bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical efficacy and safety of apatinib in treatment of alpha fetoprotein-positive advanced gastric cancer.
Authors: Chen Jia , Chen Lingxiang , Yang Li , Zhu Chunrong , Liu Chaoying
Published: September 2018

e15513

Background: Alpha fetoprotein (AFP)-producing gastric cancer (APGC) is a minor subtype of gastric cancer (GC) with high malignancy, rapid progress, high metastatic rate and poor prognosis. Treatment of AFP-positive GC is not different from that of AFP-negative GC, but the efficacy can not match for the latter. Apatinib, a novel inhibitor of VEGFR-2, has achieved survival improvement in advanced GC patients. We aimed to evaluate the efficacy and safety of apatinib in AFP-positive advanced gastric cancer patients. Methods: This was a single-arm, open-label, exploratory study design. Eligibility criteria included histologically proven GC; patient age 18-75 years; AFP-positive; clinical stage III or IV; and ECOG performance status of 1 or 2. A history of receiving previous treatment was not required. All the patients were orally given apatinib at an initial dose of 500 mg (qd) until disease progression or death. Dose reduction to 250 mg was allowed. Results: A total of 16 pts including 15 males and 1 female were eligible. The median age was 62.5 years (range 26-74 years). Poorly differentiated adenocarcinoma was the main histological type, and the main metastatic sites were liver (12/16) and abdominal (2/16). Ten pts received gastric surgery and 13 had previous chemotherapy prior to apatinib, and 10 patients received chemotherapy along with apatinib. Among the 16 pts, 14 were available for the efficacy evaluation. Two pts achieved partial response (PR), 10 had stable disease (SD), and 2 had progressive disease (PD). The objective response rate (ORR) and the disease control rate (DCR) were 14.3% (2/14) and 85.7% (12/14), respectively. All pts were included for safety analysis. The incidence of adverse events (AEs) was 87.5%. Main AEs were bone marrow suppression (43.75%), hypertension (50%), and abdominal pain (31.25%). Conclusions: Administration of apatinib make clinical benefit to AFP positive advanced gastric cancer with a comparable disease control and tolerable adverse reactions. Clinical trial information: ChiCTR-OPC-16008295. Clinical trial information: ChiCTR-OPC-16008295.
Evaluation of survival outcome of gastric cancer with pathologic stage III according to the new eighth edition of the AJCC/UICC TNM classification.
Authors: Bando Etsuro , Makuuchi Rie , Kaji Sanae , Hikage Makoto , Irino Tomoyuki , Tokunaga Masanori , Tanizawa Yutaka , Kawamura Taiichi , Kinugasa Yusuke , Sugiura Teiichi , Uesaka Katsuhiko , Terashima Masanori
Published: September 2018

e15536

Background: Postoperative adjuvant chemotherapy with administration of S-1 for one year is standard treatment in patients with pStageII/III in Japan. However, survival outcome of patients with pStageIII remains unsatisfactory, so several attempt have been made to improve the survival in these patients. However, actual survival according to sub-classification in pStage III has not been elucidated. The eighth edition of the American Joint Committee on Cancer (AJCC) TNM postoperative staging for gastric cancer was published in 2016 and included major revisions of pStageIII. The aim of the current study was to evaluate the validity of the eighth edition TNM classification, especially in pStageIII for gastric cancer based on patients treated in single Japanese high volume cancer center. Methods: A total of 646 gastric cancer patients with pStageIII who underwent R0 resection from 2002 to 2016 were included. Prognostic value was analyzed for validation and compared TNM seventh edition. Results: Some improvement was observed in the separation of pN. Patients with pN3b (5-year survival rates = ysr; 13.4%) had the significant poor survival than those with N3a (5-ysr; 39.1%) (P < 0.001). In pStage III disease, clear survival distribution was observed in eighth edition [IIIA (N = 315); 5-ysr: 67.0%, risk ratio (RR) = 1 (reference), IIIB (N = 230); 5-ysr: 51.1%, RR = 1.694, P < 0.001, IIIC (N = 101); 5-ysr: 30.9%, RR = 2.771, P = 0.002], compared to seventh edition [IIIA (N = 233); 5-ysr: 69.3%, RR = 1;, IIIB (N = 230); 5-ysr: 53.8%, RR = 1.682, P = 0.001, IIIC (N = 183); 5-ysr: 38.7%, RR = 2.571, P = 0.004]. Conclusions: Survival outcome of pStageIIIC (T3-T4bN3b, T4bN3a) in eighth edition is very poor. So, more aggressive regimen should be planned for pStageIIIC gastric cancer in eighth TNM staging.
Combined hepatocellular carcinoma and cholangiocarcinoma: Debate for the ideal surgical option.
Authors: Chhatrala Hardik Satish , Shah Chintan , Kailasam Karthik , Yadav Lokesh , Chandana Sreenivasa Rao
Published: September 2018

