bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy of sequential use of docetaxel / 5-fluorouracil / cisplatin as first-line, and irinotecan/levofolinate/5-fluorouracil as second-line chemotherapy for advanced gastric cancer
Authors: Sugiyama K. , Ishikawa A. , Sato H.
Published: March 2020

15150

Background The prognosis for advanced gastric cancer (AGC) is extremely poor, and efficacy of chemotherapy is limited with median survival times of around 9 months. Recently docetaxel (DOC) and irinotecan (CPT-11) seem to be effective for AGC as well as 5-fluorouracil (5-FU) and cisplatin (CDDP). This study was performed to evaluate the efficacy of combination chemotherapy including sequential administration of these all key drugs. Methods Patients (pts) with AGC were treated with the chemotherapy consisted of DOC / 5-FU / CDDP (DOC 50mg/m2 d1 + 5-FU 330mg/m2/bolus d1–4 + CDDP 9mg/m2 d1–4; q4weeks or DOC 50mg/m2 d1 + 5-FU1320mg/m2/48-h infusion over d1–2 + CDDP 18mg/m2 d1–2; q3weeks) as 1st-line until disease progression and/or unacceptable toxicity. 2nd-line therapy was included CPT-11 / levofolinate (l-LV) / 5-FU combination (CPT-11 90mg/m2 d1 + l-LV 75mg/m2 d1 + 5-FU 330mg/m2/bolus d1 followed by 1400mg/m2/46-h infusion over d1–2; q2weeks or CPT-11 30mg/m2 + l-LV 35mg/m2 + 5-FU 330mg/m2/bolus d1,8,15,22; q6weeks). Toxicities and efficacy were evaluated according to the CTCAE v3.0 and the RECIST guidelines. Time to progression (TTP) and overall survival time (OS) was measured from the date of diagnosis. Results Ten pts (4 unresectable stage IV diseases, 6 postoperative metastatic diseases) were enrolled between May 2004 and October 2006. Median age was 72 years. Pts with ECOG PS 1/2 were 8, PS 3 were 2. Metastatic sites were liver 6, peritoneum 3, lymph nodes 5. Histological types were papillary/tubular 2, poorly/mucinous/signet ring 4, mixed 4. Median administered number of cycles were 4.5 for 1st-line, 3.5 for 2nd-line. Toxicities were tolerable, and all pts received 1st-line therapy until disease progression. Objective response rate was 20.0% (2PR, 8 SD). TTP ranges 4.4–14.0 months for 8pts (2pts remained SD). Median OS were not reached, and median observation time was 11.7 months (range; 2.9- 28.0 months) at the date of 31 Dec 2006. Conclusions DOC / 5-FU / CDDP combination as 1st-line, CPT-11 / l-LV / 5-FU combination as 2nd-line treatment appears active against AGC and improve the survival, without severe toxicity.

No significant financial relationships to disclose.
First-line paclitaxel and cisplatin in patients with advanced squamous-cell carcinoma of the esophagus
Authors: Zhang X. , Shen L. , Li J. , Li Y. , Li J. , Jin M. L.
Published: March 2020

15157

Objectives: To evaluate response rate, survival and toxicities of paclitaxel/cisplatin combination in patients with advanced or metastatic squamous-cell carcinoma of the esophagus. Methods: Thirty-nine patients with definite measurable indices and no prior chemotherapy were enrolled. Patients were treated with paclitaxel 175 mg/m2 by 2-hour infusion day 1 and cisplatin 75 mg/m2 infusion day 1. Treatment was repeated every 21 days. Results: Thirty-nine patients were enrolled. 35 patients were eligible to be evaluated for response. The overall response rate was 48.6% (95% confidence interval [CI], 0.31∼0.65) with complete and partial response rates of 2.8% and 45.7%, respectively. The median time to progression(TTP) was 7 months, and median survival time of all patients was 13 months. There was a significant difference in median overall survival between the patients who had received responding versus those who had not (p = 0.006). Median survival was 17 (95% CI, 11.9–22.0) and 10 months (95% CI, 7.6–12.35) for responding patients and non-responding patients, respectively. The 1-yr survival probability was 39%. Relief of dysphagia and pain were observed in 86.2% of the all patients. The most common toxicities were neutropenia and alopecia. There were no grade 4 clinical toxicities and treatment-related deaths were recorded in all patients. Conclusions: Paclitaxel and cisplatin is a promising treatment for patients with squamous-cell carcinoma of the esophagus. The toxicity of this regimen is within acceptable range.

No significant financial relationships to disclose.
The role of adjuvant chemoradiotherapy (CRT) in Turkish patients with gastric carcinoma
Authors: Gumus M. , Dane F. , Kaya S. , Ozturk M. A. , Yumuk P. F. , Atasoy B. M. , Basaran G. , Salepci T. , Yaylaci M. , Turhal N. S.
Published: March 2020

