bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical impact of 18F-FDG–PET in breast cancer: Survival analysis and comparison of intrinsic subtypes with standardized uptake value.
Authors: Ahn Sung Gwe , Lee Hak Min , Lee Seung Ah , Jeon Tae Joo , Yoo Young Hoon , Sohn Eun Joo , Jeong Joon , Lee Hy-De
Published: March 2020

e12005

Background: [18F] fluorodeoxyglucose positron emission tomography (18F-FDG–PET) scans are known as an important imaging study with their reflection biological activity in various malignancies. To investigate clinical impact of 18F-FDG–PET in breast cancer, we performed survival analysis with maximum standardized uptake values (SUVmax), and compared SUVmax according to breast cancer subtypes. Methods: We reviewed the medical records of 462 patients with breast cancer who underwent primary surgery between April 2004 and December 2008 at single institute. Patients were classified as 4 subtypes: luminal A, luminal B, HER2 and triple negative. The entire patients were randomly assigned as training set (n=220) and validation set (n=242). Results: High SUVmax vs. low SUVmax group was defined with cut-off points of 4 in a training set.At a median follow-up of 6.03 years, the patients with high SUVmax had a shorter disease-free survival in a validation set (p = 0.018, log-rank test). Using multivariate analysis for disease-free survival in the entire patients, high SUVmax was demonstrated as a poor prognostic factor (hazard ratio 2.34, 95% confidence interval 1.18-4.67). In the comparison among subtypes, mean of SUVmax was higher in triple negative type and HER2 type. Also, high SUVmax was significantly associated with larger tumor size, positive node, high Ki67 (≥14%), ER negative, and high histologic grade, and HER2 positive. Conclusions: In breast cancer, the patients with higher SUVmax showed a shorter disease-free survival. Higher SUVmax found in HER-2 and triple negative type suggests that 18F-FDG PET could reflect molecular signature.
Is ypT0/isn0 acceptable for Japanese population? JBCRG’s perception.
Authors: Kuroi Katsumasa , Ohno Shinji , Nakamura Seigo , Iwata Hiroji , Masuda Norikazu , Sato Nobuaki , Toi Masakazu
Published: March 2020

e12011

Background: Pathologic complete response (pCR) is a proposed surrogate endpoint for predicting disease-free survival (DFS) or overall survival (OS). However, several definition of pCR has to be used in NAC studies, and In Japan, JBCRG conducted several study of neoadjuvant chemotherapy using QpCR(including focal residual invasive tumors as pCR) between 2002 and 2006. Methods: The regimen studied were FEC followed by Docetaxel (75 mg/m2)(FEC-DOC) (n = 186), FEC-DOC (100 mg/m2) (n = 37),DOC followed by FEC (n = 130), JBCRG-01, 02, 03, respectively. Three studies were pooled and analysed for pCR rates, DFS, OS in terms of several pCR definition and subtypes. We included patients when subtype and long-termfollow-up available for DFS and OS. We compared 5 pCR definitions: absence of invasive cancer and in situ cancer in the breast irrespective of nodal involvement (ypT0, SpCR), absence of invasive cancer and in situ cancer in the breast axillary nodes (ypT0ypN0, SpCRbn), absence of invasive cancer in the breast irrespective of nodal involvement (ypT0/is, CpCR), absence of invasive cancer in the breast axillary nodes with DCIS allowed (ypT0/isypN0, CpCRbn), and QpCR. Subtypes were classified into luminal (ER+ and/or PgR+, HER2-), luminal –HER2 (ER+ and/or PgR+, HER2+), triple-positive (TP) (ER-,PgR-, HER2-), HER2 (ER-, PgR-, HER2+) by using immunohistochemically stained specimen obtained by core needle biopsy. Results: Number of patients in each subtypes were as follows; luminal 206 (58%), luminal -HER2 34(10%), HER2 40 (11%), TN 73 (21%). pCR rate was significantly high in HER2 and TN irrespective of pCR definition (p <0.05). At median follow up 75M, pCR group showed significantly better prognosis. Cox multivariate analysis showed pCR (irrespective of pCR definition) and subtype were the significant predictors of prognosis among study, age, tumor size. Conclusions: Subtype is a useful predictive biomarker of pCR, and ypT0/isn0 is acceptable for Japanese population.
Capecitabine maintenance therapy after docetaxel/capecitabine combination chemotherapy in patients with metastatic breast cancer.
Authors: Gursoy Pinar , Surmeli Zeki Gokhan , Cakar Burcu , Arslan Cagatay , Zengel Baha , Karaca Burcak , Sezgin Canfeza , Karabulut Bulent , Sanli Ulus Ali , Uslu Ruchan
Published: March 2020

