bluuebunny/crossref_metadata_2025 huggingface dataset:
Immunogenicity of NY-ESO-1 cancer testis antigen in triple-negative breast cancer.
Authors: Ademuyiwa Foluso Olabisi , Bshara Wiam , Attwood Kristopher , Edge Stephen B , Ambrosone Christine B. , Morrison Carl D , Ritter Gerd , Miliotto Anthony , Gnjatic Sacha , Odunsi Kunle
Published: March 2020

e11563

Background: NY-ESO-1 cancer testis (CT) antigen is an attractive candidate for immunotherapy as a result of its high immunogenicity. The aim of this study was to explore the potential for NY-ESO-1 antigen directed immunotherapy in triple negative breast cancer (TNBC) by determining the frequency of expression by immunohistochemistry (IHC) and the degree of inherent immunogenicity to NY-ESO-1. Methods: 168 TNBC and 47 ER+/HER2- primary breast cancer specimens were used to determine NY-ESO-1 frequency by IHC. As previous studies have shown that patients with a robust innate humoral immune response to CT antigens are more likely to develop CD8 T-cell responses to NY-ESO-1 peptides, we evaluated the degree to which patients with NY-ESO-1 expression had inherent immunogenicity by measuring antibodies. The relationship between NY-ESO-1 expression and CD8+ T lymphocytes was also examined. Results: The frequency of NY-ESO-1 expression in the TNBC cohort was 16% versus 2% in ER+/HER2- patients. A higher NY-ESO-1 score was associated with a younger age at diagnosis in the TNBC patients with NY-ESO-1 expression (p= 0.026). No differences in OS (p=0.278) or PFS (p=0.238) by NY-ESO-1 expression status were detected. Antibody responses to NY-ESO-1 were found in 73% of TNBC patients whose tumors were NY-ESO-1 positive. NY-ESO-1 positive patients had higher CD8 counts than negative patients (p=0.018). Conclusions: NY-ESO-1 is expressed in a substantial subset of TNBC patients and leads to a high humoral immune response in a large proportion of these individuals. Given these observations, patients with TNBC may benefit from targeted therapies directed against NY-ESO-1.
Family history record and hereditary cancer risk perception after the creation of a heredofamilial cancer unit in a Spanish hospital.
Authors: Marquez-Rodas Ivan , Perez Ramirez Sara , Cavanagh Podesta Mercedes , Moya Beatriz , Ruperez Blanco Ana Belen , Lopez-Trabada Ataz Daniel , Custodio Cabello Sara , Orera Clemente Maria , Calvo Felipe A. , Martin Miguel
Published: March 2020

e12003

Background: A comprehensive family history and consideration of the criteria for hereditary cancer risk are essential for oncology practice, since patients and relatives at risk could benefit from further genetic counseling (GC). The objective of this work is to compare the family history record and the hereditary cancer perception risk according to national cancer institute (NCI) criteria before and after the creation of a heredofamilial cancer unit (HFCU). Methods: We retrospectively analyze the clinical records from new incoming patients of our medical oncology service in two cohorts: Cohort 1, from January 2009 to December 2009 (before HFCU creation); and cohort 2, from May 2010 to August 2010 (first four months after HFCU creation). Family history record (yes/no) and NCI general hereditary cancer criteria (unusually early age; one or more first-degree relatives affected with the same or a related tumor; synchronous, bilateral or metachronous cancer in the same individual; atypical presentations; suggestive pathology report) were collected. Results were compared using chi-square test. p <0.05 was considered significant. Results: The table summarizes the results. In cohort 1, 28% (175/621) of clinical records contained the family history, while in cohort 2 this percentage increased to 54% (92/171), (p<0.001). 17% (106/621) patients in cohort 1 and 23% (40/171) in cohort 2, met NCI risk criteria (N.S.) In cohort 1, 13% (14/106) of these patients were referred to GC, while in cohort 2 this percentage increased to 38% (15/40) (p<0.01). Conclusions: The creation of a multidisciplinary HFCU significantly increased the quality of family history records and the referral of patients at risk to GC. However, the percentages still remain limited and further efforts must be made in order to remark the importance of family history in oncology. [Table: see text]
PE-PCR, a novel method for detection of mutations in blood-cell-free DNA.
Authors: Platica Ovidiu , Khazan Mikhail , Martinez Manuel
Published: March 2020

e12016

Background: During the past few years, the “personalized” therapy based on specific tumor molecular alterations has become the standard of care of cancer patients . Recently, it has been shown that blood DNA is released from normal as well as tumor cells as a high molecular weight nucleic acid and carries the same genetic abnormalities as the cells of origin. However, the identification of these DNA alterations is difficult since the blood tumor DNA is found in very low concentration and it is mixed with a huge amount of normal homologous DNA. Therefore, most methods able to detect such abnormalities in cells are not applicable for blood cell free DNA. We report here a simple novel technology for mutation detection in blood DNA. Methods: The serum DNA is subject to two PCR rounds; in the first round, only DNA fragments containing the mutation are amplified by an extension primer encoding the mutation at its 3’ terminus. The DNA is then re-amplified by nested PCR for 40 cycles and the extension of mutated primer is detected by gel electrophoresis. The method was tested with DNA from the human lung cancer cell line A549 (ATCC # CCL-185) and was found to detect mutations in the presence of 10 12 [OP1] fold excess of normal DNA. Results: The sera from 10 patients with localized and metastatic lung (6) and pancreatic carcinomas (4) were tested for the presence of mutations in Kras and P53 genes. Seven patients had a mutation in a least one gene. Eleven patients without any clinical evidence of cancer tested negative. Conclusions: PE-PCR is a simple sensitive method for mutation detection in blood cell-free DNA, requiring only one ml blood and less than a 48 hour work. This method can potentially be used for mutation detection in most of the genes of clinical interest, as a non-invasive research tool, for early detection of tumor recurrence and possibly for early diagnosis of cancer when surgery can be curative.
Relationship between cancer and allergy.
Authors: Carneiro Bruno Gustavo Muzzi Carvalho , Petroianu Andy , Carvalho Rafael Augusto Ribeiro , Ribeiro Thiago Neto , Rodrigues Ana Maria Santos
Published: March 2020

