bluuebunny/crossref_metadata_2025 huggingface dataset:
Daily irinotecan and concomitant radiotherapy for locally advanced pancreatic cancer: Feasibility and MTD
Authors: Carrie C. , De La Fouchardière C. , Perol D. , Negrier S. , Desseigne F. , Meeus P. , Labrosse H. , Martel Lafay I.
Published: March 2020

15124

Background: To determine the maximal tolerated dose (MTD) of daily irinotecan with radiotherapy (RT) in patients (pts) with locally advanced adenocarcinoma of the pancreas. Methods: Between 09/2000 and 05/2006, 30 pts with histologically proved adenocarcinoma of pancreas were included in this prospective phase I/II study. Irinotecan was administrated daily, 1 hour before RT session. Doses were escalated by increment of 2 mg/m2 every 3 patients for an initial dose of 6 mg/m2/day. RT was delivered at 2 Gy per session, 5 fractions per week to a total dose of 50 Gy to the doses tumor volume. Primary endpoint was toxicity; secondary endpoints were tumor objective response (OR) defined as complete or partial response, secondary operability and overall survival (OS). Inoperability was assessed by surgeon. All images were reviewed by a radiologist. OR rates were compared using the Fisher’s exact test. Results: 30 pts were entered over 6 years through 7 dose levels from 6 mg/m2/day. Sex ratio was 1:1, median age was 58 years (range 33–71), Karnofsky score was ≥ 90 in 93%. Current median follow-up is 45 months. No dose limiting toxicity was yet observed (last level 18 mg/m2/day). Three patients experienced grade 3 toxicity at level 1 (ulcer perforation), level 6 (nausea, vomiting and abdominal pain), and level 7 (nausea, vomiting and hypokaliemia), respectively. OR rates were 33% at 4 weeks. 3/13 pts (23%) included within the 3 first levels (= 10 mg/m2/day) experienced an OR at 4 weeks, versus 7/17 (41%) in the levels > 10 mg/m2/day (P = 0.44). 3 pts underwent surgery because of control tumor. Median OS was 13 months (95% CI 11–14) with 24 patient’s death. One patient is in complete remission since 21 months. Conclusions: Maximal tolerated dose is not yet reached. Despite response rate is not the main aim of the study, results suggest that RT combined with a higher daily level of irinotecan could be associated with a better tumor control.

No significant financial relationships to disclose.
A retrospective study of surgical treatment for gastric cancer in our institute as a clinical hospital in Japan
Authors: Kishimoto T. , Imamura H. , Yamamoto K. , Miyazaki Y. , Furukawa H.
Published: March 2020

15125

Background: Two European randomized controlled trials comparing D1 and D2 gastrectomy revealed a high operative mortality in the D2 group. Based on these reports, D1 gastrectomy is a standard treatment for western patients. In contrast, D2 gastrectomy is considered a standard and safe procedure in Japan. Moreover, the operative morbidity/mortality and the incidence of the major surgical complications were not different between D2and extended para-aortic lymphadenectomy in a prospective randomized controlled trial in Japan. We report a retrospective study of surgical treatment for gastric cancer in our institute as a clinical hospital in Japan. Methods: Patients who underwent gastrectomy between January 1998 and November 2006 in our institute were analyzed. Survival according to the staging by Japanese Classification of Gastric Cancer, the level of the dissection of lymph nodes, and all complications were studied. Results: A total 1342 patients underwent gastrectomy between January 1998 and November 2006 in our institute. The male/female ratio was 2.2 and the mean age was 64.7±11.4 years(range,27–94 years). The 5-year survival according to the staging by Japanese Classification of Gastric Cancer was 98.4%, 84.7%, 77.2%, 46.1%, 40.2% and 33.4% in the stage IA, IB, II, IIIA, IIIB, and IV, respectively. D0, D1, D2, and D3 or D4 gastrectomy was performed in 48, 200, 610, and 27 patients, respectively. Complications were identified in 295 patients(22%) involving 2 patients with treatment death(0.01%) and anastomotic leak, surgical site infection, pancreatic fistula, ileus, anastomotic stenosis, abdominal abcess, liver dysfunction, postoperative bleeding, pneumonia , DIC , peritonitis, and others were identified in 66, 51, 42, 28, 26, 23, 21, 14, 13, 4, 3, and 4 patients, respectively. We analyzed the D0/D1 and D2/D3/D4 dissection subgroups about complications. There was no significant difference in the incidence of complications between the two groups (p=0.093). Conclusions: Our data suggested that gastrectomy with D2 dissection has been a safe treatment with a good prognosis in our institute. D2 gastrectomy is considered a safe treatmemt without increasing surgical complications.

No significant financial relationships to disclose.
Phase II trial of oxaliplatin, 5-FU, and leucovorin chemotherapy for the previously treated patients with advanced gastric cancer
Authors: Oh S. C. , Kim Y. , Kim J. , Choi I. , Sung H. , Seo H. , Shin S.
Published: March 2020

15138

Background: The effect of chemotherapy for advanced gastric cancer was disappointing. Most of patients have progressed after treatment of first line chemotherapy. So, many trials searching for effective combination chemotherapy to these patients are warranted. We conducted this study to ascertain the efficacy and toxicity of oxaliplatin, 5FU, and leucovorin combination chemotherapy for the previously treated patients with advanced gastric cancer. Methods: In all, 48 patients received course of oxaliplatin 100mg/m2 intravenously (i.v) for 2hour and leucovorin at 100mg/m2 intravenously (i.v) for 2hour on day 1, then 5FU 2.4 g/m2 i.v for 46 hour continuous infusion on day 1 and 2. This regimen was repeated every 2 weeks. Results: A total 220 courses were administered as second line (64.6%) and third line (29.2%), and median number of courses per patient was four. No complete response was reported and 7 partial responses (14.6%) were achieved, giving an overall disease stabilizing rate of 52.2% (95% Confidence interval, 37.85 % to 66.6%). The major toxicity was neutropenia, which reached grade 3/4 in 8 patients (16.7%). Median time to progression was 3 months (0.6 to 8 months), median survival duration was 8 months (0.5+ to 14.5 months), and median response duration was 3 months (1.6–4.3 months). Conclusions: We conclude that oxaliplatin, 5-FU, leucovorin combination chemotherapy for the treatment of previously treated advanced gastric cancer has a role for disease stabilizing and toxicity was tolerable to most of patients.

