bluuebunny/crossref_metadata_2025_split huggingface dataset:
Low-dose gemcitabine and paclitaxel combination therapy as second- or third-line treatment in patients with advanced urothelial cancer: Pain relief and tolerability.
Authors: Miyata Yasuyoshi , Ohba Kojiro , Matsuo Tomohiro , Sakai Hideki 
Published: February 2017

310 Background: Pain is the most devastating symptom of advanced urothelial cancer (UC). In addition, analgesics often decrease quality of life. So, pain relief and reduction of dosage are important goals for patients with such advanced UC. Cisplatin (CDDP)-containing chemotherapy is most effective regimen in patients with metastatic or recurrent UC. On the other hand, there is no established regimen for advanced UC after CDDP-containing chemotherapy. We performed low-dose combined therapy of gemcitabine (GEM) and paclitaxel (PTX), named GP therapy, as second- or third-line treatment for these patients. Methods: Thirty-three patients with metastatic and/or recurrent urothelial cancer (upper urinary tract = 13 and bladder =20 patients) previously treated with CDDP-containing chemotherapy were treated with GP therapy (GEM = 70 mg/m2 and PTX = 700 mg/m2 on day 1 and 8, repeated every 28 days). Survival was calculated from judgment of tumor progression. Pain was measured on a visual analog scale of 0–10. Positive effects for pain relief were defined as a decrease in analgesic consumption or a decrease in pain grade according to the visual analog scale, without increasing the dose of analgesics. Regulation of analgesics was performed by independent team that did not know this study. Pain relief and survival were compared with other chemotherapy (control; GEM alone = 9 and PTX-based chemotherapy except for GP therapy = 14). Results: At the start of this treatment, 31 patients had abdominal or back pain due to UC. In addition, 3 patients also had bone pain of metastatic tumors. In GP therapy, 28 patients (84.8%) were judged as positive in pain and only 1 patient needed to increase analgesics. On the other hand, control group showed 13 of 23 patients (56.5%) were stable and 7 (30.4%) were judged as positive in pain. Kaplan-Meier survival curves showed overall survival periods in patients with GP therapy were better compared to control group (p=0.023). All patients were received in the outpatient setting because severe side effect was not occurred. Conclusions: Low-dose GP therapy is feasible and well-tolerated as second/third-line chemotherapy in patients with advanced UC.
Methylation-specific high-resolution melting analysis (MS-HRM)-based DNA promoter profiling in paired FFPE bladder cancer samples.
Authors: Meng Wei , Chakravarti Arnab , Lautenschlaeger Tim 
Published: February 2017

315 Background: DNA methylation and histone modification are widely studied epigenetic events that can decrease gene expression levels. Promoter hypermethylation has been proposed as a potential diagnostic or prognostic biomarker in various cancers. We studied DNA promoter methylation of 5 cancer-associated genes (MRE11, APX1, ERCC1, RASSF1A and RASSF2A ) in paired FFPE bladder cancer tissues and normal adjacent tissue. The MRE11/Rad50/NBS1 complex serves as a single-strand DNA nuclease which participates in the repair of DNA double-strand breaks and replication errors. APX1 plays a key role in regulating H2O2 levels and H2O2 signaling. DNA repair machinery, ERCC1 protein levels in tumor tissue have been shown to predict response to platinum-based chemotherapy. RASSF1 is thought to be a tumor suppressor gene, while the function of RASSF2 is less well understood. Methods: 16 bladder cancer cases with available paraffin-embedded tumor and matched normal adjacent tissue specimens (32 tissue samples) were analyzed. DNA was extracted by Ambion RecoverAll Total Nucleic Acid Isolation kit. FFPE DNA bisulfite modification was performed using Zymo EZ DNA Methylation Kit. Methylation Specific-High Resolution Melting (MS-HRM) analysis was used to assess methylation status. MS-HRM monitors the melting behavior of PCR amplicons by using a DNA intercalating fluorescent dye. Results: MRE11 and APX1 promoters were not methylated in either cancer or normal adjacent samples. The ERCC1 gene was heavily methylated in 94% (30/32) of all cancer and wild type samples. RASSF1A and RASSF2A promoter methylation was significantly different between cancer and normal adjacent tissue. 50% (8/16) RASSF1A and 25% (4/16) RASSF2A had promoter methylation in cancer tissues, while only 6% (1/16) RASSF1A and 0% (0/16) RASSF2A had promoter methylation in normal adjacent tissues. 69% (11/16) of bladder cancer tissues were positive for RASSF1A or RASSF2A promotor methylation while only 1/16 normal adjacent tissue samples was positive for either promotor methylation. Conclusions: The results show that cancer and non-cancer tissue have different RASSF1A and RASSF2A promoter methylation patterns.
Urothelial cancer: Impact of gender on stage at diagnosis and survival.
Authors: du Manoir Jeanne Michelle , Richter Suzanne , Sridhar Srikala S. 
Published: February 2017

