bluuebunny/crossref_metadata_2025 huggingface dataset:
Trends in exposure to multiple lines of treatment and survival of patients with metastatic renal cell carcinoma: A real-world analysis.
Authors: Ratta Raffaele , Di Maio Massimo , Verzoni Elena , Grassi Paolo , Montone Rosanna , Sorrentino Margherita , Mennitto Alessia , Prisciandaro Michele , De Braud Filippo G. , Procopio Giuseppe
Published: September 2018

e16064

Background: In recent years, several new agents have been introduced into clinical practice for patients (pts) with metastatic renal cell carcinoma (mRCC). The aim of this study was to describe the difference in terms of exposure to multiple lines of treatment and overall survival (OS) between two groups of pts who started therapy for mRCC in two different periods of time (period 1: 2005-2010 and period 2: 2011-2016). Methods: Data were retrospectively collected from the database of the Istituto Nazionale Tumori of Milan. The proportion of pts who received subsequent lines of treatment after first disease progression (PD) was compared between the two groups of pts. OS was defined as time from the start of first-line treatment to death or last follow-up. Unadjusted and adjusted analyses for Heng risk groups were done. Results: Overall,457 pts with mRCC were evaluated: 274 pts (60%) started treatment in period 1 and 183 (40%) in period 2. Most pts in both groups had intermediate risk (65.7% and 86.3% respectively). The proportion of poor-risk pts was significantly higher in period 1 (21.2% vs 7.7%). Among pts who stopped first-line treatment due to PD, pts in period 2 had a higher chance of receiving second-line treatment as compared to pts of period 1 (80.8% vs 64.7%, 95% CI 1.31-4.04, p = 0.003). Similarly, among those who stopped second-line treatment due to PD, pts in period 2 had a higher chance of receiving a third-line treatment compared to pts in period 1 (71.2% vs 49.3%, 95% CI 1.32-4.87, p = 0.004). In the whole study population, median OS (mOS) was 24.9 months (95% CI 21.6-31.1): 21.7 months (95% CI 18.8-26.3) in pts of period 1 and 38.2 months (95% CI 27.7-49.0) in pts of period 2 (Hazard Ratio [HR] 0.65,95% CI 0.49-0.84, p = 0.001) respectively. When adjusted for Heng groups, OS remained significantly longer for pts of period 2 (HR 0.76, 95% CI 0.57-1.00, p = 0.05). Conclusions: mRCC pts who started a treatment over the last 5 years have been exposed to a higher number of treatment lines as compared to those treated before 2011. Our data suggest that the increase of treatment options as well as a better clinicians’ expertise is associated with a better outcome.
Comparative efficacy and safety of bone-modifying agents for the treatment of bone metastases in patients with advanced renal cell carcinoma: A systematic review and meta-analysis.
Authors: Omae Kenji , Tsujimoto Yasushi , Honda Michitaka , Kondo Tsunenori , Hashimoto Yasunobu , Tanabe Kazunari , Fukuhara Shunichi , Furukawa Toshi
Published: September 2018

e16067

Background: Bone-modifying agents (BMA) have been well-demonstrated to be effective for preventing and inhibiting skeletal-related events (SRE) in patients with bone metastases of breast or prostate cancer. However, the role of BMA treatment has not yet been clearly defined in patients with bone metastases of renal cell carcinoma (RCC). We, therefore, conducted a systematic review and meta-analysis to evaluate the efficacy and safety of BMA in patients with bone metastases of RCC. Methods: Literature search was conducted on MEDLINE, the Cochrane Central Register of Controlled Trials, the WHO International Clinical Trials Registry Platform, and ClinicalTrials.gov to identify randomized controlled trials of BMA for the treatment of bone metastases in RCC patients. The primary outcomes were SRE and serious adverse events (AEs). Hazard ratios (HRs) were calculated with a random effects model. The Grading of Recommendation Assessment, Development, and Evaluation (GRADE) approach was used to assess the certainty of the evidence. This review was prospectively registered on PROSPERO (No. CRD42016032742). Results: Three studies (259 patients) were identified for the systematic review. Two studies that compared zoledronic acid with placebo or non-zoledronic acid showed that zoledronic acid reduced the SRE risk by 68% (HR 0.32; 95% confidence interval (CI) 0.19–0.55; P < 0.0001). The quality of evidence was moderate. No serious osteonecrosis was reported in both studies. The incidence of serious AEs was identical (80%) on both treatment arms in one study and not reported in the other study. In the remaining study, which compared denosumab with zoledronic acid, analyses of the individual patient data shared through Amgen showed a favorable trend for denosumab in terms of SRE (HR 0.71; 95% CI 0.43–1.17) and serious AEs (risk ratio 0.86; 95% CI 0.68–1.08), but this trend did not reach statistical significance. Conclusions: The moderate-quality evidence indicates that zoledronic acid significantly reduces the risk of SRE among patients with bone metastases of RCC.
Economic burden of empiric drug utilization in metastatic renal cell carcinoma emphasizes the need for early biomarkers of response.
Authors: Chen Viola , Gong Cynthia , Zhang Chiyuan A , Srinivas Sandy , Lee Howard E , Fan Alice C.
Published: September 2018