No significant financial relationships to disclose.
Weekly paclitaxel, cisplatin, and 24-hour infusion of high-dose 5-fluorouracil plus leucovorin (weekly TP-HDFL) in patients with metastatic or recurrent esophageal cancer
Authors: Huang T. , Tsai Y. , Lin C. , Cheng A. , Yeh K. , Hsu C.
Published: March 2020

15165

Background: Paclitaxel (T), cisplatin (P), and 5-fluorouracil (5-FU) are active chemotherapy drugs for esophageal cancer. The 3-drug combination using a conventional 3-weekly schedule was active in patients with advanced esophageal cancer with response rate of 46% (Ilson DH et al: J Clin Oncol 1998;16:1826). The toxicity was substantial, with 57% grade 3/4 hematologic toxicities and 18% grade 3/4 peripheral neuropathy. We reported a multifractionated schedule using twice-weekly TP and weekly 5-FU (Lin CC et al: Anticancer Drugs 2007;18: in press). The multifractionated schedule, while induced comparable antitumor activity, had similar hematologic toxicities, less neuropathy, but more diarrhea than conventional 3-weekly schedule. The optimal way of combining T, P, and 5-FU remains to be defined. Methods: Patients with metastatic or recurrent esophageal cancer treated with weekly T, P, high-dose 5-FU plus leucovorin (weekly TP- HDFL) were retrospectively analyzed. The regimen consisted of T 70–80 mg/m2 IV 1h D1, P 35 mg/m2 IV 3h D2, 5-FU 2000 mg/m2 plus leucovorin 300 mg/m2 IV 24h D2, for 2 or 3 weeks followed by 1 week off. Results: Between Dec 2004 and Sep 2006, a total of 15 patients (male 14, squamous cell carcinoma 12) with a median age of 54 (range 37–76) were included. Eleven patients had de novo metastatic disease and 4 had recurrent disease. The disease extent included local esophageal tumor, lymph nodes, lung, liver, and bone in 13, 13, 5, 4, and 5 patients, respectively. The patients received an average of 3 cycles (range 1–5). Grade 3/4 neutropenia, leukopenia, thrombocytopenia, and infection occurred in 4, 3, 1, and 5 patients, respectively. No grade 3/4 vomiting, mucositis, diarrhea, and peripheral neuropathy occurred. The overall response rate was 33% (95% CI 12–87) (PR 5, SD 6, PD 4). With a median follow-up of 5 months, the median progression-free and overall survival were 3 (range 2–7) and 12.5 months (range 3+-12.5), respectively. Conclusions: Weekly TP-HDFL has a comparable activity and a better toxicity profile in patients with advanced esophageal cancer compared to previously reported 3-weekly or multifractionated schedule. (The study was supported by the grant of DOH95-TD-B-111- 001)

No significant financial relationships to disclose.
Combination of gemcite and cisplatin chemotherapy in unresectables gall bladder cancer
Authors: Gupta P. , Chitalkar P. , Sen A. , Sarkar S. , Mukhopadhyay S. , Sultania N. , Mukhopadhyay A.
Published: March 2020

15166

Background: Adenocarcinoma of the gall bladder accounts for approximately 4% of all malignant neoplasm of the gastro- intestinal tract. Though surgical resection is the treatment of choice, majority of the cases are unresectable. Different chemotherapeutic agents including 5Flurouracil, Mytomycin C, Cisplatin, Methotrexate, Etoposide and Doxorubicin have been tried single or in combination. Partial response lasting from weeks to several months have been observed only in about 10% - 20 % of the cases and the median survival for patients with gall bladder cancer is approximately 4 months. Gemcitabine has shown strong anti tumour activity in a variety of solid tumours. Cisplatin has synergistic activity with Gemcitabine. The aim of our study was to determine the response rate of Gemcitabine and Cisplatin combination in unresectable gall bladder cancer and to see the tolerability in Indian-Asian pollution. Methods: During period from November 2002 to December 2006 we selected 84 consecutive patients with histologicaly proven unresectable measurable, gall bladder cancer. The inclusion criteria were performance status more than 60% (Kornofsky) and normal liver (bilirubin < 2) and kidney function ( creatinine <2) function . All patient received Gemcitabine (1000mg/m2 intravenously over 30 minute) on day 1 and day 8 and Cisplatin total (100mg/m2 divided D1 to D3) every 21days. Response assessment was done by CT Scan after 3 cycles of chemotherapy. All 84 patients are eligible for efficacy and toxicity analysis. Results: There were 15 (17.8%) complete responders, 27 (32%) partial responders, 22 (26.1%) with stable disease and 20 (23.8%) shows disease progression. The median time to progression was 22 weeks (range 12- 30 weeks). The median duration of response was 16 weeks (range 5.6 - 60 weeks). The median over all survival was 24 weeks (range 11–32 weeks) with 1year survival rate of 20.2%. WHO grade III or IV anaemia was seen in 23 (18.63%) patients respectively. Sixteen (13.44%) patients experienced grade III or IV neutropenia while grade III or IV thompocytopenia was seen in 8 patients (6.72%). Conclusions: The present study showed the Gemcitabin & Cisplatine combination was very useful in advanced unresectable gall bladder cancer. It was well tolerated by the patients.