316 Background: Gender differences for disease course and survival in various cancers exist. Gender disparity for both stage at diagnosis and overall survival (OS) has been observed in urothelial cancer (UC). We report a single institution analysis of UC patients treated with chemotherapy to further investigate gender differences in outcomes. Methods: We identified 198 bladder cancer pts treated with chemotherapy since 2002. Chemotherapy was either given as adjuvant or palliative and the most common regimens used were gemcitabine and cisplatin, gemcitabine and carboplatin or gemcitabine alone. Age and stage at diagnosis, sex, smoking status, radiation exposures, bloodwork as a measure of organ dysfunction and overall survival info was collected. Outcomes were compared using Chi Square Statistic. Results: Age at diagnosis, smoking status and prior pelvic radiation were not significantly different (females 66.1 yrs vs males 63.6 yrs; 54% smokers in both groups; 8.3% females vs 7.6% males exposed to radiation). Significantly more females were diagnosed with advanced disease than men (70.8% vs 58.7%, p=0.049) vs earlier stages (stage 0-I) (12.2% vs 35.9%, p=0.03). For patients deceased, OS was not significantly different between genders when analysed for all stages combined (deceased 41.5 vs 39.9 mos), or for those diagnosed only at Stage IV (deceased 12.4 vs 8.6 mos). Of patients still alive at time of review, a survival advantage was apparent for men at all stages (54.8 vs 38.7 months), as well as with stage IV disease (35.9 vs 19.7 months). Gemcitabine-cisplatin was given more often to men with stage IV disease than females (93% vs 63%, p<0.02) despite no difference in organ dysfunction, or ECOG performance status in females. Conclusions: We observed that while both genders are similar with respect to age at UC diagnosis, risk factors exposures (smoking, radiation) and pathological variants, females were diagnosed at later stages, and receive standard first line therapy less often. Our data suggest that this impacts negatively on OS in females diagnosed in earlier disease stages. Further research is needed to identify if we can improve outcome by promoting earlier diagnosis and more aggressive management in earlier disease in females.
A single-center experience of chemotherapy for muscle-invasive bladder cancer after radical cystectomy.
Authors: Kotowski Adam S. , Stegemann Andrew , Rehman Shabnam , Attwood Kristopher , Levine Ellis Glenn , Guru Khurshid , Trump Donald L. , Pili Roberto 
Published: February 2017

318 Background: Muscle invasive bladder cancer (MIBC) is a chemo-sensitive disease that responds to therapy before or after curative-intent radical cystectomy (RC). Neoadjuvant chemotherapy (NAC) improves overall survival by 5-8% in current meta-analyses. Adjuvant chemotherapy (AC) has shown benefit but is less rigorously tested. Methods: We retrospectively reviewed the cystectomy database at our institute from 2005-2011 and analyzed patients who have received NAC or AC for MIBC. The Log rank test was used to compare survival between groups and Cox regression models were used for adjusted comparisons of survival. Results: 45 patients (p) (13 NAC and 32 AC) were evaluated with a mean age of 65.5 years (50-82), including 77% males and 23% females. Patients were most commonly offered chemotherapy because of co-morbidities and performance status. NAC was most commonly gemcitabine (G)/cisplatin (n=9) and AC was usually G/platinum (n=27). Sixty-nine percent of patients were downstaged and 23% had a complete pathologic response following NAC. Three p in AC group had positive margins; all of these cases were T4 cancers. Pathologic staging showed 84% ≥T3 and 53% node positive disease. Patients receiving AC had a mean interval of 64.8 days (42-129) to the start of treatment. NAC and AC patients received median 4.1 (3-7) and 4.5 cycles (1-12), respectively, throughout entire course of treatment. The median overall survival (OS) was 24.5 months (m) (17.1 m-not reached) and 24-month survival rate was 47%. Progression free survival (PFS) was 12.3 m (8.5-23.5 m) for all patients. There was no difference for OS or PFS based on age, gender, time after surgery to first dose of therapy, or mode of therapy (NAC or AC). When adjusted for number of cycles completed, a trend toward improved median OS (not reached vs. 22 m p= 0.092 ) and a significant PFS improvement (28.5 vs 11.5 m p=0.026) with NAC vs. AC was observed. Grade 3-4 urologic toxicity was negligible in both groups, however the AC group had a higher percentage of grade 3-4 hematologic toxicity. Conclusions: Despite a small sample size, results from our series favor NAC based upon efficacy and tolerability for patients with locally invasive bladder cancer.
Postchemotherapy AKR1B10 expression correlates with disease-free survival in muscle-invasive bladder cancer.
Authors: Hashimoto Yasuhiro , Koie Takuya , Yamamoto Hayato , Imai Atsushi , Hatakeyama Shingo , Yoneyama Takahiro , Kamimura Noritaka , Ohyama Chikara 
Published: February 2017

