bluuebunny/crossref_metadata_2025_split huggingface dataset:
Collateral damage: Molecular aging and p16INK4a senescence protein in testicular cancer survivors treated with chemotherapy.
Authors: Bourlon Maria Teresa , Velazquez Hugo Eduardo , Orozco Bello Luis Arturo , Hinojosa Juan , Rios-Corzo Ricardo , Lima Guadalupe , Llorente Luis , Atisha-Fregoso Yemil 
Published: February 2018

548 Background: Cytotoxic chemotherapy can cure patients with advanced germ cell tumors. Nevertheless, cancer treatment may induce cellular senescence and accelerate molecular aging. The aging process implies an increase of cells expressing p16INK4a and changes in lymphocyte subpopulations. Our aim was to study the potential induction of premature immunosenescence in testicular cancer patients exposed to chemotherapy. Methods: Case-control study of testicular cancer survivors (TCS) treated with chemotherapy (≥3 BEP cycles, disease-free ≥ 3 months) matched by age with healthy controls. Peripheral blood mononuclear cells were isolated, and lymphocyte subpopulations were analyzed by flow cytometry. p16INK4a expression was measured using real-time polymerase chain reaction, and the 2-ΔΔCt method was used for the p16INK4a expression analysis. Groups were compared with Mann-Whitney U test. Results are expressed as median (IQR) unless otherwise indicated. Results: We included 15 cases and 15 controls. Mean age 32.5 yo (24-54), mean time since last chemo 49.5 months (3-192). TCS had a lower percentage of CD3+ (62 (57-68) vs 72 (65-82) p = 0.026) and CD4+ (35 (27-41) vs 42 (38-53) p = 0.013) cells in total lymphocytes. TCS also had a lower % of naïve CD4+ (32 (15-44) vs 39 (32-55) p = 0.041), CD4+CD28+ (90 (85-97) vs 98 (95-99) p = 0.029) and CD8+ naïve (15 (8-26) vs 27 (22-42) p = 0.023) cells. TCS had an increased % of memory CD4+ (18 (13-26) vs 9 (6-11) p = 0.001) and memory CD19+ B cells (76 (62-88) vs 70 (64-79) p = 0.004). The relative expression of p16INK4a in CD3+ cells was higher in TCS compared to controls (1.29±0.36 vs 0.85±0.54; p = 0.035). Conclusions: TCS showed an increase in the expression of the aging biomarker p16INK4a and a lymphocyte phenotype associated with immunosenescence; characterized by a decrease in naïve cells, and concomitant increment of memory and CD28- cells. This phenomenon is believed to contribute to the development of an immune risk profile in the elderly, associated with an increased rate of infections and a diminished effect of vaccines. This is the first time this finding is reported in TCS. Further studies are warranted to define the clinical implications of this alteration.
Long-term sexual functioning in germ-cell tumor survivors.
Authors: Chovanec Michal , Vasilkova Lucia , Setteyova Lucia , Obertova Jana , Palacka Patrik , Rejlekova Katarina , Sycova-Mila Zuzana , Kalavska Katarina , Svetlovska Daniela , Mladosievicova Beata , Mardiak Jozef , Mego Michal 
Published: February 2018

549 Background: Treatment for germ-cell tumors (GCT) may lead to long-term consequences in GCT survivors. This study aimed to evaluate a long-term sexual functioning after curative treatment for GCT. Methods: GCT survivors (N = 155) from a national cancer centre completed a Sexual Function Questionnaire that was modified from PROMIS Sexual Function and Satisfaction Questionnaire at a median 10 years of follow up (range 5-32) as a primary exploratory aim. Seventeen survivors (11%) had orchiectomy alone (controls), while 138 (89%) survivors received treatment beyond orchiectomy. The study group consisted of survivors receiving a cisplatin-based chemotherapy, radiotherapy to the retroperitoneal lymph nodes or both, while the control group included survivors treated with orchiectomy only. Results: Survivors treated with both chemotherapy and radiotherapy or any treatment had difficulty maintaining erection during the intercourse compared to the controls (both P = 0.04). Moreover, patients who received chemotherapy and radiotherapy reported difficulty in achieving orgasm during the intercourse ( P = 0.04) and they were disappointed with their overall quality of sex life ( P = 0.002). No difference in education, employment, marital status and parity was observed between the study groups (all P > 0.05). GCT survivors reported no differences in their sexual desire and in the number of attempts to initiate sexual intercourse in the last month. Survivors from all treatment groups reported none or mild anxiety resulting from sexual relationships and the desire to be sexually active was moderate among all subgroups, with no significant difference. Conclusions: Our prospective study shows that an impairment insexual function is a significant issue for long-term GCT survivors. Treatment with chemotherapy plus radiotherapy had the highest impact on the quality of sex life.
Outcomes of multidisciplinary treatment in penile cancer: Experience from Thailand.
Authors: Sirithanaphol Wichien , Pachirat Kachit , Rompsaithong Ukrit , Kiatsopit Pakorn , Lumbiganon Supanut , Sookprasert Aumkhae , Chindaprasirt Jarin 
Published: February 2018