No significant financial relationships to disclose.
Deep electro-hyperthermia (EHY) with or without thermo-active agents in patients with advanced hepatic cell carcinoma: Phase II study
Authors: Ferrari V. D. , De Ponti S. , Valcamonico F. , Amoroso V. , Grisanti S. , Rangoni G. , Marpicati P. , Vassalli L. , Simoncini E. , Marini G.
Published: March 2020

15168

Background: Advanced HCC has no standard chemotherapy , all pts would be valuabled in clinical trials. We evaluated effectiveness and toxicity of capacitatively coupled low-frequency 13.56 MHz deep hyperthermia (Oncotherm-EHY 2000) treatment on chemo- refractory malignant primary liver cancer which underwent all other possible treatment. Methods: From February 2005 to July 2006, we enrolled 22 pts with advanced HCC. ECOG PS was 1 or O. Viral hepatic infection status was 7 HBV+, 8 HCV+, 1 HCV/HBV+. Median age was 67,5 y (range 63 -78), male/female 20/2 . 15 pts were uneligible for liver surgery, 3 pts received TACE, 1 PEI, 1 a lot of therapy. 7 pts were pre-treated with surgery, 2 also received TACE, 1 PEI and 1 a lot of therapy. 75% of pts were in stage C of BCLC classification. 2 pts had also distant metastases, 70% of pts had portal vein thromboses. 8 pts underwent only to EHY without CT. Schedule : EHY was achieved by arrangements of capacitative electrodes with a radiofrequency field of 13.56 Mhz (RF-DHT) at 80- 130 W equivalent to 41 °- 47° C for 60 minutes, 2 times/w for 5 weeks in combination with thermo-active agents . EHY was applied over 2 time a week over 1 hour as mono - combined therapy . Concomitant chemotherapy was oxaliplatin 50 mgr at fixed dose on D 1and D 15 . One cycle is 10 treatments of EHY ; 4 pts underwent 2 cycles and 2 pts to 3 cycles and 1 pt to 4 cycles . Median number of cycles was 1,5 (range 1–4), total EHY applications were 365. Results: EHY plus thermo-active drug is beneficial on clinical conditions off treated pts with an excellent compliance on out- patients. We observed 1 CR ( pt has only one bone metastases after 6 months without liver relapse), no PR, 25% of SD. Median survival time was 20’5 weeks (5 - 81+) We noted that 11 pts (50%) presented evidence of increasing well-being. Toxicity : 4 pts had skin reaction after application of EHY. In 3 pts we observed cutaneous hyperemia on the area of treatment and mild burn on the skin ; all symptoms disappeared after local steroid therapy , treatment was interrupted until resolution . Conclusions: Low toxicity and clinical benefit will be confirmed in further clinical studies. Capacitively coupled low-frequency 13.56 deep-hyperthermia is feasible for chemo-refractory HCC.

No significant financial relationships to disclose.
Clinical benefit of liver hanging maneuver for right-side major hepatectomy
Authors: Hayashi H. , Beppu T. , Nasu J. , Masuda T. , Mizumoto T. , Ishiko T. , Takamori H. , Kanemitsu K. , Hirota M. , Baba H.
Published: March 2020

15171

Background: Liver hanging maneuver is a new technique in anterior approach of major hepatectomy. However, the impact of the maneuver has never been fully investigated in patients with liver tumors. To evaluate the surgical benefits of liver hanging maneuver, we set up a comparative study in right-side major hepatectomy. Methods: From 2000 to 2006, 326 hepatectomy were performed in our institution. Fifty-eight patients with liver tumor (hepatocellularcarcinoma in 36, metastatic liver tumor in 13, and the others in 9) considered for right-side major hepatectomy were prospectively analyzed. Right-side hepatectomy included 26 right hepatectomy, 24 extended right hepatectomy, and 8 tri-segmentectomy. The patients were devided into a group with conventional approach (n = 21), a group with anterior approach without hanging maneuver (n = 19), and a group with approach with liver hanging maneuver (n = 18). In the three groups, age, body mass index, child-pugh classification, type of liver tumor, staging in hepatocellularcarcinoma, tumor size, resected liver weights, intraoperative blood loss, frequency of transfusion and surgical time were analyzed. Results: In conventional approach, anterior approach without hanging maneuver, and approach with liver hanging maneuver, mean age was 55, 59, and 65 years, and mean tumor size was 65, 75, and 108mm, respectively. Patients with liver hanging maneuver were significantly elder (p<0.05) and have larger tumor size (p<0.01). There were no significant differences in body mass index, child-pugh classification, type of liver tumor, staging in hepatocellularcarcinoma, and resected liver weights. Mean intraoperative blood loss was 1771, 805, and 704g, and mean surgical time was 562, 483, and 435minutes, and the frequency of red blood cell transfusion was 33, 21, and 17%, respectively. Patients with liver hanging maneuver had significantly less intraoperative blood loss (P=0.0001) and surgical time (P=0.002). The frequency of red blood cell transfusion in the liver hanging maneuver group was significantly lower than that of the conventional group (p<0.05). Postoperative morbidity rate were 33.3, 15.8, and 16.7%, respectively. Conclusions: Liver hanging maneuver is less invasive and a quite useful method for right-side major hepatectomy.