15159

Background: Increased disease free and overall survivals were seen in curatively resected patients with gastric and gastroesophageal adenocarcinoma treated with postoperative adjuvant CRT compared to surgery alone. There is no study analyzing the outcome of gastric cancer patients who received adjuvant CRT after curative resection in Turkish patients. Thus, we aimed to analyze the treatment outcome of postoperative CRT, and the prognostic significance of various parameters in these patients. Material Metod: Overall 130 patients with gastric cancer staged IB to IV(M0) were treated with chemoradiotherapy after curative resection, in two outpatient clinics in Istanbul. The chemotherapy consisted of fluorouracil 425 mg/m2 plus leucovorin 20 mg/m2 for 5 days, followed by 4500 cGy of radiotherapy for 5 weeks with fluorouracil (400 mg/m2) and leucovorin (20 mg/m2) on the first 4 days and the last 3 days of radiotherapy. Two 5-day cycles of chemotherapy with the doses used in the first cycle were given 4 weeks after the completion of radiotherapy. The demographic features and histopathological characteristics of the patients were analyzed as prognostic factors. Results: The median follow up was 13 months (range: 1–77) starting from surgery date. The median age was 58 years (range:33–75). About 28 % of the patients were female. ECOG performance score (PS) was =1 in 92.9 %, whereas it was 2 in the remaining 7.1%. Twenty-one patients had gastroesophageal junction and 109 had gastric primaries. The rates of T1, T2, T3, and T4 tumors were 3.8%, 26.9%, 61.5%, and 7.7%, respectively. A hundred and nine (83.8%) patients had regional node involvement. The 3 year disease free survival and overall survival for all patients were 50.1%, and 61.7%, respectively. The median overall survival was 54 months. In multivariate Cox regression analysis; nodal status (p: 0.003) was the only independent prognostic factor for overall survival. Tolerance was acceptable, and the main toxicity was related to gastrointestinal system. Conclusion: The adjuvant CRT after curative resection of gastric cancer was feasible, with acceptable toxicities in our Turkish patient population.

No significant financial relationships to disclose.
Gastrointestinal stromal tumors: A monoinstitutional experience
Authors: Di Battista M. , Pantaleo M. A. , Astorino M. , Brandi G. , Saponara M. , Di Scioscio V. , Santini D. , Castellucci P. , Catena F. , Biasco G.
Published: March 2020

15161

Background: Optimal management of GIST pts required a multidisciplinary approach. Novel tyrosine kinase inhibitors provide an improvement of disease treatment. Methods: We report the clinical results of 67 pts treated in our institution from January 2003 to October 2006, including 41 men and 26 women. Their ages ranged from 28 to 86 yrs (mean 65). 24% of pts were classified into low risk categories, 22% intermediate risk, 54% high risk. At diagnosis, 53/67 patients (79%) presented a localized disease and underwent to surgery, and 14/67 patients (21%) patients presented a metastatic disease. Among these 14 metastatic patients, 8 underwent to surgical removal of primary tumor and metastatic site before treatment with imatinib (2 patient R0) and 6 patients were inoperable at diagnosis and received treatment with imatinib. In total, 61/67 (91%) of patients underwent surgery, R0 resection was achieved in 51 patients. Among 61 operated patients, 24 patients developed a recurrence and received medical treatment with Imatinib. In total, 30/67 (44,7%) patients were treated with Imatinib, and 27 were enrolled in a clinical studies of second line treatment with Sunitinib because of progression or intolerance to treatment with Imatinib. Results: After a follow-up of 42 months we report a median DFS of 14.5 months for radically operated patients. The 3 year-DFS rate was 28.6%. The differential analysis according to risk showed a median DFS of 16.5 months with 16.7% of pts disease free at 3 yrs for the high risk category (36 pts); in the low-intermediate risk categories (31 pts), a median DFS of 21 months with 38% of patients disease-free at 3 yrs was observed. Considering all 38 metastatic pts, 14 at diagnosis and 24 with recurrence, a progressive disease was seen in 94% (median 12 months). In first line of treatment with Imatinib we recorded a median TTP of 17 months with 30% of responders after 2 yrs of treatment. Conclusions: Surgery remains the only curative treatment for localized disease. imatinib is the standard of care for patients with metastatic Gist. For imatinib-resistant GISTs a novel agent such as Sunitinib appears promising.

No significant financial relationships to disclose.
A single institution experience with neuroendocrine tumors
Authors: Badari Badari A. , Javle M. , Pak Y. , Khoury T. , Ramnath N. , Gibbs J. , Kuvshinoff B. , Iyer R.
Published: March 2020

15164

Background: ABSTRACT Introduction: . The aim of this study was to analyze demographic, therapy, tumor and clinical outcomes of all cases of neuroendocrine cancer at a tertiary cancer and determine the the markers that may better correlate with outcomes than histologic grade. Patients and Methods: With IRB approval , 126 charts with a diagnosis of neuroendocrine carcinoma were identified between 1–1-1999 and 1–1-2004. Ninety-five cases were selected on the basis of complete availability of baseline, therapy and at least one time point of followup data. Patient demographics, therapy details, TNM stage, tumor marker and survival data were collected. Tumors were graded as well, moderate and poorly differentiated and by site of origin. We attempted to correlate the outcome with NCAM(neural cell adhesion molecule-CD56) status, which is a homophylic binding glycoprotein to have a role in cell adhesion. Descriptive statistics and frequency tables were used to describe the data and kaplan meier methods were used to estimate the median survival. Results: There were 28 patients with lung primaries, 25 had primaries in the gut (extra pancreatic),11 had pancreatic primaries, 31 cases had unknown primaries or primaries at sites other than the lungs or the gastrointestinal tract. The estimated median survival for the whole sample was 34 months.(95% C I :20,54) and the 2 year survival rate was 55.3 %.The estimated median survival for CD56 positive group was 11 months(95% C.I :3,38) and that for CD 56 unknown group was 36(95% C .I :20,n/a). A significant difference in survival between CD56 positive group and CD56 unknown was found,based on log-rank test>(P=.02). Baseline characteristics were as follows: M:F 48:47; 19 were well differentiated, 4 were moderately differentiated and 36 of 95 tumors were poorly differentiated, the differentiation was not known in 36 cases. Surgery with curative intent was done in 52 of the patients(54.74%) and 52 received (54.74%)t chemotherapy, 4 patients(4.2%) received chemoembolization and 2 patients(2.1%) received local ablative treatments. Conclusion: These data summarize our instutions experience with this rare malignancy. In our data survival was as expected in the literature and further investigation of the CD 56 status of all patients is underway.