555 Background: Penile cancer is relatively more common in Thailand compared to western countries. We report multidisciplinary treatment outcomes of penile squamous cell carcinoma at a regional center in northeast of Thailand. Methods: Using an institutional database, a total of 68 patients with squamous cell carcinoma of penis treated during 2009-2015 were identified. Patient demographics, pathological data, and treatment modality were reviewed. Survival data was calculated using the Kaplan-Meier method. Results: Median age was 53 years (25-89 years) and the median follow-time was 2.7 years. At presentation, 39 patients (57.4%) were node positive, and 9 (13.2%) had metastatic disease. Management was penile preserving surgery in 13 patients, partial penectomy in 36 patients, total penectomy in 15 patients, and palliative with radiation and/or chemotherapy in 4 patients. The 3-year overall survival for patients with N0-1 and N2-3 was 86% and 35% respectively. For those with high risk (N2/N3) non-metastatic disease, multimodality treatment improved overall survival significantly compared with surgery alone (13.7 mo vs 8.6 mo; HR 0.32, p-value = 0.04) Conclusions: Patients present with locally advanced disease had a poor prognosis. Multidisciplinary management improved overall survival N2/N3 patients.
A qualitative analysis of the impact of Carboplatin AUC 10 on physical, work functioning, and bone marrow toxicity, in patients with metastatic seminoma: A single centre experience.
Authors: Milic Marina , Sharma Anand , Gogbashian Andrew , Hawkins Annette , Rustin Gordon J. S. , Hall Marcia 
Published: February 2018

558 Background: We studied the efficacy, safety and tolerability of dose dense Carboplatin AUC10 chemotherapy and explored the HRQoL (health-related quality of life) in metastatic seminoma patients receiving this regimen. Methods: 46 patients with metastatic seminoma treated with Carboplatin AUC10 were identified in our centre. Carboplatin dosing at AUC 10 was used and calculated based on Calvert formula and EDTA clearance. Treatment was administered as a single dose every 21 days for 3 or 4 cycles. Response to treatment was determined by radiological imaging and serum tumour markers. Toxicities were evaluated using the CTCAE Version 4.0. Quality of life (QOL) and long-term treatment related toxicities were assessed post treatment using a self-designed telephonic questionnaire consisting of 4 questions about toxicity, which included- hair loss, hearing impairment, days absence from work and neuropathy. Results: Clinical characteristics are as follows: median age 44 (range 26-77), 34 patients had stage II and 12 stage III seminoma; average dose of carboplatin administered was 1240mg per cycle. 4.3% patients received 2, 87% 3 and 8.7.% 4 cycles of chemotherapy. 93% of patients achieved a complete remission (CR), 4 (all stage IIC) patients required a fourth cycle of chemotherapy, 2 undergoing RPLND and 2 watchful waiting. There was no disease relapse at median follow-up of 27.5 (range 4-84) months. 13 patients (28%) had grade 3 and 2 (4%) grade 4 neutropenia, thirteen (28%) grade 3/4 thrombocytopenia, Nine (19.5%) patients required prophylactic filgrastim. Commonest non-heamatological toxicities were fatigue in 28 (50%) and nausea 14(28%) patients. QOL data was available for 35/46 (76%) of patients. 40/46 (87%) patients had no residual tinnitus, one had residual grade 1 peripheral neuropathy. Eight patients continued to work throughout treatment, 16(45%) took < 5 days off work during chemotherapy, 4 took 5 to 21 days, 13 > 21 days, two were retired. Conclusions: Carbo AUC10 is a safe and effective treatment. Our results suggest the lack of negative impact of Carbo AUC10 on short and intermediate QOL without compromising treatment outcomes.
Testicular Cancer Review Panel: Multidisciplinary specialist review of a rare cancer at Kaiser Permanente, Northern California.
Authors: Harzstark Andrea Lynne , Kong Max , Brinsko Robert , Mamtora Kavita , Herrinton Lisa J. , Liu Liyan , Kumar Sonali , Kolevska Tatjana , Baer David M. , Dinesh M. Kotak , St. Lezin Mark , Presti Joseph C 
Published: February 2018