No significant financial relationships to disclose.
GEMOX as first-line chemotherapy in advanced pancreatic cancer (APC): A monoinstitutional experience
Authors: Di Marco M. , Nobili E. , Di Cicilia R. , Brandi G. , Bertolini S. , Derenzini E. , Dell’Arte S. , Casadei R. , Calculli L. , Biasco G.
Published: March 2020

15179

Background: To date, gemcitabine (GEM) remains the cornerstone of chemotherapy (CHT) for APC. According to GERCOR and GISCAD phase III trials the combination of GEM and oxaliplatin (GEMOX) has proven superior to GEM alone in terms of response rate (RR), time to progression (TTP) and clinical benefit rate (CBR). Methods: We conducted a retrospective analysis on 19 patients (pts) affected with histologically-confirmed APC, in order to determine the impact of GEMOX as first-line chemotherapy in terms of objective responses (OR) and TTP, using the Kaplan-Meier method. Among the 19 pts considered there were 15 males and 4 females (median age at diagnosis of 60.84 yrs; ECOG 0–2). The staging, according to AJCC criteria, was: IIB in 1 case, III in 5 cases and IV in the 13 remaning cases. The only metastatic site was the liver (in 13/19 pts). Ten of the 19 pts underwent surgical treatment prior to CHT: 2 radically resected (R0) subsequently treated with GEMOX after recurrence, 4 with positive margins (R1) and 4 surgically palliated. All pts received GEM 1000 mg/m2/d1 + oxaliplatin 100 mg/m2/d2 every 2 weeks. The median number of cycles was 5.89. Results: Among the 19 pts, 3 had a partial response (PR, 15.69%), 6 had stable disease (SD, 31.57%); no complete response was observed and 10 pts had progressive disease (PD, 52.63%). The overall disease control rate (DCR: PR + SD) was 47.37% while the OR were 15.69%. The median survival observed was 9.03 months (95% C.I. 5.15–12.91) and the median TTP was 6.13 months (95% C.I. 2.81–9.46). The main toxicities were: leucopenia, piastrinopenia, diarrhoea, nausea, fever and peripheral neuropathy; 3 pts discontinued the treatment due to grade 3–4 neurotoxicity. Conclusions: In our experience GEMOX gives an improved control of APC in terms of OR and TTP, with acceptable toxicity. The OS is in accordance to literature as well as the other data.

No significant financial relationships to disclose.
Efficacy of oxaliplatin, 5 FU and gemcitabine in advanced pancreato-biliary cancer
Authors: Aggarwal S. , Negi A. , Banerjee N. , Buxi T. , Kumar M. , Singhal M. , Tageja N. , Nundy S.
Published: March 2020

15182

Background: The treatment of advanced pancreato-biliary cancer remains an unmet need. The drugs known to be effective are oxaliplatin, gemcitabine. Method: The records of twenty patients suffering with cancers of advanced gall bladder (10), common bile duct (3), ampulle of vater (3) and pancreas (4) were analysed. Twenty patients were treated in the year 2006. Median age was 52 years. The common sites of metastatis were liver (12), lymphnodes (10), peritoneum (4), lungs (1). The patients with normal bilirubin & LFT (< 3 times upper limit of normal) were included. The chemotherapy protocol was given as: oxaliplatin 50 mg, leucovorin 30 mg, and 5FU 500 mg/m2 on day 1, 2, & 3. Gemcitabine was given 800 mg/m2 on day 2, 9, and 16. The cycle was repeated every 4 weeks. Response: The regimen was well tolerated. Pancytopenia requiring G-CSF, delays in drug administration occurred in 70% cases. The response was as follows-partial response 6/20 (30%), stable disease 5/20 (25%), progressive disease 9/20 (45%). The median survival was 5.5 months, four patients completed six cycles of chemotherapy and survival for at least 12 months. Conclusion: Oxaliplatin, 5 FU, gemcitabine and leucovorin is an effective chemo-protocol in advanced pancreato-biliary cancer. However, there is a need to improve upon the existing results.

No significant financial relationships to disclose.
Physician initiated cancer screening discussions and patient intention to engage in screening behavior
Authors: Gray S. W. , Wong N. , Kelly B. , Romantan A. , Ramirez S. , Fraze T. , Smith-McLallen A. , Armstrong K. , Schwartz J. , Hornik R.
Published: March 2020

1528

Background: Cancer screening for colon, breast, and prostate cancer remains underutilized. Physician (MD)-patient discussions of screening are common but the impact of these discussions is unknown. Methods: 2489 40–70 year old subjects completed a national survey of cancer prevention information acquisition and decision making (median age 53, 49% male, 77% white, 59% married, 61% some college). Subjects reported whether their MD initiated discussions (MDID) about colonoscopy, mammography, & PSA within the past year. Age eligible subjects were “non-routine screeners” (NRS: never screened or colonoscopy >10 yrs, mammography >2 yrs or PSA>2 yrs prior) or “routine screeners” (RS).The endpoint was intention to screen when next eligible. Results: 46%, 75% and 60% of subjects reported intentions to obtain colonoscopy, mammography and/or PSA. Logistic regression was used to determine the association between MDID and intentions to screen controlling for sociodemographics and recency of screening. For colonoscopy and mammography, MDID was significantly associated with intention to screen for NRS but not RS groups; the opposite was true for PSA. For the NRS group: comparing those saying no versus yes to MDID, intentions were 15% vs. 43% for colonoscopy, 29% to 61% for mammography (RS: 85% vs. 91% and 82% vs. 85%). For PSA, NRS: 46% vs.52% but RS group 65% vs. 85%. All interactions (screening by MDID) were significant, p<.001. Conclusions: Given high intentions to undergo colon and breast cancer screening among patients who have been screened routinely, physician discussion preferentially increases intentions for colon and breast cancer screening among patients who are not routinely undergoing the screening test. Conversely, physician discussion preferentially influences prostate cancer screening intentions among patients who have been screened in the past two years- perhaps because men who have not undergone screening are more resolved in their decision not to screen. These results define subgroups of patients where physician attention may have the greatest impact on screening adherence.