e16072

Background: While targeted therapies have significantly changed clinical practice for metastatic renal cell carcinoma (RCC), the economic burden of these drugs is increasing without concomitant advances in strategies for choosing among such agents. We present a model of cost savings using a hypothetical biomarker panel of early response to guide selection of targeted and immune therapies in metastatic RCC patients. Methods: Using the Stanford RCC Outcomes database, we identified patients diagnosed with metastatic RCC who received any of the following: sunitinib, pazopanib, axitinib, sorafenib, cabozantinib, nivolumab, lenvatinib & everolimus, temsirolimus from 2003 through 2016 at Stanford Cancer Center. Primary outcomes included short-term and long-term costs of treatment according to standard-of-care imaging criteria. Drug costs were inferred from the 2017 Veterans Affairs Federal Supply Schedule pricing in USD. A hypothetical biomarker cost was set at $4,620—the current market price of an actively employed diagnostic test in breast cancer, OncotypeDX. These parameters were combined in a Markov model to simulate patient treatment courses and to assess the impact of an early response biomarker on drug expenditures. Results: 370 patients received a range of one to six lines of successive therapy. 170 (45.9%) were long-term patients with cumulative drugs costs totaling $31 million, or on average $185,362 per patient, and $104,521 per individual line of therapy received. 200 (54%) were short-term patients who received less than 3 months of targeted therapy. The costs of such potentially ineffective treatment totaled $4.1 million, or $15,455 per patient per individual line of therapy received. Application of an early biomarker panel at the outset would result in a potential cost savings of up to $6,215 per patient. Conclusions: Bothmetastatic RCC patients and payers suffer high costs from ineffective therapy. Our findings suggest an economic benefit for developing biomarker panels to predict early therapeutic response. Such biomarkers can result in immediate cost savings, and possibly improved quality-of-life for those liberated from unnecessary drug toxicity.
Incidental vs. clinical diagnosis of renal cell carcinoma (RCC): Population, treatment and outcome in a cohort of 828 patients followed at Instituto Oncológico Henry Moore (IOHM).
Authors: Niewiadomski Dario , Acuna Claudia Lorena , Morgenfeld Eduardo L. , Tognelli Flavio , Smolje Leonardo , Montiel Monica , Garcia Gerardi Carlos Fernando , Abal Mariana , Gil Deza Ernesto , Rivarola Edgardo G. J. , Gercovich Felipe G.
Published: September 2018

e16075

Background: For the past three decades, it has been observed in developed countries an increase in the incidence of RCC, at the expense of small tumors incidentally found. This study compares the epidemiology, treatment and evolution of the patients (pt) with incidental RCC (Group A) or clinical RCC (Group B). Methods: Between 1/1/2001 and 11/30/2016, 29,440 new pt with histological diagnosis of cancer were incorporated to the IOHM database. We selected all those coded under the WHO ICD10 code C64. The medical records were reviewed, registering the epidemiological data, treatments and evolution of each patient Results: We identified 828 pt out of 29,940 pt (2.8%) who met the inclusion criteria. Group A = 507 pt (61%) and Group B = 321 pt (39%). The table below shows the characteristics of both groups. Conclusions: 1) In this cohort the incidental diagnosis of RCC represented 60% of the cases and correlated with early stages and less aggressive tumors. 2) The appropriate selection of patients allowed partial nephrectomies in 103/828 Pt. (12% of the cases). 3) With a median follow-up of 30 months the survival rate of this population exceeded 90% in the early stages and was close to 50% in advanced cases. [Table: see text]
Predictors of clinical outcomes in metastatic castration-resistant prostate cancer (mCRPC) patients treated with abiraterone acetate or placebo: An exploratory post-hoc analysis of COU-AA-302 trial data.
Authors: Pilon Dominic , Behl Ajay S. , Kamstra, Rhiannon , Xiao Yongling , Lafeuille Marie-Helene , Lefebvre Patrick , Freedland Stephen J.
Published: September 2018

e16529

Background: A post-hoc analysis of COU-AA-302 trial data showed that brief pain inventory (BPI), lactate dehydrogenase (LDH), alkaline phosphatase (ALP), and bone metastases were predictors for overall survival in men with mCRPC treated with AA+P. This study aimed to identify baseline predictors of other clinical outcomes. Methods: COU-AA-302 trial data were used to develop predictive models for prostate-specific antigen (PSA) progression, Eastern Cooperative Oncology Group performance status (ECOG PS) deterioration, and opiate use. Associations between baseline factors and outcomes were first assessed using multivariable Cox models among AA+P patients (Step 1). In Step 2, interaction testing was conducted between treatment (AA+P vs. placebo) and each potential predictor (P < 0.2) identified in Step 1. Final Cox models included predictors and any significant interactions (p < 0.05). Results: A total of 1,034 men (525 AA+P; 509 placebo) were included in the analysis. Baseline BPI, PSA, LDH, and ALP were predictors of PSA progression and opiate use regardless of AA+P or placebo with higher values indicating higher risks (all P < 0.05). Younger age, shorter time from luteinizing hormone-releasing hormone to randomization, higher Gleason score, and lower PSA at diagnosis were also associated with higher risks of opiate use: (all P < 0.05). For ECOG PS deterioration, higher baseline BPI, PSA, LDH, and Gleason score, older age, and lower baseline ECOG were associated with higher risks regardless of AA+P or placebo (all P < 0.05). Baseline ALP and site of metastasis also predicted ECOG PS deterioration but the effect varied by treatment (lower risk in AA+P versus placebo; both interactions’ P < 0.05). Conclusions: Predictors of PSA progression, ECOG PS deterioration, and opiate use were identified in AA+P and placebo-treated men with mCRPC. No predictors were associated with worse outcomes for AA+P versus placebo, while the negative impact of certain predictors on ECOG PS was favorably modified by AA+P. Further study is needed on the relationship between AA+P and prognostic factors.
Germline variants and family history in caucasian and African-American prostate cancer.
Authors: Ledet Elisa M. , Ernst Emma M. , Schiff Joshua , Lin Shuwen , Lewis Brian E. , Sartor A. Oliver
Published: September 2018