e12018

Background: Many studies have suggested an inverse association between allergies and cancer, while others have found no relation between them, and still others have shown an increased risk of cancer in allergy patients. The conflicting findings from prior studies are partially due to the chosen research method, such as different definitions and measures for atopy, in addition to variations in the control of confusion factors, such as smoking and obesity. Objectives: Verify if there is a relation between certain types of cancer and allergies; investigate if there is a difference between individuals with and without cancer in relation to allergies. Methods: Case-control study carried out at the Alberto Cavalcanti Hospital of the Hospital Foundation of the State of Minas Gerais (FHEMIG), Brazil, from 2009 to 2011. The study included patients over 18 years of age, from both genders, who presented a diagnosis of cancer, as compared to healthy individuals, paired by gender and age. An anamnesis was gathered considering the medical history of the allergy, as diagnosed by a doctor, as well as the patients’ habits, associated illnesses, and the use of medications. For cancer patients, data concerning the tumor were recorded. Subsequently, an allergy percutaneous test was performed in each group to detect allergic hyperreactivity toward common inhalable, bacterial, and food antigens within our everyday environment. A blood sample was collected to quantitatively evaluate the eosinophils. Results: Both groups were paired according to interest variables, and eventual deviations were adjusted by means of multivariate analysis. Reports of allergies occurred in 30% of the patients in the cancer group, as compared to 53% in the control group (p<0.05), whereas in the cutaneous tests, a greater positivity occurred in the cancer group (69%) than in the control group (51%, p<0.05). No difference in the eosinophil values could be observed within the groups. Conclusions: Cancer patients present fewer allergies. By contrast, in cancer patients, positive cutaneous tests detected allergies which did not correspond to the clinical findings. Therefore, in cancer patients, the positive cutaneous test for allergies does not present a direct relation to the presence of clinically detectable allergies.
Disease-free survival pattern in breast cancer patients in India treated in a single institution.
Authors: Ajaikumar Basavalinga S. , Gopinath Kodaganur Srinivasachar , Srinath B S , S Ramesh Bilimagga , Rao Nalini K , Patil Shekhar , Diwakar Ravi B , Prabhudesai Shilpa A. , Kallur Kumar G , Raghavendra Rao M. , Shashidhar H P
Published: March 2020

e12030

Background: This study elucidates data from a 5 year retrospective study evaluating survival rates and prognostic factors in breast carcinoma patients in a private cancer set up in south India. Methods: 1046 patients who were treated between years 2003 to 2008 were analyzed. Clinical data including stage, histopathology type, age, node positivity, treatment plan, chemotherapy regimen, ER/ PR and Her2 Neu status, type of surgery etc were abstracted in a database. Five year disease free survival, local failure free survival and distant failure free survival was calculated using Kaplan Meier survival curves. Log rank mantel hazel tests were used to compare two survival curves. Results: Local recurrence was seen in 4% and distant metastases in 22% of the study sample. 62% of patients presented with early breast cancer (AJCC Stage I, II and IIIA). 85.6% of early and 73.1% of locally advanced breast cancers were disease free at 5 years (p<0.001).90.6% of early and 82.4% of locally advanced breast cancers had distant failure free survival at 5 years (p=0.001). Local failure free survival was 96.1% in both early and locally advanced breast disease at 5 years.94.9% of her 2 negative and 83.5% Her 2 positive were disease free at 5 years (p=0.001). 5 years progression free survival was 91.5% for breast conservation surgery vs 84.1% for mastectomy with axillary clearance (p=0.01). 75.4% with triple negative status and 80.8% non triple negative receptor status had 5 years DFS. Conclusion: This is a first report of survival patterns of breast cancer patients treated in a single centre in India. High early stage patient numbers and high median disease free survival times could be because of improvement in screening and treatment of breast cancer in a developing country like India.
Analysis of clinical features of ovarian cancer (OC) and breast cancer (BC) among BRCA-mutated (BRCA+) and sporadic (NH) double tumors.
Authors: Nicoletto Maria Ornella , Borgato Lucia , Artioli Grazia , Perin Alessandra , Zustovich Fable , Ghiotto Cristina , Koussis Haralabos , Cappetta Alessandro , Mocellin Simone , Furini Lara , Dalla Palma Maurizia , Ercoli Alfredo , Litta Pietro , Nardelli Giovanni B. , Zagonel Vittorina
Published: March 2020