No significant financial relationships to disclose.
Participant characteristics on an international NCIC CTG breast cancer prevention trial
Authors: Richardson H. , Johnston D. , Goss P. E.
Published: March 2020

1531

Background: Antagonizing estrogen with tamoxifen has set the precedent for preventing breast cancer. Aromatase inhibitors reduce contralateral breast cancer in the adjuvant setting more than tamoxifen. The goal of MAP.3 is to determine whether exemestane reduces invasive breast cancers in post-menopausal women at risk for the disease. Methods: NCIC CTG MAP.3 is a randomized placebo controlled double blind trial of exemestane versus placebo. Recruitment began in September 2004 in North America and Spain. Criteria for entry on MAP.3 include: a Gail score of 1.66%; previous benign breast disease including LCIS; age over 60. The target sample size for the trial is 4560. Baseline characteristics of women enrolled thus far on MAP.3 were reviewed to determine whether their projected risk of breast cancer is consistent with the assumptions made in designing the trial. Results: Baseline characteristics are available on the 1784 women enrolled to MAP.3 to date. Over 70% of participants are over 60 years old (mean 64; SD=8.2 years) and the majority of the women are Caucasian (85%). The average 5-year risk of breast cancer is 2.7% (median, 2.2%). However, a greater proportion of women over 60 (30%) have a substantially lower Gail score (<1.66) compared to women less than 60 years of age (8%). Few women in the MAP.3 cohort have been enrolled on a basis of a history of prior breast atypical hyperplasia or LCIS (8%), or DCIS treated with mastectomy (2%). Nearly half the MAP.3 participants (45%) have at least one first degree relative with malignant breast cancer, and 7.5% of these women have 2 or more first degree relatives with the disease. Conclusions: The risk profile of the women on MAP.3 will determine the event rate and therefore the time to trial unblinding and analysis. This initial description of the MAP.3 population enrolled thus far indicates a slightly lower baseline breast cancer risk in comparison to the risk profile of those enrolled in previous breast cancer prevention trials with tamoxifen or raloxifene (NSABP P1, IBIS-1 and STAR). Reasons for this difference are being explored.

[Table: see text]
Content and method of parental disclosure of genetic risk to young adult and minor children in BRCA families
Authors: Pawlowski K. , Patrick-Miller L. , Daugherty C. K. , Olopade O. I. , Dignam J. J. , Ibe C. N. , Hlubocky F. J. , Cummings S. A. , White M. A. , Dudlicek L. , Bradbury A. R.
Published: March 2020

1536

Background: Prior research has found that many BRCA mutation carriers report discussing their genetic test results with their minor children. The content, method and process of this communication have not been previously described. Methods: 20 parents (yielding 42 parent-offspring pairs, POP) have completed a 62-item questionnaire regarding the content and methods of communication of genetic risk to offspring. Results: Of 19 (45%) POP where parents reported disclosure of their BRCA mutation to offspring in response to a binary (yes/no) question, all reported telling their children about the genetic mutation itself, as well as the parents’ risk for cancer. In 74% of POP the offspring’s chance of inheriting the mutation or risk for cancer were said to have been communicated. In 53% of POP parents reported discussion of parental risk reduction measures, and in only 37% of POP parents reported communication of offspring risk reduction measures. Of the POP where parents reported some communication of cancer risk, 22% described incorporating written materials. In 75% of POP parents reported communication through multiple conversations over time (1 -20 conversations, up to 4 years). Conclusions: Although many BRCA carriers report discussing their genetic mutation with offspring, the content and extent of parental communication is variable, often including information regarding the genetic mutation, but less frequently the offspring’s risk of inheriting the gene and infrequently communication regarding risk reduction measures. Further research on this expanding cohort will allow for analyses of parent and child factors associated with disclosure content in order to guide the development of interventions to facilitate age and content-appropriate communication of genetic risk to at-risk offspring.

No significant financial relationships to disclose.
The effects of licofelone, a dual lipoxygenase and cyclooxygenase inhibitor, with and without rosiglitazone in human MCF-7 and MDA-MB-231 breast cancer cells
Authors: Kurkjian C. , Janakiram N. B. , Guruswamy S. , Rao C. V. , Ozer H.
Published: March 2020

1537

Background: Clinical and preclinical studies suggest that cyclooxygenase (COX)-2 inhibitors reduce the risk of various cancers, however, their administration is associated with an increased cardiovascular risk. Agents with 5-LOX/COX inhibition provide a possible approach for improving chemopreventive efficacy without unwanted side effects. COX and LOX inhibition have also been associated with an increase in PPAR γ expression. The present experiments tested the effects of licofelone (L) in breast cancer cell lines and assessed whether dual inhibition of LOX and COX may potentiate the action of rosiglitazone (R). Methods: MDA-MB-231 and MCF-7 cells were exposed to sub-toxic concentrations of L and R alone and in combination and analyzed for growth inhibition (MTT method), apoptosis (EB-AO and DAPI methods), cell-cycle analysis (flow cytometry), and protein expression (immunoblot method). Results: L and R inhibited cell growth in a dose-dependent manner in both cell lines. Combination therapy resulted in significant rates of apoptosis, particularly at high doses in both cell lines (p<0.001). Flow cytometric analysis showed that L and R exhibited cell cycle arrest at the G0/G1 phase in MDA-MB-231 cells. The low dose combination did not promote cell cycle arrest while the higher dose combination therapy demonstrated significant inhibition (p <0.0009). In MCF-7 cells, G0/G1 phase blockade was noted in L and R treated cells as well as in the low dose simultaneous combination therapy. Intermediate and high dose combination therapy exhibited increased cell cycle arrest at G0/G1 when L was administered 12 hours before R (p = 0.0030 and 0.0017). Western blot analysis showed increased expression of p21WAFI/CIPI and decreased cyclin D1 expression in both cell lines after therapy. Both agents induced caspase-3 expression in MDA-MB-231 cells at high concentrations, with even higher expression observed in the combination treatment. MCF-7 cells demonstrated PARP cleavage at all doses when compared to control. Conclusions: Our results suggest that L is a potential agent for prevention and treatment of breast cancer and the combination of low doses of L and R provide further promise in improving efficacy against breast cancer.