e15644

Background: Current limited evidence from observational studies suggest lack of survival benefit from liver transplantation (LT) for combined hepatocellular carcinoma with cholangiocarcinoma (cHCC-CC) when compared to surgical resection. This is in contrast to hepatocellular carcinoma (HCC) which has clear survival benefit with LT. We hypothesized that cHCC–CC patients have similar overall survival (OS) after LT compared to resection. Methods: Localized HCC and cHCC–CC patients treated with surgical resection versus transplant were identified in SEER Database (1973–2013). Kaplan-Meier method was used to examine survival with LT versus resection. Results: In the total period between 1973-2013, we identified 9,306 (5496 [59.06%] resection, 3810 [40.94%] transplant) patients with HCC, and 175 (107 [61.14%] resection, 68 [38.85%] transplant) patients with cHCC–CC. 3-year OS of patients undergoing LT remains significantly greater for HCC than for cHCC–CC (80.5% vs 59.9%, P < 0.01). Interesting, for period 2008-13, 3-yr OS for cHCC-CC patients undergoing LT was better than resection, although the difference was not statistically significant (66.4% vs 46.27%, p > 0.10). While there has been improved 3-year and 5-year OS from period 2002-07 to 2008-13 after LT for localized HCC patients (83.6% vs 79.4%, p < 0.002 and 76.4% vs 73.6, p < 0.01, respectively), there has been no significant improvement in 3-year or 5-year survival after for HCC-CC (66.4% vs 65.2%, p < 0.4 and 58.3% vs 55.3%, p > 0.4 respectively). Conclusions: Over the past decade, 3-yr OS of cHCC-CC with LT remains dismal and has not improved. However, LT in patients with localized cHCC–CC may have a potential survival benefit over liver resection, although clearly lower than the survival benefit of LT for HCC. Our results argue for a randomized trial for LT versus resection for localized cHCC-CC patients to obtain better understanding of survival benefit from the two surgical options.
Do pancreas cancer stem cells play crucial role in survival outcome?
Authors: Askan Gokce , Sahin Ibrahim Halil , Capanu Marinela , Turkekul Mesruh , Yu Kenneth H. , Lowery Maeve Aine , Basturk Olca , Iacobuzio-Donahue Christine , O'Reilly Eileen Mary
Published: September 2018

e15721

Background: Recent studies indicate that pancreatic cancer stem cells (CSC) may predict disease behavior and survival outcomes of pancreatic ductal adenocarcinomas (PDACs) patients (pts). Several CSC markers have been reported in PDAC (Fitzgerald, TL, 2014). We herein evaluated the impact of CSC markers including CD44 and Epithelial Specific Antigen (ESA) on survival outcome of PDAC pts who had liver or lung metastasis after initial surgical resection (IR). Methods: Clinicopathologic features and survival of 59 PDACs were analyzed. Pts with IRB approval, and whom had available primary tumor tissue, were included. All neoplasms were immuno labeled with CD44 and ESA. Staining intensity was scored as weak (1), moderate (2), strong (3), while the staining pattern was scored as: few (1), patchy (2), and diffuse (3). The expression for CD44 and ESA was accepted positive if total score ≥4. Time from relapse to death (TRD) was estimated using the Kaplan-Meier method censoring patients that were alive at the last follow up. Survival curves were compared using the log-rank test Results: Of 59 pts, 42 (71 %) had liver, 10 (17%) had lung and 7 (12%) had both liver and lung metastasis. M/F = 34/25; mean age = 64.2 (range, 34-90). Patients were subcategorized as follows; thirteen cases were CD44 (+)/ESA (-) (group1) and 13 were CD44 (-)/ESA (+) (group 2). Eight (61.5%) of group 1 tumors and 2 (15.3%) of group 2 were poorly differentiated. At last follow-up, except one with 63 months survival, all pts died of disease with 23.3 months (range, 3-67) median OS. No significant difference in TRD was observed between group 1 (6.9 months) and 2 (13.8 months) (p = 0.62). However, we observed group 1 tumors had worse OS (12 months) compared to group 2 (36 months). Conclusions:A worse outcome trend was observed for pts with CD44 (+)/ESA (-), albeit not statistically significant and likely limited by small numbers. Further studies are warranted to evaluate the robustness of this observation.
Evolution of pancreatic cancer survival over the past two decades.
Authors: Mariotti Veronica , Parrondo Ricardo Daniel , Gonzalez Velez Miguel , Duma Narjust , Leslie Lori Ann , Gutierrez Martin
Published: September 2018

e15722

Background: Pancreatic cancer (PaCa) is a highly lethal disease, with a 5-year overall survival (OS) rate of approximately 6%, and a median OS of only 3–6 months (m). Despite recent improvements in surgical techniques and increased use of combination chemotherapy (CT), OS remains poor. This study aims to examine the factors that led to increased OS in PaCa patients (pts) over the past two decades in a single academic institution. Methods: All medical records of pts diagnosed with PaCa at the John Theurer Cancer Center from 1990 to 2012 were reviewed, and 916 PaCa pts were included in this analysis. We compared one group of pts diagnosed from 1990 to 2003 (G1, n = 482), with a group of pts diagnosed from 2004 to 2012 (G2, n = 434) in terms of OS, demographics, tumor features and treatment (tx). Results: Median age at diagnosis was 70.5 years (range 26-96). There was no significant difference between G1 and G2 in terms of age at diagnosis, stage of disease and number of pts who received surgery. A significantly higher percentage of pts received CT in G2 compared to G1 (66.5% vs 51.0%, p = .00). Tumors of the pancreatic head were more common in G1 compared to G2 (51.8% vs 44.4% p = .02). More pts in G2 received two or more CT agents compared to G1 (49.0% vs 34.1%, p = .00). Median OS was significantly longer in G2 compared to G1 (9m vs 5m, p = .00), in pts who received CT compared to pts who did not (3m vs 9m, p = .00) and in pts who received surgery compared to pts who did not (5m vs 19m, p = .00). Pancreatic head location was associated with improved OS compared to other locations (9m vs 5m, p = .00). No OS difference was found between pts who received combination with two or more agents vs single agent CT. Conclusions: In line with multiple studies, analysis of PaCa data from our institution showed an increase OS in pts diagnosed with PaCa in more recent years, and in those who received surgery and CT. CT was administered in a larger number of pts in G2, which might account for the better OS in this group. Pts diagnosed with tumors of the pancreatic head had better survival, which could be explained by earlier presentation leading to earlier diagnosis and tx. Further research in PaCa therapeutics is needed, as long-term OS in PaCa pts remains poor despite recent advances.
Atorvastatin to inhibit pancreatic cancer cells proliferation and invasion via suppression neurotrophin receptor signaling.
Authors: Ji Shengjun
Published: September 2018

