bluuebunny/crossref_metadata_2025_split huggingface dataset:
New approaches to cancer prevention—preventive medical examination of patients from the high-risk pre-cancer registry
Authors: Lazarev A. F. , Petrova V. D. , Sinkina T. V. , Terekhova S. A. 
Published: March 2020

1546 Background: Such methods of cancer prevention as checkup in rooms for seeing patients’ examination, mass prophylactic examination, screening tests, which are currently in use in Russian Federation, are able to provide detectability of malignancies no more than 0.1%. The research objective was to increase the effectiveness of cancer detection by means of forming of the high-risk pre-cancer registry. Methods: With the help of multivariative analysis the patients with the high risk of malignancies (80–100%) were selected for the high-risk pre-cancer registry. It included patients with obligatory precancerous lesions (531), victims of radiation catastrophes (1024), members of ‘cancer’ families (1833) and patients cured from polyneoplasia (386). All of them were examined, got diagnostic procedures, treatment and rehabilitation according to specially designed schemes. Results: All patients with obligatory precancerous lesions underwent surgery. In 2003–2006 among them there were 23 (4.3%) cases of cancer revealed - 22- in I stage, 1 - in IV stage. In the group of patients from cancer ‘families’ in 2003–2006 69 (3.8%) cases of cancer were revealed - 67 (97.2%) in I and II stages, 2 - in III stage. Among the victims of radiation catastrophes in 2003–2006 there were 28 (2.7%) cases of cancer revealed - 26 (92.8%) in I and II stages, 2 - in III stage. General detectability of cancers among the patients the high-risk pre-cancer registry was 3.2%, the share of early stage (I and II) cancers- 95.9%, cancers in III stage - 4.1%, and there was only 1 case of cancer in IV stage (1.1%) revealed. Besides 65 cases of cancer in situ were detected among the patients of the registry. Conclusions: Preventive medical examination of patients from the high-risk pre-cancer registry makes it possible to increase the effectiveness of detection of precancerous lesions and early cancers. No significant financial relationships to disclose.
Clinical experience with the new manual and automated large core biopsy systems based on a rotational cutting on a helix
Authors: Janssens J. P. , Rotenberg L. , Sentis M. , Schultz-Wendtland R. 
Published: March 2020

1550 Background: Survival from breast cancer has increased significantly in recent years mainly as a result from better imaging techniques, earlier detection and improved tissue sampling. Newer technologies should improve existing biopsies because major drawbacks, including tumor cell displacement, preclude women and physicians to biopsy suspect lesions. A new large core biopsy device with a direct frontal approach, lesser side effects, less sampling needs, lower costs and improved yields has been evaluated in clinical practice. Methods: The results of 70 subsequent transdermal biopsies with rotational cutting on a helix are evaluated with regard to quality of the sample, patient satisfaction and completeness of diagnosis. The patients with a suspect lesion in the breast are selected in an oncological practice. Malignancy was verified by subsequent excision of the lesion. Attention was given to tumor cell displacement. Benign disease was verified by the subsequent clinical course. Results: In 69 patients at least one high quality sample with an average length of 1.8 cm and 0.3 cm diameter could be obtained. One patient refused the procedure. The average number of biopsy cores needed to obtain a reliable diagnosis was 1.5 (mininum 1 - maximum 5). No complication was noted with regard to pain, hemorrhagy, infection or other wound problems. 64 patients quoted the procedure as relative pain free. In 69 patients the diagnosis was complete with regard to the diagnosis of malignancy or benign disease. No destruction, biopsy artefacts or cell displacement was noted on histopathology. In all diagnoses with malignancy the grade of the tumor could be reliably given as well as steroid receptor content and HER2 immunohistochemistry. FISH-HER2 tests were possible in all HER2 positive tumors. Automated biopsies with vacuumassistance had slightly larger samples compared to the manual technique. Conclusions: The new large core biopsy technique with a rotational cutting on a helix performs well in clinical practice. All developmental goals with regard to quality of sample, patient satisfaction and cost price per biopsy have been met. Large core biopsies are now available for a larger population of women at risk for breast cancer with less risk of complication. No significant financial relationships to disclose.
