosis and estimated prognosis by Adjuvant! Online in breast cancer in sites of Itajaí, Brazil.
Authors: Santos Borges Giuliano , De Azambuja Evandro , Rovere Rodrigo , Colchon Paulo Henrique , Staak Junior Marcos Cesar 
Published: March 2020

e12035 Background: Internet-available programme Adjuvant! Online is widely regarded as one of the best tools to estimate prognosis as well as benefit of adjuvant therapy in breast cancer. Methods: It is a retrospective cohort study, with a post hoc analysis with 214 patients of three different Brazilian services in which were measured the year overall and disease free survivals in a follow up of three years, and the same endpoints were estimated on a 10 year basis by the Adjuvant! Online programme. Results: See table. Conclusions: Our study shows interesting trends in breast cancer survival, even though the number of patients accrued may not be enough to have full external validity. We conclude that the OS and DFS rates in our sample compared to the one calculated by the Adjuvant! Online programme display agreement, following the same pattern, considering different periods of follow up (much longer in the internet tool). The only group which had poor concordance was the group of younger patients (i.e., under 40), even though it was the least represented group in our sample. Nevertheless, it can be suggested that the programme underestimates the usually bad prognosis in these cases, as broadly documented in medical literature. Our study shows interesting trends in breast cancer survival, even though the number of patients accrued may not be enough to have full external validity. [Table: see text]
Ten-year trends in colorectal cancer (CRC) control in Texas.
Authors: Vugrin Davor 
Published: March 2020

e12044 Background: The 2015 colorectal cancer control goals are to reduce age-adjusted incidence to 34.8/100,000 and mortality to 12.0/100,000 and to increase the number of 50 year and older undergoing screening per national guidelines up to 75%. Methods: In order to determine progress and trends toward meeting the 2015 objectives we have reviewed Texas Cancer Registry 2000 – 2009 data for incidence, 1999 – 2008 data for mortality, and BRFSS 2002 0 2010 data for screening rates. Results: 91,260 Texans were diagnosed with CRC and 32,840 died from it. Non-Hispanics represent 50.1% of population they account for 66.4% of cases diagnosed with it. Hispanics account for 34.7% of population and contribute to 18.7% of diagnoses. Blacks, 12.1% of population contribute 12.6% of cases. Male and female contribution to diagnosed CRC was 53.5 % and 46.% of cases. Black male incidence rates were highest 74.7 and Hispanic females lowest 32.7/100,000. While NH White and Blacks reduced incidence rates by about 1% per year, Hispanics rate of decrease was 0.5/yr. Gender and race played role in this decrease. Mortality rates declined most in Blacks and NH Whites, while no appreciable improvement was observed in Hispanics. Race and gender mortality rates varied. Black male mortality rates were highest, 36.0 and Hispanic females lowest, 10.5. Frequency of sigmoidoscopy-colonoscopy increased in all 3 racial/ethnic groups, but was lowest among Hispanics. Lack of insurance is big obstacle to progress. Conclusions: Major coordinated screening push will be needed to reach 2015 goals.
Small business technology transfer (STTR) phase I study (1 R41 MD006148-01) of an automated voice response (AVR) system to improve symptom management in neuro-oncology patients.
Authors: Chowdhary Sajeel A. , Given Barbara Ann , Given Charles W , Majeske Cindy , Decker Paul D , Decker Brian 
Published: March 2020

e12500 Background: This STTR Phase 1 study focused on enhancing and improving the technology of a prior AVR system (Grant #R01 CA30724) to manage symptoms in cancer patients. Neuro-Oncology patients were enrolled to test our proof of concept (POC). Methods: Previous AVR function was replicated using Asterisk software enhancing the branching logic, configurability and operational capacity on multiple operating systems; limitations of the previous AVR. Eligibility criteria: access to a telephone; actively on chemotherapy. Nurse recruiters provided detailed information about the study and answered questions. Following signed consent patients provided a preferred phone number and chose a day and time of the week to receive AVR calls. Patients received a Symptom Management Guide (SMG) at time of consent. Patients were contacted a total of 4 times over a 4 week period by the AVR. At each contact patients were asked to rate 17 symptoms on a scale of 1-9 for severity and interference with 4 domains of quality of life on a 1-5 scale. Patient’s reporting a 4 or higher severity level were directed by the AVR to reference their SMG for self-care strategies to manage their symptoms. At the end of the study patients completed a satisfaction survey. Results: Ten patients were enrolled. The AVR placed 38 of 40 scheduled calls. No errors in survey branching were evident with confirmation. Patient satisfaction surveys were completed with 70% of patients. One patient did not complete any scheduled calls and was not contacted, two patients were unreachable. All patients reported satisfaction. 86% reported they would recommend this system to their oncology provider. 71% felt it was helpful in individualized monitoring of symptoms between visits. 57% liked knowing their symptom(s) were being checked regularly. One indicated the system was too overwhelming. Complaints included: not being able to change responses (1) and not allowing them to answer questions as fast as they wanted (2). Conclusions: Patient satisfaction results and system performance confirmed that the POC was feasible and that this system should be studied in larger groups of oncology patients.
Analysis of two consecutive series of unresectable high-grade glioma (HGG) patients (pts) treated with or without neoadjuvant chemotherapy before estandar radiochemotherapy (CRT) and adjuvant temozolamide (TMZ).
Authors: Capdevila Laia , Cros Sara , Pardo Nuria , Cuadra Jose Luis , Etxaniz Olatz , Villà Salvador , Balana Carmen 
Published: March 2020