No significant financial relationships to disclose.
Prevention of MEK1-associated tumours in murine epidermis by inhibition of interleukin-1
Authors: Lal R. , Watt F. M.
Published: March 2020

1541

Background: Pro-inflammatory cytokines have a role in facilitating a pro-tumourigenic microenvironment in chronic inflammatory diseases and may identify targets for chemoprevention. The host microenvironment has a role in driving the malignant capacity of tumours, determining whether they develop into squamous cell cancers or benign tumours. For example, suprabasal β1 integrin expression, as seen in some squamous cell carcinomas, activates extra-cellular signal regulated kinase (ERK) in basal and suprabasal keratinocytes and profoundly affects the susceptibility of the underlying proliferating cells to chemical carcinogenesis. I present the results of experiments using transgenic mice, hereafter referred to as InvEE, that express activated mitogen activated protein kinase kinase-1 (MEK1) in suprabasal layers of the epidermis resulting in constitutive ERK overexpression and results in increased keratinocyte expression of interleukin- 1a (IL-1 alpha), triggers epidermal hyperplasia, skin inflammation and benign tumours. Methods: I developed a protocol for inducing tumour formation in InvEE mice by full-thickness skin punch biopsy. I negated the affect of IL-1 alpha activation of inflammatory cells by generating InvEE bone marrow chimeras using MyD-88-/- mice or litter-mate InvEE mice as a control. InvEE/InvEE and InvEE/Myd- 88-/- chimeric mice were wounded and observed for tumour formation for 60 days. The experiment was conducted twice and the number of tumours in each group was analysed using a chi-squared test. Results: Spontaneous benign tumours occurred in 27 of 295 (9%) InvEE mice correlating with cutaneous injury. Punch-biopsy wounding induced tumours after 3–4 weeks in 37 of 92 (40%) InvEE mice compared to no tumours in 40 (0%) wild-type litter-mates (p<0.0001). The percentage of wound-induced tumours in bone-marrow chimeras of InvEE/InvEE and InvEE/MyD-88-/- was 40% and 8% respectively (p<0.005). Resident inflammatory cells demonstrated differential responses to wounding in InvEE/MyD-88-/- chimeric skin. Conclusions: This study demonstrated that inhibition of IL-1 alpha signalling from MEK1-activated keratinocytes prevented tumour formation in a chronic inflammatory microenvironment.

No significant financial relationships to disclose.
Successful changes in the diagnosis of earlier stages in invasive cervical cancer following a cancer detection program in Tucuman, Argentina
Authors: Zarba J. J. , Holgado S. V. , Segura M. Sanchez , Gonzalez A. , Audi V. , Elias A.
Published: March 2020

1544

Background: The PDCCUT provides annually free cancer screening to many low-income, underinsured women. Effective control of cervical cancer depends primarily on early detection of precancerous lesions and also on the diagnosis of earlier stages of invasive lesions through use of the Papanicolaou test, followed by timely evaluation and treatment. The goal of this study is to determine the impact of the PDCCUT on the stage at initial diagnosis of invasive cervical cancer. Methods:This is a retrospective, cross-sectional and exploratory study of data registered in CRRCGMT from 376 women with cervical cancer diagnosis. UICC/FIGO is the staging system used. Every 3 years -from 1985 to 2005- rates were calculated; also trend of stages I-IIa and IIb-IV were estimated. Patients-stages were analyzed, before and after 2001 (beginning of the program). Changes in cervical cancer rates before and after the introduction of organized screening were compared. Conclusion: The results showed a progressive increase in the diagnosis of earlier stages of cervical cancer indicating the impact of PDCCUT. The last trienium rate is coincident with the increase of citological diagnosis (Papanicolaou). A lower rate in the diagnosis of EIIb-IV stages is expected in the next trienium. Evaluation of clinical practice in a Cancer Program allows to improve asistencial quality.

[Table: see text] [Table: see text]

No significant financial relationships to disclose.
The accuracy of colposcopy in diagnostic and screening settings
Authors: Cantor S. B. , Cárdenas-Turanzas M. , Follen M. , Cox D. D.
Published: March 2020

1545

Background: We sought to determine the accuracy of colposcopy to diagnose cervical precancer in screening and diagnostic settings. Methods: As part of a larger clinical trial, 1850 patients were recruited into a diagnostic group or a screening group depending on their history of abnormal Papanicolaou smear results. For all patients, colposcopic examination was performed and biopsies were obtained from abnormal and normal colposcopic sites. The gold standard of test result accuracy was the histologic report of biopsies. Results: The diagnostic group had a 29.0% prevalence of high-grade squamous intraepithelial lesions (HGSIL) or cancer, and the screening group had a 2.2% prevalence of HGSIL or cancer. Using a disease threshold of HGSIL or worse, the diagnostic group had a sensitivity of 71.4% and a specificity of 81.3%, and the screening group had a sensitivity of 19.1% and a specificity of 96.1%. The areas under the receiver operating characteristic (ROC) curves for the diagnostic and screening groups at the same disease threshold were 0.854 and 0.511, respectively. Conclusions: We demonstrated that colposcopy performs well in the diagnostic setting and poorly in the screening setting. Colposcopy should not be used for the screening of cervical intraepithelial neoplasia.