e12037

Background: Women BRCA+ are at significant risk of developing both OC and BC. Double tumors could arise also in NH patients. Whether the clinical outcome of double OC and BC is different in BRCA+ and in NH subjects is unknown. Methods: The databases of the Istituto Oncologico Veneto (IOV), Medical Oncology Department of Mirano (VE) and Thiene (VI) were searched to identify the clinical and pathological features of (BC) and (OC) arisen in BRCA+ subjects as well as patients with both malignancy but tested negative/no-tested/unknown for BRCA1/2 mutation (NH). The primary endpoint was to establish if OC instead of BC needs a more intensive follow-up because it principally affects patient’s prognosis. Patients were censored at last follow-up or death (any cause) for determination of overall survival (OS). OS estimates were determined using the Kaplan-Meier method and compared by means of log-rank test. The Fisher’s exact test and the t-test were used to compare frequencies and means between groups, respectively. Results: 24/31 (77%) BRCA+ and 30/49 (61%) NH had BC as their first malignancy (p=0.15). Among NH, 20 were BRCA test negative, 20 were untested and 9 unknown. BRCA+ were younger than NH at diagnosis of first malignancy (mean age 51 vs 56y, p=0.055). Bilateral BC was more frequent in BRCA+ than in NH (78.6% vs 28.6% p=0.001). Stage III-IV OC at diagnosis were 74% in BRCA vs 61% in NH (p=0.34). Locally advanced (stage II-III) BC was significantly more frequent in BRCA+ vs NH (75% vs 42%, p=0.03). No OS difference was observed between BRCA+ and NH subjects (P=0.99). Death for progression of ovarian cancer was observed in 11/31 (35%) in BRCA+ vs 10/49 (20%) patients in NH (p=0.19). No progression of breast cancer was reported in either groups. Conclusions: OC is the killer malignancy among patients affected by OC and BC, both in BRCA+ and in NH subjects. In patients with double tumors, irrespective of their pathological features, a more conserving management for BC and an intensive follow-up for OC are suggested.
Effect of interferon-α/β on temozolomide activity against MGMT-positive glioma stem-like cells in vitro and in vivo.
Authors: Chen Zhong-ping , Shen Dong , Wang Jie , Yang Qun-ying
Published: March 2020

e12503

Background: O6-methylguanine DNA methyltranferase (MGMT) is one of the main mechanisms of chemoresistance for alkylating agents in malignant gliomas. Recent studies have showed that glioma stem-like cells (GSCs) could be the main reason for tumor recurrence and chemoresistance. In this study, we aimed to explore the effects of interferon-α/β against MGMT-positive glioma stem-like cells, and to investigate whether interferon-α/β can enhance the efficiency of temozolomide (TMZ) and the possible mechanism Methods: The growth inhibition effect of TMZ, with interferon-α or interferon-β, against the MGMT-positive GSCs from human glioma cell lines U251 and SKMG-4 (U251G and SKMG-4G) was evaluated by using Cell Counting Kit-8 (CCK-8) assay in vitro, and in xenograft models. MGMT and NF-κB expression in the tumor samples were determined by RT-PCR and Western blot analysis. Results: Our results revealed that the anti-tumor activity of TMZ was significantly enhanced by combined using interferon-α/β in vitro. In xenograft models, the tumor growth inhibit rate (IR) of TMZ to SKMG-4G and U251G was 35.2%±2.28% and 16.7%±1.96%, respectively. When TMZ combined with interferon-α or interferon-β, the IR to SKMG-4G was 58.4%±4.34% and 63.4%±1.08%; and to U251G was 41.1%±8.66% and 44.5%±1.90%, respectively(P<0.05). The expression of NF-κB and MGMT in MGMT-positive GSCs decreased significantly in both mRNA and protein levels after using interferon-α/β. Conclusions: Our results indicate that IFN-α/β can enhance the sensitivity of TMZ, possibly through down-regulate NF-κB expression resulting in lower MGMT transcription expression.
Prognostic factors in survival of patients with cerebral metastases.
Authors: Markulin-Grgic Lijerka , Kukura Vlastimir
Published: March 2020

e12505

Background: The problem of cerebral metastases is a great one and seems to become more and more important thanks to earlier diagnosis and the possibilities of effective treatment. In this analysis 330 patients with cerebral metastases, treated at the Clinic of Oncology, School of Medicine, Zagreb, Croatia, over 13 years, from 1995 - 2007 are dealt with. The most common primary tumor was bronchus carcinoma in 201/330 patients (60.91%), then breast carcinoma in 48/330 patients (14.54%), melanoma in 16/330 patients (4.85%), gastrointestinal tumors in 17/330 patients (5.15%), hypernephroma in 9/330 patients (2.73%), ovarian carcinoma in 10/330 patients (3.03%), cervical small cell carcinoma in 4/330 patients (1.21%), testicular tumors in 5/330 patients (1.52%) and in 20/330 patients (6.06%) the primary was not found. Methods: The patients were treated by surgery, radiotherapy and chemotherapy in various combinations. Results: There is a significantly better survival in female patients with cerebral metastases from breast carcinoma in comparison to other primary tumors (p<0.001). The patients with longer symptom-free period up to the diagnosis of the secondaries in the brain had significantly better survival (p<0.001). Better survival was achieved in younger patients (p<0.05). Conclusions: Considering the applied therapy methods, the best survival results were obtained in patients treated by a combination of surgery, radiotherapy and chemotherapy.
“Long extended” temozolomide in a selected population with not radically resected high-grade gliomas.
Authors: Spinelli Gian Paolo , Lo Russo Giuseppe , Miele Evelina , Alberti Antonio Maria , Strudel Martina , Stati Valeria , Zoratto Federica , Papa Anselmo , Rossi Luigi , Verrico Monica , Basso Enrico , Giordani Erika , Zaccarelli Eleonora , Minozzi Marina , Codacci Pisanelli Giovanni , Tomao Silverio
Published: March 2020