e12504 Background: Standard treatment of HGG is based in CRT with TMZ. Neoadjuvant treatment before radiotherapy has been studied in small series. Methods: We retrospectively analyzed 2 consecutive series of non-resectable HGG pts treated with neoadjuvant chemotherapy (TMZ & cisplatin) before the 2005 with those treated with TMZ and concurrent and adjuvant TMZ & radiotherapy (after 2005). Results: 46pts diagnosed between August 2003 and October 2010 were selected. 23 received neoadjuvant therapy with TMZ (200mg/m2/d x 5d) and cisplatin (75mg/m2) followed by radiotherapy -60Gy 6w- (NA group), and the remaining 23pts received standard treatment with concomitant TMZ and radiotherapy -60Gy 6w- and adjuvant TMZ (CRT group). In the NA group, 87% of pts were ≥50 years, 43.5% were men, 65.2% had performance status (PS) <2, 38.4% Barthel index <70. Histology: 78.3% were glioblastoma (GB). 30.4% of pts had multifocal lesions and 43.5% had seizures at the diagnosis. 95.7% of pts required dexamethasone. In the CRT group, 91.3% of pts were ≥50 years, 78.3% were men, PS was <2 in 60.9% and Barthel index <70 in 21.7% of cases. Histology: 69.6% were GB, 26.1% pts had multifocal lesions and 26.1% had seizures at diagnosis. 87% of pts required dexamethasone. All factors were uniformly distributed in the two groups. 82.6% of pts completed scheduled radiotherapy in NA group in front 91.3% in the CRT group (P= 0.66). PFS was 2.9 months (m) (CI 95%: 0.5 – 5.5) in NA group versus 5.1m (CI 95%: 3.1 – 7.1) in the CRT group (p=0.62), OS was 8.5m (CI 95%: 4.0 – 12.9) vs 8.2m (CI 95%: 1.2 – 15.2) respectively (p=0.45). Conclusions: No differences were found in either PFS or OS between the two treatment groups. The administration of neoadjuvant therapy does no have a negative impact on the ability to receive radiotherapy. These results provide a basis to justify clinical trials in this setting with promising drugs before radiotherapy treatment.
Correlation of pharmacokinetics of CPT-11 in FOLFIRI with phenotyping of CYP3A4 and UGT1A1 activity.
Authors: Chan Daniel Boon Yeow , Lee Lawrence Soon-U , Wang Ling-Zhi , Yong Wei-Peng , Fan Lu , Chuah Benjamin , Hee Kim-Hor , Ling Winnie Hui Yee , Soh I Peng Thomas , Babu Thambidurai Ganesh , Cheong Pei Fen , Voon Pei Jye , Soo Ross A. , Lee How-Sung , Lee Soo-Chin , Goh Boon C. 
Published: March 2020

e13002 Background: CPT-11 has complex PK and PD; genotyping of UGT1A1 is recommended for higher doses in *28 carriers (Caucasian) and *6 carriers (Asian) because of a higher risk of toxicity. Raltegravir is mainly metabolized to raltegravir glucuronide by UGT1A1. CPT-11 is mainly eliminated by cytochrome P450 isoform 3A (CYP3A)-mediated oxidation and by esterase cleavage to form SN-38, which is further conjugated by uridine-diphosphate glucuronosyltransferase (UGT) isozymes to the inactive SN-38 glucuronide. We prospectively explored the correlation of midazolam and raltegravir PK with CPT-11 clearance (CL) and SN-38 levels respectively and toxicity in patients undergoing chemotherapy with CPT-11. Methods: Twenty-five Asian patients with advanced cancer received CPT-11 as a 2-weekly 90-minute infusion (180 mg/m2) as part of the FOLFIRI regimen. Subjects were administered raltegravir 400 mg orally (as a UGT1A1 probe) and intravenous midazolam 1 mg (as a CYP3A4 probe) one day before the first dose of their chemotherapy. Blood sampling for drug concentrations was performed for 2 days after probe drug administration. Non-compartmental PK analyses were performed using WinNonLin. Genomic DNA was isolated and screened for the known genetic variants in UGT1A1*6. Results: One patient developed grade 3 diarrhea and 16 developed grade 3-4 neutropenia. The mean CPT-11 CL was 21.9 + 7.8L/h. SN-38G/SN-38 AUC ratio was highly correlated with Raltegravir glucuronide/ Raltegravir AUC ratio (r=0.784 p<0.01). Midazolam CL was highly correlated with CPT-11 CL (r=0.563 p<0.01). SN38 AUC correlated well with neutropenia (Log10Nadir Absolute Neutrophil Count (ANC) (r=-0.397 p<0.05). Neither CPT-11 nor midazolam CL correlated with Log10 Nadir ANC. Of the 24 patients with genotyping of UGT1A1*6 done, 17 were wild type (GG), 7 heterozygotes (AG) and 0 were mutant (AA). No differences in toxicity or SN38 pharmacokinetics were observed in the UGT1A1*6 variants. Conclusions: Raltegravir glucuronide ratio is a good predictor of SN-38 glucuronidation, and has potential to predict neutropenia from FOLFIRI treatment. Prospective studies with dose adjustments should be done to develop raltegravir as a probe to optimize CPT-11 therapy.