e12018

Background: Addition of capecitabine to docetaxel improves survival outcomes compared with single agent docetaxel in metastatic breast cancer (MBC). In this study we analyzed efficacy of maintenance therapy with single agent capecitabine after six cycles of docetaxel/capecitabine chemotherapy in MBC patients. Methods: Patients with metastatic HER2 negative breast cancer were included. Six cycles of docetaxel (75mg/m2 q3wk) / capecitabine (1650mg/m2/day on days 1 to 14) followed by capecitabine (2000 mg/m2/day on days 1 to 14) were administered. Demographic features, progression free (PFS) and overall survival (OS) and response to treatment were recorded. Results: Fifty-four patients were included. Thirty-five patients (65%) were postmenopausal, and 40 (74%) were ER/PR positive. Median age was 53 (range 28 – 70). Number of metastatic sites was one in 23 patients, two in 21, three or more in 10 patients. Most common metastatic sites were bone (67%), lymph nodes (33%), lungs (30%), liver (13%); 13 patients (24%) had bone only disease. Forty-four (81.5%) patients received treatment in first-line, 10 (18.5%) received in second line setting. Median number of cycles applied (including docetaxel/capecitabine combination) was 9 (range 2 – 31, total 576). Median PFS was 9 months (10.4 for hormone receptor positive, 7.3 for negative patients) and median OS was 28 months. Objective response was assessable in 38 patients. Overall response rate (partial + complete response) was 42.6% (95% CI 29.6 – 55.6) with 1 complete response. Toxicities were evaluated in 41 patients; grade 3/4 neutropenia was observed in 10% and grade 3/4 hand-foot syndrome was observed in 24% of patients. Dose reduction was performed in capecitabine in 37%, and in docetaxel in 20% of patients. Conclusions: Maintenance with single agent capecitabine therapy after six cycles of docetaxel/capecitabine chemotherapy is an effective and tolerable treatment option for HER2 negative MBC patients.
Value of Ki-67 in prediction of response to neoadjuvant chemotherapy in breast cancer.
Authors: Kim Kwanil , Lee Kyunghee , Park Heungkyu
Published: March 2020

e12025

Background: The expression of the human Ki-67 protein has been described as being associated with cellular proliferative activity. The objective of this study is to assess the potential value of Ki-67 for the prediction of therapeutic response after neoadjuvant chemotherapy in breast cancer. Methods: Sixty-eight patients who underwent anthracyclin based neoadjuvant chemotherapy between 2007 and 2012 were included for this study. The chemotherapy response was evaluated by comparing the pre- and post-neoadjuvant chemotherapy tumor size on radiologic imaging study with the tumor size at pathologic specimens according to RECIST (response evaluation criteria in solid tumors) version 1.1. We analyzed immunohistochemical(ER, PR, HER2, Ki-67, p53) profiles from both pre-neoadjuvant core biopsy and postoperative specimens to find their correlations with chemotherapy response. Results: Ten patients(14.7%) achieved pathologic complete response(pCR), 38 patients(55.9%) had pathologic partial response(pPR) and 20 patients(29.4%) had pathologic stable disease(pSD). The mean Ki-67 value of tumors with pCR was 61.0%, the Ki-67 value of tumors with pPR was 35.9%, and the Ki-67 value of tumors with pSD was 21.0%(p = 0.013). The analysis of Ki-67 values of the patients also showed that 25% of Ki-67 level is a reasonable cut-off value for defining higher Ki-67 level. In subgroup analysis, the higher Ki-67 level was significant factor of the response to neoadjuvant chemotherapy, especially in ER negative patients(p = 0.009) and HER2 negative patients(p = 0.009). In addition, the analaysis of response group showed that ER negative(p = 0.027), HER2 positive(p = 0.048), and higher Ki-67 level(p = 0.002) were predictive indicators of complete response. Conclusions: The higher Ki-67 level of breast cancer tissue may effectively indicate the higher response rate to chemotherapy and also the higher complete response rate. The results of our study suggest that the Ki-67 value before neoadjuvant chemotherapy is a predictive factor for the response to neoadjuvant chemotherapy. Moreover, the Ki-67 is a predictive factor of the pathologic complete response especially in patients with ER negative or HER2 positive.
Are breast cancers in India different from Western populations? Results of a tertiary center retrospective analysis.
Authors: Chakraborty Sayan , Sarkar Sandip , Agarwal Namrata , Ahmed Rosina , Chatterjee Sanjoy , Ghosh Indranil
Published: March 2020

e12039

Background: Breast cancer is the commonest cancer in the urban Indian female population but comprehensive data on the details of tumor types, outcomes post treatment and comparison with Western data is not readily available. We present a robust database of Eastern Indian breast cancers reported from a tertiary center. Methods: Retrospective analysis of 407 unselected medical records of breast cancer cases between June 2011 and October 2012 were undertaken. Clinico-pathological details, Nottingham Prognostic Index (NPI) Score post surgery (conservation and mastectomy) and follow-up were analyzed. Adjuvant chemotherapy details were recorded. Following Institutional guidelines a hypofractionated Radiotherapy (RT) schedule was delivered (40Gy in 15 Fractions over 3 weeks), with boost delivered in patients receiving conservation surgery. Acute radiation toxicity following hypofractionation was recorded. Results: Mean age at presentation was 52.42 years. 383 (94%) underwent surgery; breast-conservation in 37%. 34% received neo-adjuvant anthracycline-taxane sequential chemotherapy prior to surgery. For those who underwent upfront surgery, 12% patients had pT3 disease and 83% pT1/T2. 41%, 31%, 16% and 12% had pN0, N1, N2 and N3 disease respectively. 89% cases had infiltrating ductal carcinoma with 57% Grade III disease. 73% were ER positive and 35% were Her-2 positive. 31% patients were intermediate risk and 36% high risk (>5.5) by NPI Score. After upfront surgery 54% received adjuvant chemotherapy of which 63% received both anthracycline and taxanes sequentially. 67.4% patients received adjuvant RT where the median time between date of surgery and starting of RT was 5 months. Median post hypofractionated RT follow-up was 6 months when 7 out of 97 patients had > Grade 0 Skin toxicity, 4 had breast edema, 6 shrinkage, 8 patients had Grade I Lymphedema. Conclusions: Indian patients were younger and had advanced stage at presentation and higher NPI scores requiring more combined systemic chemotherapy. Hypofractionated RT schedule was tolerated well and further hypofractionation could now be investigated in clinical studies to improve throughput in moderate resource countries like India.
The rise in appendix cancer incidence: 2000-2009.
Authors: Marmor Schelomo , Portschy Pamela R. , Tuttle Todd M. , Virnig Beth A.
Published: March 2020