319 Background: AKR1B10 is a member of the aldo-keto reductase superfamily of NAD(P)H-dependent oxidoreductases.AKR1B10 is considered to contribute to cell proliferation and chemo-resistance. In the present study, we examined whether AKR1B10 expression correlates with disease free survival in bladder cancer specimens. Methods: The cohort includes consecutive 57 patients with muscle-invasive bladder cancer who received neoadjuvant chemotherapy followed by radical cystectomy. All patients received two cycles of neoadjuvant chemotherapy with gemcitabine plus carboplatin. Bladder cancer specimens were obtained at pre- and post-neoadjuvant chemotherapy, which were subjected to quantitative real-time PCR and immunohistochemistry to evaluate AKR1B10 expression. Intensity scoring for immunohistochemistry was categorized using a 4-graded scoring system according to a previously published method, with positive cells for each specific marker expressed as a percentage of the total number of cells as follows: 0%–10% = 0; 11%–30% = 1; 31%–70% = 2; 71%–100% = 3. Results: AKR1B10 mRNA expression was significantly higher in the post-chemotherapy groups than in the pre-chemotherapy groups (p < 0.001). The average immunohistochemical intensity score in the pre-chemotherapy group was 0.83 ± 1.08, compared to a significantly higher average intensity score of 2.03 ± 1.03 in the post-chemotherapy group (p < 0.001) Disease free survival of the post-chemotherapy AKR1B10(+) patients (61.2%) was significantly lower than that of AKR1B10(−) patients (100%) (log-rank test: p = 0.039). Conclusions: Although the present study is small and preliminary, post-chemotherapy AKR1B10 expression may have a predictive potential for response of chemotherapy and disease recurrence after definitive therapy for muscle-invasive bladder cancer. Further study is warranted to elucidate its clinical significance.
Radiotherapy planning study comparing volumetric modulated arc therapy (VMAT) with intensity modulated radiotherapy (IMRT) in the treatment of bladder and pelvic lymph nodes.
Authors: Harris Victoria , Warren-Oseni Karole , Huddart Robert Anthony 
Published: February 2017

320 Background: VMAT is increasingly used as an alternative to IMRT and has been shown to reduce treatment time and monitor units delivered. We report a radiotherapy (RT) planning study of bladder and pelvic lymph node (LN) RT comparing dosimetric outcomes of VMAT and IMRT techniques. Methods: 8 patients with/at high risk of LN+ bladder cancer were treated with bladder/pelvic LN IMRT. 4 clinical target volumes (CTVs) were defined: Whole bladder (CTV1), Pelvic LN (CTV2), Involved Bladder (CTV3) and Involved LNs (CTV4). Margins were applied to create 4 corresponding PTVs. IMRT plans were compared with VMAT plans in order to assess planning target volume (PTV) and organ at risk (OAR) coverage. The same PTV/OAR volumes and doses were used for each technique. Results: The mean dose statistics were compared for each dosimetric parameter for both techniques. The Wilcoxon signed-rank test was used to compare techniques with statistical significance assumed as p<0.05. Both techniques met prescription goals for PTV coverage. Comparison of conformity indices revealed no significant difference between techniques. VMAT achieved significantly better homogeneity in coverage of PTV2, although this finding was not replicated in the other PTVs (Table). Homogeneity index (HI) was defined as HI = 100x(D2-D98)/ Dp, where Dp = prescribed dose. VMAT resulted in significantly larger volumes of bowel (4.7%) and rectum (4.8%) receiving low dose radiation (15 Gy) than IMRT, although there was no significant difference seen at higher dose levels. Comparison with 3D conformal radiotherapy (3D-CRT) showed that both techniques resulted in a large reduction in bowel irradiation to 45Gy (IMRT = 123cc, VMAT = 145cc and 3D-CRT = 218cc). Conclusions: VMAT offers an attractive alternative to IMRT with similar conformality. Whilst increased low dose RT to OARs was seen with VMAT, it is of doubtful significance relative to the higher doses received by these structures. [Table: see text]
Prevalence of testicular microlithiasis association with testicular and extragonadal germ cell tumors in a Latin American population.
Authors: Neciosup Silvia P. , Quesada Jose , Callacondo David , Aguilar Ivan 
Published: February 2017