No significant financial relationships to disclose.
Consequences of modifying an adjuvant treatment protocol for resected gastric carcinoma: A retrospective study at a single institution in western Canada
Authors: Bebb D. G. , Ziouzina O. , Lupichuk S. , Stefaniuk M. , Dowden S. , Chan A. , Walley B. , Chan S. , Wong A. , Doll C.
Published: March 2020

15176

Background: Gastric adenocarcinoma has a poor outcome: surgical resection alone in stage IA-IVA is curative in < 30%. Adjuvant chemo-radiotherapy (INT-0116 protocol) increases median overall survival from 27 to 36 months but is associated with high morbidity with many patients requiring protocol modifications to complete treatment. The benefit of modified protocols in this setting has not been well studied. We set out to compare the morbidity and mortality of the INT-0116 protocol with that of modified protocols in a single institution in Western Canada. Methods: We conducted a retrospective review of stage IA-IVA gastric adenocarcinoma patients treated with adjuvant chemo-radiation at our institution after curative-intent surgical resection. Patients were identified from Tom Baker Cancer Centre records. End points were: survival, completion of therapy, local, regional and distant failure. The modified protocol was defined as: combined modality component postponed from the second to the third or fourth chemotherapy cycle or radiation given alone after two or three cycles of chemotherapy. Results: Twenty three consecutive patients were identified; 11 received standard protocol, twelve a modified protocol. Demographic characteristics / staging at resection of those two groups did not significantly differ. Outcomes are summarized in Table 1 . Conclusions: Many patients were unable to complete the INT-0116 protocol as described, while patients placed on a modified protocol had a greater chance of completing treatment. Survival at 12 and 36 months in patients treated with the modified protocol was at least as good as those who underwent the standard protocol. This limited study at a single institution suggests that modifying the INT 0116 protocol can make this treatment more palatable to patients while not compromising outcome. Further research is warranted. Data on a further nine patients more recently treated is being analyzed and will be presented.

[Table: see text]

No significant financial relationships to disclose.
The effect of raloxifene on breast MRI volume in premenopausal women at increased risk for invasive breast cancer
Authors: Eng-Wong J. , Chow C. K. , Orzano J. , Venzon D. , Zujewski J. , Yao J. , Prindiville S.
Published: March 2020

1518

Background: Breast MRI volume (MRIV) and mammographic density (MD) assess the amount of fibroglandular tissue in the breast. While increased MD is associated with a 4 to 6 fold increase in breast cancer risk, the association between MRIV and breast cancer is unknown. Previous studies have shown that MRIV and MD can be modulated with hormonal interventions. We evaluated the effect of raloxifene on MRIV in premenopausal women at increased risk for breast cancer. We have previously reported that raloxifene did not change MD in this cohort. Raloxifene is indicated for the prevention and treatment of osteoporosis but not for prevention of breast cancer or for use in premenopausal women. Methods: Premenopausal women at increased risk by virtue of: Gail model risk > 1.7% over 5 years; lobular neoplasia, ductal carcinoma in situ, BRCA1/2 mutation positive, or a very strong family history were eligible for this phase II chemoprevention study. MRIs obtained at baseline and after two years on raloxifene 60 mg daily, and one year after discontinuing the drug were evaluated.T1 weighted spoiled gradient-echo MRI with fat suppression was used to determine volume using a semiautomatic method, after visual verification. Median relative change in MRIV was assessed by the Wilcoxon signed rank test. Results: 19 of 30 subjects who started study drug had breast MRI at baseline and after 2 years on raloxifene; median relative change was -16% (range -57 to +25%) (p=0.0004). 17 subjects had MRI at year 2 and one year after stopping drug. No significant change in MRIV was observed after stopping raloxifene, median relative change -9% (p=0.64). Conclusions: MRIV significantly declined while on raloxifene. In contrast no significant change in percent mammographic density in this same cohort was seen. Our findings suggest that MRIV may be a better surrogate biomarker than MD in premenopausal women at risk for breast cancer because of less variation in its measurement. MRIV should be further evaluated as a potential surrogate biomarker in prevention studies.