e12506

Background: Cancer of the appendix is a rare and potentially aggressive malignancy. The objectives of this study were to characterize secular demographic patterns of disease and to determine survival by using a population-based data source. Methods: Using the Surveillance Epidemiology and End Results database we identified all appendiceal neoplasms reported to the registry between 2000 and 2009.Tumors were classified as carcinoid, adenocarcinoma, mucinous and signet ring cell carcinoma. We compared overall incidence, age distribution by tumor type and overall survival rates by extent of disease at diagnosis. To assess whether the incidence rate, tumor size, and cancer stage changed over time, the Cochrane-Armitage trend test was used. Logistic regression models were used to determine the odds of distant disease at diagnosis and Cox proportional-hazards modeling was used to identify the factors associated with overall survival rates. Results: We identified 4,765 patients with appendix cancer. The incidence of appendiceal cancer increased by 54% from 2000 (0.63 per 100,000) to 2009 (0.97 per 100,000). Incidence rates increased across all tumor types, stages, age groups and gender. The most common malignancies were mucinous (38%), followed by carcinoids (28%) adenocarcinoma (27%), and signet ring cell carcinoma (7%). Distant stage at diagnosis was most common among, signet ring cell tumors (60%). Larger tumor size and older patient age were significantly associated with higher relative odds of distant disease at diagnosis (P < .0001). Tumor type, older age, black race, males, tumor size of 2 cm and greater, cancer stage and registry were significantly associated with higher relative hazard of death (P< .0001). Mean 5-year survival was 55% for carcinoid patients, 49% for adenocarcinoma, 50% for mucinous and 38% for the signet ring cell cohort. Conclusions: Although appendiceal cancer is rare, the incidence increased significantly in the U.S. from 2000 to 2009. The cause of this trend is not obvious. We did not see increases differentially associated with stage, histology, registry or demographic characteristics. Further investigation is needed to examine factors underlying this increase. This research was generously supported by the Betti Boers Maloney Appendix Cancer Research Fund at the University of Minnesota Foundation.
Understanding international genomic diversity for breast cancer: Comparison of molecular subtypes of breast cancer in very young women (age ≤ 35) between Izmir (Western Turkey) and Boston (Massachusetts, USA).
Authors: Karaca Burcak , Battaglia Tracy Ann , Ko Naomi , McCoy Moly , Yasdik Hatice , Sherman Bonnie , Durusoy Raika , Sezgin Canfeza , Karabulut Bulent , Uslu Ruchan
Published: March 2020

e12509

Background: One in forty women is diagnosed with breast cancer at a very young age (≤35 years). Studies suggest breast cancer molecular subtypes are different in young women, with a higher prevalence of triple negative and HER-2+ disease. Objective: Explore the impact of genetic diversity on molecular subtyping of very young breast cancer patients in geographically and ethnically diverse populations: Turkey and the United States. Methods: A retrospective analysis of women ≤35 years of age diagnosed with breast cancer from 1999-2011 at Ege University Faculty of Medicine (EUFM) and Boston Medical Center (BMC). Data were collected and abstracted from hospital cancer registries and electronic medical records. Molecular subtyping was based on immunohistochemical evaluation of estrogen, progesterone receptors, Ki-67, and HER2/neu. Bivariate analysis was conducted using Chi-Square and Fisher’s Exact tests. Results: There were 206 and 45 patients from EUFM and BMC, respectively. Mean age at diagnosis was 31.4±3; most were white (87%), parous (70%), had breast fed (74%), and no1st degree relatives with breast cancer (92%). BMC patients were younger (31.7±3 v. 29.9±3 p=.0006) and more racially diverse (0% v. 60% black/hispanic p <.0001). There were clinicopathological differences between EUFM and BMC, including: histological subtype (IDC 68% v. 93% p=.02), HER-2/neu positivity (60% v. 16% p <.0001), and Ki67 ≥15% (54% v. 83% p=.008). Missing data precluded subtyping in 25% and 22% of women at EUFM and BMC. Of subtypes determined, prevalence was the same; however, EUFM had more Luminal B and less Triple negative patients then BMC. Conclusions: Population-level similarities and proportional distinctions exist in molecular subtypes of breast cancer for women ≤35 years. In both countries, Luminal B and triple negative sybtypes were most common suggesting younger age rather than genetic diversity is an important determinant of molecular subtyping. [Table: see text]
High-throughput parallel amplicon sequencing of common driver mutations from FFPE lung cancer samples in molecular pathologic routine diagnostics for a regional health care provider network.
Authors: Buettner Reinhard , Koenig Katharina , Peifer Martin , Stamm Katrin , Bos Marc Christiaan Allardt , Nogova Lucia , Zander Thomas , Gardizi Masyar , Merkelbach-Bruse Sabine , Henkel Thomas , Wolf Juergen , Heukamp Lukas Carl
Published: March 2020