Impact of PSA decrease at the end of radiotherapy for localized prostate cancer on clinical recurrence and specific cause survival
Authors: de Crevoisier R. , Messai T. , Plantade A. , Slimane K. , Eschwege F. , Koscielny S. , Bridier A. , Wibault P. , Fizazi K. 
Published: March 2020

15501 Background: The objective was to identify early predictors of outcome in a large retrospective series of patients treated by external beam radiotherapy only (without androgen deprivation). All the patients had a PSA at the 6th week (PSA6wRT) in the course of RT. Methods: From 1990 to 2004, 409 pts with localized prostate cancer were treated by RT. Median pretreatment PSA (PSApreRT) was 13 ng/mL (0.5–133). Clinical stage was T1 (26%), T2 (60%), and T3 (14%). Gleason score was 4–6 (59%), 7 (31%) and 8–10 (10%). Prognosis was classified as low risk (24%), intermediate (39%) and high risk (37%). The prostate received 65 Gy (2.5 Gy/day) (34%) or 70 Gy (2 or 2.5 Gy/day) (66%). Results: The median follow-up was 57 months (6–190). The median ratio of : PSA6wRT / PSApreRT was 71% (1–374). The 5-year biochemical disease free survival (DFS) rates (RTOG-ASTRO 2006) by PSA6wRT / PSApreRT < 71% or ≥ 71% were: 66% (95% CI: 58–74) and 56% (95% CI: 48–64), respectively (Log rank, p=0.048),. The 5-year clinical (local or metastases) DFS rates by PSA6wRT / PSApreRT < 71% or ≥ 71% were: 96% (95% CI: 93–99) and 85% (95% CI: 79–91), respectively (p=0.03). In multivariate analysis, the prognostic values of PSA6wRT / PSApreRT (as a continuous variable) on biochemical DFS, clinical DFS and cause specific survival are shown in the table . Conclusions: The PSA6wRT / PSApreRT predicts for biochemical DFS, clinical DFS and cause specific survival in localized prostate cancer. This factor could be used to propose adjuvant treatment after radiotherapy, in case of high: PSA6wRT / PSApreRT. [Table: see text] No significant financial relationships to disclose.
A phase II study of paclitaxel and vinorelbine (Pac-Vin) in hormone-refractory metastatic prostate cancer (HRPC): A final update
Authors: Sewak S. , Kosmider S. , Ganju V. , Woollett A. , Le B. , Yeo E. , Henry M. , Bell R. 
Published: March 2020

15505 Background: Phase 2 trials of Paclitaxel + corticosteroid or Vinorelbine + corticosteroid have shown 20–40% PSA responses. Preclinical models have shown synergy between Paclitaxel and Vinorelbine. A phase I trial showed this to be a tolerable combination. Methods: The aim of this study was to determine the efficacy and safety of Paclitaxel and Vinorelbine. 30 castrate pts with progressive, metastatic prostate cancer were enrolled. Previous radiotherapy, strontium therapy, 1 line of chemotherapy, and concurrent bisphosphonate therapy were allowed. Pts were treated with Paclitaxel 40 mg/m2 (1 hr), and Vinorelbine 20 mg/m2 iv on day-1 & day- 8 of a 21-day cycle. All pts received standard premedication for Paclitaxel including dexamethasone. Results: Baseline pt characteristics were: median ECOG PS of 1 (range 0–2), median age 70.5, mean PSA 413 ng/mL, mean Hb 11.9 g/dL. For 10 pts with measureable disease the partial response rate was 20%, with 70% of pts achieving stable disease (SD). Of 30 assessable pts, 20% had a 50% or greater decline in PSA, and 63% SD, maintained for at least 4 weeks. Median overall survival was 9.7 months. Median progression free survival was 5.1 months. All pts completed quality of life (QOL) questionnaires. Patient’s pain, fatigue, appetite, constipation, and mood improved after 3 cycles of therapy, however, statistical significance was not reached. Grade 3&4 toxicities were: neutropenia 8%, febrile neutropenia 4%, infection 2%, anemia 3%, lethargy 1%, and somnolescence 1%. 1 pt died as a result of neutropenic sepsis. Conclusions: In this poor prognostic cohort of pts (where 17% of pts had received 1 prior chemotherapy regimen) the combination of Paclitaxel and Vinorelbine is a tolerable regimen, which has demonstrated a 20% PSA response. The majority of pts achieved PSA stability. There was similar rate of objective response to this regimen and importantly it stabilized disease in a majority of pts. Furthermore, QOL parameters such as pain were improved. This regimen is one that requires further testing in a poor prognostic cohort of HRPC pts. No significant financial relationships to disclose.
