bluuebunny/crossref_metadata_2025_split huggingface dataset:
Trimodality treatment (TMT) for locally advanced esophageal cancer in Pakistan; Analysis of prognostic factors influencing survival
Authors: Syed A. A. , Jamshed A. , Muhammad B. , Azhar R. , Yusuf M. A. , Khan Y. I. , Ahmed Q. , Shehzad K. , Rehman K. , Faruqui Z. 
Published: March 2020

15185 Background: The prognosis of patients with locally advanced esophageal cancer is poor. TMT for locally advanced esophageal cancer is being utilized with increasing frequency. In this study, we investigate the prognostic factors influencing survival in patients with locally advanced esophageal cancer following TMT. Methods: The study included 22 patients with esophageal carcinoma treated between January 2003 and December 2005 at Shaukat Khanum Memorial Hospital and Research Centre. Median age was 49 years (range 26 - 68). There were 15 (68%) males and 7 (32%) females. All patients had EGD with biopsy and CT chest. Twelve (54.5%) had squamous cell carcinoma and 10 (45.5%) patients had adenocarcinoma. Five patients (23%) had tumour in the middle third and 17 (77%) had lower/gastroesophageal lesions. Preoperative radiation consisted of 50.4 Gy / 28 fractions with concomitant chemotherapy day 1 and 29 (Cisplatin 75 mg/m2 day 1 and infusional 5FU 1000 mg/m2 day 1–5). Esophagectomy was done at 6 - 12 weeks following chemoradiation. The pathologic down-staging was evaluated by the 5-score tumor regression grade (TRG) of Mandard. Results: Post TMT pathologic TNM stage was; Stage 0 in 8 pts (36%), stage II in 5 pts (23%) and stage III in 9 pts (41%). 13 (59%) pts had R0 and 9 (41%) pts had R1 resection. The 4-year disease free survival was 29% with a median survival of 19 months. The number of patients with TRG score 1, 2, 3, 4 and 5 were 7 (32%), 4 (18%), 5 (23%), 2 (9%) and 4 (18%) respectively. Tumor regression grade 1–2 (p=.0016) and negative circumferential margins >2 mm (p=.0019) had a positive influence on DFS. Age (< 50 vs ≥ 50 years), sex, hemoglobin at presentation (≤ 12 vs > 12 gm/dl), tumor site (middle vs lower/GE junction), pathological nodal status (node positive vs node negative) and histological subtype (squamous cell vs adenocarcinoma) did not influence survival (p= 0.92, p= 0.82, p= 0.69, p= 0.79, p= 0.41 and p= 0.32 respectively). Conclusions: TMT results in prolonged disease free survival in patients with complete response or microscopic residual foci (TRG 1–2). Positive or circumferential margins <2mm is associated with poor prognosis. No significant financial relationships to disclose.
Major changes in breast cancer incidence in the United States over the period 2002 to 2004
Authors: Ravdin P. , Cronin K. A. , Howlader N. , Berg C. D. , Feuer E. J. , Berry D. A. 
Published: March 2020

1533 Background: We have recently reported that a steep decrease in the incidence of breast cancer occurred in the United States in 2003 relative to 2002 (BCRT 100: S5, 2006). This decrease was most evident in patients older than 50, and largely occurred because of a decrease in the incidence of estrogen receptor positive breast cancer. This decrease occurred after the report in 2002 of the results of first of the Women s Health Initiative trials of postmenopausal hormone therapy (HT). This publication showed that use of a combined estrogen/progestin combination was associated with increased risk of breast cancer and heart disease and led to an immediate and substantial decrease in the use of HT in the US. Dramatic shifts in breast cancer incidence are unusual, and provide unique opportunities to test models that have been developed to explain trends in breast cancer incidence and mortality. We have been engaged in modeling trends in breast cancer incidence and mortality, in collaborative effects such as the Cancer Intervention and Surveillance Modeling Network (CISNET), to understand these and other processes (NEJM 353:1784–1792,2005). These models have practical implications for understanding the impact of changes in risk factors, use of prevention strategies, screening, and treatment of breast cancer. Methods: SEER public use incidence data from 1990 to the end of 2003 will be updated with information from the release in the spring of 2007 of incidence data for 2004. We will analyze the full data set through 2004 and report on the trends in incidence of breast cancer in the population as a whole and by subsets (such as age, estrogen receptor status, stage etc). We will also use the most recent and detailed data about HT use and screening mammography during this period as part of modeling. Results: We are awaiting SEER data from 2004 which will be released by April of 2007. Conclusions: Our first SEER based multi-year analysis of breast cancer incidence following the change in HT use in the US will be presented. Modeling of these trends in incidence will be discussed in the context of understanding the role of various contributors to the change in breast cancer incidence and what insights on the evolution of preclinical disease might be possible. No significant financial relationships to disclose.
Algorithm of monitoring of patients with family history of cancer as a method of cancer prevention
Authors: Petrova V. D. , Sinkina T. V. , Zarubina N. A. , Terekhova S. A. , Dimitriadi J. N. , Selezneva I. A. , Lazarev A. F. 
Published: March 2020