e12517

Background: Treatment paradigms for non–small-cell lung cancer have shifted from histology based towards incorporation of molecular subtypes involving particular genetic alterations such as mutations in EGFR or translocations of ALK. The list of targetable lesions is rapidly increasing including mutations in genes such as EGFR, HER2, KRAS, ALK, BRAF, PIK3CA, AKT1, ROS1, NRAS, FGFR1 and MAP2K1. Analysis of these potential targets is becoming a challenge in terms of work load, tissue availability as well as cost. Within the Network Genomic Medicine Lung Cancer (NGM), a regional molecular screening network of the Center for Integrated Oncology Köln Bonn, we aimed to improve the sequential analysis of a set of 9 target amplicons by Sanger sequencing using bench top ultra-deep parallel sequencing platforms. We aimed to reduce 1) the time requirement for comprehensive molecular diagnostics, 2) the minimal amount of formalin fixed paraffin embedded (FFPE) derived input DNA, 3) while at the same time increasing the number of target regions analysed. Methods: We established a multiplex PCR to amplify up to 640 lung cancer relevant target regions from at least 20ng of FFPE derived tumor DNA. The amplicon libraries were ligated to adapters encompassing medical identifier sequences that allowed multiplexing of up to 48 patients. The resulting libraries were sequenced on a benchtop Illumina platform (MiSeq). Mutations identified by parallel sequencing were confirmed by Sanger sequencing. Results: 330 patients were analyzed by traditional Sanger sequencing of 9 amplicons and the newly established parallel sequencing protocol. The time needed to complete the mutation screening was significantly reduced to 7 working days from previously 21 days. A total of at least 300ng of DNA was needed to complete the analysis of 9 amplicons by Sanger sequencing compared to 20 to 100ng of DNA needed for up to 640 amplicons analyzed by parallel sequencing. Conclusions: Newly multiplex PCR based parallel sequencing allows rapid comprehensive mutation testing in routine molecular pathological diagnostics even on small transbronchial biopsies.
Risk of lymphoma in patients with chronic hepatitis C: A retrospective analysis on East Harlem population.
Authors: Alderuccio Juan Pablo , Quiel Luis , Ntalageorgos Themis , Popescu-Martinez Andrea M. , Bergasa Nora V.
Published: March 2020

e12526

Background: The association between chronic hepatitis C (HCV) and lymphoma, especially non-Hodgkin lymphoma (NHL), has been conflicting, varies among different geographical regions, and its prevalence has been calculated to be 10-15%. It is postulated that HCV may produce a sustained stimulation of B-cells, providing a rationale for a potential association between this virus and NHL. Accordingly, the aim of this study was to explore the prevalence of NHL on HCV patients in a population subgroup of New York City. Methods: IRB approved retrospective study of adult patients with HCV seen at our Institution from January 2001 to July 2006 with at least one year of follow-up. HCV serology data were collected. Pathology reports were reviewed. Patients on chronic immunosuppressive therapy, previous oncologic treatment, autoimmune disease or HIV with CD4 count <200/mm3 for two years were excluded. Results: 510 patients were included, 3 of which (0.6%) developed NHL after the HCV diagnosis. NHL subtypes were marginal zone and diffuse large B-cell (2 patients). 354(69.4%) were men and median age was 58 years (29-96). Ethnicity distribution was Hispanic 303(59.4%), Black 150(29.4%), Caucasian 49(9.6%) and Asian 8(1.6%). Risks for viral hepatitis were IV drugs 393(77%), not identified 92(18%) and 25(5%) had others factors including hemodialysis, sex and blood transfusion. 504(98.8%) patients had positive HCV antibodies, 6(1.2%) with only positive PCR and 402(78.8%) with both positive. HCV-PCR was not performed in 102(20%) subjects with positive antibodies. Hepatitis B surface antigen was also positive in 7(1.3%) patients. Median follow-up was 72 months (12-468) with an interquartile range of 68.8, 181(35.6%) patients were alive, 90(17.6%) had died and 239(46.8%) were not seen for 2 or more years. The margin of error of the study was 0.04(4%). Conclusions: The prevalence of NHL in our population was 0.6% and is lower than current published data. This finding may be explained by the high prevalence of Hispanics in our study and their known lower incidence of lymphoma respect to Caucasians. Longer periods of follow-up and further investigations in environmental and genetic factors are necessary to confirm these results.
Validation of BRCA mutation-carrier probability model, BRCAPRO, in Japanese.
Authors: Ito Masahiro , Yasuda Yuri , Furuta Akihiko , Ohuchi Noriaki
Published: March 2020

e12532

Background: Genetic testing has not been widely performed in Japan. It is not known whether BRCA mutation-carrier model is useful for selecting eligible person of genetic testing. We studied the validation of BRCAPRO in Japanese. Methods: Twenty-six hundred sixty-five people visited to our hospital between 2011 and 2012.They were surveyed family history as a risk factor of inheriting breast cancer according to NCCN guideline. Among them, those who have a number of family history of breast cancer, ovarian cancer, pancreatic cancer, prostate cancer were selected and in addition, genetic counselor constructed family tree. We also calculated BRCA1/2 mutation probability by BRCAPRO.Those who had more than 10% mutation probability and early onset breast cancer, triple negative breast cancer were received genetic counseling and genetic testing for applicants. We also calculated sensitivity, specificity and predictive value at 10% estimated probability. Results: One hundred five people (3.9%) were selected as a risk of inheriting breast cancer, of which sixty-three people (2.3%) were constructed family tree.The number of people who had more than 10% and 30% mutation probability by BRCAPRO was seven (0.26%) and three (0.11%).Nine people performed BRCA1/2 genetic testing (proband : eight, relative: one)Four people carried a deleterious BRCA mutation (BRCA1: three, BRCA2: one).In the cases which had more than 30% mutation probability, all of them carried a deleterious BRCA mutation. Most of their mutation site was L63X which was most frequent in Japan. Using a 10% cut-off, sensitivity was 75%, specificity was 80%,positive predictive value was 75%. When it comes to the cases which had more than 30% mutation probability, Sensitivity, specificity, positive predictive value were all 100%. Conclusions: Our findings suggest BRCAPRO is useful in Japanese, especially those who have more than 30% mutation probability.
Needs assessment and utilization of an educational workshop and support group for Lynch syndrome patients.
Authors: Rau-Murthy Rohini , Anrig Christopher , Glogowski Emily , Salo-Mullen Erin E. , Harlan Fleischut Megan , Sarrel Kara , Corines Marina , Niehaus Kate , Robson Mark E. , Markowitz Arnold , Kauff Noah D. , Offit Kenneth , Stadler Zsofia Kinga
Published: March 2020