11C-coline-positron emission tomography/computerized tomography (C-PET/CT) for tumor localization of locally recurrent prostate cancer after radiation therapy
Authors: Sahi D. , Ohlmann C. , Pfister D. , Engelmann U. , Heidenreich A. 
Published: March 2020

15519 Background: Radical salvage prostatectomy (sRPE) represents one local secondary treatment option with curative intent in patients failing radiation therapy for localized PCA. C-PET/CT is an innovative imaging technique for the evaluation of PCA. It was the purpose of our study to assess the sensitivity of C-PET/CT to predict local intra- and extraglandular extent of PCA and the presence of lymph node involvement. Methods: 45 patients with biopsy-proven locally recurrent PCA scheduled for sRPE underwent preoperative C-PET/CT. All patients underwent retropubic sRPE with extended pelvic lymphadenectomy. The prostatectomy specimens were processed according to the Stanford protocol and pathohistological results were compared to C-PET/CT findings. Intraglandular location of cancer nodules = 5mm was correlated with PET/CT findings. Results: A total of 45 patients underwent sRPE; mean preop. serum PSA was 7.8 (2–24) ng/ml; mean biopsy Gleason score was 5.6 (4–9). A mean of 19 (10 - 32) lymph nodes were removed. Pathohistology showed stage pT1–2pN0 in 27 (60%), stage pT3a/b and pTxpN1 PCA in 9 (20%) and 9 (20%) of patients, respectively. Positive surgical margins were identified in 5 (11%) patients. C-PET/CT identified 1, 2, 3 or more than 3 intraprostatic cancer nodules in 23 (51.1%), 13 (28.9%) and 9 (20%) patients, respectively. Correlation of prostate biopsy findings with PET/CT findings demonstrated a sensitivity of 90% for PET/CT. There was a low sensitivity for PET/CT detecting lymph node metastases. A positive uptake was identified in 14 (31.1%) patients; pathohistology revealed positive lymph nodes in 9 patients with only 4 patients exhibiting positive 11C-choline uptake and 5 patients having demonstrated a negative preoperative PET/CT scan. Conclusions: C-PET/CT is a valuable imaging modality for the detection of locally recurrent prostate cancer after radiation therapy. Due to its high sensitivity it might replace prostate biopsy prior to sRPE and it might be of additional value in patients with a negative biopsy but a high suspicion of local recurrence. The value of PET/CT for the identification pN1 disease is of modest value and not reliable. No significant financial relationships to disclose.
Prognostic and biologic impact of molecular markers in papillary renal cell carcinoma
Authors: Riggs S. B. , Klatte T. , Seligson D. B. , Pantuck A. J. , Leppert J. T. , Lam J. S. , Zomorodian N. , Kabbinavar F. F. , Belldegrun A. S. 