No significant financial relationships to disclose.
Tobacco use among individuals presenting for cancer risk assessment
Authors: Shen W. , Ross L. F. , Patrick-Miller L. , Olopade O. I. , Cummings S. A. , White M. A. , Dudlicek L. , Bradbury A. R.
Published: March 2020

1547

Background: An important component of cancer risk assessment (CRA) is the evaluation of exposures and preventive health behaviors. Tobacco use (TU) remains a significant contributor to cancer risk and decreasing tobacco use is a major national health objective. Methods: Clinical charts were reviewed to evaluate the incidence of TU and characteristics of tobacco users (TUs) among individuals presenting to the University of Chicago Cancer Risk Clinic for cancer risk assessment (CRA). Results: Among 98 individuals (97% female) presenting for CRA from 12/05–10/06, 51% (50/98) reported no TU, 38% (37/98) reported prior TU and 11% (11/98) reported current TU. Current tobacco users included 10% (7/73) of whites and 18% (4/22) of blacks with no TU among other racial groups (0/3). 45% of TUs (5/11) had a personal history of cancer. 45% of TUs reported compliance with self-breast examination, 73% with cervical cancer screening. Among TUs over 40 years old (YO), 67% (6/9) reported a mammogram in the last year and the 2 TUs over 50 YO reported a screening colonoscopy. All TUs reported interest in tobacco cessation interventions. Conclusions: Tobacco use among individuals presenting for CRA is lower than reported general population rates of TU (23%). Despite this, a proportion of individuals presenting for CRA report current TU, despite engaging in other cancer prevention behaviors. Continued review of clinical encounters from 2004- 06 (n=425) will allow for multi-variate analysis of predictors of current TU, which will inform future research employing cancer risk assessment encounters as “teachable moments” to optimize tobacco cessation outcomes.

No significant financial relationships to disclose.
Frequency and accuracy of the first-degree family history of cancer in a community-based sample of women with low literacy in the South of Brazil
Authors: Roth F. L. , Bochi C. , Palmeiro E. I. , Kalakun L. , Callefi M. , Giugliani R. , Prolla P. A.
Published: March 2020

1549

A positive family history (FH) in first-degree relatives (FDR) is one of the most important risk factors for breast cancer. However, there are few published studies about its prevalence in community-based samples. The aim of this study was to evaluate the prevalence of first-degree cancer FH in an unselected sample of low-literacy women recruited in primary-care health centers through an interview and questionnaire. Accuracy of self- reported cancer history in a FDR was also evaluated. Of 6514 women, 4.5% were illiterate and 66% had elementary education. When asked about cancer FH, 23.3% had at least one FDR with cancer. The accuracy of reported FDR history was evaluated by telephone 12 months after the initial interview. Of the 1516 women reporting at least one FDR with cancer, a random telephone contact was made with 710 (46%). In 88% of the patients, the history reported by phone was exactly the same as the one reported initially. In addition, 29 of 710 patients contacted by phone denied cancer history in FDR. In 7.9% of the patients, FDR history of cancer was confirmed, but one of the following inconsistencies in relation to the original report was described: the type of cancer was different or the relative affected was different. We conclude that a significant proportion of women report history of cancer in a FDR accurately, despite of low literacy. These findings have considerable relevance to clinical practice and are important to validate FH taking in cancer risk estimation models that use this variable.

No significant financial relationships to disclose.
Classification of renal cell carcinoma (RCC) based on the expression of VEGF and its receptors on tumor cells and microvessels: Identification of subsets with distinct patterns of expression, microvessel density, and outcome
Authors: Camp R. L. , Siddiqui S. F. , Kelly W. K. , Uchio E. , Kluger H. M.
Published: March 2020

15503

Background: The recent development of anti-angiogenic therapy for RCC has significantly improved the treatment of these often refractory tumors. However not all patients respond to therapy and assays for predicting outcome are needed. As a first step, we analyzed a retrospective cohort of tumors and assessed the ability of VEGF and VEGF receptors (VEGF-Rs) to classify tumors. Methods: Tissue microarray analysis of 330 RCC (clear cell = 234, papillary = 46) was performed using a novel method of Automated Quantitative Analysis (AQUA) of VEGF and VEGF-Rs (R1, R2 & R3) expression by fluorescent immunohistochemistry. The expression of VEGF and VEGF-Rs were separately quantitated within tumor cells, endothelial cells, and adjacent normal epithelium. Expression was recorded on a continuous scale and represents the average of two histocores. Results: VEGF and VEGF-Rs exhibited distinct expression patterns on tumor cells, tumor endothelium, and adjacent normal tissue. Within each component, expression of VEGF and its receptors was tightly correlated (all p-values < 0.001). Although tumor cell expression of VEGF did not correlate with microvessel density (p- value = 0.1848), tumor cell expression of R1 and R2 were strongly and inversely correlated with microvessel density [p-values <0.0001]. Unsupervised hierarchical clustering classified tumors according to the coordinated expression of VEGF and VEGF-Rs within the three tissue components - tumor (T), normal (N), and vessel (V). Tumors were classified into 5 clusters: 1) high T, N & V; 2) low T, high N & V; 3) high T, low N & V; 4) low T, N & V; and 5) high T & N for R3 only. Of these, clusters 1 and 3 exhibited poor survival, whereas clusters 2 and 4 contained tumors with high vessel densities. The distribution of clear cell and papillary tumors was not significantly different between clusters. Conclusions: VEGF and its receptors exhibit a complex pattern of coordinated expression in RCC. Clustering of tumors based on VEGF and VEGF-R in tissue components may provide a prognostic assay as well as a means for determining which tumors will respond to what anti-angiogenic therapies.

No significant financial relationships to disclose.
Identification of ABCA5 as a tissue and urine diagnostic marker for PIN
Authors: Stearns M. E. , Hu Y. , Wang M. , Veverka K. A.
Published: March 2020