e16548

Background: Family history (FH) is a well-documented risk factor for prostate cancer (PCa). Previously, germline pathogenic variants (PVs) have been identified in metastatic PCa. The goal of this study was to fully evaluate cancer FH and assess PVs detected in PCa patients undergoing both detailed FH ascertainment and germline genetic testing. Methods: FHs were collected from 535 PCa pts (Caucasian (Ca) n = 359, African American (AA) n = 85, Other n = 18) at Tulane from 2015-2016. Age at diagnosis, Gleasons, and the presence of metastases at any time were noted for these pts. Chi-square and the Mann-Whitney U tests were performed to identify relationships between clinical parameters and FH. 124 PCa pts including those with both localized and metastatic disease were identified with FHs that met guidelines for genetic testing. Genetic testing was done using a commercially available panel (Invitae, San Francisco, CA) of 25-79 cancer-related genes for mutations/selected exon deletions/duplications. Results: Of the 124 tested pts, 20 pts (16.1%) had ≥ 1 germline PV and 47 pts (37.9%) had ≥ 1 germline variant unknown significance. PVs included: BRCA2 (n = 4), BRCA1 (n = 3), CHEK2 (n = 3), MUTYH (n = 3), ATM (n = 2), TP53 (n = 1), MITF (n = 1), NBN (n = 1), PMS2 (n = 1), and RAD51D (n = 1). No PVs were detected in AA pts (n = 20). 435 of 535 PCa pts (81.3%) had a cancer FH with prostate (37.8%), breast (28.2%), lung (16.4%), colorectal (14.8%), and pancreatic (7.5%) cancer being most common. 281 pts (52.5%) had ≥ 2 relatives with cancer. Pts with PCa FH were more likely to be dx age ≤ 55 (p = 0.017). Median age was younger at dx for pts with PCa FH (p = 0.0005). PCa FH did not alter Gleason or metastatic rate. FH influenced age at dx for Ca men (p = 0.0009, 58 vs. 62.5 and Ca men with PCa FH) were 1.55x more likely to develop metastases (p = 0.035). In AA pts, there were no significant associations between FH, and metastases or age at dx. Conclusions: The most prevalent germline mutations in this cohort were in DNA repair pathway genes. Pts with PCa FH were younger at dx than those without PCa FH. Further studies are needed to understand the co-segregation of PCa with other cancers and genetic studies are needed to clarify the mechanisms of these trends which may differ between Ca and AA men.
The prostate clinical outlook (PCO) classifier for predicting biochemical recurrences in patients treated by stereotactic body radiation therapy.
Authors: Rho Mi Jung , Park Jihwan , Dritschilo Anatoly , Collins Sean P. , Suy Simeng , Choi In Young , Mun Seong K.
Published: September 2018

e16552

Background: Although prostate cancer risk classifiers have been developed for predicting surgical and radiation therapy outcomes, a classifier suitable for predicting biochemical recurrence (BCR) in patients undergoing stereotactic body radiation therapy (SBRT) remains to be defined. SBRT is delivered in large fractions of highly conformal radiation therapy and such treatments are believed to be radiobiologically more effective in treating prostate cancers. The aim of this study is to develop a new classifier specifically for informing patients electing to undergo prostate cancer treatment with SBRT. Methods: We have studied outcomes of 809 patients treated with SBRT between August 2007 and November 2016 at MedStar-Georgetown University Hospital. A Cox regression to BCR was performed and the Prostate Clinical Outlook (PCO) score was calculated at diagnosis based on age at diagnosis, clinical-radiological staging, pre-treatment PSA and Gleason score. Accuracy of the PCO classifier was assessed with concordance (c)-indexes. The results were also compared to classifications by D’Amico and National Comprehensive Cancer Network (NCCN) recurrence risk groups. Results: PCO total scores range from zero to 156 points. The PCO classifier splits patients into 3 risk-groups with the following 5-year BCR-free survival: for low-risk 98%; for intermediate-risk 95%; for high-risk 86%. Our classifier outperforms D’Amico and NCCN for all of the evaluated end-points, with concordance indices of 74 % versus 64 % and 66%, respectively. Conclusions: The PCO classifier is a potential tool for employing readily available parameters to stratify prostate cancer patients and to predict probabilities of BCR after SBRT.
Moore criteria application by an Argentinean public institution on patients with advanced cervical cancer (ACC).
Authors: Caceres Maria V. , Lopez Vanesa , Albi Laura Marcela , Cagnoni Ana Lucila , Savignano Mariana , Almada Carolina , Zapata Caamano Maria Gabriela , Roganovich Gustavo , Durand Alfonso Javier , Aguilar Andrea
Published: September 2018

e17010

Background: Moore criteria allows stratifying the risk of patients with ACC, predicting the rate of response (RR), the progression free survival (PFS) and the overall survival (OS), being an important prognostic tool being an important prognostic tool that can be used on Argentine population. Methods: Prospective, observational and descriptive analysis of 41 patients with ACC treated at Roffo Hospital in Buenos Aires, from 10/2013 to 1/2017. 35/41 (85%) patients received the planned treatment (6 cycles of Carboplatin AUC x 5 day 1, Paclitaxel 175 mg/m2 day 1) +/- Bevacizumab 15 mg/m2 day 1 every 21 days until progression. 6 patients (15%) received no treatment (2 for socioeconomic reasons and 4 due to poor performance status). 7/35 (20%) were treated without antiangiogenic (3 for the presence of a rectal-vaginal fistula and 4 due to socioeconomic reasons). These risk factors proposed by Moore were analyzed in all of the patients: performance status, previous treatment with cisplatin, pelvic disease and progression-free interval <365 days. Given the characteristics of our population, black race was not included as a prognostic factor. Results: 41 patients with ACC were analyzed: 19 (46%) were Stage IV, 5 (12%) had a persistent disease and 17 (42%) evidenced disease recurrence. Pursuant to Moore criteria, 19 patients (46%) were stratified as mid-risk, 18 (44%) as high-risk and 4 (10%) as low-risk. Treatment of mid-risk patients with Bevacizumab showed a 94% (17/18) clinical benefit rate (CBR) and the high-risk patients were 78 % (7/9) CBR. The 2 low-risk patients had partial response. Of the 7 patients treated without antiangiogenic, 2 mid-risk progressed; 1 low-risk had partial response and 4 high-risk showed 50% (2/4) partial response, and 50% (2/4) was pending at the moment this abstract was drafted. Conclusions: It is feasible to useMoore criteria to evaluate our population with ACC in order to estimate the prognosis of the disease. The percentage of low risk patients is poor in our population. Due to short follow-up time, only prognostic factors associated with CBR was assessed. Homologation of the black race factor with other socio-economical parameters related to access to healthcare is planned.
Institutional retrospective analysis of definitive chemo-radiotherapeutic treatment (QRT) in locally advanced cervical cancer.
Authors: Soule Tomas Jose , Mando Pablo , Sade Juan Pablo , Giornelli Gomez Gonzalo , Rivero Sergio Gabriel , Chacon Matias , Chacon Reinaldo D. , Orlando Mauro
Published: September 2018