e12510

Background: Despite the important progress in the treatment of solid tumors, high grade gliomas (HGGs) remain neoplasm with poor prognosis, especially when are not radically resected. Here we report the results of a selected population treated with standard schedule of Radiotherapy (RT) + Temozolomide (TMZ) followed by TMZ until progression. Methods: From January 2008 to January 2010, 14 newly diagnosed HGG patients, with median age of 50.6 years (range 27-75 yrs), were enrolled at Oncology Unit of S. Maria Goretti Hospital in Latina (University of Rome “Sapienza”). All patients were not radically resected and with ECOG PS=O. Furthermore patients were selected according to O6 Methyl-Guanine-DNA-Methyl Transferase (MGMT) promoter methylation status. Only methylated patients were included in our study. After surgery, patients received standard treatment with TMZ (75 mg/m2) concomitant with RT (60 Gy total dose). After a break of six weeks, Magnetic Resonance Imaging (MRI) was performed and all patients with stable or responsive disease received TMZ (150mg/200mg/m2/d x 5dq 28d) until progression. The response to treatment was evaluated according to RANO criteria Results: In our study the results showed one year overall survival (OS) and progression free survival (PFS) rates of 85,7% and 71,4% respectively. Moreover we observed two years OS rate of 70% and two years PFS rate of 10%. A total of 108 cycles of adjuvant TMZ were administered with average number of 9 per patient (range 1-16). The most frequent side effects observed were haematological toxicity and fatigue. Thrombocytopenia (G2-G3) was observed in 42% of patients, neutropenia (G2-G3), fatigue (G2-G3) and nausea (G2-G3) in 30%, 32% and 25% of patients respectively. Conclusions: Despite the small number of patients, our experience suggests a manageable safety profile and a good efficacy of TMZ until progression in a selected population of patients (HGGs not radically resected, with a good ECOG PS). These data also confirms the literature knowledge, underlining the prognostic positive impact of MGMT promoter methylation in patients with HGG.
Phase Ib study of the safety, pharmacokinetics (PK), pharmacodynamics (PD), and antitumor activity of the humanized monoclonal antibody (huMAb) anti-EGFL7 (MEGF0444A) in combination with bevacizumab (bev) with or without paclitaxel.
Authors: Goldman Jonathan Wade , Gordon Michael S. , Munster Pamela N. , Bergsland Emily K. , Moore Amy Patricia , Bai Shuang , Hegde Priti , Fredrickson Jill O. , Chang Ilsung , Chandler G. Scott , Funke Roel Peter , Rhee Ina Park , Chen Daniel S. , Rosen Lee S.
Published: March 2020

e13000

Background: Epidermal growth factor-like domain 7 (EGFL7), is a vascular-restricted, tumor selective, extracellular matrix protein that forms peri-vascular tracks and promotes endothelial cell adhesion and survival. These activities are inhibited by the huMAb anti-EGFL7 (MEGF0444A), which significantly enhances the efficacy of anti-VEGF in murine tumor models. A Phase Ia dose escalation of single agent MEGF0444A demonstrated no dose-limiting toxicities (DLTs). Methods: A standard 3+3 dose escalation design was used to study safety, PK, PD, and anti-tumor activity of MEGF0444A in a 2-arm Phase Ib trial in patients (pts) with advanced solid tumors. In Arm A, 22 pts received MEGF0444A at doses of 2, 5, or 10 mg/kg with bev 10 mg/kg q2w. In Arm B, 18 pts additionally received paclitaxel 90 mg/m2 weekly. Subsequent Arm A expansion cohorts have examined flat dosing of MEGF0444A (600 mg) as a rapid infusion, serial tumor biopsies, and pts with renal cell carcinoma (RCC), respectively. Circulating progenitor cells (CPCs) and dynamic contrast enhanced MRI (DCE-MRI) were assessed as PD biomarkers. Results: The combination of MEGF0444A and bev with or without paclitaxel was well-tolerated without DLTs, exacerbation of bev-related adverse events (AEs), or AEs attributed to rapid infusion. MEGF0444A demonstrated linear PK, and flat dosing yielded MEGF0444A exposures similar to those predicted using Phase Ia weight-based dosing data. CPCs decreased in a subset of pts at the 5 mg/kg q2w dose. DCE-MRI showed a trend toward decreased Ktrans at this dose, supporting combination activity with bev. Eight partial responses, 2 in Arm A and 6 in Arm B, were observed across multiple tumor types. Conclusions: MEGF0444A has demonstrated safety, favorable PK, and clinical activity in combination with bev and bev/paclitaxel. PD biomarker modulation supports a recommended Phase II dose equivalent to 5 mg/kg q2w. RCC and tumor biopsy cohorts remain active. Randomized Phase II trials of MEGF0444A in combination with chemotherapy and bev in colorectal cancer and non-small cell lung cancer are underway.
Bronchial artery infusion of recombinant adenovirus-p53 and chemotherapeutic agents in treatment of bronchogenic carcinoma in advanced stage and failed to response to standard treatments.
Authors: Zu Maoheng , Zang Qingqiao , Wei Ning , Xu Wei Xu
Published: March 2020

e13004

Background: Patients with advanced bronchogenic carcinoma (BC), who failed common standard treatments, poses a big challenge for clinicians. Here we report success cases of using bronchial artery infusion of recombinant adenovirus-p53 (rAd-p53) and chemotherapeutic agents in treatment of advanced BC failed to response to standard treatments. Methods: Sixteen patients with advanced unresectable BC, who failed standard chemo- and radio-therapy, were included in this study. There were 11 males and 5 Females with an average age of 59.4 years old. They received bronchial artery infusion of 2×1012 rAd-p53 viral particles (VP), 40 mg of cisplatin (PPD), 20 mg of pirarubicin (THP), 0.5 g of 5-Fu, and 30 mg of endostatin. The infusion was given daily for 3 days. Response rate and overall survival were evaluated. Results: At 3 months follow-up after the last infusion, the partial response rate was 68.8% (11/16). Symptoms like cough and short of breath were significantly relieved in those patients responding to the treatment. Overall survival rate of one year was 81.3% and median survival time was 11.6 months. No significant adverse events were found in those patients. Conclusions: Bronchial artery infusion of rAd-p53 combined with chemotherapeutic agents is effective and safe treatment for patients with advanced BC, who failed common standard treatments.
Breast cancer stem cells: A novel therapy for breast cancer.
Authors: Mukhopadhyay Soma , Gangopadhyay Sudeshna , Dasgupta Swati , Sengupta Saubhik , Ray Ujjal Kanti , Hor Pooja , Mukhopadhyay Ashis
Published: March 2020