561 Background: Testicular cancer is a rare disease; multidisciplinary management by experienced clinicians is recommended. Methods: Multidisciplinary specialized review of all new testicular cancer cases was established in a community setting by creating a twice monthly Testicular Cancer Review Panel, comprised of two subspecialized medical oncologists and two surgical urologic oncologists, at Kaiser Permanente in Northern California. An early ascertainment list of new testicular cancer diagnoses was obtained and review of the history, labs, pathology reports, and all relevant imaging was performed via a web-based conference. Urologic cancer fellowship trained pathologists and body fellowship trained radiologists were available for secondary review when requested. All recommendations were documented in patient charts. Results: From June 2016 to June 2017, 131 cases were reviewed. Review by the panel resulted in significant changes in care in 19 of 131 patients (14.5%). Pathology and radiology re-reviews were the most common sources of changes in treatment recommendations. Embryonal predominant T1 disease was referred for GU pathology review in 14 cases; in 8, lymphovascular invasion was identified, upstaging 6.1% of patients from 1A to 1B, changing treatment from observation to chemotherapy. Radiology re-review changed the stage and treatment in 11 patients (8.4%), identifying lymphadenopathy not previously noted in 7 patients and reassessing previously identified lymphadenopathy as a non-pathologic finding in 4 patients. The percentage of patients with stage I seminoma observed rather than undergoing adjuvant therapy increased from 11/15 (73.3%) over the first six months of the panel to 18/20 (90%) over the second six months. Convening the panel also resulted in dissemination of oncologic knowledge among treating physicians. Conclusions: Multidisciplinary specialized case review for a rare disease is feasible in the community setting and frequently alters care.
Development of multi-institutional nation-wide tumor board system for testicular cancer in Japan.
Authors: Kawahara Takashi , Kawai Koji , Kojima Takahiro , Kishida Takeshi , Shinohara Nobuo , Kondo Yukihiro , Nonomura Norio , Kakehi Yoshiyuki , Nishiyama Hiroyuki 
Published: February 2018

562 Background: The standard treatments have been established for metastatic germ cell tumors and the cure rates are quite improving. Cumulative experience by centralization is required for expertise in all aspects of care but it is quite difficult due to its rarity and the present medical situations in Japan. To resolve this problem, we established the nation-wide internet tumor board system for testicular cancer from 2012. Methods: To start with, 28 members from 14 institutions were registered in the internet mailing list (ML) for this tumor board, then the members who wanted to join this system were added to this ML. The tumor board was operated in semi-closed system and with no consultant fee. The member can present the case by e-mail at any time when he encounters the difficult case. Then the other members replied and commented their opinions or experiences against his questions by e-mail. All members could read his case-presentation and comments of consultants in e-mail. In this study, we summarized the initial 5-year experience and the discussed contents and the usage status were analyzed to assess the quality of this internet nation-wide reference system. Results: The number of members and discussed cases increased gradually. At the present, this ML consists with 179 members from 79 institutions all over Japan. We discussed 100 testicular cancer cases during 5 years. Discussed cases were categorized into 10 categories. 44% of the cases discussed in the ML were poor prognostic cases or extragonadal cases. In 63 cases, the consultants were replied within 24 hours when the case was presented in ML, and some comments were replied within at 5 days in all cases. The median number of comments was 6, and active discussions with 10 or more comments were performed in 26 cases (26%). Conclusions: The nation-wide internet tumor board system for testicular tumor was growing in Japan and useful to decide treatment strategy for difficult cases. It might be helpful for members in low volume centers to gain cumulative experience.
Refractory testicular pure seminoma (PS) and non-seminomatous(NS) germ cell tumors (GCT): A comprehensive genomic profiling (CGP) study.
Authors: Jacob Joseph M , Ferry Elizabeth Kate , Shapiro Oleg , Millis Sherri Z. , Chung Jon , Elvin Julia Andrea , Vergilio Jo-Anne , Ramkissoon Shakti , Suh James , Severson Eric Allan , Daniel Sugganth , Ali Siraj Mahamed , Schrock Alexa Betzig , Miller Vincent A. , Stephens Philip J. , Gay Laurie M. , Bratslavsky Gennady , Ross Jeffrey S. 
Published: February 2018