1542 Background: Existent genetic tests are not able to provide effective forecasting of all cancer sites and all those methods are generally expensive. At the same time approximately 50% of population has cancer susceptibility and 10% - hereditary cancer syndromes. The purpose of this study was to develop the algorithm of monitoring to provide effective forecasting and prevention of cancer in patients with hereditary cancer susceptibility. Methods: The algorithm of monitoring of patients with family history of cancer includes 2 stage: I - diagnostic, II - treatment and rehabilitation. In the I stage patients with 3 and more relatives by blood who had cancers of any site are revealed by oncologist. Their genealogical trees are analyzed by geneticist. All those patients are registered in the registry of “cancer”-families’ members, interviewed and got all the necessary diagnostic procedures with the following multivariative analysis (of more than 200 geno- and phenotypic characteristics). Patients with determined high risk of malignancies undergo deep clinical and instrumental examination, site-by-site searching for cancer, molecular genetic tests. In the II stage individual recommendations for the patients are developed, pretumour lesions are treated, preventative surgery is performed (resection of a target organ) and the measures for strengthening of anti-tumour resistance are taken. All the patients of the registry get the periodic health examination for term of life: preventive examination once per 6 months, multivariative analysis once per 3 years. Results: The registry of “cancer”-families’ members included 421 families - 1833 patients (232 men and 1601 women at the age of 28–74). In 2003–2006 there were revealed obligatory pre-cancer lesions in 637 patients, cancers in situ - in 45 patients, and cancers of different sites - in 69 patients (in I stage - 78.3%, II stage - 18.9%, III stage - 2.8%, IV stage - 0). Conclusions: This algorithm of monitoring of the patients from the registry of “cancer”-families’ members made it possible to provide high effectiveness of cancer prevention and early detection. No significant financial relationships to disclose.
Self-exam is the most common method of breast cancer identification
Authors: Rosenberg A. , Burke L. , Vos P. , Liles D. 
Published: March 2020

1543 Background: Breast cancer survival is improved by early diagnosis. The role of self-exam as an adjunct to screening mammography has been questioned as some studies suggest that self-examinations lead to unnecessary diagnostic procedures without improving survival. Methods: Patients who had been diagnosed with breast cancer and who were attending a university-based cancer clinic were interviewed, using a structured questionnaire, to determine the way in which their breast cancers were first identified. Inference was conducted using exact methods (Clopper-Pearson intervals for proportions and Fisher’s test for odds ratios). Results: Breast cancers were first identified by mammogram in 16% of women, by provider in 9%, by the spouse in 2%. Seventy-five percent (95% CI=61% to 85%) of patients first identified their tumors by self exam. Self-identifiers occurred in all demographic groups. These women included those with all types of insurance: private insurance (68%), Medicare (60%), Medicaid (100%), or no insurance (85%); all levels of education: 77% with college education and 75% with high school; all income levels: for example, among 79% with annual incomes of <$10K and 73% with incomes >$50K; and among both black (91%) and white (66%) women. Of the women who reported both regular mammograms and regular self-examination (N=35), 77% (95% CI=60 to 90%) were self-identifiers. However, cancers found by mammography were more likely to be Stage I than were those identified by self-examination (odds ratio=3.9, 95% CI .9 to 17.5, p=.047). Conclusions: Most breast cancers (75%) were found by self-examination, even among women who had regular mammography. We did not find any demographic factor that predicted mammography as the primary method of tumor identification. These findings suggest that self-examination remains an important method of breast cancer identification. No significant financial relationships to disclose.
Phase II multicenter, two-stage study of E7389 in patients with hormone refractory prostate cancer with advanced and/or metastatic disease stratified by prior chemotherapy
Authors: Molife R. , Cartwright T. H. , Loesch D. M. , Garbo L. E. , Sonpavde G. , Calvo E. , Das A. , Wanders J. , Petrylak D. P. , de Bono J. 
Published: March 2020