e13030

Background: Simple BRCA screening is insufficient for ‘event-free survival’ as breast cancer is clinically and pathologically an extremely heterogeneous disease. Targeting Breast Cancer Stem Cells (BCSCs) present in bone marrow and breast tissues is a lucrative alternative. Identification of BCSCs is salient aspect of our research. Invasive and mesenchymal property of BCSCs with CD44+/CD24low/ALDH1+ phenotype has made them a promising target for eliminating metastatic capacity of primary tumors. We hypothesize that ability to therapeutically attack stem cell hinges upon identifying unique targets like cell surface markers and this will decide development of specific target therapies. Methods: A total of 10 early chemo-naive patients with biopsy proven triple-negative metastatic breast cancer in the age group of 18-36 yr.s (mean age 28 yr.s) were selected randomly and tested for CD44/CD24 cell surface markers following immunosorting using magnetic cell sorter and immunophenotyping by flowcytometric analysis. Isolated BCSCs were cultured for in vitro drug sensitivity towards platinum, anthracycline and docetaxel. Correlation was drawn between cell differentiation, % of stem cells and drug response. Accordingly chemotherapy was designed for a particular patient. % of BCSCs in pre- and post-chemotherapeutic condition was further compared. Results: We have detected BCSCs in 90% of cases. Among positive samples, 89% patients showed platinum sensitivity and rest were found to be anthracycline sensitive. No sensitivity to docetaxel was observed. In lieu of this, cisplatin was applied in vivo and % of BCSCs came down to 6.58% from initial 11.16% (for a representative case). Conclusions: Thus primary aim to target BCSCs at the onset of tumors in breast cancer patients to control metastasis and relapse of disease was somewhat obtained. We further plan to correlate ratio of selected markers present in patients in pre- and post-chemotherapeutic condition with time to recurrence, mortality, morbidity and progression-free survival. Finally, if no BCSCs prevail after chemotherapy, then patients would be kept under observation and if traces are found, we would proceed to targeted therapy trial like PARP inhibitor or autologous stem cell replacement.
Fractures and health care resource use in cancer patients with chemotherapy-associated peripheral neuropathy (CAPN).
Authors: Ganguli Arijit , Reilly Patrick J , Ray Saurabh
Published: March 2020

e13038

Background: Chemotherapy has been associated with increased risk of fractures1. This study examines the real-world incidence of fractures and healthcare resource use (HRU) that may be associated with CAPN in cancer patients. Methods: A retrospective analysis utilized a national health insurer claims -database (2001-2009), to identify patients ≥18 yrs with a cancer ICD-9-code (140-239) and a chemotherapy drug code (J9xxx). The 1st chemotherapy date was the "index date." Patients with a record of peripheral neuropathy (PN) in the pre-index date were excluded. Patients with a PN post-index were matched with no-PN post-index (non-PN) based on gender, age and index date. Both groups were compared for number of fractures, HRU (hospital outpatient (OP), office, and emergency-room [ER] visits) and all-cause costs in their 365-days post-index period. Time to 1st fracture post-index was compared using Kaplan Meier time to event analysis. Results: Of 34,625 patient meeting the inclusion criteria, 1675 patients (4.3%) formed the PN group and were matched to non-PN group. At baseline, mean age was 54.9 yrs, 62.5% were females, and no difference in % of bone metastasis (p=0.12) between the groups. In PN group, 5.3% (n=87) had a fracture 365-days post-index compared to 3.5% (n=58) in non-PN group (p<0.05). Mean days to fracture from index date in PN group was shorter than the non-PN group (150.9 vs. 153.4, p<0.05). In PN group, annual mean number of OP visit (14.6 vs. 12.0, p<0.0001), ER visit (0.47 vs. 0.30, p<0.001), and office visits (30.4 vs. 23.3, p<0.0001), were higher compared to non-PN group. Annual healthcare cost of PN patients was 21% higher than non-PN patients ($64,578 vs. $53,221) and CAPN-related cost in PN group was estimated to be $5,580 annually. Conclusions: Patients with CAPN were associated with higher incidence of fractures, HRU and cost.
Immunological evaluation of personalized peptide vaccination for metastatic breast cancer patients with triple-negative types.
Authors: Takahashi Ryuji , Toh Uhi , Iwakuma Nobutaka , Otsuka Hiroko , Shirouzu Kazuo , Matsueda Satoko , Shichijo Shigeki , Sasada Tetsuro , Itoh Kyogo
Published: March 2020

e13046

Background: To develop cancer vaccine, we investigated immune responses of the patients (pts) with metastatic breast cancer (MBC) with triple negative (TN) types to personalized peptide vaccine (PPV). Methods: Thirty-four pts including 8 TN-MBC were enrolled a phase II study of PPV. A maximum of four HLA-class IA (A2, A3s, A24, A26)-matched peptides showing higher antigen-specific IgG responses were administered. Levels of IgG reactive to each of the 31 peptides in the pre- and post-treatment plasma at every 6 times of vaccination were measured using LUMNEX system. Peptide-specific CTL responses were examined by INF-g ELISPOT. Results: All 34 pts had significant pre-existing humoral immunity, whereas only 13 of 31 patients, including 3 of 6 TN cases, showed pre-existing cellular immunity. Thirty-one of 34 pts, including 6 TN cases, achieved more than one cycle (6 times) of vaccination. The augmentation of the IgG responses specific to at least one of the vaccinated peptides was observed in 18 of 31 pts, including 3 of 6 TN cases. CTL responses were augmented in 16 of 31 pts, including 5 of 6 TN cases. IgG responses were boosted to greater levels with 12th vaccination in all 31 pts tested including 6 TN cases. Best clinical responses of 6 TN cases were 1 CR, 0 PR, 5 SD, and 0 PD, while those of the other 25 cases were 1 CR, 1 PR, 17 SD, and 6 PD, respectively. Conclusions: There were no significant differences between TN cases and the other cases of MBC with regard to immunological humoral and/or cellular responses to PPV.
Efficacy endpoints (EEPs) in melanoma randomized controlled adjuvant trials (RCATs).
Authors: Monzon Jose Gerard , Petrella Teresa M. , Dancey Janet
Published: March 2020