Published: March 2020

15525 Background: Papillary renal cell carcinoma (PRCC) is the second most common histological subtype among patients undergoing surgery for kidney cancer, but the molecular profile of this entity is not well characterized. The goals of this study were (1) to evaluate differences in expression between type 1 and 2 PRCC, and (2) to analyze the prognostic impact of molecular markers. Methods: We examined clinicopathological and molecular parameters of 42 patients treated with nephrectomy with the final pathology being PRCC. A tissue microarray consisting of the tumor specimens was constructed. Immunohistochemical staining was performed with antibodies directed against CAIX, CAXII, CXCR3, Gelsolin, HIF-1a, Ki-67, Vimentin, EpCAM, p21, p27, p53, pS6, pAkt, PTEN, VEGF-A, VEGF-C, VEGF-D, VEGF-R1, VEGF-R2, and VEGF-R3. Staining was analyzed by one anatomical pathologist (DS) who was blinded to outcome. Mann- Whitney’s U-test was used to compare marker expressions between type 1 and 2. Endpoint was disease-specific survival (DSS). Expression cut-offs were detected by using recursive partitioning. The Kaplan-Meier curves were compared using the log-rank test. Results: At last follow-up, 21 patients (50%) had died including 12 (29%) of RCC. The median follow-up for the patients alive was 8 years. Type 1 PRCC had significantly higher expression of nuclear p27, nuclear pAkt, and p53 compared with type 2. Since none of these 3 markers provided prognostic information, survival analyses were performed together for both types. Using the cut-offs identified with recursive partitioning, higher expression of Ki-67 (p=0.02), lower gelsolin (p<0.001), lower p21 (p=0.01), higher cytoplasmic p27 (p=0.01), higher endothelial VEGF-A (p=0.01), lower epithelial VEGF-D (p=0.04), and lower endothelial VEGFR-3 (p=0.01) were adverse prognostic factors. Conclusions: Out of 19 molecular markers, a specific molecular profile for PRCC was identified. pAkt, p27, and p53 can assist in subdividing type 1 and type 2 PRCC. Ki-67, gelsolin, p21, p27 and proteins of the VEGF family were found to be important prognostic factors among these patients. Although prognostic relevant, the VEGF proteins cannot be used to differentiate type 1 and 2 PRCC. No significant financial relationships to disclose.
A phase I study of bevacizumab in combination with sunitinib in advanced solid tumors
Authors: Cooney M. M. , Garcia J. , Brell J. , Dreicer R. , Beatty K. , Mekhail T. , Bukowski R. , Zwiebel J. , Remick S. C. , Rini B. I. 
Published: March 2020

15532 Background: Bevacizumab is a humanized monoclonal antibody that binds to all biologically active isoforms of human vascular endothelial growth factor (VEGF). Sunitinib is a potent tyrosine kinase inhibitor of VEGFR-2, PDGFR, KIT, and FLT3. This phase I trial of bevacizumab and sunitinib was undertaken to determine the maximal tolerated dose (MTD), dose-limiting toxicity (DLT), and to evaluate for any tumor response for this novel combination. Methods: Patients (pts) with advanced solid tumors, ECOG performance status 0 or 1, and having adequate organ function were eligible. Patients received bevacizumab IV on days 1, 15, and 29 of a 42 day cycle. Sunitinib was given for 28 days with a 14 day rest. DLT was defined as any grade 4 toxicity, grade 3 cardiac event, hypertension not controlled to < 160/90 mmHg with medication, or proteinuria > 3.5 gm/24 hours. Results: Nine patients, 6 male and 3 female, with tumor types including renal carcinoma (2), bladder (2), pancreatic, testicular, melanoma, gastric, and neuroendocrine were enrolled. The median patient age was 55 years (range 37 to 83). Median number of prior systemic therapies was 2 (range 0 to 3). A total of 15 cycles have been administered (cycles range 1 to 4). Grade 1 or 2 toxicities that occurred with a > 20% incidence included anorexia, bleeding, diarrhea, dyspnea, fatigue, fever, hypomagnesemia, nausea, pain, vomiting, and weight loss. Grade 3 toxicities included hypertension (3 pts), fatigue and hypokalemia (2 pts) and one episode each of hand-foot syndrome, and hypophosphatemia. At the dose level bevacizumab 3 mg/kg and sunitnib 25 mg/day no DLTs were observed. One patient experienced DLTs of grade 4 hypertension and headache at the dose level of bevacizumab 5 mg/kg and sunitinib 37.5 mg/day. This dose level has expanded to six patients and toxicity assessment is continuing. One patient with papillary renal carcinoma has an unconfirmed partial response and three patients have experienced stable disease. Conclusions: Enrollment and toxicity evaluations are ongoing. DLTs of headache and hypertension have occurred. This trial will determine the maximal tolerated dose of this novel anti-angiogenic combination for future renal cell carcinoma studies. Supported by the NCI/Clinical Therapeutic Evaluation Program Grant U01 CA62502. No significant financial relationships to disclose.