e17016

Background: Retrospective analysis of toxicity and treatment impact of gemcitabine and platinum plus radiotherapy in patients with locally advanced cervix cancer. Methods: Descriptive, retrospective and observational study of patients with locally advanced cervix cancer (EIla/IVa).The analysis included toxicity Grade III/V and it impact in treatment. Results: We analyze 56 pts, median age: 46.5, median follow up: 24 months. Patients and tumoral characteristics are described in the table below. Regarding platinum group, 2pts required dose reductions of chemotherapy, 2pts suspended a cycle due to toxicity and 4pts needed RT split. 100% pts completed chemo radiotherapy concurrent treatment. Regarding platinum+gemcitabine group: 11pts required CT dose reductions, 14pts suspended a cycle due to toxicity and 5 didn´t complete CT due to toxicity; 6 had a RT split and 18 completed RT. Grade 3-4 toxicity was more frequent in the platinum+gemcitabine group (38.9% vs 73.7%, p=0.01) In platinum group, 14 pts presented disease recurrence. In the platinum + gem group 3pts had a recurrence. Median disease free interval (DFI) was not reached in both groups, but in the univariate analysis statistical significance was achieve, favouring the combine treatment (Log rank test, p=0.03). 2 year global survival rate was 82.1% in platinum group and 91.7% in platinum+gemcitabine groups. Conclusions: This report shows that the scheme of concurrent combine chemotherapy offers higher toxicity, requiring treatment discontinuation in some patients. Nevertheless, in a univariate analysis the platinum+gemcitabine group showed better results, even in a population with more advance disease with greater risk of relapse, understanding that the retrospective evaluation may miss confounders. A correct institutional manage of toxicities may allow the use of intense treatment to obtain potential benefits. [Table: see text]
Clinical trial of biopsies in oncology: Patient-reported impact (BIOPSY).
Authors: Wilson Michelle K. , Lheureux Stephanie , Cyriac Sunu , Dhani Neesha C. , Butler Marcus O. , Gutierrez David , Mandilaras Victoria , Ethier Josee-Lyne , Colombo Ilaria , Lee Yeh Chen , Kanjanapan Yada , Bonilla Luisa , Hunt Wendy , Bowering Valerie , Oza Amit M.
Published: September 2018

e17034

Background: Modest prospective data reports the impact of biopsies on patients (pts) with respect to adverse events (A/E) and anxiety. With increasing use of biopsies in clinical practice and trials, BIOPSY was designed to prospectively assess this. Methods: Pts undergoing a biopsy for diagnosis and/or research at Princess Margaret Cancer Centre were eligible. Surveys at 1 wk prior to biopsy and 1 wk and 1 mth post-biopsy assessed anxiety, A/E and pt experience. Anxiety was measured with a modified hospital anxiety and depression scale (HADS) score. Results: From 3/2015 to 1/2017, 51, 47 and 39 pts completed 1, 2 and 3 surveys respectively. Median age was 61 years. 40 biopsies were for research (78%) and 11 for diagnosis (22%). 46 pts were involved in a clinical trial (90%). 47 pts had a gynecological cancer (92%). 45 pts felt well-informed of the possible risks of the biopsy (88%). 23 pts noted the biopsy would not impact them directly (45%). 48 pts supported the use of tissue for future unrelated research (94%). Feelings of anxiety about the biopsy improved with time (table 1). 28 pts had pain 1 wk post-biopsy (60%) which was a moderate or major problem in 9 pts (19%). 2 pts reported reduced dignity with the biopsy (4%). 12 pts at 1 wk (26%) felt another biopsy would be a moderate-major issue. At 1 mth 3 of these pts reported a biopsy was now a mild problem. No significant A/E occurred. At baseline only 2 pts felt a biopsy would deter them from entering a clinical trial (4%). 42 pts at 1 wk (89%) and 30 pts at 1 mth (77%) felt they would consent to another biopsy for research. On univariate analysis pts with at least moderate pain post-biopsy at 1 wk or 1 mth (p=0.03) or an elevated HADS score at 1 mth (p=0.02) appeared less likely to agree to a further research biopsy but numbers were small. Conclusions: Anxiety and pain are potentially modifiable A/E that impact whether a pt will agree to a further biopsy. Overall, most pts tolerated their biopsy well, supported its use for future unspecified research and were open to further biopsies. [Table: see text]
Immunohistochemical changes in ovaries caused by chemoimmunotherapy.
Authors: Nepomnyashchaya Evgeniya M. , Nerodo Galina Andreevna , Ardzha Anna , Novikova Inna Arnoldovna , Ulianova Elena Petrovna , Zakora Galina I.
Published: September 2018