e13049

Background: Inconsistencies in RCAT EEPs definitions and reporting complicate the evaluation of EEPs as adequate surrogates for overall survival (OS) and the comparison of the EEPs between trials. We aimed to identify issues in reporting and defining of EEPs used in melanoma RCATs. Methods: To identify phase 3 melanoma RCATs published in English language journals from 1994- 2011, a Pubmed database search and systematic review of published meta-analyses were performed. RCAT characteristics and endpoint definitions were obtained. Original protocols were requested. Results: A total of 34 RCATs met the criteria for review. Interferon alone or in combination with another agent was the most commonly tested treatment. Node positive disease was included in 24 studies with 1 including resected metastatic disease. The eligibility criteria in regards to age, previous treatment, and performance status were not reported in 26%, 32%, and 53% of studies respectively. The baseline and follow-up radiological tests were not specified in 35% and 26% of studies respectively. Eight time-to-event (TTE) EEPs were identified, with most studies using more than one (See Table). The primary EEP was not specified 23% of the time. Clear definitions of TTE EEPs start and end time criteria were absent in 58% and 44% of studies, respectively. Conclusions: The inconsistencies in the reporting of EEPs in melanoma RCATs is due to a lack of standardization in their definition and measurement. Standardizing EEPs will reduce resource consumption and enhance the comparison of agents across studies in melanoma RCATs. [Table: see text]
Chalazion in multiple myeloma patients treated with bortezomib.
Authors: Mundia Mubasir , Mundia Abdul G. , Ali Mohammed Faisal , Ali Sana
Published: March 2020

e13053

Background: Bortezomib, a proteosome inhibitor is an effective drug in treatment of multiple myeloma (MM). As single agent and in combination with other drugs it not only has antitumor effect but has also increased survival. There are many side effects associated with its use, including peripheral neuropathy. We report incidence of chalazion in myeloma patients treated with bortezomib. Methods: On clinical Chart review, there were 34 patients with stage 3 MM treated with bortezomib in 2010 and 2011 in a community oncology practice. There were 18 females, and 16 males. Their age ranging from 52-76 years with a median of 68years. There were 17 African American (AA) and 17 non African American (NAA) patients. 14 patients received single agent bortezomib, 10 received it in combination with dexamethasone, and other 10 in combination with lenalidomide, cyclophosphamide and steroids. All patients received bisphosphantes. Results: Four patients developed chalazion 11 to 22 months into treatment with bortezomib. Chalazion was relatively resistant to conventional therapy offered by the ophthalmologists, and persisted during therapy with bortezomib. 1 patient needed surgical intervention. 3 out of 4 patients were AA. There was no incidence of chalazion noted in solid tumor patients treated with chemotherapy that did not include bortezomib in the same time period. Conclusions: We believe, prolonged use of bortezomib is associated with 12-15% incidence of chalazion, which is relatively resistant to conventional therapy, and persist during use of bortezomib.
Prediction of the non-sentinel node metastasis in patients without clinically axillary lymph node metastasis, with implication of breast cancer subtypes.
Authors: Tominaga Shusei
Published: March 2020

e13060

Background: The accuracy of the nomogram about non-sentinel lymph node metastasis (NSLNM ) in breast cancer patients is still controversial to avoid axillary dissection particularly sentinel lymph node biopsy was positive. The aim of this study was to evaluate the necessity of adding breast cancer subtypes to the NSLNM nomgram variables. Methods: Between 2009 and 2011, consecutive breast cancer patients without clinically axillary lymph node metastasis (n=140) who received sentinel lymph node biopsy at Higashiosaka General Hospital were studied retrospectively. Twenty-two patients were turned out that breast cancer already spread to the sentinel nodes and all of 22 patients received complete axillary lymph node dissection. Results: Twelve patients had only sentinel lymph node metastases(Group S), 10 patients had non-SLN metastases (Group A). Patient characteristics and average probability of spread to additional lymph node developed by Memorial Sloan-Kettering Cancer Center (MSKCC) Nomogram were almost the same results in both groups. However, subtypes of Group S consisted of 8 HER2 positive , 2 triple negative, and 2 luminal A cases, subtypes of Group A consisted of 4 luminal A and 6 luminal B cases. Conclusions: Our data suggested that luminal type breast cancer tends to spread to non-sentinel lymph node metastasis and adding HER2, Ki-67, and intrinsic biological subtypes may improve predictivity of MSKCC nomogram.
Expression of PRAME and MAGE-A3 in Asian and European patients with non-small cell lung cancer (NSCLC), bladder cancer, or hepatocellular carcinoma (HCC).
Authors: Therasse Patrick , Linder Albert , Thongprasert Sumitra , Yang Pan-Chyr , Lee Po-Huang , Tanwandee Tawesak , Kang Jin Hyoung , Lee Jungsin , Sittampalam Kesavan , Chotirosniramit Anon , Soo Ross A. , Van Poppel Hendrik , Lerut Evelyne , Joniau Steven , Coche Thierry , Gruselle Olivier , D'Agostino Diego , Myo Aung , Louahed Jamila
Published: March 2020