No significant financial relationships to disclose.
Improved survival with combination oxaliplatin, irinotecan, cetuximab for metastatic pancreatic cancer
Authors: Lee F. , Roach M. , Duong L. , Heywood G. , Parasher G. , Rasila K.
Published: March 2020

15180

Background: For metastatic pancreatic cancer, no combination chemotherapy has been shown to improve survival significantly in comparison to single agent gemcitabine. A novel combination with oxaliplatin 60 mg/m2, irinotecan 90 mg/m2, cetuximab 250 mg/m2 (OIC) given every two weeks appears to produce a high rate of radiographic response. Since our reporting (ASCO 2007 GI Conference), we continue to see a high rate of clinical and radiographic responses (50% by Recist Criteria). We therefore decided to look carefully on the survival data of OIC versus control (mainly gemcitabine single agent or in combination with other agents). Methods: We retrospective reviewed patients seen from 10/2002 to 10/2006 with diagnosis of metastatic pancreatic cancer. The survival duration was calculated from the date of diagnosis to the date of death. We included only patients whose dates of death could be confirmed with death certificates. Results: A total of 37 patients were identified. 11 of those were in the OIC arm and 26 were treated with other regimens (17 with gemcitabine-based regimens, 9 with either capecitabine or 5-FU-based regimens) that function as control. The range of survival duration was 4 - 28 months for OIC arm and 1 - 28 months for the control. Median survival was 10 months for the OIC arm versus 5 months for the control. Conclusions: OIC regimen produces a high rate of tumor response and may have a survival advantage with this retrospective analysis. We believe it is a regimen deserves further evaluation.

No significant financial relationships to disclose.
Esophageal cancer treatment in our institute from 1999 to 2005
Authors: Miyazaki Y. , Imamura H. , Kishimoto T. , Yamamoto K. , Furukawa H.
Published: March 2020

15183

Background: 5 year survival rate of esophageal cancer in Japan reported to the Japanese Society for Esophageal Diseases from 1988 to 1994 (9,143 cases) was improved to 35.5% comparing to the rate of the beginning of 1980 which remained around 20%. This result was given by the increase of early cancer cases attributed to the progress of the ability of diagnosis, the improvement of the postoperative management, and the 3 field lymph node dissection introduced from the middle of 1980. Biological malignant potential and the modality of treatment for esophageal cancer in Japan differs from those in the United States. Methods: We studied clinicopathological characteristic and treatment results of 63 esophageal cancer patients in our institute from 1999 to 2005. Results: 63 patients consisted of 47 males and 16 females with mean age of 63.4±11.4. Out of 47 patients who underwent surgical treatment, 6 and 4 patients underwent neoadjuvant chemoradiotherapy and chemotherapy, respectively. 15 patients without surgical treatment consisted of 12 patients, including one patient after endoscopical mucosal resection, undergoing chemoradiotherapy, 2 patients undergoing chemotherapy, and 3 patients undergoing radiotherapy, respectively. Most common histological type was squamous cell carcinoma (55 patients), followed by adenocarcinoma (3 patients), small cell carcinoma(3 patients), others(2 patients), and unknown(1 patients). There was 1 surgical treatment-related death. The major complications were SSI (18 patients), anastomotic leakage(7 patients) and recurrent nerve palsy (5 patients). The 2-year survival rate of patients with surgical resection was 68.1%, while the rate of the unresectable patients was 38.9%.Since 2002, we have adopted posterior mediastinal route as a prime choice, rather than retrosternal route. The median amount of blood loss, rate of complications and duration of post operative hospital stay of each routes are 650/415(ml), 65/45(%), 35/22(day), respectively. These results suggested that posterior mediastinal route showed superiority comparing to restrosternal route. Conclusions: Backed by these outcomes, we will aim to establish a logical strategy for esophageal cancer therapy which could accompany fewer complications, respect quality of life and prolong survival time.

No significant financial relationships to disclose.
Second-line chemotherapy in advanced pancreatic cancer: A retrospective, single-center analysis
Authors: Herrmann T. , Jaeger D. , Stremmel W. , Herrmann C.
Published: March 2020

15187

Background: Patients with advanced pancreatic cancer profit from palliative chemotherapy. The role of second-line chemotherapy is not yet established. Methods: We performed a retrospective analysis in 98 patients who were treated at our department from 1/2004–6/2006 due to locally advanced or metastatic adenocarcinoma of the pancreas. Results: At the time of analysis 67 patients had died (median overall survival 9 months), 31 patients are still alive (median follow up 9 months). 12 patients were initially treated with radiochemotherapy. 86 patients received systemic chemotherapy; 43 of these patients were treated with second-line chemotherapy after disease progression. OS was significantly longer in patients who received second-line chemotherapy (10 months versus 5.0 months, p=0.023). Response to second-line chemotherapy was partial remission in 2 patients (4.6 %), stable disease in 18 patients (44.8 %), and progressive disease in 19 patients (44.2 %), in 3 patients the treatment was stopped due to toxicity (6.9 %). 12 patients received second-line treatment after early disease progression under first-line chemotherapy. 9 of these patients did not respond to second-line treatment, 2 achieved stable disease and 1 patient had partial remission. Elevated LDH and CA19.9 serum levels at the time of diagnosis were identified as negative prognostic factors. Conclusions: Prognosis of patients with advanced pancreatic cancer is still poor. Selected patients may benefit from salvage chemotherapy after failure of first-line chemotherapy.