e17038

Background: The purpose of the study was to analyze morphological and immunohistochemical changes in patients with ovarian serous carcinomas under the influence of chemoimmunotherapy. Methods: The study included patients aged 52-76 years with stage IIIC-IV ovarian cancer with ascites. The patients were divided into two groups according to the treatment received: group A – 22 patients receiving neoadjuvant chemoimmunotherapy, 500 000 IU interferon-gamma (ingaron) on the 1st day and 1 000 000 IU on days 2, 3 and 5, and chemotherapy (carboplatin AUC-6 and paclitaxel 175 mg/m2) on day 4; group B – 24 patients receiving neoadjuvant chemoimmunotherapy and the same regimen of intraperitoneal interferon-gamma. The patients in two groups were similar in terms of disease stages, health condition and age. All patients received further surgery. Immunohistochemical study was performed on paraffin sections for the standard morphological study using Ki-67 rabbit monoclonal antibodies (Thermo scientific) and P-53 mouse monoclonal antibodies (Cell Marque). UltraVision Quanto Detection System HRP DAB was used for visualization. Results: Chemoimmunotherapy plus intraperitoneal interferon-gamma resulted in grade III-IV pathomorphosis, decreased apoptosis index and proliferation activity (р53 – 19.3±2.5%; Ki-67 – 6.2±0.58%) in comparison with the group receiving intramuscular interferon-gamma (р53 –27.6±3.11%; Ki-67 – 16.2±3.09%). The group with chemotherapy and intramuscular interferon-gamma showed grade II pathomorphosis. Conclusions: The study showed that chemotherapy with intraperitoneal interferon-gamma administration, compared with intramuscular one, resulted in more enhanced morphological changes.
Ovarian cancer with peritoneal carcinomatosis: Comparing of photodynamic treatment and HIPEC.
Authors: Privalov Alexey , Vazenin Andrey , Chernova Ludmila , Taratonov Alexey , Gubaydulina Tatiana
Published: September 2018

e17040

Background: Peritoneal carcinomatosis is a very common by ovarian cancer (OC). Usual treatment`s approaches such as systemic drugs are not very effective. 5-year survival by OC depends of stage and are 15-20% in III stage and only 5% in IV stage. Most part of this patients die with progression of peritoneal disease. Standart treatment`s approach by OC is radical surgery with adjuvant chemotherapy. But in many cases this tactic can`t control peritoneal lesions and, therefore, outcomes. Methods: In our oncology center we are performing retrospective non-randomized prospective study comparing two different treatment options by ovarian`s peritoneal carcinomatosis - photodynamic therapy (PDT) and hyperthermic intraperitoneal chemotherapy (HIPEC). There were 25 patients in PDT-group and 21 patients in HIPEC-group. Treatment in PDT-group included 2-4 cycles of neo-adjuvant chemotherapy (cyclophosphamid+cisplatinum /CP/, n=7 or paclitaxel+cisplatinum /TC/, n=18 ), after which we performed surgery+PDT and then 4-6 cycles same chemotherapy. We used iv. photolon (Russia) as photosensitizer and 630-680 nm diod laser. Time of procedure was 20 minutes. Peritoneal Carcinomatosis Index (PCI) was 4,2 an averege (1-12). Treatment in HIPEC-group included 2-4 cycles of neo-adjuvant chemotherapy (cyclophosphamid+cisplatinum /CP/, n=21), after which we performed surgery+HIPEC and then 4-6 cycles the same chemotherapy. Medium PCI was 5,6 (2-11). We used “closed” HIPEC technique, with 3 inflow and 3 outflow catheters, Performer HT device by RanD and 7 liters of saline solution with 200 mg cisplatunum or 100 mg/m2 taxans were used. Results: There were 11 recurrence in PDT-group (44%) and 10 recurrence in HIPEC-group (38%), t=1,06. Median of time to progression was 11.6 months in PDT-group and 13,5 months in HIPEC-group. Median of overall surviving was 18,4 and 24,1 months respectively. Conclusions: Using of PDT by ovarian cancer with peritoneal carcinomatosis didn`t show increasing of overall survival. We can also notice the non-statistical tendency of increasing time to progression in HIPEC-group. We run our study further and hope to collect more data for analysis.
Kinetics of HE4 and CA125 markers in metastatic ovarian cancer: The META4 study.
Authors: Lamy Pierre-Jean , Touraine Célia , Mollevi Caroline , Roques Sylvie , Viglianti Catherine , Montels Frederic , Floquet Anne , Ray-Coquard Isabelle Laure , Fabbro Michel
Published: September 2018