e12536

Background: Lynch syndrome (LS) requires a lifelong commitment to multi-organ cancer surveillance and/or prophylactic surgery. Emotional and informational support for LS patients is not readily available. Through an LS Educational Workshop (LSEW) we assessed the need and interest in an educational and support group for LS families. Methods: LS patients identified at Memorial Sloan-Kettering Cancer Center (MSKCC) were sent LSEW invitations and a pre-workshop survey. All patients underwent prior genetic counseling. Though family members could attend, only index patients completed the surveys. All attendees were asked to complete both an evaluation of the LSEW and a needs assessment regarding implementation of a support group. Results: Invitations to 213 LS patients were mailed. Of 8 potential discussion topics, the most desired were chemoprevention and cancer screening recommendations. Thus, the 1st hour of the LSEW was a didactic session by physicians on these topics and LS research. The 2nd hour was a panel on patient experiences, family communication and Q&A. Fifty-three patients (25% of those invited) and 22 family members attended. The LSEW evaluation was completed by 26 index attendees, with 88% overall satisfied or extremely satisfied. Common requests for improvement were better division of informational and support aspects, and more Q&A. Of 23 who completed the needs assessment, 73% considered an LS support group as either somewhat or extremely useful. The group was equally divided on preference for a free-flow vs topic-focused approach; 57% felt a support group would have increased utility immediately after genetic testing. An in person venue was preferred by 87% over a virtual one, and 73% preferred every 3-6 month meetings. Respondents preferred a group inclusive of gender and cancer history. Based on this, the MSKCC Lynch Syndrome Patient Advocacy Network was created in 2012 with an in-person, every 4 month meeting facilitated by a social worker. Conclusions: Following genetic counseling, there is a continued need for informational sessions and support groups for LS patients/family members. Implementation of an in-person support group is feasible and responsive to the needs of our LS population.
Identification of breast cancer (BC) patients (pts) fulfilling NCCN criteria for genetic risk assessment.
Authors: Lypas Georgios , Papageorgiou Konstantina , Georgiou Georgia , Zoulamoglou Menelaos , Tsoukalas Nikolaos , Zografos Georgios , Papakostas Pavlos , Barbounis Vasileios
Published: March 2020

e12537

Background: Five to 10% of BC pts develop the disease due to an inherited predisposition syndrome; BRCA1/2 germline mutations are most commonly associated. NCCN guidelines help identify a somewhat broad group of pts requiring further genetic evaluation and a narrower one, for whom genetic testing is specifically recommended. Aims: The identification of pts requiring genetic guidance and the description of subgroups fulfilling NCCN criteria for genetic testing, according to family history (FH), demographic and clinical features, in a group of unselected Greek BC pts. Methods: This is a retrospective, medical records analysis of all histologically confirmed, unselected BC pts who who visited our department (Medical Oncology Unit, Hippocratio Hospital) between 2009 and 2012. Demographic, histopathologic and family history data was extracted and analyzed. Results: Among 690 pts eligible for analysis, 682 of which (98.8%) of Greek ethnicity, 233 (33.7% ) had a HER2+ subtype, 311 (45%) ER/PR+, and 69 (10%) triple-negative. Information was incomplete for the remaining 76 (11.1%). General criteria for furthr genetic evaluation were fulfilled by 301 patient (43.6%). Two hundred and eighty-six of them (41.44% ) were diagnosed with BC at age ≤50 and 15 (2.17%) at age older than 50; 12 (1.7%) had at least 2 close relatives with BC and 3 (0.43%) had a personal history of ovarian cancer (OC). BRCA1/2 testing criteria were fulfilled by 259 pts (37.5%). 172 (24.9%) were diagnosed at age ≤45. Seventy-five (10.8%) were diagnosed at age 46-50, 22 of which (3.1%) had one close relative with BC or OC and 16 (2.3% ) had two close relatives with BC or OC. Thirty-six pts (5.2%) with triple negative BC were diagnosed at age <60, 16 of which (2.3%) < 45 years old. No pts had a personal or FamHx of sarcoma, thus did not fulfill the relevant TP53 testing criteria. However 7 (1%) were diagnosed under age 30. Only 11 patients (1.6%) underwent genetic testing, revealing 5 (0.7%) carriers of a deleterious BRCA1 mutation. Conclusions: Almost half pts with BC require further genetic evaluation. The need for genetic counseling services and insurance coverage of genetic testing is highlighted by this study.
Breast cancer in the young (≤35 years): A single center study from the All India Institute of Medical Sciences.
Authors: Raina Vinod , Gogia Ajay , Mohanti B. K. , Deo S. V. S. , Shukla N. K. , Sreenivas Vishnu kumar
Published: March 2020