A phase II trial of 13-cis retinoic acid, interferon, docetaxel, and estramustine (RITE) for the treatment of hormone refractory prostate cancer (HRPC)
Authors: Mehta A. , Stein M. N. , Goodin S. , Doyle-Lindrud S. , Todd M. , Rubin E. , White E. , Jeyamohan C. , Metzger D. , DiPaola R. S. 
Published: March 2020

15542 Background: Efficacy of chemotherapy for the treatment of HRPC is limited secondary to the development of multiple mechanisms of resistance. In our prior studies, we demonstrated the safety and activity of docetaxel (T) 40 mg/m2 given with 13-cis retinoic acid (R), interferon alpha (I) and estramustine (E), along with a decrease in the expression of the anti-apoptotic protein Bcl-2. To test whether this regimen had clinical activity in HRPC, we conducted a phase II trial with the combination of these drugs. Methods: Eligible patients (pts) received 13-cis retinoic acid 1 mg/kg on days 1 to 4, interferon alfa 6 million units/m2 on days 1 to 4, estramustine 280 mg three times a day on days 1 to 5, and docetaxel 40 mg/m2 on day 2, all repeated every 21 days. Pts had peripheral blood mononuclear cells (PBMCs) obtained prior to therapy and on days 2 through 4 of the first cycle to assess the effect of therapy on the expression of Bcl-2. Results: Nineteen of 20 registered pts (mean age 66) have been treated in this trial. The median pre-treatment PSA was 33.3 ng/mL. A PSA decrease was seen in 13/19 pts (68%) with a mean decrease of 50.3%. A PSA decrease ≥ 50% was seen in 7/19 pts (37%), with an average PSA decrease of 70.4% in these pts. One patient had an objective response (partial remission). The median time to progression (TTP) was 16.3 weeks (range: 3.1 - 132.6 weeks). Three pts remain on study with a median TTP of 25.1 weeks (range: 6.1 - 132.6 weeks). Grade 3 toxicities included 2 pts with hypophosphatemia, 1 patient with neutropenia, and 1 patient with flu-like symptoms. One patient experienced a pulmonary embolism and one patient had a portal vein thrombosis. Common Grade 2 toxicities included fatigue (21%), cytopenias (21%) and GI side effects (16%). There was no treatment-related mortality. Conclusions: These data support the efficacy of the RITE regimen, and the possibility of using alternative Bcl-2 modulating agents in combination with docetaxel in future studies. In addition, long term treatment with low dose docetaxel may be feasible. The assessment of an effect on PBMC Bcl-2 expression is ongoing. No significant financial relationships to disclose.
Predictive value of PSA halving index (PSAHI) in patients (pts) with hormone refractory prostate cancer (HPRC): Results from a randomized phase II trial with docetaxel (D) ± estramustine phopshate (E)
Authors: Sava T. , Comploj E. , Fariello G. , Zustovich F. , Segati R. , Sacco C. , Perin A. , Mandarà M. , Cetto G. , Caffo O. 