e15725

Background: Pancreatic cancer is an uncommon but fatal malignant tumor, only 20% of which show any significant response to chemo-radiotherapy. Tumor metabolism research revealed that pancreatic cancer cells highly dependent on cholesterol uptake. So, in the present study, we have determined the effectiveness of atorvastatin, one drug originally used to lower cholesterol, against pancreatic carcinogenesis in various pancreatic cancer cell lines. Methods: To investigate atorvastatin effects in pancreatic cancer cells, two cell lines (PANC-1 and SW1990) were treated with different atorvastatin doses. The anti-proliferative, apoptotic and anti-invasive properties of atorvastatin were evaluated using MTS, cytoplasmic histone-DNA fragmentation and matrigel invasive assays, respectively. And western blot was used to evaluate the neurotrophin receptor signaling of NGF/Trk A, BDNF/TrkB and NT3/Trk C. Results: Atorvastatin suppressed pancreatic cancer cells proliferation, clone formation and invasion in a dose-dependent manner. The dose of atorvastatin at 10^-5mmol/L would be able to achieve obvious anti-tumor effect in vitro. Cell-cycle analysis demonstrated that cells were arrested in the S phase. Western blot showed increased protein expression of cleaved caspase-3, caspase-9, p21, p-chk2 and decrease in protein level of NGF/Trk A and NT3/Trk C. Conclusions: The current results demonstrated the anti-tumor effects of atorvastatin on pancreatic cancer cells, providing initial evidence towards its potential therapeutic use. Acknowledgment:This study was supported by Suzhou Cancer Clinical Medical Center Szzx201506.
A systemic review and meta-analysis to evaluate the efficacy and postprogression survival of second-line chemotherapy for gemcitabine-refractory pancreatic cancer.
Authors: Kasuga Akiyoshi , Hamamoto Yasuo , Aoki Yu , Kawasaki Kenta , Suzuki Takeshi , Hirata Kenro , Sukawa Yasutaka , Takaishi Hiromasa , Kanai Takanori
Published: September 2018

e15768

Background: We previously reported positive relationship between overall survival (OS) and both of postprogression survival (PPS) and post-trial anti-cancer therapies in first-line pancreatic cancer patients. We conducted a meta-analysis to gain a better understanding of the impact of PPS and post-trial anti-cancer therapies on OS and to determine the efficacy of second-line systemic therapy. Methods: We searched randomized trials of second-line systemic therapy for pancreatic cancer patients. We evaluated the relation between OS and either progression-free survival (PFS) or PPS and calculated the pooled effect size by using random effects models. Results: Eleven randomized trials with 23 treatment arms that involved examining 2267 patients were analyzed. Median OS was strongly associated with median PPS and PFS (r = 0.908 and 0.754, respectively), but no correlation between rate of post-trial anti-cancer therapies and OS was detected (r = 0.050). Average OS, PFS and PPS were significantly longer in recent trials than in older trials, (6.08 versus 4.17 months, p < 0.001), (2.65 versus 1.95 months, p < 0.001) and (3.43 versus 2.25 months, p < 0.001), respectively. Overall, experimental therapies compared to control did not significantly improve PFS (HR, 0.83; 95% CI, 0.67-1.03; I2 = 73%) or OS (HR, 0.89; 95% CI, 0.72-1.11; I2 = 69%). When the analysis was restricted to fluoropyrimidine compared to irinotecan or oxaliplatin in combination with fluoropyrimidine, each therapy produced advantage in a term of PFS (HR, 0.65; 95% CI, 0.47-0.88; I2 = 39% for irinotecan, HR, 0.81; 95% CI, 0.67-0.98; I2 = 13% for oxaliplatin) but only irinotecan produced advantage in a term of OS (HR, 0.70; 95% CI, 0.55-0.89; I2 = 0% for irinotecan, HR, 1.04; 95% CI, 0.65-1.65; I2 = 82% for oxaliplatin). Conclusions: Although second-line treatment benefit for OS can be skewed by PPS in patients with gemcitabine-refractory pancreatic cancer, the effects of subsequent therapies are weak in the salvage setting.
Individualized treatment with sunitinib versus standard dosing with sunitinib or pazopanib in patients with metastatic renal cell carcinoma (mRCC): Results from the Canadian Kidney Cancer information system (CKCis).
Authors: Basappa Naveen S. , Lalani Aly-Khan A. , Kalirai Austin , Li Haocheng , Wood Lori , Kollmannsberger Christian K. , Sim Hao-Wen , Kapoor Anil , Hotte Sebastien J. , Czaykowski Piotr , Canil Christina M. , Reaume M. Neil , Bjarnason Georg A. , Vanhuyse Marie , Soulieres Denis , North Scott A. , Heng Daniel Yick Chin
Published: September 2018

e16078

Background: Recent analysis using CKCis showed that mRCC patients receiving first-line sunitinib (S) had better survival than patients receiving pazopanib (P) and greater than expected survival for a real world sampling. We conducted further analyses to see if an individualized approach (treatment starting at standard dose/schedule with subsequent schedule/dose alterations based on toxicity) using S results in better outcomes in mRCC patients. Methods: Patients within CKCis diagnosed with clear cell mRCC treated with first-line S or P between January 2011 through December 2015 were analyzed by three treatment groups: 1) S as per individualized approach (SI) 2) S as per product monograph (SS) 3) P as per product monograph (PS). Overall survival (OS) and time-to-treatment failure (TTF) were calculated. Cox regression analysis allowed for adjustment of International Metastatic RCC Database Consortium (IMDC) criteria with age as a continuous variable. Results: A total of 598 patients were identified, 351 patients in SI, 151 patients in SS, and 92 patients in PS. Baseline characteristics are noted in Table 1. Median OS was improved in SI vs SS (37.9 vs 22.3 months (m), p<0.001) and SI vs PS (37.9 vs 19.6 m, p<0.001). TTF was better in SI vs SS (12.9 vs 5.6 m, p<0.001) and SI vs PS (12.9 vs 7.0 m, p<0.001). SS vs PS showed no difference in median OS (22.3 vs 19.6 m, p=0.51) or TTF (5.6 vs 7.0 m, p=0.24). Adjusted hazard ratios were: SS vs SI (OS 1.41, p=0.056; TTF 1.77, p<0.001) and PS vs SI (OS 2.18, p<0.001; TTF 1.43, p=0.040). Conclusions: Improvement in OS and TTF is seen using an individualized approach to mRCC patients supporting the growing body of evidence endorsing this practice. Further prospective validation awaits the NCT01499121 study. [Table: see text]
Prognostic score to predict time to castration-resistance in underserved patients with metastatic prostate cancer.
Authors: Mangla Ankit , Mushtaq Muhammad Umair , Yadav Udit , Ahmed Ahmed T , Liu Jiaxiang , Go Muriel Tania , Hassan Ahmed S , Bedrose Sara , Mann Hashim , Mullane Michael Russell
Published: September 2018