e12539

Background: Breast cancer in young women (</= 35 years) is uncommon and accounts for 1-2 % of all breast cancer in the West. There is limited data on breast cancer in the young from India. The aim of our study was to assess clinical, pathological parameters and outcome in young breast cancer patients. Methods: We carried out an analysis of 271 patients of young breast cancer patients (</=35 years) registered between 2000 to 2012 at I.R.C.H, AIIMS, New Delhi, India. Results: The median age was 31 years (range 18-35). The median duration of symptoms was 10 months (range 0.25-60). Breast lump was the commonest (93%) presenting symptom (left >right side). Ninety percent of patients were married and median age at first child birth was 23 years. Positive family history was elicited in only 15 patients. The TNM stage distribution was: stage I was 3 %, stage II- 20%, stage III- 55%, and stage IV- 22%. The median clinical tumour size was 5.1 cm. Modified radical mastectomy was the commonest surgical procedure and this was done in 80 % of cases. The histopathological analysis showed 93% had infiltrating ductal carcinoma. Thirty percent of tumours were high grade and 55% had pathological node positive disease. ER/PR and her-2neu positivity was 33% and 30% respectively. Triple negative breast cancer (TNBC) constituted 33%. Fifty five patients presented with metastasis. A combination of anthracycline and taxanes were used in the majority of patients and Trastuzumab could be used only in 6 cases out of 72 patients who were Her-2 neu positive. With a median follow up of 30 months (non metastatic group), three years disease free survival (DFS) and overall survival (OS) was 50% and 60%. Higher nodal stage, tumour size (>5 cm), negative hormonal status (triple negative) and visceral metastasis at baseline predicted poor outcome. Conclusions: Young women constituted 8 % of breast cancer cases, this proportion is much higher than the published Western figures of 1-2 % and reflects younger age of our population. Even in this young group ER/ PR positivity was 33% and almost a third were her-2 neu positive. Higher nodal stage, tumour size (>5 cm), triple negativity and visceral metastasis at baseline predicted poor outcome.
Epidemiologic model estimating number of Hodgkin lymphoma patients who relapsed after autologous stem cell transplant in the United States.
Authors: Lee Andrew , Abbe Adeline , Hamed Alaa , Neumann Frank , Olivares Robert , Younes Anas
Published: March 2020

e12554

Background: Hodgkin Lymphoma (HL) is an uncommon lymphoid malignancy with an estimated 9,060 new cases and 1,170 patients dying of disease each year in the US. High dose chemotherapy followed by autologous stem cell transplant (ASCT) is standard treatment for relapsed or refractory HL. Patients who do not respond to or relapse after ASCT have a short survival and are candidates for investigational agents. In the absence of published studies, the primary objective of this study was to estimate the percent and number of patients with HL who relapsed after ASCT. Methods: Number of ASCT performed for HL patients and relapse rate reported in the literature was used to estimate number of HL patients who relapsed after ASCT. Number of ASCT in US with HL was extracted from 2008-2010 CIBMTR (Center for International Blood and Marrow Transplant Research) data assuming a stable number for 2010-2012. A literature review (1993-2012) using EMBASE identified relapse rate after ASCT in HL. A model was built using relapse rates at 12, 24, 36, 48 and 60 months. If there was no relapse rate at a time point, it was estimated by dividing nearest data point following relapse rate by period length. Rate differences at 12 and 24 months were used to estimate relapse rate for 2ndyear. Same methods were used to calculate other year rates. Results: An estimated 791 patients underwent ASCT for HL in 2012 based on prior years data. Three clinical trials and 9 epidemiological studies providing post-ASCT relapse rate were identified from the literature review. Relapse rates over 5 years and number of patients with relapsed HL after ASCT were estimated to be 44.7% and 352 patients, respectively, in 2012. Conclusions: : In the absence of published literature, a model was built to estimate the number of HL patients who relapsed after ASCT suggesting a high rate at 44.7% over 5 years. Because not all US centers participate in the CIBMTR registry, these numbers are likely to be conservative and actual rate may be higher. Clinical trials targeting this relatively small patient population with clear unmet medical need require collaborative efforts to enroll patients and more research to understand factors for patients relapsing post-ASCT.
Hereditary cancer families’ perceptions about biobanking as a healthy control.
Authors: Quinn Gwendolyn P. , Gwede Clement K , Sehovic Ivana , Pal Tuya , Meade Cathy
Published: March 2020

e12556

Background: Biobanks are a promising way to identify links between genetic and environmental factors in relation to disease, particularly cancer. However, there has been skepticism among the general public about the purpose of biospecimen donation. Healthy people are beginning to be approached for participation in biobanking based on NIH initiative to establish national repositories. There is a great need to address public concerns about biospecimen donation. There may be additional and unique concerns among families with a history of hereditary cancer. Methods: Participants were recruited through research networks of families across the US who had received genetic counseling/testing. At-risk individuals (18 and over, no personal cancer diagnosis, first degree family member with cancer, had a test for hereditary cancer) completed a 15-item biobanking statement rating worksheet, selecting from 1 (strongly disagree), 2 (agree), 3 (not sure), 4 (disagree) and 5 (strongly agree). Results: 39 participants (100% white, 92.5% female) completed the worksheet. Most participants (87%) agreed confidentiality with medical information was important. 89% thought genetic research and biobanks were useful even if they only produced scientific knowledge instead of cancer cures. 87% felt the public should be consulted on ethical issues in biospecimen research, and permission should be acquired before conducting research on their samples (74%). 56% were unsure if they were exposing themselves to risk if they donated a specimen, while 46% were concerned that their specimen would be connected to their identity. Participants were uncertain if researchers should explain the use of each biospecimen (36% agreed, 33% unsure, 31% disagreed). 92% felt public education about biobanking would increase biospecimen donation. Conclusions: While participants were supportive of genetic research and biobanks, concerns regarding confidentiality and loss of privacy remain among unaffected carriers. There is a need to enhance existing training for researchers to improve understanding of high genetic risk community members’ perceptions about biobanking.
Long-term responders to first-line bevacizumab-based therapy among patients (pts) with HER2-negative metastatic breast cancer (MBC): Retrospective results of an ambispective observational study.
Authors: Ramos Vazquez Manuel , Redondo Andrés , Ghanem Ismael , Gil Gil Miguel J. , Garau Llinas Isabel , Perez-Carrion Ramon , Garcia-Garre Elisa , Rodriguez Cesar Augusto , Chacon Jose Ignacio , Lopez-Vivanco Guillermo , Perello Antonia , Espinosa Aunion Ruth , Morales Serafin , Ortega Vanessa , Garcia Saenz José Ángel , Martinez Noelia , Gonzalez Paula , Arcusa Lanza Angels , Echarri Maria Jose , Medina Ana
Published: March 2020