Published: March 2020

15548 Background: D-based chemotherapy represents the standard treatment for HRPC pts. For several years PSA has been considered as a surrogate endpoint for studies involving pts with HRPC. The possibility of predicting a clinical advantage through the biochemical response rate is controversial. The PSAHI may represent a predictive parameter more than the simple PSA trend. We retrospectively evaluated the role of PSAHI in a consecutive series of patients affected by HRPC and treated in a randomized phase II trial with D±E. Methods: 95 pts affected by HRPC were randomized to D 70 mg/m2 IV d1 q3w (arm A: 49 pts) or D 70 mg/m2 IV d1 q3w + E 280 mg/TID PO starting 1 day prior to D, for 5 consecutive days (arm B: 46 pts). The treatment continued until best PSA response achievement or PSA progression. PSAHI was calculated comparing basal value (the day before first D administration) with those reached after every cycle at 21, 42, 63 and 84 days: each median value was then correlated across all pts. Correlations were made with response, time to progression (TTP) and overall survival (OS). Results: Responses, in terms of PSA? >50% were: 40% in arm A and 75%in arm B with PSA normalization in 5% and 32% respectively. After a median follow-up of 17 months, 65 patients are died (31 in Arm A and 34 in Arm B). Progression free survival (biochemical) was 20 weeks in arm A and 30 in B. Median PSAHI was 2.1 (0.8–8.8) and resulted significantly related to response and TTP: pts with PSAHI less than 1 and more than 1 had a median TTP of 14 and 34 weeks respectively. Between the 4 PSAHI analyzed (after 21, 42, 63 and 84 day), those at 42 and, particularly, 63 day resulted statistically related to response, TTP and OS. After 3 cycles, the PSA decline (63-PSAHI) was highly predicyive of OS which was 63, 72 and 90 weeks respectively (p=0.03), for pts with PSAHI of less than 1, between 1 and 3 and more than 3. Conclusions: PSAHI seems to be highly predictive of TTP and OS. 63-PSAHI seems to be a good surrogate marker of D response and may help in discriminating pts who need to be further treated with D and those who do not. No significant financial relationships to disclose.
Health status in senior adult prostate cancer patients: Limits for active treatment and clinical trials inclusion
Authors: Droz J. , Albrand G. , Chaladaj A. , Fléchon A. , Terret C. 
Published: March 2020

15550 Background: Two-third of patients (pts) with prostate cancer are older than 70 years. Patients are likely to receive active treatments in the curative and palliative settings if they have good health status, moreover they are likely to be offered to participate to clinical trials. Health status evaluation is performed by Comprehensive Geriatric Assessement (CGA). Methods: We have prospectively performed a mini- CGA (Terret C, Expert Rev Anticancer Ther. 2004; 4 : 469–75.) in 69 patients with prostate cancer : 33% pts had localized disease, median age was 78.7 years (68–92). Mini-CGA was based on a careful clinical examination with analysis of physical function, nutritional status (MNA), functional domain (ADL, IADL), cognitive and emotional domains (MMSE, GDS), identification and grading of comorbid conditions (CIRS-G), and a medication review. Social and familial evaluations complete the procedure. Results: Dependancy: only 12% pts are fully independant for ADL and 11% for IADL; 20% pts experienced falls and 32% were at risk of fall. Cognitive functions and depression: 60% pts had normal cognitive funtions, 46% and 4% were moderately and deeply depressed respectively. Nutrition: 22% pts had severe weight loss, 23% were mal nourished and 41% at risk of denutrition. Comorbidities: median CISR-G score was 8 (3–12), 80% and 21% pts had at least one grade 3 and one grade 4 comorbidity respectively. The most frequent comorbidities were by decreasing order of incidence : psychologic, hematologic, endocrine and osteo-articular pathologies. Polymedication: median number of drugs taken by pts was 5 (0–14) and iatrogenicity was observed in 30% pts. A caregiver was identified in 83% pts and 16% pts were living alone. None of the pts were fully independant with no major comorbidity. Conclusions: Health status of prostate cancer patients older than 70 years must be evaluated with the objective to either tailor specific clinical trials or apply adapted standard treatments. Task forces of the International Society of Geriatric Oncology (SIOG) are on the process to establish specific guidelines for prostate cancer treatment in the senior adults and for selection of manageable CGA procedures. [Table: see text]