331 Background: Testicular microlithiasis (TM) is a entity characterized by multiple areas of increased echogenicity on scrotal ultrasonography (U.S.). Studies have reported association between TM and testicular germ cell tumors (TGCT). However, a study assessing the association of TM and extragonadal germ cell tumors (EGCT) has not been performed. Methods: Scrotal U.S. were reviewed in 441 men randomly selected from our computerized database during the period 1998 and 2010 at our tertiary-care cancer hospital. The association of U.S. findings with medical records and a history of germ cell tumors (GCT) were evaluated. The type of tumor was confirmed at histology after surgery or biopsy. Exclusion criteria included age <15 years and history of orchidectomy. Results: The median age was 32 years (range 15 – 88). TM was present in 95 patients (22%) and GCT were found in 130 patients (29%). 105 of these had TGCT (seminoma, n=56 and no seminoma, n=49) and 25 had EGCT (mediastinal, n=16, retroperitoneal, n=6 and CNS, n=3). Concurrent diagnosis of a TGCT was more prevalent in TM patients than in patients without TM (36/95 [38%] versus 69/346[20%] OR 2.45 95% CI 1.49–4.0; p<0.0001) while a diagnosis of an EGCT was present in 13 patients with TM and 12 patient without TM (13/95 [14%] versus 12/346 [3%] OR 4.41 95% CI 1.94–10.03; p<0.0001). No statistical differences were found for histology type. Conclusions: The prevalence in Latin American of TM is higher than previous reports and strongly associated with TCGT and EGCT. The clinical impact of the relationship between EGCT and TM is yet unknown and further studies are needed to clarify its role in the management. We suggest that young high-risk referral patients with TM should undergo scrotal U.S. annually; when a testicular tumor is not evident by U.S., investigations to rule out an EGCT, as thoracic or abdominal CT scans, should be considered individually in each case.
Normal tissue exposure during retroperitoneal radiotherapy for pure seminoma of the testis.
Authors: Katz Leah Minnie , Efstathiou Jason Alexander , Opraseuth Jonathan , Killoran Joseph , Paly Jonathan J. , Weathers Rita , Stovall Marilyn , Beard Clair 
Published: February 2017

334 Background: Emerging data suggest risk of cardiovascular disease following radiotherapy to the retroperitoneal nodes in stage I/II seminoma patients. This study quantifies radiation dose to organs contributing to cardiovascular disease. Methods: Organs at risk (OAR) were contoured using Eclipse. OARs consisted of the cardiac ventricles, kidneys, abdominal aorta, renal arteries, common iliac arteries, and external iliac arteries. Four dose-volume histograms corresponding to 4 treatment plans were generated for each patient. Each patient was planned as if being treated for a left primary seminoma. Plans 1/2 consisted of a standard PA strip field, while plans 3/4 consisted of a standard extended-field configuration. Field width for plans 1/3 spanned the transverse processes, while plans 2/4 included treatment of the left renal hilum. OAR doses were cumulatively reported for all 22. Results: Median doses to the left kidney for plans 1, 2, 3 and 4 were 1.2, 2.2, 1.3 and 2.7 Gy, respectively. The median dose in treatment plan 2 was 1.0 Gy higher than plan 1, and in plan 4 it was 1.4 Gy higher than plan 3; suggesting increased left kidney dose when the renal hilum was included. The maximum distance between the top of the treatment field and the inferior ventricle was 7.1 cm, while the maximum ventricular-field overlap measured 1.81 cm. There were 4 of 22 patients (18%) who had overlap with 16.7 to 46.44 cm3 of contoured ventricle within the field. The dose received by the cardiac ventricles ranged from 0–26.5 Gy, with the maximum dose of 26.5 Gy received by the patient with the greatest amount of overlap (1.81 cm). Conclusions: Adjusting treatment fields to include the renal hilum results in a higher dose to the kidneys and a mild increase in dose to the heart. While most patients have good separation of the heart and treatment field with extremely low cardiac doses, those whose ventricles are in field experience potentially significant cardiac doses. Our data suggests that for those patients with less than 2 cm between the superior portion of the treatment field and the inferior ventricle, the dose to the ventricles is at or approaches prescription dose. Clinicians treating seminoma patients may wish to consider this when determining candidacy for RT.
Multimodality treatment of locally advanced penile cancer: A contemporary dosimetric comparison and case presentation.
Authors: Cox John A. , Suri Jaipreet S. , Jana Bagi RP , Orihuela Eduardo , Sturgeon Jared D. , Endres Eugene C. , Colman Martin , Swanson Todd A. 
Published: February 2017