e16518

Background: This study aimed to identify predictors of time to castration-resistance prostate cancer (tCRPC) from initial diagnosis of metastatic prostate cancer (mPC) and develop a prognostic score in the underserved population of an inner-city tertiary care hospital. Methods: We retrospectively reviewed charts of 278 men diagnosed with mPC between 2001 and 2015, of which 155 patients were analyzed. Socio-demographic, clinical and pathologic factors were ascertained at the time of diagnosis. Kaplan-Meier and cox regression analyses were done to explore correlates tCRPC. Crude (HR) and adjusted (aHR) hazard ratios with 95% confidence intervals (CI) were obtained. Results: Over a median follow-up of 46 months (95% CI 23-69), 73.5% of men developed castration-resistance. Median tCRPC was 16 months (95% CI 12.5-19.5). All patients received medical or surgical castration at the time of diagnosis. Significant correlates of short tCRPC included: prostate specific antigen >20 ng/mL (HR 2.56, 95% CI 1.25-5.23, P=0.010), core involvement >50% (HR 2.11, 95% CI 1.43-3.11, P<0.001), bone metastases (HR 2.94, 95% CI 1.36-6.35, P=0.006), visceral metastases (HR 01.65, 95% CI 1.08-2.53, P=0.021), hemoglobin <10 g/dL (HR 2.02, 95% CI 1.26-3.23, P=0.003), alkaline phosphatase (ALP) >240 U/L (HR 2.42, 95% CI 1.62-3.61, P<0.001), lactate dehydrogenase (LDH) >200 U/L (HR 1.68, 95% CI 1.16-2.43, P=0.006) and neutrophil-lymphocyte ratio >2.4 (HR 1.50, 95% CI 1.03-2.20, P=0.035). In multivariate model, core involvement >50% (aHR 2.99, 95% CI 1.79-5.01, P<0.001), ALP >240 U/L (aHR 2.08, 95% CI 1.13-3.84, P=0.019) and LDH >200 U/L (aHR 1.71, 95% CI 1.02-2.86, P=0.043) independently predicted short tCRPC and each factor decreased tCRPC by almost 50%. Mean prognostic score (PS), based on 1 point for each independent predictor (scale 0-3), was 1.23 (SD 0.91) and significantly predicted short tCRPC (P<0.001). [Table] Conclusions: Our PS based on core involvement (>50%), high ALP (>240 U/L) and high LDH (>200 U/L) significantly predicts tCRPC in men with mPC. Prospective studies are warranted to further validate this score. [Table: see text]
Evaluation of self-reported symptoms and interference issues in patients with prostate cancer.
Authors: Taha Mahdi
Published: September 2018

e16547

Background: Prostate cancer (PC) is a leading cause of global mortality and is expected to become the leading cause of death among men in the U.S.A. Both the disease and its treatments produce a variety of symptoms (sx) that impact PC outcomes, of which the more common sxs are in relation to sexual dysfunction. A large body of literature has established that systematic patient (pt) reporting of symptoms during routine oncology care leads to clinical benefits. At our comprehensive cancer center we evaluate pts’ reported sxs using the Symptom Inventory Tool (SIT), an assessment (asst) tool that captures the pts’ perceived sx burden for real-time clinical intervention taken at the point of no intervention (baseline) and every ≥ 21 days thereafter. Methods: The 27-question SIT is comprised of the M.D. Anderson Symptom Inventory Tool (MDASI), a validated asst instrument, with 8 supplementary questions by Cancer Treatment Centers of America (CTCA). Sxs are rated “at the worst” on a numeric scale ranging from 0 (“none present”) to 10 (“as bad as you can imagine”), as experienced by pts in the past 24 hours. Results: Over a 45 month period (9/1/2012 to 05/31/2016), PC pts at CTCA completed the SIT at intake and again ≥ 21 days after. A total of 2,937 assts were analyzed. The assts consisted of 1,065 completed at baseline (BL), 1,065 completed at the 2nd follow up (FU), and 807 completed at 3rd FU or greater. BL mean, standard deviation (STD), and interquartile ranges (IQR) are shown in Table 1. Further analysis of assts identified that pts who rated their sxs as “very burdensome” (≥ 5) at BL would be more likely to report a significant decrease (dec) in their sxs burden than the average PC pt population. Conclusions: The SIT was successful in identifying sxs burden and interference with life issues in PC pts. Sexual dysfunction and disturbed sleep were the most common reported sxs. Early identification of pts with heavy sx-burden allowed immediate intervention and improvement in 1/4 to 2/3 of pts. [Table: see text]
PRUNE2 and PCA3 expression in paired non-malignant and tumor specimens from radical prostatectomy patients with gleason score 7 prostate cancer.
Authors: Lauer Richard C. , Barry Marc , Wu Jin , Lee Ji-Hyun , McCance Dennis J. , Du Ruofei , Rao Arpit , Dobroff Andrey S. , Dias-Neto Emmanuel , Chen Isan , Pasqualini Renata , Arap Wadih
Published: September 2018