e17059

Background: HE4 is a new marker that could improve the detection of ovarian cancer (OC). The objective of the present study was to compare the prognostic value of the HE4 and CA125 markers in patients (pts) with metastatic epithelial OC, considering the progression-free survival (PFS). Methods: 101 pts, treated with 2nd/3rd line of chemotherapy, were included in 3 cancer centers between 2010 and 2014. Serums were prospectively collected before the 1stchemotherapy cycle, during chemotherapy and every 3 months until disease progression. The primary endpoint was HE4 and CA125 marker level evolution under treatment. Secondary endpoints were the markers’ main kinetic parameters: initial concentration, nadir, time to nadir, time to normalisation, half-life, doubling time and time to exceed the clinical threshold (CA125≥35UI/L; HE4≥75pM) (NCT01768156). Results: 89 pts were included in the final analysis. Median age was 65 (34-83). Histological sub-types were mainly serous (88%). The median PFS was 45 weeks (95%CI: 33.4-52). At baseline, median CA125 and HE4 levels were 210UI/L (7-10310) and 184pM (31-4836), respectively. Among 12 pts (13%) CA125- (with CA125 < 35UI/L), 8 were HE4+ (with HE4≥75pM) and among 16 pts (18%) HE4-, 12 were CA125+. The median nadir was 31UI/L (3-8744) for CA125 and 75pM (20-4836) for HE4. Median time to nadir was 14 (0-130) and 12 weeks (0-52) for CA125 and HE4, respectively. The median time to normalization was 17 (3-247) and 17 weeks (2-203) for CA125 and HE4, and the median half-life was 8 (1-193) and 12 weeks (2-166), respectively. The median doubling time and the time to exceed the clinical threshold were respectively of 13.5 and 40.2 weeks for CA125, and 23 and 23.6 weeks for HE4. In multivariate analysis, the CA125 nadir ( < 35 vs ≥35: HR = 3.13; 95%CI: 1.75-5.58), CA125 time to nadir ( < 14 vs ≥14: HR = 0.46, 95%CI: 0.28-0.76), HE4 nadir ( < 75 vs ≥75: HR = 1.95; 95%CI 1.16-3.27), and HE4 time to nadir ( < 12 vs≥12: HR = 0.39; 95%CI: 0.23-0.67) were found significant prognostic factors for PFS. Conclusions: Nadir and time to nadir were significant for both HE4 and CA125 markers in multivariate analysis. Further investigations on HE4 kinetic could be helpful for monitoring pts presenting no variation of CA125. Clinical trial information: NCT01768156.
The influence of chemotherapy induced nausea and vomiting (CINV) on survival: An individual participant data meta-analysis of the North-Eastern German Society of Gynecological Oncology (NOGGO) of 1213 recurrent ovarian cancer patients.
Authors: Woopen Hannah , Richter Rolf , Inci Guelhan , Chekerov Radoslav , Oskay-Oezcelik Gulten , Sehouli Jalid
Published: September 2018

e17062

Background: Nausea and vomiting are frequent side effects of chemotherapy and are the most feared toxicities of our patients. Aim of this study is to evaluate the potential influence of chemotherapy induced nausea and vomiting (CINV) on survival. Methods: Synthesized raw data of three phase II/III studies (“Tower”, “Topotecan phase III” and “Hector”) of the North-Eastern German Society of Gynecological Oncology (NOGGO) including 1213 patients were analyzed using logistic regression and cox regression analyses. Results: In this analysis 661 patients (54.5%) developed grade I/II and 44 patients (3.6%) grade III/IV nausea. 343 patients (28.3%) had grade I/II vomiting and 33 patients (2.7%) grade III/IV. There were no differences between severity of CINV regarding FIGO, grading, histology and amount of recurrences. Patients <65 years developed more frequently grade III/IV nausea than patients ≥ 65 years (p<0.001, OR 1.29, 95% CI 0.68-2.46). Polypharmacy was also associated with grade III/IV CINV (p<0.001 and p=0.002 respectively). Progression free survival was worse in patients with grade III/IV nausea (p=0.023, HR 1.58, 95% CI 1.14-2.20). Median overall survival (OAS) in patients without nausea was 19.0 months compared to patients with grade III/IV nausea with 11.0 months (p<0.001, HR for grade III/IV 2.35, 95% CI 1.64-3.37). Grade III/IV vomiting was also highly associated with worse OAS (median of 22.0 months in patients without vs. 5.9 months in patients with grade III/IV vomiting, p<0.001, HR for grade III/IV vomiting 3.4, 95% CI 2.32-5.00). However, dose reductions and prior discontinuation of chemotherapy were not more frequent in patients with nausea and vomiting. Conclusions: Patients with nausea and vomiting had a decreased progression and overall survival. This study underlines once again the importance of early best supportive care on survival.
Is there a correlation between serum Epstein-Barr virus DNA level and tumor metabolic activity, TNM staging and tumor load in nasopharyngeal cancer patients?
Authors: Ahmedova Aysel , Ozkaya Kubra , Tambas Makbule , Gezer Ugur , Ozgur Emre , Sahin Dilek , Sanli Yasemin , Altun Musa
Published: September 2018

e17543

Background: To investigate the relationship between pretreatment Epstein-Barr virus (EBV) DNA copy number and tumor metabolic activity, TNM stage and tumor volume in nasopharyngeal cancer (NPC) patients. Methods: Blood samples were collected 0-3 weeks before treatment and number of EBV DNA copies were determined by PCR . MRI and PET-CT were performed 0-4 weeks before treatment. The primary tumor volume (TVnp) and total volume of metastatic lymph nodes (TLV) were delineated separately on MRI by the same radiologist by the aid of program “Osirix” and recorded in cm3. Maximum SUV values of primary tumor (Tsuv) and metastatic lymph nodes (LNsuv) were determined with each PET-CT images. Kruskal Wallis test and Spearman's Correlation Analysis were used for the comparison of 3 or more groups with no normal distribution and the evaluation of the inter-parameter relations, respectively. Results: The study included 50 NPC patients treated between 2011 and 2015. There was no significant relation between serum EBV DNA copy number and the distribution of T stage (p = 0.81), N stage (p = 0.08), TVnp (r:0.009; p = 0.95), and Tsuv (r:-0.007, p = 0.96). However, a significant correlation was detected between EBV DNA copy number and both LNsuv (r:0.337; p = 0.017) and TLV (r:0.579; p = 0.001) (LNsuv and TLV increased as virus load increased). Conclusions: There is no significant relation between pretreatment EBV DNA load and T and N stages and TVnp in NPC patients. However, EBV DNA load has a significant correlation with TLV and LNsuv. These results may imply that TLV can be included in nodal staging and together with LNsuv be integrated in treatment planning.[Table: see text]