15513 Background: E7389 is a synthetic macrocyclic ketone derivative of the marine sponge product halichondrin B. A unique tubulin depolymerizer, E7389 induces nonproductive tubulin aggregates and inhibits tubulin polymerization. E7389 has demonstrated activity in refractory breast cancer and non small cell lung cancer with response rates of 14.7% and 9.7%, respectively. E7389 inhibits the growth of prostate cancer cell lines, including those (DU145) with over-expression of beta-tubulin III, which may confer resistance to taxanes. Methods: Phase II Simon two-stage study explores the activity and safety of E7389 as monotherapy without concomitant steroids in patients with histologically proven adenocarcinoma of the prostate that has progressed despite maintained castration. Patients are stratified into two groups that are analyzed separately, including those who failed either no prior chemotherapy (except mitoxanthrone or estramustine) or no more than one prior regimen with a tubulin binding agent, such as docetaxel. E7389 1.4 mg/m2 is administered as a 2 to 5 minute bolus IV infusion on Days 1 and 8 of 21-day cycles. PSA measurements are obtained at the end of each cycle. The primary objective is to assess PSA response using Bubley criteria. Results: Thus far, 57 patients (37 taxane pretreated and 20 taxane naïve) have been treated. The median age is 71 (range 48–91) with 43% of patients over 75. A total of 160 treatment cycles have been given (median: 2; range: 2–7). Twelve study drug related serious adverse events have been reported in 9 patients: PE (2), melena (2), fever, neutropenia, febrile neutropenia, UTI, anemia, DVT, chest pain, and renal failure (1). Based on preliminary data, the taxane-treated group has 2 PSA responses in the first 21 patients, and the taxane-naïve group has 4 PSA responses in the first 14 patients, allowing both groups to progress to Stage 2 with further accrual. Conclusions: In patients with hormone refractory prostate cancer, there is some evidence of single agent activity for E7389 in taxane naïve and taxane pretreated patients with acceptable toxicity. Preliminary results of activity allow further recruitment to proceed. [Table: see text]
Durable complete responses and near complete responses to sunitinib in metastatic renal cell carcinoma
Authors: Heng D. Y. , Rini B. I. , Garcia J. , Wood L. , Bukowski R. M. 
Published: March 2020

15514 Introduction: Sunitinib is a tyrosine kinase inhibitor with activity against VEGFR and PDGFR recently approved by the FDA for the treatment of advanced renal cell carcinoma (RCC). There is no existing literature that details complete responses (CRs) in patients taking sunitinib for metastatic RCC. Methods: Seventy-four patients with metastatic RCC receiving sunitinib at the Cleveland Clinic Taussig Cancer Center on clinical trials were reviewed to determine the number of patients with RECIST-defined CRs. Additionally, patients who achieved near-CRs defined as a greater than 90% reduction in composite tumor volume or residual disease of less than or equal to 1 cm were reviewed. Results: Two patients (2.7%) achieved a RECIST-defined CR lasting >15 months. The patients who obtained CRs had non-bulky pulmonary metastases, favorable or intermediate MSKCC risk profiles, were treated with sunitinib in the first-line setting and had a significant reduction in composite tumor measurements within the first two cycles. An additional 2 patients achieved near-CRs, including one patient that previously progressed on bevacizumab. These 2 near-CR patients remain progression-free for more than 19 months. Finally, 1 patient achieved sufficient downstaging and reduction of tumor volume such that the remaining lesion could be excised, resulting in a surgical CR. This patient is currently off sunitinib and remains progression-free 4 months after surgery. Conclusion: Sunitinib is capable of producing durable CRs in cytokine-naïve metastatic RCC patients with non-bulky pulmonary metastases. Additionally, near-CRs can be seen despite non-pulmonary metastatic sites and prior VEGF-targeted therapy. No significant financial relationships to disclose.
Is the natural history of prostate cancer different according to serum neuroendocrine profile?
Authors: Banu E. , Scotte F. , Banu A. , Medioni J. , Brizard M. , Levy E. , Oudard S. 
Published: March 2020