e16582

Background: PCA3 is an FDA-approved biomarker for prostate cancer. We have recently reported that PRUNE2 is a tumor suppressor gene in human prostate cancer that it is inactivated through a PCA3-mediated regulatory axis. Based upon this previous work, here we investigated if PRUNE2 and PCA3expression levels would be different in non-malignant versus tumor paired samples obtained from Gleason 7 Score prostate cancer patients undergoing radical prostatectomy. Methods: We examined Gleason Score 7 prostate cancer specimens, obtained from a cohort of patients (n=24) who have undergone radical prostatectomy at UNM Hospital. Paired non-malignant and tumor tissues were recovered from these specimens after tissue microdissection and processed for RNA extraction. PRUNE2 and PCA3transcripts were measured by qRT-PCR using three and two different primer sets, respectively, and normalized using appropriate internal controls. Each experiment was carried out in triplicates. The Wilcoxon signed rank test was used to test whether the differences between the paired tumor and non-malignant tissue samples were significant. Results: Gene expression analyses showed PRUNE2 levels to be consistently lower in tumor samples compared to non-malignant areas of the same gland (P<0.0001). In contrast, the opposite trend was seen for PCA3, which has a marked upregulation in tumor areas (P<0.0001). Conclusions: Both PRUNE2 and PCA3 expression levels were significantly different between matched non-malignant and malignant tissue pairs in Gleason Score 7 prostate cancer patients post radical prostatectomy. This retrospective dataset provides additional support for a mechanistic role for the molecular interplay between PRUNE2 and PCA3 in human prostate cancer, which may lead to the development of novel diagnostic and therapeutic approaches in this disease. Prospective studies targeting our original finding are either ongoing or planned. [Table: see text]
Sexual function, quality of life, and cancer-related distress among prostate cancer survivors.
Authors: Buzaglo Joanne S , Zaleta Alexandra K , Miller Melissa F , Johnson Jamese , Diefenbach Michael A , Lepore Stephen J , Nelson Christian J , O'Rourke Mark Allen , Geynisman Daniel M.
Published: September 2018

e16587

Background: Prostate cancer (PC) survivors experience long-term disease consequences that can affect quality of life (QoL). This study examined QoL in key areas affected by PC and its association with cancer-related distress. Methods: Of 225 PC survivors enrolled in the Cancer Support Community’s online Cancer Experience Registry, 50 completed questions about cancer-related distress, cancer history, and the Prostate Cancer-Related QoL Scales. Results: Participant median age was 66 years; 21% had surgery, 32% underwent radiation, and 19% reported both. 31% currently and 18% previously received hormone therapy. 38% were diagnosed 5+ years ago; 26% reported recurrence, 30% reported metastatic disease. 76% reported erectile dysfunction (ED) since diagnosis. ED was more common (84%) among those who underwent surgery/radiation than those who had not (44%; chi2= 6.1, p < .05) and among those currently (100%) or previously (88%) receiving hormone therapy than those who had not (60%; chi2= 9.1, p < .05). 23% reported that incontinence made sexual activity/intimacy difficult. 20% “somewhat to very much” agreed they would choose a different treatment if they could redo their decision. QoL scores (mean±SD; scale range 0-100; higher = better QoL) were: Marital Affection (84.4±26.2); Masculine Self-Esteem (78.4±23.4); PSA Concern (77.2±21.6); Informed Decision (67.8±23.5); Urinary Control (62.1±23.6); Sexual Intimacy (59.1±34.9); Outlook (54.9±38.0); Cancer Control (49.1±31.1); and Sexual Confidence (44.1±33.7). Health Worry and Treatment Regret scores (higher = lower QoL) were 39.5±27.9 and 16.1±19.9, respectively. All QoL scales except Outlook and PSA Concern were correlated with overall cancer-related distress (r = .43 to .77; ps < .05), where lower QoL was associated with greater distress. Conclusions: Some PC survivors report substantial treatment regret, and many also endorse health concerns about uncertainty and disease progression, as well as reduced sexual confidence and intimacy. Lower perceived QoL, including sexual confidence and intimacy, is associated with greater cancer-related distress among survivors. Efforts are needed to address reduced QoL in a variety of life domains among PC survivors.
On Bacteroides Fragilis participation in vulvar carcinogenesis.
Authors: Zykova Tatiana , Kit Oleg Ivanovich , Nerodo Galina Andreevna , Ivanova Victoria A. , Nikitina Vera P. , Verenikina Ekaterina V. , Kravtsova Oksana E. , Bogomolova Olga A.
Published: September 2018

e17026

Background: The purpose of the study was to identify the rate of Bacteroides spp. infection in vulvar cancer tissues. Methods: FFPE samples of tumor and peritumoral area and healthy tissues of 44 patients with vulvar cancer, as well as frozen tumor tissues of 34 cervical cancer and 29 uterine cancer patients were studied. DNAs of Bacteroides spp. were detected by real-time PCR. Results: 18.75% of patients had stage I disease, 75.0% - stage II, 6.25% - stage III. The analysis of tumor histological type showed squamous cell carcinoma: G1 - 31.25%, G2 - 68.75%. B. fragilis were found in all vulvar tissues: tumor tissue – in 87.5%, perifocal area – in 76.9% and healthy tissue – in 71.4% of patients. Bacteroids of other groups were not found. For comparison, B. fragilis DNAs were detected in 20.7% in uterine cancer and in 15.4% in cervical cancer. DNA amount in samples was assessed by the Ct value. This index is inversely proportional to the DNA amount in the sample. Mean Ct level in tumor tissue was 23.2, in peritumoral area – 23.7, and in healthy tissue – 26.1; so, the amount of B. fragilis DNAs was similar in tumor and peritumoral area and was lower in healthy tissues. Differences in bacterial contamination of tumor tissue were found between vulvar cancer, cervical and uterine cancer. The amount of B. fragilis DNAs was maximal in vulvar cancer. We did not establish clear relationships between the rate of B. fragilis infection in tumor and the disease stage, tumor grade and the rate of metastasis. Conclusions: B .fragilis infection was found in tissues of the entire vulva; however, the infection rate and bacterial contamination level were higher in tumor tissue compared to the perifocal area and healthy tissue. Tumor tissues in vulvar cancer were infected more often than in uterine and cervical cancers. Bacterial contamination level in tumor tissue was higher in vulvar cancer than in uterine and cervical cancers which was undoubtedly significant in vulvar cancer pathogenesis.
Natural history of mucinous ovarian cancer in Ireland.
Authors: Cowzer Darren , O'Donovan Emily , Brown Therese , Gleeson Noreen , Gallagher David James
Published: September 2018