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Endovascular treatment for locally advanced head and neck tumors.
Authors: Aedinova Irina V. , Chernyak M. N. , Ulianova Yulia , Volkova Viktoriya L. , Chertova Natalia A. , Bauzhadze Mamuka
Published: September 2018

e17554

Background: Treatment of locally advanced head and neck tumors is an extremely difficult task. Preoperative polychemotherapy allows improving the efficiency of combined treatment in most cases. We performed 6 chemoembolization procedures for locally advanced head and neck cancer in order to increase the effectiveness of chemotherapy with minimal systemic side effects and to reach cytostatic concentrations in tumors higher than at their intravenous administration. Methods: We performed the standard puncture femoral approach and selective catheterization of the external carotid artery followed by angiography. Superselective catheterization of targeted vessels using 2.6 F microcatheter was performed after evaluation of blood supply to the affected area. Chemoembolization was performed with platinum drugs (cisplatin at a mean dose of 50 mg/m2) in an oil emulsion with Lipiodol (4 patients) and saturable microspheres (2 patients). Results: All patients showed a severe pain syndrome during embolization with its increase by the evening of the day and its regression on the third day after surgery; general toxic symptoms were not observed. Significant perioperative complications were not registered. A marked necrosis of the tongue base tumor was observed in one patient after 10 days. All patients showed a partial positive response to the therapy which allowed radical surgical treatment. Conclusions: Chemoembolization with polymeric microspheres provides a longer (up to one month) contact between malignant cells and antitumor agents; chemoembolization is not accompanied by the development of adverse reactions and complications or immunosuppressive effect which allows its use in the most serious cases.
Induction chemotherapy followed by concurrent chemotherapy and proton beam for sinonasal undifferentiated carcinoma.
Authors: Lu Yue Christine , Adams Judith A. , Clark John Ross , Liebsch Norbert , Chan Annie W
Published: September 2018

e17557

Background: The optimal treatment of sinonasal undifferentiated carcinoma (SNUC) remains to be defined given its aggressiveness and dismal outcome with traditional treatment. We examined the treatment outcomes of SNUC treated with combined proton beam with concurrent chemotherapy +/- induction chemotherapy. Methods: Between 2005 and 2016, 15 patients with SNUC were treated at our institution. All patients had T4 disease, with 20% had nodal involvement and 87% with orbital invasion. Forty-seven percent of patients underwent induction chemotherapy followed by concurrent chemoradiotherapy (sequential group) and 53% underwent or concurrent chemoradiotherapy alone. All patients underwent proton beam for the primary site and upper neck, and photon irradiation for the lower neck. The median dose to the primary site was 70Gy(RBE). Locoreigonal control, freedom from distant metastasis, disease-free survival, and overall survival were estimated by the Kaplan-Meier method. Results: With a median follow-up of 25 months, there were 2 local, 2 regional, 4 distant, and 5 dural-leptomeningeal failures. The 2-year locoregional control rates were 100% and 60% (95%CI:33%-100%) for the sequential and concurrent alone groups, respectively, (p=0.10). The 2-year overall survival was 100% for the sequential group and 58% (95%CI:31%-100%) for the concurrent group (p=0.03). The 2-year distant-metastasis-free survival was 83% (95%CI:58%-100%) and 31% (95%CI:10%-96%) for the sequential and concurrent group, respectively (p= 0.03). Furthermore, the sequential group has a 2-year disease-free survival rate of 100% compared with 58% (95%CI:31%-100%) for the concurrent group (p=0.02). Conclusions: Induction chemotherapy followed by concurrent chemotherapy and proton beam results in promising outcome in patients with SNUC.
Addition of concurrent chemotherapy to adjuvant radiotherapy versus radiotherapy alone for resected salivary gland cancers: A systematic review and meta-analysis.
Authors: Sogono Paolo Generato , Mejia Michael Benedict A. , Agas Ryan Anthony Francisco
Published: September 2018

e17563

Background: Surgery remains to be the standard definitive treatment for malignant tumors of the salivary gland. Post-operative radiotherapy (RT) is warranted for high risk individuals having tumors with high grade, advanced disease or inadequate resection, showing local control and survival benefit. Despite lack of evidence, adjuvant chemoradiation (CRT) has been suggested for worse prognosis patients. Two recent population-based studies showed that adding chemotherapy to RT did not demonstrate a survival advantage, and no randomized study answers this question. Our aim is to review current evidence comparing RT with and without concurrent chemotherapy in non-metastatic, resected salivary gland cancer. Methods: Literature was searched using: CINAHL plus, EBSCOhost, Medline Complete, Science Direct, Proquest, Scopus, and Pubmed. Eligible studies were experimental or observational which compare adjuvant radiotherapy alone versus radiotherapy with concurrent chemotherapy after primary surgery. Pooled analysis for eligible studies was conducted utilizing the Mantel-Haenzel model (random effects) for the outcomes of interest. The NHMRC of Australia Body of Evidence Framework was used to provide an overall evidence recommendation. Results: Eight retrospective studies were included in the qualitative analysis and two were cancer database studies. Pooled analysis from 4 studies showed inferior 3-year overall survival in patients receiving adjuvant CRT(RR 2.15, 95% CI 1.23-6.75). There were no significant differences in 3-year LRC, DMFS or PFS between both groups, although a trend for worse 3-year DMFS and PFS was observed in the CRT group. G3 hematologic toxicity was worse in patients receiving adjuvant CRT vs RT alone (RR 8.63, 95% CI 1.69-44). Critical appraisal revealed that more patients with adverse risk features (T3-T4, node positive, LVSI, PNI, close or positive margins) received CRT. Conclusions: The addition of concurrent chemotherapy to RT in resected salivary gland cancer does not improve overall survival is associated with worse outcomes and greater toxicity.
Floor of mouth window to improve surgical access for trans-oral cancer surgery.
Authors: Chung Jeffson Chia-Hsien , Bender-Heine Adam , Lambert H. Wayne
Published: September 2018