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Background: LORENA is an ambispective observational study evaluating B-based therapy in a real world setting which purpose is to assess clinical features, treatments and prognosis of HER2-negative MBC pts with ≥12 months (mo.) of PFS to 1st-line B-based chemotherapy (CT). Methods: Pts with MBC receiving 1st-line CT and B are enrolled. No prespecified schedules, doses or assessments. Data since the introduction of the treatment with B were collected at inclusion (retrospective phase), and prospectively at 18 mo. after enrollment for the patients alive at the time of inclusion, including B-targeted adverse events (AEs). Relevant baseline and on-study variables were analyzed by Cox model to identify independent effects on PFS. Results: By Jan 2013, complete retrospective data were available for 84 pts, 33 (39.3%) of them having stage III-IV at diagnosis. Median age, 50 years (r: 29–77); age ≥65 years, 13%; triple negative, 20.2%; bone/liver/lung metastases (%), 55/27/40; ≥2 metastases sites: 46.4%; ECOG status 0-1: 91.7%, ≥2: 5.9%, UK: 2.3%. 67% of pts have received prior (neo)adjuvant CT, with 56 and 30% of them with anthracyclines and taxanes, respectively. The objective response was 78%, including complete responses in 23%. A further 22% had stable disease. Median duration of B-based therapy was 12.4 mo. PFS events had been recorded in 44% of pts. Median PFS: 19.5 mo. (95%CI: 15.6-23.2). Cox proportional hazard multivariate regression model showed that B-based therapy ≥15 vs <15 mo was associated with improved PFS (26.5 vs 14.0 mo, p= 0.009; HR 0.40 [95%CI: 0.19-0.81]). The most common grade ≥3 B-related AEs were: Hypertension 9.5%, proteinuria 3.5%, bleeding 3.5%, and thromboembolic events 1.1%. No B-related death was reported. Conclusions: Outcomes in routine oncology practice for LORENA patients are consistent with those from prospective trials of 1st-line B-containing therapy and ATHENA study. These results suggest a benefit from a maintained VEGF suppression and that B continuation either as a single agent or combined with CT, until disease progression is recommended. Follow-up is ongoing.
Effect of beta blocker on breast cancer progression in minority population.
Authors: Chakraborty Rajshekhar , Mukkamalla Shiva Kumar Reddy , Calderon Natalia , Bulone Linda
Published: March 2020

e12564

Background: Recent pharmaco-epidemiological studies have shown positive effects of beta blockers (BB) on breast cancer progression, recurrence, metastasis, and cancer specific mortality. To the best of our knowledge none of these studies specifically targeted the minority population. The purpose of our study was to determine the effect of beta blockers on the Progression Free Survival (PFS) of breast cancer patients belonging to the minority subgroup of US population. Methods: We retrospectively reviewed 142 consecutive cases of breast cancer in a city hospital in Queens County of New York City (Asians 36%, Blacks 42%, Hispanics 18% and Whites 4%) diagnosed between January 2007 and December 2009. Patients using beta blockers prior to diagnosis were compared to those who were not on any in terms of PFS after adjusting for the confounding effect of stage at presentation. Kaplan-Meier survival curves were used to look for any significant difference in the PFS between these two groups in minority population. Results: Patients on beta blockers (n=25) were compared to those who were not (n=111). The median follow-up time of this study was 54 months. The study population was stratified according to the stage of presentation (Stage I=32%, Stage II=36%, Stage III=22%, Stage IV=10%).Using Kaplan Meier survival analysis we found significant differences in PFS of patients in stages II and IV (Wilcoxon Test p<0.0001, Log-Rank Test p<0.0001). There was no progression of disease in stage I irrespective of beta blocker intake. In stage II, PFS at the end of study in patients on BB vs. not on BB was 91% vs. 87%. In stage IV the PFS was 100% vs. 10% in patients on BB vs. not on BB. However, in stage III the PFS was better in patients not on BB, which could be explained by the small number of patients on BB (50% vs. 77% in BB vs. no BB subgroup). Conclusions: In this study of breast cancer PFS in minority population, we found that beta blocker use was associated with improved PFS in stages II and IV. However, additional studies with larger sample size are required to substantiate this finding.
Therapeutic effect of gemcitabine on experimental tumors of the brain.
Authors: Chubenko Viacheslav , Stukov Aleksandr Nikolaevich , Belyaeva Olesya , Bespalov Vladimir , Moiseenko Fedor Vladimirovich , Lukyanchikova Valentina , Semiglazova Tatyana , Murazov Yaroslav , Vershinina Sofia
Published: March 2020