565 Background: Although PSand NS testicular GCT have a favorable prognosis, on occasion these tumors can be refractory to conventional systemic treatments. Methods: FFPE tissues from 22 PS and 86 NSunderwent hybrid-capture based CGP to evaluate all classes of genomic alterations (GA). Tumor mutational burden (TMB) was determined on 1.1 Mbp of sequenced DNA and reported as mutations (mut) per megabase (Mb) and microsatellite instability (MSI) was determined on 114 loci. Results: PS patients were older than NS (P=0.007). The primary tumor was sequenced in 41% of PS and 18% of NS with a metastasis sample in 59% of PS and 82% of NS.Four (18%) of PS had syncytial trophoblast cells identified. The mean GA frequency at 4.1 mut/case for NS was higher than that seen in PS and this difference reached near significance (P=0.08). The KRAS, TP53, CCND2 and FGF6/23 GA frequencies were similar in both tumor types (Table). GA in KIT, PIK3CA/ MTOR, PTEN and BRCA2 were more frequent in PS than NS whereas BRAF and ERBB2 GA were more frequent in NS (Table). MSI-High status was absent in in PS (0%) and identified in 2% of NS. Higher levels of TMB were not encountered in PS (0% TMB ≥10 mut/Mb), but higher TMB levels were more frequent in NS (5% ≥ 10 mut/B and 1% ≥ 20 mut/Mb). Conclusions: The GA found in refractory PS and NS differ significantly. PS features a lower GA frequency with slightly higher potential for targeted therapies in kinase (KIT) and MTOR pathways but, has very low TMB predicting limited opportunities for immunotherapy for these patients. For NS targeted therapy biomarkers appear even more uncommon than seen in PS with only extremely rare kinase inhibitor opportunities. However, based on rare high TMB and MSI-High status, immunotherapies may be of benefit in a small subset of NS patients. Further study of genomic findings in relapsed and clinically aggressive PS and NS appears warranted. [Table: see text]
Management of growing teratoma syndrome (GTS): Results of the German Testicular Cancer Study Group.
Authors: Paffenholz Pia , Pfister David , Busch Jonas , Dieckmann Klaus Peter , Schmelz Hans U. , Heidenreich Axel 
Published: February 2018

566 Background: Growing teratoma syndrome (GTS) is an infrequent clinical phenomenon constituting only about 2 to 8% of all testis cancer patients. Data in the literature on the therapy of GTS are sparse, reflecting the rarity of the disease. The objective of was to determine the diagnostic, surgical and oncological outcome of patients with GTS treated in the 21st century. Methods: Between 01/2000 and 01/2010 post-chemotherapeutic retroperitoneal lymph node dissections (PCRLND) were performed in 296 patients with advanced NSGCT. We analysed the peri- and postoperative outcome of 16 patients (5.4%) that fulfilled the criteria of a GTS: enlarging metastatic mass in the retroperitoneum or visceral organs during systemic chemotherapy with normalized or decreasing tumour markers. Results: Mean patient age was 31 years (17-57). Initially, all patients had NSGCT with a good or intermediate prognosis according to IGCCCG; one patient had a poor prognosis. In all cases the primary tumour predominantly contained mature teratoma; two patients had a clinical stage IIb, nine and three presented with clinical stage IIc and III respectively. Median tumour diameter at time of surgery was 8.1 cm (1.5-32). Tumour markers were plateauing or normalized in all patients. Tumour masses were localized in the retroperitoneum in 15 patients; one patient demonstrated a pulmonary mass. After a median follow-up of 4.2 years, 2 patients developed outfield recurrences; all but one patients are alive. Conclusions: GTS is a rare disease among patients with advanced NSGCT and necessitates complete surgical resection of the masses with curative intention. Surgery should be considered at time of progression to facilitate complete removal of the growing teratoma and be performed in tertiary referral centers only.
Adjuvant etoposide plus cisplatin (EP) for pathologic stage (PS) II nonseminomatous germ cell tumor (NSGCT).
Authors: McHugh Deaglan Joseph , Funt Samuel , Silber Deborah , Knezevic Andrea , Patil Sujata , O'Donnell Devon , Tsai Stephanie , Reuter Victor E. , Sheinfeld Joel , Carver Brett Stewart , Motzer Robert J. , Bajorin Dean F. , Bosl George J. , Feldman Darren R. 
Published: February 2018