No significant financial relationships to disclose.
Differential gene expression in preoperative study of selenium and vitamin E chemoprevention in prostate cancer
Authors: Kim J. , Tsavachidou D. , Do K. , Wen S. , Babaian R. , Pisters L. , Pettaway C. , Troncoso P. , Logothetis C. , McDonnell T.
Published: March 2020

1523

Background: To identify genes that distinguish between treatments, tumor types, and their interaction, we undertook a microarray analysis of tissue in a preoperative chemoprevention study of L-selenomethionine (SeMet) and vitamin E (VE) in prostate cancer. Methods: Forty-eight men with prostate cancer were enrolled in a single-institution, double-blind, placebo-controlled trial that randomized patients into four groups receiving 200 μg SeMet, 400 IU VE, a combination of the two, or placebo (see 2006 ASCO abstract 1007). All patients also received a multivitamin and vitamin C (250 mg) daily. Modeled on the Selenium and Vitamin E Cancer Prevention Trial, this study included patients scheduled for prostatectomy within 3 to 6 wk of registration who had a prostate-specific antigen level <10 ng/mL within 3 mo of registration, clinical stage T1c/T2 disease, and a Gleason score =7. From core biopsy specimens, we isolated cancerous and noncancerous cells, tumor-adjacent stroma, and non-tumor adjacent stroma of 38 evaluable radical prostatectomy specimens using laser capture microdissection. The cDNA hybridized to oligonucleotide microarrays was generated from extracted RNA, which had undergone two rounds of linear amplification. Expression levels were extracted using the positional-dependent nearest-neighbor model, and after ANOVA model analysis, effects were contrasted using the approximate z-test with statistic z. The beta-uniform mixture model was used to analyze p values and control the false discovery rate. Ingenuity Pathway Analysis followed. Results: Differentially expressed genes were selected that were common in the combination and selenium arms or in the combination and VE arms: unique in tumor-69 in combination and selenium, 71 in combination and VE; unique in stroma-64 in combination and selenium, 45 in combination and VE; unique in normal tissue-48 in combination and selenium, 38 in combination and VE. Conclusions: This work demonstrates that gene expression may be correlated with specific therapeutic interventions, and this analysis indicates that dietary antioxidants modulate gene expression in human prostate cancer cells and pathways relevant to prostate carcinogenesis.

No significant financial relationships to disclose.
Management strategies for women at high risk for breast and ovarian cancer: Are women satisfied?
Authors: Westin S. N. , Sun C. C. , Lu K. H. , Schmeler K. M. , Soliman P. T. , White K. G. , Daniels M. S. , Arun B. K. , Peterson S. K. , Bodurka D. C.
Published: March 2020

1524

Background: Women at high risk for breast and ovarian cancer have two major management options to reduce their risk of ovarian cancer, periodic screening (PS) or prophylactic oophorectomy (PO). Little is known regarding patient satisfaction levels with choice of risk reduction strategy. Our objective was to determine levels of patient satisfaction with PO versus PS and to identify factors which may influence satisfaction. Methods: As part of a larger study, women who received BRCA1/2 testing before July 2005 were sent a follow-up patient questionnaire packet. We are reporting on the Cancer Worry Scale and Satisfaction With Decision (SWD) scale (range of possible scores, 6–30). The lowest 10th percentile of the SWD score (21) was used to define low satisfaction. Chi-square, t-Test and Mann-Whitney tests were used for statistical analyses. Results: A total of 540 surveys were mailed and 309 responses were received (57%). We excluded 127 patients due to history of an oophorectomy for benign or malignant indications or incomplete SWD scale. The median age of respondents was 48.2. 60/182 women (33%) had BRCA mutations and 64/182 (35.2%) underwent PO. The overall satisfaction rate among respondents was high (median score 29, range 14–30). Median SWD score was significantly higher in patients in the PO group compared to the PS group (30.0 vs. 26.5, p<.001). Patients with BRCA mutations had higher median SWD scores, regardless of management type (30.0 vs. 28.0, p=.013). Low satisfaction scores were associated with the perception that the decision between PO and PS was difficult to make (p=.001). Patients who expressed ongoing difficulty in their decision-making also had lower satisfaction scores (p=.016). Satisfaction was unrelated to demographics, clinical factors, or concerns of cancer risk. Conclusions: In our study, the majority of women at high risk for breast and ovarian cancer were satisfied with their choice of risk reduction strategy. In particular, women who chose PO had higher levels of overall satisfaction. Difficulty with decision-making was associated with lower satisfaction levels. Improved education and support of these women through the decision-making process may enhance overall levels of satisfaction with risk reduction strategy.

No significant financial relationships to disclose.
Socioeconomic status of women attending an oncogenetic counseling clinic
Authors: von Wachenfeldt A. , Brandberg Y. , Johansson H. , Fornander T.
Published: March 2020

1526

Background: In women with a family history (FH) of breast cancer the risk can be substantially increased and starts at an earlier age compared with the general population. Women with FH of breast cancer are not suggested oncogenetic counselling unless the subject is brought up in the contact with medical professionals. Consequently, a woman with FH for breast cancer has to have knowledge about the possibility of counselling to come into question for information, advice and special surveillance program. The aim of this study was to characterize women at an oncogenetic counselling clinic in terms of socioeconomic status (SES) and to compare these data with population based figures from the same catchment area. Methods: All healthy women who had, once or repeatedly, been visiting the oncogenetic clinic at the Department of Oncology, Karolinska University Hospital / Sodersjukhuset, between April, 1998 - June, 2004 were eligible for study. A total of 307 out of 378 consecutive women consented to participate (81%) in the survey by returning mailed questionnaires. SES data were compared with official data for all women aged 24 -75 year from the same catchment area (n= 277 783 women). Results: See table . Conclusions: Women visiting the oncogenetic counselling clinic were higher educated, more often married and had a better economic situation than comparable women from the same catchment area. These findings indicate that efforts should be elaborated to increase the knowledge about the possibility of genetic counselling among women with FH for breast cancers.