e13005

Background: Gemcitabine has a very modest potency to penetrate blood-brain barrier (BBB). So far it's therapeutic activity in intracranial tumors is unknown. Methods: we explored the effect of gemcitabine (G) on overall survival in models of intracranial Ehrlich's tumor and lymphosarcoma LIO-1. As a comparison for the investigation group we've chosen drugs with different ability to penetrate into brain. We injected BCNU (50 mg/kg), cyclophosphamide (C) (150 mg/kg) and CDDP (9 mg/kg) intraperitoneally once 24 hours after transplantation. Results: The mean overall survival (OS) of mice in a selected model is 9,6+/-0,4 days. The injection of G resulted in substantial increase in OS up to 16,2 +/-0,4 (69%, p = 0,0000). In comparative groups administration of BCNU resulted in an increase in OS of 49% (the average OS 14,3+/-0,8, p = 0.000289), C - in 20% OS increase (11,5+/-0,4, p = 0.00272) and CDDP did not influence OS comparing with control group (10,2+0,4 days, p = 0.315). In other experiment mice with intracranial transplantated lymphosarcoma LIO-1 lived 15.4+1.3 days after single i.p. administration of G (25 mg/kg in 24 hours after transplantation) in comparison with 11.2+0.4 days in control group. The absolute increase of life expectancy was 37.5% (p = 0.013). In control group at 14 day after the transplantation all animals died whereas in G group only 3 mice out of 10 (30 %, g = 0.0003) died. Single i.p. administration of 25 mg/kg G on the 5th day after the intracranial transplantation of LIO-1, increased average OS of the animals from 10,9+ 0,4 days in control group to 13.5±0.5 days (increase in OS 24%, p = 0.0003). Conclusions: In our series of experiment we showed the potency of gemcitabine in treatment of various intracranial tumors. Until our work we can not find any data obtained on efficacy of gemcitabine in this tumor types.
Treatment outcomes of patients with primary central nervous system lymphoma: Single center experience from south India.
Authors: Mallavarapu Krishna Mohan V T , Ayyagari Santa , Rajappa Senthil Jagannathan , Alluri Krishnam Raju , S Sudha Murthy
Published: March 2020

e13010

Background: Primary CNS Lymphoma (PCNSL) is a rare neoplasm of the brain accounting for 1-2% of all brain tumours. Incidence and histopathologic features of PCNSL in India has been reported; however, reports on therapy outcomes of the disease are lacking. We report treatment outcomes of patients with PCNSL at our institute. Methods: Case records of all patients treated for PCNSL between 2008 and 2012 were retrospectively analysed. Epidemiologic details, treatments given, progression free and overall survival were calculated. Patients who completed at least high dose methotrexate (1.5 gram/ m2) for 5 courses with or without RT were included for analysis. Overall survival (OS) was defined as time from diagnosis till death/lost to follow up. Results: A total of seventeen patients were analysed. The median age at diagnosis was 58 years and M: F ratio was 1.14:1. Thirteen out of seventeen patients were eligible for analysis; six could complete the total treatment protocol which included methotrexate, vincristine, procarbazine, Dexamethasone, Radiation therapy followed by high dose cytarabine. Median overall survival was 20 months (range 2-54 months). Among those who completed the protocol, median survival at 21 months was not reached with 66% survival. Conclusions: Treatment of PCNSL with at least high dose methotrexate with or without whole brain radiation offers moderate results. Completion of treatment protocol is associated with better overall survival.
Phase II trial for patients with newly diagnosed glioblastoma (GBM) treated with carmustine wafers followed by concurrent radiation therapy (RT), temozolomide (TMZ), and bevacizumab (BV), then followed by TMZ and BV post-RT.
Authors: Ranjan Tulika , Peters Katherine B. , Vlahovic Gordana , Alderson Lloyd M , Herndon James Emmett , McSherry Frances , Threatt Stevie , Sampson John Howard , Friedman Allan H. , Bigner Darell D. , Friedman Henry S. , Vredenburgh James J , Desjardins Annick
Published: March 2020

e13015^

Background: Standard treatment for GBM includes RT and TMZ, followed by six cycles of TMZ, for a median overall survival (OS) and progression-free survival (PFS) of 14.6 and 6.9 months, respectively. BV is FDA approved for recurrent GBM and carmustine wafers are approved for newly diagnosed and recurrent GBM. We evaluated the safety and efficacy of carmustine wafers insertion followed by concurrent RT, TMZ and BV, followed by TMZ and BV for newly diagnosed GBM patients. Methods: Treatment consisted of: Part A- carmustine wafers insertion at resection followed by RT and TMZ at 75 mg/m2/day. BV at 10 mg/kg every two weeks started at least 28 days post-operatively. Part B- Patients received 12 cycles of TMZ (200 mg/m2on days 1-5 of a 28-day cycle) and BV every two weeks (day 1 and 15). Results: Forty one patients of a planned accrual of 72 were enrolled. The study was closed early due to six grade 4-5 toxicities related to study intervention, which met the safety criteria to discontinue the trial. Three patients had grade 4 cerebral edema and one each had grade 4 fatigue, wound infection and meningitis. Median age was 56 years (range, 27-77 years) and 28 patients were men. Of 41 patients, 36 completed part A and 31 started part B. Eleven patients are still on study and 4 have completed part B. Twenty six patients are off study due to progression (n = 16), adverse events (n = 8) and consent withdrawal (n = 2). At a median follow-up of 12.6 months (95% CI: 10.8-15.6 months) the median PFS is 11.3 months (95% CI: 9.2-12.9 months) and the median OS is 16.1 months (95% CI: 15.8 months- ∞). Grade 3-5 toxicities so far include: thrombocytopenia (grade 3, n = 2; grade 4, n = 2), stroke (grade 3, n = 1; grade 5, n = 1), infection (grade 3, n = 2), meningitis (grade 3, n = 1; grade 4, n=1), venous thromboembolic events (grade 3, n = 5), cerebral edema (grade 4, n = 3), fatigue (grade 4, n = 1), enterocolitis (grade 3, n = 1), and wound infection (grade 3, n = 2; grade 4, n = 1). Conclusions: For the patients who did well post carmustine wafers insertion, the treatment was tolerable and median PFS and OS has improved. Updated survival and toxicity results will be presented. Clinical trial information: NT01186406.