567 Background: The risk of relapse after primary retroperitoneal lymph node dissection (RPLND) for patients (pts) with PS IIA NSGCT is 10-20% and increases to over 50% for pts with PS IIB NSGCT. Cisplatin-based chemotherapy reduces the relapse risk to approximately 1%. Standard adjuvant chemotherapy regimens consist of 2 cycles of EP or 2 cycles of bleomycin plus EP (BEP). Methods: From March 1989 to April 2016, 156 pts with PS II NSGCT seen at Memorial Sloan Kettering Cancer Center and assigned to two cycles of EP chemotherapy following RPLND were included. Pts from a prior analysis (Kondagunta, JCO, 2004) were included with updated survival outcomes and expanded histopathologic parameters. Each cycle consisted of cisplatin 20mg/m2 and etoposide 100mg/m2 administered on days 1 to 5 at 21-day intervals. Demographics, histopathologic features, therapeutic and survival outcomes were recorded. Results: Median age was 28 years (range 15-52). 30 pts (19%) had pN1 disease, 122 (78%) pN2 disease and 4 (3%) pN3 disease. Median number of positive lymph nodes was 3 (range 1-37) and median size of the largest positive node was 2.0cm (range 0.4-7.0cm). 69 pts (45%) had extranodal tumor extension. Embryonal carcinoma, seminoma, mature teratoma and yolk sac were the predominant histological subtypes in the RPLND pathology in 115 (90%), 8 (6%), 4 (3%) and 1 (1%) pts respectively. 150 pts (96%) received 2 cycles of EP, 5 (3%) received 1 cycle of EP and one received 4 cycles of EP due to a transient marker increase following his first cycle. Dose delays occurred in 54 (38%) pts, mostly due to neutropenia (44/54 delays). With a median follow-up of 9 years, 2 pts (1 pN2 and 1 pN3) relapsed; both achieved a complete response to paclitaxel, ifosfamide and cisplatin (TIP), remaining disease-free at 65 and 143 months respectively. 3 pts died, all unrelated to GCT or treatment, for 10-year relapse-free and overall survival rates of 98% and 99%, respectively. Conclusions: This is the largest series reported to date on adjuvant chemotherapy with EP for PS II NSGCT. With 100% disease-specific survival and acceptable toxicity, these data confirm the efficacy of 2 cycles of EP and suggest that inclusion of bleomycin (e.g. BEP) in this setting is not necessary.
Clinical characteristics and treatment outcomes of patients (pts) with advanced germ cell tumor (aGCT) treated at a tertiary cancer center in Brazil.
Authors: Vasconcellos Vitor Fiorin de , Bastos Diogo Assed , Pereira Allan Andresson Lima , Pereira Bruno Rodriguez , Silva Jamile Almeida , Muniz David Queiroz Borges , Guglielmetti Giuliano , Nahas William Carlos , Dzik Carlos 
Published: February 2018

568 Background: Reported treatment outcomes for pts with aGCT are largely based on series from developed countries. Data from less developed countries are lacking. Methods: From 2000 to 2015, a retrospective analysis identified 302 pts with aGCT treated at Instituto do Cancer do Estado de São Paulo (ICESP). Kaplan-Meier methods were used for analysis of progression-free survival (PFS) and overall survival (OS) according to the International Germ Cell Consensus Classification Group (IGCCCG). Results: Median follow-up was 46 months and median age was 28 years old. Clinical features and management are detailed in the Table. 54 pts (18%) had ECOG performance status (PS) ≥ 2 at baseline. According to the IGCCCG, 57% were good-, 18.3% intermediate-, and 24.7% poor-risk disease. Median AFP was 2.9, 243, and 3.998 and HCG was 0.4, 113 and 301 in IGCCCG good-, intermediate-, and poor-risk groups, respectively. 5-year PFS and OS were 69% and 85%, respectively, including 83% and 95.3% in good-risk, 70.9% and 83.6% in intermediate-risk and 35.1% and 62.2% in poor-risk pts. Only 3 pts (3%) received high-dose chemotherapy (HDCT) as first salvage therapy. Conclusions: Brazilian pts with advanced GCT in this cohort had similar outcomes as pts in the IGCCCG database. In comparison to contemporary series, pts with intermediate- and poor-risk GCT had slightly inferior PFS and OS, possibly due to a high percentage of pts with poor PS and less use of HDCT. [Table: see text]