e13061

Background: Antigen (Ag)-specific cancer immunotherapy is based on induction of immune responses (humoral and cell-mediated) specifically targeting Ags expressed by tumor cells. This may be achieved by delivering the Ag as a recombinant protein combined with potent immunostimulants. PRAME and MAGE-A3 are tumor Ags with distinct tumor expression patterns, both under investigation as targets for immunotherapy in NSCLC and malignant melanoma. For additional clinical development of these immunotherapies in other cancer types, expression of PRAME and MAGE-A3 in these cancers must be investigated taking into account patient ethnicity and tumor characteristics. Methods: 4 retrospective studies were performed, each including all tumor stages: NSCLC pts (in Asia and Europe); bladder cancer pts in Europe; HCC pts in Asia. Formalin-fixed paraffin embedded tumor tissues were tested for PRAME and MAGE-A3 expression by quantitative RT-PCR using an expression cut-off value for positivity. Exploratory analyses of possible associations with patient and tumor characteristics were done to identify factors that may impact Ag expression. Results: The overall Ag expression rates are shown in the table below. In NSCLC, both Ags were expressed less frequently in Asian than in European patients (the histological distribution was the same). NSCLC tumors more frequently expressed PRAME than MAGE-A3 while the reverse tendency was seen for bladder tumors and HCC. In the NSCLC studies, squamous cell carcinomas expressed both Ags more frequently than adenocarcinomas. No study found any association between tumor stage and Ag expression. Some 60% of the tumors express at least one of the Ags. Conclusions: The expression rates of PRAME and MAGE-A3 are sufficiently high to consider these Ags as targets for immunotherapy against NSCLC, bladder cancer and HCC. [Table: see text]
Pharmacokinetic advantage of hyperthermic intraoperative intraperitoneal cisplatin and oxaliplatin.
Authors: Lewin Sharyn Nan , Leinwand Joshua , Slavkovic Vesna , Webb Christopher , Weyker Paul , Raker Richard K , Graziano Joseph , Taub Robert N.
Published: March 2020

e13066

Background: Hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC) is used to treat peritoneal surface-spreading malignancies in order to maximize local drug concentrations while minimizing systemic effects. The pharmacokinetic advantage (PKA) of HIPEC is defined as the intraperitoneal to intravascular ratio of drug concentrations. We hypothesized that body surface area (BSA) and intravenous fluid (IVF) administration, by affecting intravascular volume, would correlate with PKA. Methods: On an IRB-approved study, we collected blood and peritoneal perfusate from 13 patients undergoing HIPEC with a set dose of 100 mg cisplatin (n=4) or a BSA-based dose of 250 mg/m2 oxaliplatin (n=9), and measured Pt concentrations by Inductively Coupled Plasma Mass Spectrophotometry. Areas under concentration-time curves from 0-60 minutes (AUC0-60) were calculated by Trapezoidal Rule. PKA was calculated by (AUC0-60[peritoneal fluid]/AUC0-60[plasma]). Linear regression and Wilcoxon rank-sum test were performed using SAS. Results: Models with both BSA and IVF as predictors of PKA fit better than BSA alone for cisplatin (p=.022 vs. p=.076) but not for oxaliplatin (p=.119 vs. p=.037). The BSA and IVF model was a better fit for peritoneal cisplatin (p=.003) than for plasma cisplatin (p=.146). The BSA-only model was a better fit for plasma oxaliplatin (p=.013) than for peritoneal oxaliplatin (p=.778). There was no statistically-significant difference between the median PKA of cisplatin vs. oxaliplatin (p=.706). Conclusions: Our results suggest that BSA is a better PKA predictor than the compound’s diffusion properties. When a set drug dose is used, rather than a BSA-based dose, IVF is also an important predictor. This is likely due to HIPEC’s limited duration, thus the drug does not reach equilibrium between the peritoneal and vascular compartments. When monitoring the pharmacokinetic parameters of HIPEC administration, factors influencing intravascular volume, including BSA and IVF, should be considered. Maintaining intravascular volume repletion is a key strategy for maximizing PKA, and thereby minimizing systemic side effects due to HIPEC.
Endocrine therapy in patients with metastatic breast cancers (MBC): Prognosis and measures of outcome.
Authors: Driol Pamela , Bonotto Marta , Fontanella Caterina , Gerratana Lorenzo , Valent Francesca , Russo Stefania , Andreetta Claudia , Minisini Alessandro , Sottile Roberta , Mansutti Mauro , Fasola Gianpiero , Puglisi Fabio
Published: March 2020

e13070

Background: Endocrine manipulation is the cornerstone of therapy in hormone receptor (HR)-positive breast cancer. However, a significant percentage of patients who receive endocrine therapy (ET) as metastatic treatment experience de novo or acquired resistance. New clinical trials for HR-positive MBC should be tailored around immunophenotypical and clinical features. This study evaluates different potential prognostic factors in patients treated with ET for MBC. Methods: We analyzed retrospectively data from a series of 280 consecutive patients with HR-positive MBC diagnosed from January 2004 to February 2011 at University Hospital of Udine, Italy. Multivariate analysis was performed to establish the independent value of different disease and patients’ characteristics in influencing progression-free survival (PFS), overall survival (OS) and survival post-progression (SPP). Results: Median OS was 38.44 months (mo), median PFS at first-line ET was 10.05 mo. Median SPP was 22.74 mo, 15.18 mo, and 15.47 mo after first, second and third-line ET, respectively. Age >70 years and ECOG performance status >1 were independent prognostic factors for both shorter OS (HR 2.55, p = 0.019; HR 2.46, p = 0.025, respectively) and shorter SPP (HR 2.99, p = 0.003; HR 2.82, p = 0.011, respectively). Number of chemotherapy lines before first ET was an independent prognostic factor for both PFS (HR 1.45, p < 0.001) and OS (HR 1.62, p = 0.001). MIB-1 >14% was associated with shorter PFS (HR 1.98, p = 0.012); this finding underlines the poor prognosis of luminal B subtype in comparison with luminal A disease. Conclusions: Determinants of treatment decision-making in MBC include patients’ characteristics, prognostic factors, disease biology, and mechanisms of resistance. This study confirms the worse prognosis of luminal B subtype, also in presence of endocrine manipulation. Innovative therapeutic approaches are eagerly waited in order to overcome resistance to ET. This study also provides some insights for the choice of optimal endpoints in trials that enroll patients with HR-positive MBC. In particular, based on long SPP values, OS does not seem to be an appropriate endpoint in studies involving such patients’ population.
Phase I trial in advanced refractory solid tumors of the new drug first-in-class PDM08.
Authors: Barriuso Jorge , Moreno Victor , Coronado Monica , Galicia Ignacio , Soria Irene , de Castro Javier , Belda-Iniesta Cristobal , Martinez Marín Virginia , Custodio Ana , Redondo Andres , Lamarca Angela , Hindi Nadia , Subiza Jose Luis , Frias Jesus , Feliu Jaime , Carcas Antonio
Published: March 2020