[Table: see text]

No significant financial relationships to disclose.
Prevalence of breast cancer risk factors in two different cohorts in relation to health care access and preventive programs in southern Brazil
Authors: Caleffi M. , Bedin A. J. , Zignani J. M. , Artico L. G. , Viegas-Butzke J. M. , Rutta R. , Schmidt A. , Giacomazzi J. , Ashton-Prolla P. , Weber B.
Published: March 2020

1538

Background: Breast cancer (BC) represents a public issue of great impact also in developing countries as Brazil, where BC incidence and mortality rates are continuosly increasing, the latter probably due to late diagnosis and lack of health care programs.Studies are needed to identified BC risk factors in different groups of women in Porto Alegre (POA), where BC incidence is 3-fold higher than other Brazilian cities. Preliminary analysis are presented to enable specialists to design preventive strategies of breast health care models. Methods: The study included a survey of risk factors of two social economic distinct groups of women over 15 years old with different access to health care programs in POA: 1) Núcleo Mama Porto Alegre (NMPOA): underserved women derived from public health care units, and 2) Núcleo Mama Moinhos (NMHMV): women with private insurance. Results: Data of 785 from NMHMV and 8921 from NMPOA are summarized in the table . Obesity and smokers are more frequent in the underserved population whereas a positive familial history is more common in the NMHMV group. Conclusions: Preliminary results showed significant differences among the two studied population demanding distinct strategies of prevention and management. The total number of 15.000 women will be presented together with reproductive factors and the their Gail model access.

[Table: see text]

No significant financial relationships to disclose.
MRI background enhancement: Its relationship with breast density and breast cancer risk
Authors: Kwong A. , Rosenberg J. , Van den Bosch M. A. , Daniel B. L. , Lo G. , Ikeda D. M.
Published: March 2020

1539

Background: Increased breast density increases breast cancer risk. MRI breast is increasingly used for imaging as unlike mammography, the sensitivity of MRI breast is not affected by breast density but rather, the amount of background enhancement. It has been suggested that increased background enhancement may be related to the amount of proliferative breast tissue present; hence this may also be related to increased breast cancer risk. To date there have been no study published assessing background enhancement and its relation to breast cancer risk. Method: A retrospective review 45 mammography films and breast MRI scans of 36 patients (9 bilateral) with normal breast imaging was performed and scored independently by 3 radiologists for breast density using BI-RADS criteria. MRI breast density was scored on the non-contrast enhanced T1-weighted series whereas background enhancement was quantified on the first contrast-enhanced T1-weighted fat-suppressed series. Background enhancement was scored as none-minimal, mild, moderate, marked. Weighted kappa was used to assess the inter-modality agreement. A partial approximation to the Gail risk score was calculated from the available risk factors (age, menarche, number of biopsies, births and relatives with breast cancer), using coefficients from a Caucasian population; the resulting values were converted to ranks and was correlated with background enhancement. Result: There was substantial within-reader agreement between mammographic and MRI density (kappa=0.68; p=0.001). There were no correlation between background enhancement and breast density. All 6 patients with background-enhancement were pre-menopausal. Although not statistically significant (p<0.37), it is suggestive that 4 of the 6 (67%) had a history of breast cancer while only 6 of the 13 premenopausal non-enhancers (46%) had cancer. Moreover, the mean of the rank risk for enhancing premenopausal women was 29.5 while the non-enhancing pre-menopausal women was 16.6 (p=0.048 by one-tailed t-test). Conclusion: We found good correlation between mammographic and MRI breast density. There was no correlation between breast density and MRI background enhancement. There is a suggestion that MRI background enhancement may be associated with a higher risk of breast cancer.

No significant financial relationships to disclose.
Discriminatory analysis in determination of high risk of gastric cancer
Authors: Terekhova S. A. , Lazarev A. F. , Petrova V. D. , Sinkina T. V. , Selezneva I. A. , Dimitriadi J. N.
Published: March 2020

1540

Background: Determination of the high risk of gastric cancer and target examination of patients from high-risk groups makes early detection of gastric cancer possible and contributes to the decrease of mortality rates as the outcome of gastric cancer treatment is primarily dependant on the stage of disease. Methods: 700 patients with gastric cancer and 1069 persons without any oncopathology referred to Altay oncological center for consultation in 2002–2004 were interviewed and examined to get the data on different factors known as risk factors for gastric cancer (endogenic, environmental, lifestyle, nutritive factors, results of blood-tests and non-oncological stomach diseases, etc.). Results: By means of discriminatory analysis from 131 investigated factors there were 26 factors distinguished and corresponding coefficients of canonical function of discrimination calculated, on the basis of which the prognosis of gastric cancer development may be ascertained (p<0.001): age, body mass, education, duration of stress, insomnia, extrasleep during daylight hours, family history of gastric cancer, family history of cancer, presence of clinical symptoms, lifetime history of smoking, usage of strong spirits, amount of spirits used per month, regularity of nutrition (eating patterns), time intervals between food intakes, variety of food allowance, usage of food and drinks of high temperature, animal fats, spicy food, canned and preserved food, bakery, strong black tea and coffee, fresh vegetables and fruit, sour milk products, green tea, level of haemoglobin, ESR. Multiplying the interval values of those significant factors and corresponding coefficients of canonical function of discrimination and subsequent summarizing of the results and the constant gives an <>, the positive value of which is the evidence of high risk of gastric cancer either to be developed or already exists. Negative integral rate is the evidence of low risk. Cross check up showed the 95.1% test-sensitivity and 95.0% test-specificity. Conclusions: Thus, the value of the integral rate can be used as a criterion for selection of concrete patients with high risk of gastric cancer to be deeply examined and to be under monitoring for detection of early gastric cancer.