e17056

Background: Mucinous ovarian neoplasmscan arise as benign, borderline or malignant disease. Primary mucinous epithelial ovarian carcinoma (mEOC) represents 3% of invasive EOC. Differentiating primary from metastatic mucinous ovarian cancer is challenging. Systemic management of mucinous ovarian cancer increasingly follow GI cancer treatment protocols. We examined retrospective data at our institution to investigate incidence, management and site of origin of mEOC. Methods: 1,333 ovarian malignancies either diagnosed at or referred to St James Hospital, Dublin (from 2000 – 2016) were evaluated. The diagnosis was based on reported pathology. Patient demographics and investigations were retrospectively analyzed. Tumours were graded according to FIGO criteria. Results: Between 1/1/2000 and 9/12/2016 1,333 primary ovarian malignancies were diagnosed at our institution. 48 (3.6%) of these were mucinous adenocarcinoma and a further 5 (0.38%) were endometriod carcinoma of the ovary with mucinous differentiation. The average age at diagnosis was 48 (range 19-77 years). The majority of cases (87.5%) were stage I (IA 23, IB 2, IC 17, II 0, IIIA 1, IIIB 1, IIIC 3, IV 1) Staging CT thorax, abdomen and pelvis was completed in 44/48 cases and 24/48 (50%) patients underwent endoscopic evaluation of the uper or lower GI tract: 11 (22.9%) patients had both upper and lower GI endoscopy, 8 (16.7%) underwent OGD only and 5 (10.4%) had colonoscopy only. Gastrointestinal malignancy was not diagnosed in any of the patients. A total of 3 patients had immunohistochemistry for mismatch repair proteins performed, all of which demonstrated normal staining. All patients underwent surgical resection, 14 (29.2%) received adjuvant chemotherapy. 12 (25%) patients have died with a median OS of 11.5 months (range 7-108 months). Median follow up is 20.5 months (range 1-85 months) Conclusions: The incidence of mEOC in our population is 3.6%. The majority of patients diagnosed with mEOC over a 16 year period are still alive without evidence of disease, suggesting the diagnosis were ovarian in origin rather than metastatic. Immunohistochemistry for mismatch repair proteins is ongoing and will be presented at the meeting.
Comparing surgical staging methods for type II endometrial cancers.
Authors: Gattoc Leda Portia A. , Park Hyo K. , Carney Laura , Srivastava Shashank , Chiu Monica , Patel Mukti , Winer Ira Seth
Published: September 2018

e17107

Background: Type II endometrial cancers account for 10% of endoemetrial cancers, but their aggresive nature account for a significant proportion of the morbidity and mortality. The goal of this study was to compare outcomes type II endometrial cancer patients who underwent staging via laparotomy vs. minimally invasive approach (MIS). Methods: All patients who underwent surgery for Type II endometrial cancer at two cancer centers in Detroit MI from January 2005 and December 2015 were reviewed. Endometrioid histology and those who never had surgery were excluded. Clinical, demographic characteristics, surgical outcomes and progression free survival were examined using univariate and multivariable analysis, Kaplan-Meier estimates and Cox proportional hazards regression. Results: A total of 249 patients were included, 193 underwent laparotomy, and 58 MIS, including laparoscopic or robotic surgery. The majority had stage I disease (IA, 104 [41.3%] and IB, 20[7.9%]). Stages II, III, and IV were identified in 18 (7.1%), 79 (31.6%), and 31 (12.4%) respectively. Multivariate analysis demonstrated being African American (OR 3.43; 95%CI 1.64-7.15), having mixed histology(OR 2.54; 95% CI 1.02-6.32), and stage III-IV disease (OR 2.20; 95%CI 1.04-4.67) was associated with undergoing laparotomy. Higher perioperative complications, EBL >250 cc and blood transfusion were associated with laparotomy. Higher lymph node yield was associated with MIS approaches vs. laparotomy (26 vs. 14 p =<0.001). Recurrence rate was 38 % for the laparotomy group and 19% for MIS. There was no difference in 3 year-PFS after controlling for age, race, procedure, histology, stage and adjuvant therapy. There was no difference in overall survival between laparotomy and MIS for type II endometrial cancers. Conclusions: Being African American race, having mixed histology and stage were associated with undergoing laparotomy for type II endometrial cancers. MIS approaches offered less morbidity and ability to complete staging. However, patient selection likely played a role in this given earlier stage of these cancers. The route of surgery was not associated with PFS or OS, suggesting that MIS approach should be considered especially for ealry stage disease.
Analysis of adjuvant chemotherapy and radiotherapy for stage II endometroid type endometrial cancer.
Authors: Alter Raanan , Adams William , Block Alec , Small William , Harkenrider Matthew M.
Published: September 2018