15536 Background: Elevated neuron-specific enolase (NSE) and chromogranine (CgA) values correlate with poor prognosis in prostate cancer (PC) patients (pts). They are correlated with the histological phenotype and a short hormone-sensitivity interval. The impact on the outcome was less explored. Methods: Eligible PC pts were required to have serial CgA and NSE specimens after the initial diagnosis in the venous blood, using commercial kits. Markers were defined as abnormal (+) or normal (-) with a threshold of 20,6 and 100 ng/mL for NSE and CgA, respectively. The endpoint was to evaluate the clinical impact of serum NSE and CgA on the natural history (NH) of the PC using the multivariate Cox regression analysis, stratified by Gleason score and adjusted by age at diagnosis. NH was calculated between the initial diagnosis and death or last follow-up for censored pts. Results: Blood samples were obtained from 213 PC pts, 53% with a metastatic hormone-refractory disease at the moment of the analysis. Seven, 36% and 10% of pts had either an abnormal NSE, CgA or both. Normal serum NSE and CgA were found in 47% of all pts and only in 35% of metastatic hormone-refractory PC pts. Median age was 64 years (range 41–82), 41% of pts had a Gleason score 8–10. Median NSE and CgA levels were 13.3 and 92 ng/mL, respectively. The median of the NH was not reached yet. The adjusted risk of death was multiplied by 3.1 for pts with abnormal NSE or/and CgA (HR=3.5, unadjusted for age). A borderline relationship was observed at the multivariate analysis between NH and the neuroendocrine profile ( Table ). Conclusions: NSE was the most powerful predictor of the NH in PC pts, regardless the moment of the rise during the NH. A systematic NSE and CgA assessment could be proposed for all pts. [Table: see text] No significant financial relationships to disclose.
Phase II study of single-agent vinflunine in platinum-refractory transitional cell carcinoma of the urothelium (TCCU)
Authors: Vaughn D. J. , Srinivas S. , Stadler W. M. , Pili R. , Petrylak D. , De Marco S. , Smith D. C. , Nason S. , De Wit E. , George C. 
Published: March 2020

15543 Background: Vinflunine (VFL) is a new microtubule inhibitor of the vinca alkaloid class with clinical activity in TCCU (S. Culine, BJC 2006). This trial was conducted to define VFL activity in platinum-refractory TCCU patients (pts). Methods: Multicenter, single-arm study. Primary endpoint: Objective response rate (Independent Review; WHO criteria). Planned sample size: 150 pts. Main pt eligibility: at least one measurable lesion; documented progression within 12 months of last dose of platinum-containing regimen; calculated creatinine clearance (Cr Cl) = 20 mL/min. VFL 320 mg/m2 IV infusion over 20 minutes was administered every 3 weeks. In pts with poor performance status, prior pelvic irradiation, or renal impairment (Cr Cl 20–60 mL/min), initial dose (ID) was 280 mg/m2, escalated to 320 mg/m2 if well tolerated. Results: Enrollment of 150 pts complete. Baseline pt characteristics (first 118 pts treated): Gender: male 78%, female 22%. Median age: 66 years (range 40–83). Renal impairment: 32%. Prior chemotherapy: cisplatin: 69%; carboplatin: 47%, gemcitabine: 94%. Total of 402 VFL cycles administered (range: 1–12). 320 mg/m2 ID: 35 pts; 280 mg/m2 ID: 83 pts. Main toxicity was hematologic (Grade (G) 3/4): neutropenia: 19%/37%; thrombocytopenia: 3%/0%; anemia: 13%/0%; febrile neutropenia: 320 mg/m2 ID: 5 pts; 280 mg/m2 ID: 3 pts. Main non-hematologic toxicities: constipation: 320 mg/m2 ID: 63% (G3/4: 14%/3%); 280 mg/m2 ID: 59% (G3/4: 12%/1%); fatigue: 320 mg/m2 ID: 43% (G3/4: 6%/0%); 280 mg/m2 ID: 35% (G3/4: 7%/0%). Severe diarrhea or vomiting was infrequent. No G3/4 peripheral neuropathy was noted. Responses have been observed by the investigators, but independent review is on-going. Conclusions: VFL has a manageable toxicity profile in pts with platinum-refractory TCCU. Independently reviewed response rate and other efficacy endpoints of the entire cohort will be presented. No significant financial relationships to disclose.
The role of neoadjuvant chemotherapy in muscle invasive bladder cancer and correlation of clinical outcome with translational studies
Authors: Hussain S. A. , Ward D. , Palmer D. H. , Barton D. , Veeranna V. , Porfiri E. , Martin A. , Wallace M. , James N. D. 
Published: March 2020