No significant financial relationships to disclose.
Glomerular filtration rate (GFR) in patients with stage I testicular seminoma treated with adjuvant carboplatin: A comparison of six formulae compared to a radioisotope gold standard
Authors: Cathomas R. , Harle A. , Mead G. M. , von Moos R. , Simmonds P. , Geldart T. R.
Published: March 2020

15504

Background: Carboplatin (Carbo) is an effective adjuvant treatment for patients (pts) with stage I testicular seminoma. Accurate estimation of GFR is necessary to establish carbo dose. Calculation of GFR following injection of a radiolabelled isotope (e.g. Tc99mDTPA) is considered the gold standard, but may not be readily available in all centres. Calculation of creatinine clearence via 24-h urine collection is often unreliable. The aim of this study was to assess different formulae for GFR calculation in this patient population. Methods: We performed a retrospective analysis of all patients with stage I seminoma treated with adjuvant carbo in Southampton between 1999 and 2005. All patients underwent GFR measurement with Tc99mDTPA and this was compared with six standard formulae for the calculation of GFR based on serum creatinine. Bias was quantified by Mean Percentage Error (MPE %) and precision by Mean Absolute Percentage Error (MAPE%). Tc99mDTPA GFR was not corrected for body surface area (BSA). Results: 202 Caucasian male pts were included (mean age 40 yrs; mean Tc99mDTPA GFR 123ml/min). Results are illustrated in Table 1 . Conclusions: In general, formulae underestimate GFR leading to significant decreases in carbo dose. The Cockcroft-Gault and Martin formulae were most accurate in this cohort of pts. Formulae developed for use in pts with chronic kidney disease (MDRD), elderly cancer patients (Wright) or which correct for BSA (Jelliffe, MDRD, Mayo), greatly underestimate GFR and should not be used in this setting.

[Table: see text]

No significant financial relationships to disclose.
A new mechanism of estrogen action in prostate cancer: Inhibition of tissue androgen production and prostate cancer growth by Estradiol in androgen independent prostate cancer xenografts
Authors: Montgomery B. , Nelson P. , Hess D. L. , Vessella R. , Corey E.
Published: March 2020

15509

Background: Estrogens are effective agents in treating prostate cancer in patients in which serum androgens are already at ‘castrate‘ or anorchid levels. The mechanisms whereby estrogens inhibit ‘androgen-independent‘ prostate cancer are unclear. Methods: The androgen-independent human prostate cancer xenograft LuCaP 35V was implanted into orchiectomized male SCID mice and established tumors were treated with placebo pellets, 17β-estradiol (E2) slow-release pellets or E2 with the estrogen receptor antagonist ICI 182,780 as previously described (Clin Cancer Res 8:1003). Effects of E2 on tumor growth and tissue testosterone (T) and dihydrotestosterone (DHT) levels were evaluated by radioimmunoassay. Results: E2 significantly inhibited growth of androgen-independent LuCaP35V ( ∼35% inhibition at 4 weeks, p=0.0047, and increased survival of tumor bearing animals, (p trend =0.03) . The estrogen receptor antagonist ICI 182,780 did not block E2 inhibition of tumor growth, suggesting a receptor independent mechanism of tumor suppression. We then examined the effect of E2 on tissue T and DHT. E2 suppressed levels of tumor T and DHT in treated tumors. Tissue androgens in placebo treated LuCaP35V xenografts were; T=1.21 (± 0.18) pg/mg and DHT=3.54 (±1.07) pg/mg, and in E2-treated LuCaP35V T=0.23 (±0.09) pg/mg and DHT =0.44 (±0.14) pg/mg, (p<0.001). Levels of T and DHT in control liver tissue from both placebo and E2-treated animals were equivalent, at less than 0.2 pg/mg. Conclusions: We have shown that E2 inhibits growth of the androgen- independent human prostate cancer xenograft LuCaP35V, and that this inhibition is estrogen receptor independent. E2 significantly suppressed tumor tissue T and DHT suggesting a new mechanism of E2 mediated growth inhibition of androgen independent prostate cancer, potentially through inhibition of tumoral steroidogenesis. This model of ‘intracrine‘ tumor androgen production can be used to evaluate other inhibitors of tissue steroidogenesis.

No significant financial relationships to disclose.
The importance of continued surveillance of high risk cancer families as illustrated in a family with Gardner’s syndrome
Authors: Legare R. D. , Scalia-Wilbur J. , Kent J.
Published: March 2020