e17118

Background: Endometrial cancer (EC) is the most common gynecologic malignancy. Stage II EC - involving the cervix - is ideally treated with primary surgical staging; however, adjuvant treatment is not well defined. Methods: The population included 8,506 patients with 2009 FIGO Stage II endometrioid-type EC treated surgically within the National Cancer Database. Patients were categorized into six treatment groups: 1. hysterectomy (HYS) alone; 2. HYS with external beam radiation therapy (EBRT); 3. HYS with chemotherapy (CT); 4. HYS with CT and EBRT; 5. HYS with vaginal brachytherapy (VBT); and 6. HYS with CT and VBT. Univariable frailty survival analysis (UVA) that allowed for clustering of patients was used to determine the effect of sociodemographic factors and comorbidities on time to death; a generalized linear mixed effects allowing random intercepts for each treatment facility type was also used to estimate the odds of receiving any treatment beyond HYS. Results: 3,571 (42%) underwent HYS alone, while 4,312 (51%) received HYS with adjuvant radiation therapy (ART), 251 (3%) received HYS with CT, and 372 (4%) received all three modalities. Of those that received ART, 2,951 (68%) had EBRT while 1,361 (32%) had VBT. On UVA, black race, years of education, government insurance or uninsured status, higher tumor grade, greater Charlson-Deyo comorbidity count (CDCC), increased age, tumor grade, and tumor size all predicted poor survival. On MVA, patients receiving ART were only 0.747 (95% CI: 0.641 – 0.871) times as likely to die at any given time when compared with HYS alone ( p = .0002). There was no difference in survival between radiation modalities. Further, compared to patients who only received HYS, those who received HYS+CT had comparable survival estimates ( p = .20) as did patients who received HYS+ART+CT ( p = .24). When controlling for all other factors, higher tumor grade, increased CDCC, age, or tumor size, and Medicaid insurance were hazardous predictors of time to death ( p< .05). Conclusions: In stage II EC patients, adjuvant EBRT and VBT improved survival. Adjuvant CT did not improve survival though this should be further studied given the infrequency it was delivered in this population.
Medical literature on mobile applications related to cancer.
Authors: Anampa-Guzman Andrea Carolina , Contreras Chavez Pamela , Gutiérrez César , Jeter Joanne M.
Published: September 2018

e18044

Background: In 2014, there existed 166 mobile applications related to cancer. However, many mobile applications are being developed without published validation by the medical community. The aim of this review was to provide an overview of the studies about mobile applications related to cancer. Methods: Scopus, PubMed, PMC, BVS and Scielo were systematically searched for studies published up to December 2016. A broad search using the terms “neoplasia”, “cancer”, “neoplasm”, “smartphone application” and “mobile app” was conducted. Article abstracts were reviewed for study eligibility, followed by reviews of full papers. We found 195 articles and 48 were included. Articles were included if they reviewed commercial mobile applications or if they described the development and evaluation of a mobile application related to cancer. Articles were excluded if they were about other telehealth technologies, primarily editorials, solely described study protocols, abstracts of congresses or books. Results: The earliest article was published in 2012 and there is an increasing rate of articles published. The majority of articles are original articles (85.42%) and 10 of them are clinical trials. Almost all articles were written in English (95.83%). Nearly 40% of the articles talked about mobile applications for the management of cancer. The intended audience of the mobile applications described in the studies was mostly patients. The cancers most popular among the articles were breast and skin cancers. The countries with the most studies on mobile applications related to cancer are the United States and South Korea. Conclusions: There is a large number of cancer related mobile applications. Further studies would help us understand the current and future use of these health related technologies. [Table: see text]
Comparative effectiveness of primary radiotherapy versus surgery in oropharyngeal squamous cell carcinoma in elderly patients: A SEER-Medicare analysis.
Authors: Sher David Jonathan , Yan Jingsheng , Strom Tobin Joel , Khan Saad A. , Zhu Hong
Published: September 2018

e18124

Background: Primary radiotherapy (RT) and primary surgery (PS) are considered equally viable local therapy modalities for oropharyngeal squamous cell carcinoma (OPSCC). The relative efficacy and toxicity of these competing therapies are often debated, and treatment choice is based on a paucity of comparative data. Methods: Eligible individuals were elderly patients in the SEER-Medicare registry diagnosed with OPSCC between 2000 and 2011. Patients were categorized as receiving either primary RT +/- chemotherapy, or PS +/- adjuvant RT or chemoradiotherapy (CRT). Overall survival (OS) was analyzed using Cox multivariable analysis (MVA). Risks of gastrostomy dependence (GD), esophageal stricture (ES), and osteoradionecrosis (ORN) at 1 year were determined through claims and analyzed using logistic regression. Results: A total of 3,804 patients (70% RT, 30% PS) were included in this cohort. At a median follow-up of 24.2 months, median and 2-year OS were 37.9 months and 61.1%, respectively. Patients treated with RT and PS experienced 2-year OS and median survival outcomes of 58.5%/34.9 months and 66.4%/48.0 months, respectively (p < 0.001). In early-stage OPSCC, MVA found older age, unmarried status, increasing comorbidity, SEER region, tumor site, and no prior PET associated with inferior OS; treatment was not associated with OS. For locally advanced OPSCC, increasing age, unmarried status, increasing comorbidity, lower income, tumor site, higher stage, no prior PET, and RT alone (HR = 1.24 for RT alone vs. PS, p = 0.0020, whereas HR 1.08 for CRT vs. PS, p = 0.1955) were associated with inferior OS. Multivariable predictors of ES (9.5% of cohort) were SEER region, grade, and PS treatment (OR = 1.03 and 0.70 for RT and CRT vs. PS, p = 0.015). Independent predictors of GD at 6 months (21.5%) included married status, smoking, tongue site, advanced stage, and CRT treatment (OR = 1.13 and 2.30 for RT and CRT vs PS, p < 0.001). The 1 year risk of ORN was 3.8% and not associated with treatment. Conclusions: Without a clearly dominant modality in elderly patients, local therapy decisions for OPSCC must be individualized to each patient’s disease and functional status.
Sofosbuvir-based therapy in patients with chronic hepatitis C virus infection and malignancies: A prospective study of 143 patients.
Authors: Torres Harrys A. , Economides Minas P. , Kyvernitakis Andreas , Mahale Parag , Hosry Jeff , Naing Aung , Turturro Francesco , Kaseb Ahmed Omar , Raad Issam I. , Granwehr Bruno Palma
Published: September 2018