e17568

Background: The increasing incidence of HPV associated oropharyngeal cancer has sparked interest in minimally invasive transoral surgery as a primary treatment modality. However, adequate surgical exposure and access to the tongue base is difficult to achieve. Many complex oral retraction systems have been developed in attempt to solve this problem but none work consistently or efficiently. Methods: This cadaveric study introduces the floor of mouth window – a simple adjunctive procedure done at the time of transoral resection and concurrent neck dissection that greatly improves surgical access to the tongue base while eliminating the need for oral retractors. It involves passing the oral tongue through the floor of mouth into the neck dissection field, thereby creating space for robotic or laser instruments to perform cancer resection. The floor of mouth is closed primarily in layers at the end of the procedure. Results: This study compares the tongue base exposure achievable with existing oral retractors to that achievable utilizing this novel technique. Our finding is that superior surgical exposure is attainable without retractors using the floor of mouth window. In fact, laser resection of the base of tongue was successfully performed in cadavers without the use of any retractors. Conclusions: We believe this technique may have a major impact on the management of oropharyngeal cancers because having a simple, reproducible method to access the tongue base will encourage greater adoption of transoral surgery as a treatment modality. It is a technique that can be helpful regardless of any future advances in robot or laser technology. Furthermore, this technique reduces the reliance on multiple complicated and expensive retraction systems. Finally, the improved exposure and visualization of the tongue base attainable by this new procedure may facilitate clear surgical margins and thus maximize the potential for cure, which is ultimately the objective of all head and neck surgeons.
Relationship between sarcopenia and dose-limiting toxicity (DLT) of sorafenib (SOR) in patients (pts) with advanced radioactive iodine-refractory differentiated thyroid cancer (RAI-R DTC) in the phase III DECISION trial.
Authors: Huillard Olivier , Brose Marcia S. , Jouinot Anne , Tlemsani Camille , ARRONDEAU Jennifer , Meinhardt Gerold , Fellous Marc Mardoche , De Sanctis Yoriko , Schlumberger Martin , Goldwasser Francois
Published: September 2018

e17594

Background: In the phase III DECISION trial comparing SOR with placebo, pts with advanced RAI-R DTC treated with SOR experienced higher rates of adverse events (AEs) than pts with renal cell carcinoma and hepatocellular carcinoma treated with SOR (Brose et al. Lancet 2014). We hypothesized that long-term thyroxine suppressive therapy might result in a high prevalence of sarcopenia, which is known to be associated with increased toxicity of SOR (Antoun et al. Ann Oncol 2010), and we investigated whether sarcopenia at baseline correlated with DLT. Methods: In DECISION, pts with an analyzable baseline lumbar CT scan were eligible. Skeletal muscle cross-sectional area at the third lumbar vertebra was measured, and the median value for each sex defined the cut-off points for sarcopenia. DLT was defined as any AE leading to dose modification; early toxicities occurred ≤30 days after treatment initiation. Results: Of 365 eligible pts, 199 (55%) were sarcopenic (SOR n = 100, placebo n = 99) with large geographic differences: 65/91 Asians (71%), 29/62 North Americans (47%), and 105/212 Europeans (50%). Sarcopenia was 3-fold more frequent than non-sarcopenia in pts ≥75 years of age (19% vs 6%) and was associated with lower body weight (mean [standard deviation]: 71.3 [16.8] vs 80.8 [19.5]; P < 0.0001). Among SOR pts, 76/180 (42%) experienced early DLT of which 44/76 (58%) occurred in sarcopenic pts (P = 0.6497). Among the 90 males, 61 (68%) were sarcopenic and of the 35 males with early DLT, 27 (77%) were sarcopenic. Median time to DLT in sarcopenic vs non-sarcopenic pts who received SOR was 63 vs 95 days, respectively (log-rank P = 0.5328). Conclusions: In this exploratory analysis from DECISION, approximately half of the pts were sarcopenic. In the overall population, no association between sarcopenia and early DLT or DLT were found. Clinical trial information: NCT00984282.
Oncocontraception in cancer care.
Authors: Radeke Erika K. , Zimmerman Lindsay , Bridge Rebecca , Adam Megan , Patel Ashlesha
Published: September 2018

e18018

Background: Focus on fertility preservation has overshadowed other aspects of reproductive health including sexuality and contraception in cancer care. Regardless of future childbearing interest, the first 18-months post-diagnosis of cancer are considered suboptimal for childbearing. We have coined the term, oncocontraception, for the application of contraception in cancer care. To address this need at our institution, we used the novel Family Planning Quotient/Reproductive Life Index (FPQ/RepLI) which allows providers to better understand patients’ reproductive health goals and counsel them towards appropriate family planning services. These tools aid providers in implementing clinical care to prevent pregnancy during this critical time. They are routinely utilized at Stroger Hospital in the Family Planning Clinic for women within the reproductive age, between the ages of 18 and 55. Methods: FPQ and RepLI were adapted for use with oncology patients. They were used to visually depict and quantify a woman’s reproductive life plan and assist health care providers in speaking to a woman regarding family planning as it pertains to and aligns with her cancer treatment. Results: During our study period, 36 reproductive aged women were seen in our family planning clinic after a cancer diagnosis. Our study population was comprised of mostly Hispanic/Latino women (58.3.0%) and 50.0% were between the ages of 31-40. The majority of the study group had breast cancer (77.8%) and were being treated with chemotherapy (52.8%). Among the study population, 80.6% received a form of contraception (44.8% short-term, 55.2% long-term). Conclusions: We established a link between the Oncology and Family Planning Clinics to incorporate contraceptive counseling as an essential piece of comprehensive cancer care. Approximately 45% of the women newly diagnosed with cancer are in the reproductive age range. With improvements in treatments and prognosis, quality of life factors are of increasing importance for these women. With this essential clinical relationship, patient counseling and provider-patient communication regarding contraceptive care in the context of cancer diagnosis will continue to grow and improve.