1551

Background: The scientific community continues to rapidly discover cancer predisposition genes allowing high risk families to identify underlying genetic abnormalities providing more individualized medical management. Therefore, continued follow-up becomes critical and is exemplified by Family A, a case that had been lost to follow-up for almost 40 years. Family A was first reported in the literature in 1955 by Weiner and Cooper presenting with a dominant inheritance pattern of osteomatosis, multiple soft tissue tumors and colorectal adenomatosis polyposis consistent with several families previously reported by Gardner et al. between 1950–1953. The clinical diagnosis of Gardner syndrome was established. In 1969 Coli et al. further described the phenotypic manifestations of Family A’s second and third generations after which the family was largely lost to follow-up until two second generation members presented to our high-risk clinic. Methods: An updated family history was collected and compared to that previously reported in the literature. Results: An updated pedigree revealed new cases of breast, ovarian and primary peritioneal cancers in the second and third generations. A 39 year old woman diagnosed with a glioblastoma was also discovered. No family members had undergone genetic testing, however, analyses of the APC and BRCA genes are underway. Conclusions: The presence of multiple newly reported cases of breast and ovarian cancers within Family A raises concern for two independent cancer predisposition syndromes, Hereditary Breast and Ovarian Cancer Susceptibility syndrome (HBOCS) as well as Familial Adenomatous Polyposis (FAP). Though rarely gynecological tumors have been reported in FAP, this case emphasizes the need for practitioners to be aware of the potential presence of multiple hereditary cancer syndromes in one family. The dynamic changes in the pedigree of Family A underscore the importance of continued follow up for cancer families in which the underlying etiology is unknown. Such families should be followed in cancer genetics clinics to update family histories, ensure that appropriate screening regimens are followed, and to offer genetic testing if the appropriate analysis becomes available.

No significant financial relationships to disclose.
An open label phase I study of ABR-215050 in patients with prostate cancer refractory to hormone therapy and with rising PSA for determination of MTD and long-term tolerability and safety
Authors: Damber J. , Bratt O. , Ahlgren G. , Häggman M. , Björk A. , Kilany S. , Hannander K.
Published: March 2020

15510

Background: Preclinical studies have demonstrated that ABR-215050, an orally active 3-quinoline-carboxamide derivative with anti-angiogenic abilities, consistently inhibits growth of established prostate cancer in rodent and human xenografts model systems. Tumor vessel density was inhibited by 44–65% consistent with the 41–78% inhibition in tumor weights. The anti-angiogenic response was correlated with an increase in both tumor hypoxic and apoptotic fraction. Based upon these results, ABR-215050 is now tested in the clinical setting. Methods: Cohorts of 6 patients (pts) with hormone refractory prostate cancer and rising PSA were to receive escalating doses of ABR- 215050 (0.5, 1.0, 2.0 and 3.0 mg daily) for 28 days in addition to the androgen ablative therapy. Pts showing stable disease at day 28 were offered to enter a one year extension period at the MTD level to assess long-term tolerability and safety. The primary endpoint in the 28-day study was determination of MTD. Secondary endpoints included changes in PSA levels. Results: Two DLTs (sinus tachycardia and amylase, G3) occurred in the 1.0 mg cohort. The MTD was therefore set to 0.5 mg. Additional 11 pts were enrolled at the MTD level. A total of 17 pts received 0.5 mg and 7 pts 1.0 mg of ABR-215050 once daily. The most frequently related AEs reported during the first 28 days were muscle or joint pain, nausea and fatigue, all of which being mild and transient. Laboratory changes were also seen, such as a transient increase in CRP and amylase. Fifteen out of 17 pts continued into the extension period. Fourteen out of 15 pts remained on treatment = 4 months. The AE profile in the extension period was similar to that reported during the first 28 days of treatment. Nine out of 14 pts had a >50% decrease in PSA velocity at 4 months compared to the pre-treatment period. Six of these pts exhibited a decrease in PSA from baseline, ranging from 8% to 58% (mean 29%). Conclusions: ABR-215050 0.5 mg is well tolerated with manageable side effects. In addition available PSA results suggest stabilization/lowering of the PSA levels.

No significant financial relationships to disclose.
Delayed toxicity of whole brain radiotherapy (WBRT) in germ cell tumor (GCT) patients with central nervous system (CNS) metastases
Authors: Doyle D. M. , Einhorn L. H.
Published: March 2020

15511

Background: CNS metastases are uncommon in GCT. Incidence is 2–3% and is usually associated with extensive pulmonary metastases and/or high serum human chorionic gonadotropin levels. CNS metastases have been managed with WBRT and concomitant cisplatin-based combination chemotherapy. Our prior publication did not observe serious CNS toxicity (Int J Rad Oncol Biol Phys 22:17–22, 1991). Methods: We observed 5 patients with delayed CNS toxicity. Initial diagnosis was 1981 through 2003. Median age 23 years (range 21–34). All 5 patients had advanced disease by the International Germ Cell Consensus Collaborative Group. Three of five patients had CNS metastases at the time of diagnosis, and two patients relapsed with CNS metastases. These 5 patients received WBRT 4,000–5,000 cGy in 18- 28 fractions concurrently with cisplatin-based chemotherapy. Results: All five patients developed delayed symptoms consistent with progressive multifocal leukoencephalopathy (PMLE), including seizures, hemiparesis, expressive and receptive aphasia, cranial neuropathies including facial droop, tremors, headaches, blindness, dementia, decreased level of consciousness, ataxia, and parasthesias. Median time from WBRT to CNS symptoms was 72 months (range 9–228 months). Brain imaging revealed multiple abnormalities consistent with gliosis and diffuse cerebral atrophy. One patient was diagnosed with glioblastoma multiforme in the area of radiation-induced gliosis. 3 of 5 patients had progressive symptoms, and the other 2 had stable symptoms. Treatment with surgery and steroids had modest benefit. The PMLE resulted in significant debility in all five patients, resulting in death (2 patients), loss of work, steroid-induced morbidity, and recurrent hospitalizations. Conclusions: WBRT is not innocuous in young patients with GCT and can cause late CNS toxicity. We are now cautious about the use of WBRT and reserve it for multiple CNS metastases that are symptomatic or resistant to chemotherapy.

No significant financial relationships to disclose.