e18152

Background: Data on the management of chronic hepatitis C virus (HCV) infection in cancer patients (pts) are sparse with many of them excluded from cancer clinical trials (CCT). We evaluated the efficacy and safety of sofosbuvir-based therapy (SOFBT) in such pts. Methods: Consecutiveptstreated with SOFBT at MD Anderson (1/2014-2/2017) were included in a prospective observational study. Efficacy (sustained virological response 12 weeks [SVR12] after SOFBT) was assessed based on intention to treat (ITT) analysis. A posthoc per-protocol analysis (PPA) was performed on pts with 12 weeks of follow-up post SOFBT. Adverse events (AEs) and drug-drug interactions (DDIs) were evaluated. Results: Of the 143 pts studied, the majority were men (102; 89%), white (89; 62%) and had genotype 1 (103; 72%). The most common cancers were non-Hodgkin lymphoma (NHL), hepatocellular carcinoma (HCC) (24; 17%, each) and breast cancer (11; 8%). Of the 31 infected pts excluded from CCTs, 27 (87%) were granted access after SVR. The overall SVR12 were 90% ITT (129/143) and 91% PPA (118/130). SVR12 ITT were 80% (8/10) for SOF+peg-interferon+ ribavirin, 86% (24/28) for SOF+ ribavirin, 95% (20/21) for SOF+simeprevir, 90% (64/71) for SOF/ledipasvir, 100% (8/8) for SOF+daclatasvir and 100% (5/5) for SOF/velpatasvir. The most common AEs were grade 1 (50; 35%), predominantly anemia (22%). DDIs or grade 4 AEs did not occur. Two pts died during the study period, both from reasons unrelated to SOFBT. In 3 pts with HCV-associated NHL, SOFBT was used alone without chemotherapy. Two of them had splenic marginal zone NHL and achieved complete remission (CR); the remaining pt had follicular lymphoma with stable cancer (SC) after SOFBT. No cases of de novo HCC occurred within 6 months of SOFBT. In the same period, 10% (4/40) of pts with SC had progression (acute leukemia, breast cancer, HCC and NHL in 1 each) and 5% (4/75) of pts with CR developed relapse (acute leukemia in 3, NHL in 1). More pts who failed SOFBT had cirrhosis (77% vs 27%, P = .001) and poorer adherence (≥ 2 missed appointments) (43% vs 4%, P = .001) than those with SVR. Conclusions: SOFBT is effective and safe in cancer pts; it improves access to CCT and may induce CR in selected NHL pts.
Large scale training of oncology providers and staff to improve care delivery.
Authors: Salama Monica , Steele Joseph Rodgers
Published: September 2018

e18282

Background: UT MD Anderson Cancer Center began participating in the Press Ganey survey in 2014, and the initial feedback was disappointing. Imaging outpatient services scores were lower than expected, and a difference of opinion between providers and patients was believed to be a contributing factor. Imaging providers defined “care” as the technical quality of the study and the accuracy of the report, while patients associated the term “care” with their healthcare experience. Methods: To improve the patient and family experience and better equip the staff and providers, the Service Excellence Academy (SEA) was created. This ten-hour, three-module program was developed at UT MD Anderson Cancer Center in collaboration with UNLV and MGM Resorts. The program combined didactic and interactive education by leveraging clinical examples and role-playing. A train-the-trainer format was used, including Institutional and Departmental leaders to facilitate the classes. Over 800 participants completed the SEA over 9 months. Questionnaires were administered to the participants before and after the sessions. Results: Since launching the SEA June of 2015, the outpatient Press Ganey scores have improved, and continue their upward trend. All metrics show percentile improvement ranging from 9% to 34%. Additionally, participants felt a greater connection with the institutional mission, vision, and heritage, were more comfortable making decisions, felt more empowered, and had developed greater empathy and skills to meet the needs of others. Conclusions: Large scale training of oncology providers and staff is possible and effective. Implementation of a Service Excellence Academy demonstrated both objective and subjective improvement of patient and employee satisfaction.
The effect of aspirin and anticoagulation on tyrosine kinase inhibitors induced thrombotic events in chronic myeloid leukemia: A retrospective cohort.
Authors: Numan Yazan , Jamil Muhammad , Cortes Jorge E.
Published: September 2018

e18550

Background: The newer Tyrosine Kinase Inhibitors (TKI) versus imatinib recently were called into question due to reported long-term toxic effects. These include cardiovascular adverse events, arterial and venous thrombosis. Our objective is to determine the effect of antiplatelet and anticoagulation on arterial and venous thrombotic events during the use of TKI for chronic myeloid leukemia (CML). Methods: Multi-center retrospective cohort based on the use of antiplatelet and anticoagulation medications. Chi square test was used and regression analysis for the recorded confounding variables applied. Results: a total of 968 patients were identified from 4 large cancer centers. Preliminary results on the first 168 entered are the following: Average age of the sample is 48 years. 41% were females and the rest were male patients. Average BMI was 29. Average duration of treatment on TKI was 66 months. 20 % of patients were using Aspirin and 11% were using anticoagulation with therapeutic INR. 8% were using dual therapy. 10% developed a thrombotic event during TKI use, namely: MI (2.4%), DVT (3.1%), PE (0.7%), Stroke (2.4%). Our results show that Aspirin or dual therapy decrease the thrombotic events excluding MI only in newer TKI (26% vs 11% P value = 0.002) Fig-1. Conclusions: This study is the first to investigate the effect of anticoagulation and antiplatelet medications on patients receiving TKI. Our main objective after completion of analysis of 968 patients is to answer the question whether patients receiving TKI should receive a prophylactic antiplatelet or anticoagulation therapy and if TKI mediated thrombotic event has “Vasculitis induced thrombosis” pathway that is resistant to anticoagulation/antiplatelet therapy.