15508

Background: Bostwick and colleagues have suggested that prostatic intraepithelial neoplasia or PIN is the precursor of prostate cancer, and that a significant percentage of men with PIN develop prostate cancer (Sakr, 1994; Bostwick, 1995b; Arakawa, 1995; Qian, 1995; Qian, 1997). Currently there are no molecular diagnostic markers for PIN. Methods: Recently, we have developed ‘DNA-protein’ binding assays for the identification of novel transcriptional regulatory proteins associated with PIN glands. Electrophoretic mobility shift assays (EMSAs) with the 32P-labeled DNA probe was used for analysis of protein extracts from tissues and urine. Immunolabeling was carried out with rabbit antibodies specific for ABCA5. Results: Electrophoretic mobility assays (EMSAs) revealed that 1 DNA sequence (1 of 4,096 sequences screened) specifically bound a ∼160 Kda protein which was over-expressed in PIN and not found in BPH, SV or PCA glands (n=11). The gene encoding for the 160 Kda protein was cloned from a cDNA expression library by ‘in situ’ hybridization assays with the 32P-labeled DNA sequence. Sequencing revealed that the gene encoding for the 160 Kda protein was ABCA5, a member of the superfamily of ATP-binding cassette (ABC) transporters of multi-drug resistant genes. RT-PCR assays indicated the mRNA was over-expressed in PIN tissue, and was not present in BPH, or SV tissue. Rabbit polyclonal antibodies and immunolabeling showed that the antibodies specifically labeled the cell junctions of 3% glutaraldehyde fixed prostate cells. Immunohistochemistry indicated that ABCA5 was over expressed in foci of intermediate basal cells in normal glands, and in HGPIN. ABCA5 was faintly expressed in PCA glands. Enzyme linked immunoabsorbent assays (ELISAs) demonstrated in blinded studies that ABCA5 was a highly sensitive (>98% sensitivity) urine diagnostic marker for HGPIN in biopsy positive patients (n=107) at a cut off” of 25 ng/ml. ABCA5 was present at very low levels (i.e. <25 ng/ml) in the urine of patients diagnosed with BPH (n=79) or prostatitis or kidney and bladder cancer (>86% specificity). Conclusions: The data suggest that the expression of ABCA5 is over-expressed by PIN and may be a highly sensitive and specific urine diagnostic marker for detection of early stage prostate cancer.

No significant financial relationships to disclose.
Correlation of preoperative citology/histology in radiologically detected lesions and histologic findings at excision
Authors: Manente P. , Vicario G. , Scelzi E. , Sartor L. , Nicolardi L. , Rizzo A. , Pinarello A. , Spaliviero B. , Sbeghen R.
Published: March 2020

1552

Background: The major techniques used to diagnose breast abnormality has been for many years fine-needle aspiration (FNA) cytology and core needle biopsy (CNB) and more recently vacuum-assisted core biopsy (VACB). These techniques are accurate and allow definitive therapeutic surgery. The aim of our study was to detemine whether cytology/histologic findings mach histologic findings at excision. Methods: In our Institution, between January 2004 and June 2006, 43,138 mammographic exams were performed. 1,012 patients had patological lesions at mammography: 617 FNA cytology ( C due to European guidelines for breast cancer screening assessment) and 395 CNB/VACB (B) were performed. Patients with respectively suspicious and malignant FNA cytology (C4 and C5) and respectively uncertain malignant potential, suspicious and malignant histology (B3, B4 and B5) underwent to surgery. Results: The number of cancer identified by FNA cytology was 158 and the number of cancer identified by CNB/VACB was 253. The correlation of preoparative citology/histology with definitive histology had showed: false negative rate respectively 0.79% for histology (B) and 3.16% for cytology (C). False positive rate was respectively 0.4% for B and 0.63 for C. Complete sensitivity was 98.2% for B and 89.87% for C. Absolute sensitivity was 90.51% for B and 76.58% for C. Conclusions: Our data demostrated very high performance of diagnostic preoperative procedures due to multidisciplinary approach between the radiologists, the clinicians and the pathologists.

No significant financial relationships to disclose.
Phase II trial of 177Lutetium radiolabeled anti-prostate-specific membrane antigen (PSMA) monoclonal antibody J591 (177Lu- J591) in patients (pts) with metastatic androgen-independent prostate cancer (AIPC)
Authors: Bander N. H. , Nanus D. M. , Milowsky M. I. , Morris M. J. , Jeske S. , Vallabhajosula S. , Goldsmith S. J.
Published: March 2020

15523

Background: A phase 1 trial of 177Lu-J591 in pts with metastatic AIPC demonstrated acceptable toxicity, excellent targeting of metastatic sites and biologic activity. Methods: Pts with progressive, metastatic AIPC receive one dose of 177Lu-J591 in two- cohorts: cohort 1 (65 mCi/m2), 15 pts; cohort 2: (70 mCi/m2), 17 pts. The primary endpoint is PSA and/or measurable disease response; secondary endpoint is toxicity. A 177Lu-J591 imaging study is done to confirm tumor targeting. Results: 21 pts (8 chemo-naive), median age 73, have been treated to date, 15 in cohort 1, 6 in cohort 2. Two pts with bone-only metastases achieved PSA declines of >50%. One had an 87% PSA decline lasting 126 days with resolution of bone pain. A 2nd pt has a PSA decline of 58% that continues without progression at 6 mo post-rx. PSA stabilization (<25% PSA rise above baseline) occurred in an additional 9 pts (43%), 7 through wk 8 (1 of whom is still under follow-up) and 2 pts through wk 12. Of 7 pts with measurable disease, 6 have had post-rx CT scans completed, 3 were stable, 3 progressed. In these pts with measurable disease, PSA was more likely to diagnose progression, with only 1 stable and 5 progressed by PSA criteria. Platelet nadir <20 x 10e9/L occurred in 6 pts, 3 of whom required platelet transfusions (mean = 2). 17/19 evaluable pts recovered normal platelet counts; the remaining 2 pts had rapidly progressive disease, 1 of whom had biopsy confirmed marrow replacement by tumor. Neutropenia </= 0.5 x 10e9/L occurred in 4 pts, 2 of whom received brief rx with growth factors. All 19 evaluable pts had normal neutrophil recovery. No significant drug-related non-hematologic toxicity has occurred. Targeting of known sites of PC metastases has been observed in all pts. Conclusions: Single dose 177Lu-J591 demonstrates anti-tumor activity in pts with progressive, metastatic AIPC with reversible myelosuppression. Accrual is continuing.

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