e13085

Background: PDM08 is a new active compound with antitumor activity in different cancer models. It is a synthetic derivative of the pyroglutamic acid. The lack of direct effect on tumour cells and antitumor activity in immunodeficient models indicates an immune response mediated mechanism. Toxicology and pharmacology preclinical studies showed a favourable safety profile, confirmed by a single-dose placebo controlled healthy volunteer phase I trial. Methods: A single institution open label phase I study was designed (NCT01380249). PDM08 was administered twice a week for four-week cycles. Initially an accelerate escalation phase was chosen with cohorts of 2 patients who after completing the safety period (2 weeks after last dose) had the possibility of escalate to the next dose level if no grade ≥ 2 toxicity and no progressive disease was observed. After 4 cohorts without meaningful toxicity, this design was amended to open new dose levels after a two-week period of treatment completed by the last patient of the cohort if no grade ≥ 2 toxicity was found. The trial was approved by the Ethics Committee and the Spanish Drug Agency. Extensive pharmacokinetic (PK) and pharmacodynamic (PD) data including serum cytokines, lymphoid subpopulations and immunoglobulins are collected. Preliminary efficacy was evaluated by PET-CT. Results: Since July 2011, 10 patients (pts) were recruited into 6 different dose levels (2pts were escalated) ranged from 0.560 mg to 14 mg. Pt characteristics were: female-male ratio 1:1. Median age: 67 (47-76). ECOG 0: 6 pts. 8 pts had colorectal cancer, 1 lung adenocarcinoma and 1 ovarian carcinoma. Median of previous treatments was 3 ranged 2 to 5. 3 pts presented G1 headache. No Dose Limiting Toxicities were found. Preliminary outcome data showed: best response stable disease for 4 patients, 2 of them being stable for 12 weeks. After 40 target lesions evaluated by PET-CT 6 (15%) showed a reduction in the maximum Standard Uptake Value (SUV) of 18-FDG. Conclusions: PDM08 is the first compound of a new class of drugs that can be dose-escalated safely in an accelerated manner and has promising activity. Last patient will be included in March 2012 so final data for toxicity, PK, PD and efficacy will be provided at the meeting.
Quality of life in patients with malignant ascites during catumaxomab treatment: Results from the CASIMAS trial.
Authors: Lordick Florian , Sehouli Jalid , Vergote Ignace B. , Rosenberg Per , Schneeweiss Andreas , Block Andreas , Salat Christoph , Scambia Giovanni , Berton-Rigaud Dominique , Siena Salvatore , Santoro Armando , Cervantes-Ruiperez Andres , Guastalla Jean Paul , Tournigand Christophe , Colombo Nicoletta , Dudnitchenko Alexander Serg , Bondar Vladimir , Westermann A.M. , Gonschior Ann-Katrin , Wimberger Pauline
Published: March 2020

e13095^

Background: Malignant Ascites (MA) is associated with a poor prognosis and limited palliative treatment options. To demonstrate the value of a new treatment the assessment of quality of life (QoL) is of particular importance. Following the demonstration of catumaxomab’s potential to stabilize QoL and prolong the time to first deterioration of QoL, results from CASIMAS give evidence that the QoL of patients remains unaffected during catumaxomab treatment Methods: In a two-arm, open-label, multicentre phase II/III study 219 patients were randomized to catumaxomab plus premedication of 25 mg prednisolone (111 pts) or to catumaxomab alone (108 pts) QoL was measured using the EQ-5D visual analogue scale (EQ-VAS). The EQ-VAS reports the respondent’s self-rated health on a vertical scale where the endpoints are labelled “Best imaginable health state” (100) and “Worst imaginable health state” (0). This information is used as a quantitative measure of health outcome. Patients were asked to complete EQ-VAS during the treatment period (d 0, 3 and 10) and follow-up (d8, 28). Descriptive analyses were performed according to EQ-5D User Guide (Version 4.0). Additionally ascites related symptoms were measured with a disease specific FACIT patient questionnaire. Results: For the pooled population (catumaxomab plus prednisolone and catumaxomab alone) longitudinal analysis of the EQ-VAS showed no relevant changes in mean score during the treatment period of catumaxomab (d0: 51.5; d3: 50.9; d10: 51.0) and compared to screening (52.7). An increase in mean values was observed in the follow-up period (d8: 53.9, d28: 57.1). Descriptive comparison of both treatment groups revealed no major differences in QoL and ascites related symptoms during the treatment and follow-up period, indicating that prednisolone has no impact on patient`s self-rated health. Conclusions: This analysis shows that QoL as measured by EQ-VAS remains unaltered during the treatment with catumaxomab and improves after the treatment period. The improvement is plausible due to the prolonged-puncture-free survival and is consistent with previous observations of QoL changes during and after intraperitoneal treatment with catumaxomab.