346 Background: There is a paucity of data on the optimal therapy for locally advanced penile cancer (PC). However, advances in other HPV associated neoplasms utilizing combined modality therapy (CMT) have been encouraging. We describe the management of advanced PC with such an approach. Methods: The patient presented following partial penectomy and inguinal dissection with T2N3 disease and extra-capsular extension (ECE). In a multi-disciplinary setting, it was decided to treat him post-operatively with concurrent chemoradiation. CT data sets were used for dosimetric comparison of critical structures (small bowel, rectum, bladder, scrotum, testes, bone marrow, skin, bowel, and femoral heads) and plans were generated using conventional penile fields (3D), Intensity Modulated Radiation Therapy (IMRT), and Volumetric Modulated Arc Therapy (VMAT), minimizing dose to organs at risk while optimizing treatment dose. Results: The patient was treated with IMRT (45 Gy to penile stump, pelvic and inguinal nodes (INs) with a 9 Gy boost to left INs and 15 Gy boost to right INs, due to ECE) and weekly Cisplatin (20 mg/m2). IMRT gave similar coverage and avoidance of normal structures compared to VMAT but with lower mean scrotal dose ( IMRT 27.0 Gy , VMAT 29.9 Gy, 3D 45.6 Gy). There was no >grade II toxicities, with grade II scrotal edema and moist desquamation of bilateral inguinal folds, not requiring treatment breaks. Acute RT toxicities had near resolution at 1 month. The IMRT and VMAT plans vs. the 3D plan had lower mean doses to the normal structures. 3D planning had unacceptable max doses to femoral head (62 Gy) and scrotum (55 Gy). Small bowel, V15Gy ≤ 150 cc was achieved by all plans. Dose homogeneity was improved for IMRT/VMAT vs. 3D planning (max dose 119%). Conclusions: This is one of the first comparisons of contemporary radiation techniques in the multimodality setting of PC. We demonstrate that utilizing IMRT concurrently with Cisplatin is feasible and well tolerated suggesting it a reasonable strategy to obtain durable local control, without which the prognosis is uniformly dismal. Larger studies are warranted to explore this contemporary CMT approach to locally advanced PC.
Mesenteric lymphadenopathy in patients with germ cell tumor.
Authors: Djaladat Hooman , Nichols Craig R. , Daneshmand Siamak 
Published: February 2017

347 Background: Mesenteric lymphadenopathy may be secondary to inflammatory, infectious or tumoral pathologies. The most common malignancies causing mesenteric adenopathy are gastrointestinal and lymphoma. To the best of our knowledge, there are no reports of germ cell tumor (GCT) presenting with mesenteric adenopathy. Methods: Four patients with GCTs presenting with mesenteric adenopathies were treated in two academic centers (OHSU and USC) by a single surgeon since 2004. All pathologies were non-seminomatous GCT. Their presentation, clinico-pathologic findings and outcome are reviewed. Results: Two cases (19 and 51 yo) were IGCCC poor risk, stage II, testicular GCTs presenting with bulky retroperitoneal, periportal and mesenteric adenopathy. They both underwent post-chemo RPLND with mesenteric lymph node biopsy/resection. The intraoperative mesenteric lymph node frozen section study in one case revealed embryonal cell carcinoma and teratoma; he had early postoperative recurrence and is awaiting high dose chemotherapy and autologous stem cell transplant (HDC/ASCT). The other was teratoma and underwent resection, however he developed lung metastases with elevated AFP 6 months later and was treated with HDC/ASCT, being disease free for 2.5 years. The third case was a 29 yo IGCCC good risk testicular GCT who presented with retroperitoneal (II B) and mesenteric lymphadenopathy. He underwent post-chemo exploration and intraoperative frozen section of the mesenteric lymph nodes showed fibrosis and histiocytic infiltration; therefore classic RPLND was completed. The fourth case was a 24 yo HIV (-) patient with extragonadal GCT originating from the rectosigmoid. At presentation, he had a widespread mesenteric adenopathy, partially responded to primary (BEP) and salvage chemotherapy (VIP); he underwent recto/sigmoid resection, RPLND and PLND and had 52/104 lymph nodes positive for yolk sac tumor. He was referred for HDC/ASCT. Three cases were done recently with limited follow-up. Conclusions: The most common etiologies for mesenteric adenopathy are inflammatory, infection and neoplastic diseases. In the presence of germ cell tumor however, mesenteric adenopathy is most likely secondary to metastasis rather than secondary pathology.