15551 Background The aim of this study was to investigate the outcome in patients with muscle-invasive bladder cancer (MIBC) receiving neo-adjuvant chemotherapy (neo-CT) prior to organ-preservation (chemo-radiation) or cystectomy. Additional translational studies were performed. Methods Patients with stage T2-T4, N0, M0 TCC bladder with calculated GFR =40ml/min were eligible. Neo-CT comprised gemcitabine (1,000 mg/m2 d1, d8, q21) plus cisplatin (35 mg/m2 d1, d8, q21) for 4 cycles . Following chemotherapy (CT) patients underwent surgery or radiotherapy (RT) with or without chemotherapy (CRT) treatment based on response to neo-CT and clinician and patient preference. Serial blood samples were collected for proteomic analysis. Results 20 patients have been recruited : 18 males 2 females; median age 70 years (range 47–86); stage T2; 9, T3A; 7, T3B; 4, all G3. 1 patient progressed before CT. 61 cycles of CT have been administered. Treatment has been well tolerated with only 1 neutropenic sepsis episode. 3 of 20 patients developed early progression and did not receive radical treatment. For the remaining 17 patients, choice of definitive treatment (surgery vs. RT/CRT) was based on response to neo-CT. 6 patients with residual disease at post-neo CT cystoscopy underwent surgery. 11/19 (58%) patients had a complete response (CR) to neo-CT, 9 of whom were treated by RT/CRT and 2 patients with pCR declined radical treatment (both alive at 10 and 19 months follow-up (FU)). At median FU of 12 months, 3/6 patients treated surgically and 2/9 patients treated by RT/CRT have died. 1-year survival by intention to treat analysis was 70%. We have used SELDI using the IMAC protein chip array to generate proteomic profiles of the patient sera collected to date. Although the number of samples is limited, the data suggest that there are changes in the pre- chemotherapy serum proteome of 3 patients that developed early progression (relative to 8 patients with CR to neo-CT ). Conclusions Neo-CT is active and well tolerated in MIBC. Proteomic profiling may further improve patient selection. Early data show serum proteome analysis can detect markers of early progression, and may therefore help select patients for different modalities more appropriately. Recruitment is ongoing. No significant financial relationships to disclose.
Effect of complementary alternative medical (CAM) therapy on tumor response, control and recurrence in prostate cancer patients (PCpts) treated with radiation therapy (RT)
Authors: Cain L. R. , Flynn J. , Kelly D. , Eden B. , Sumner M. , Anderson K. , Birdsall S. , Martin J. , Dounaevskaia L. , Alschuler L. 
Published: March 2020

15585 Background. CAM therapy in pts receiving RT has been questioned due to possible interference with oxidative mechanisms aimed at killing tumor cells. We addressed this controversy by analyzing tumor response, control and recurrence in PCpts treated with RT + CAM. Methods. The population consisted of 125 RT-treated PCpts with localized tumors: CAM cohort (n=69; median age=62.5 yrs; range=46–81); nonCAM cohort (n=56; median age=61.0 yrs; range=48–80). For the CAM cohort, 41%, 42%, 9% and 7% had T1c, T2a, T2b and T2c tumors respectively with 1 T3b tumor; for the nonCAM cohort, 39%, 38%, 14% and 7% had T1c, T2a, T2b and T2c tumors respectively with 1 T3a tumor. RT consisted of external beam therapy (4500–5000 cGy) in conjunction with high dose rate brachytherapy (600- 650 cGy/fraction x 2–3 fractions) administered over 6–8 weeks; this occurred for 65/69 CAM and 52/56 nonCAM pts. The remaining pts received either HDR monotherapy, tomotherapy, or IMRT + tomotherapy. In addition, 5/69 CAM and 2/56 nonCAM pts received hormonal therapy. CAM regimens included at least one antioxidant (range=1–7) including Green Tea Extract; Melatonin; and high-potency multivitamins. All pts were monitored ≥ 24 months post radiation therapy. Results. In the CAM cohort, median pretreatment PSA was 5.95ng; nadir PSA was 0.08ng; and last PSA was 0.18ng with median followup of 28.96 (range=24–46) months; 3 biochemical failures were seen at 6, 10 and 12 months. In the nonCAM cohort, median pretreatment PSA was 6.4ng; nadir PSA was 0.06ng; and last PSA was 0.166ng with median followup of 28.26 (range=24–43) months; 2 biochemical failures at 13 and 28 months with 1 death at 37 months were seen. Conclusion. Concomitant CAM treatment does not effect RT-mediated tumor response, control or recurrence rates in PCpts with localized disease. Neither the magnitude of the response or its durability for at least 2 years are negatively affected by CAM-based antioxidant supplements designed to improve patient tolerance and quality of life. Investigations in well-defined populations receiving consistent CAM regimens offer the opportunity to elucidate positive benefits for patient management. No significant financial relationships to disclose.