bluuebunny/crossref_metadata_2025_split huggingface dataset:
Activity of pazopanib in chemo-resistant patients with germ cell tumors (GCT): First results of the open-label, single-group, phase II PAZOTEST-01 trial.
Authors: Giannatempo Patrizia , Nicolai Nicola , Farè Elena , Raggi Daniele , Piva Luigi , Biasoni Davide , Catanzaro Mario , Torelli Tullio , Stagni Silvia , Maffezzini Massimo , Crestani Alessandro , Togliardi Elena , Salvioni Roberto , Gianni Alessandro M. , Necchi Andrea 
Published: February 2017

376 Background: Patients (pts) with germ cell tumors (GCT) who fail to be cured following multiple chemotherapy (CT) courses (± high-dose CT) have an extremely poor prognosis and long-term remissions are anecdotal. Pazopanib (PZP) is a potent and selective, orally available, TKI of VEGFR1, 2, and 3, PDGFRα, PDGFRβ, and cKit. Here we report the initial results of the ongoing open-label, single-group, phase II study which is sponsored by INT Milano (ClinicalTrials.gov NCT01743482). Methods: Pts with refractory GCT received pazopanib 800 mg/day orally until disease progression or evidence of unacceptable toxicity/side effects. Eligibility requirements included failure of at least two platinum-based CT, including high-dose CT. All pts underwent measurement of serum tumor markers (STM), a computed tomography and a FDG-PET after one month of treatment and q2 months thereafter. Results: From May 2013 to July 2013, five pts were enrolled, three in fourth, and two in fifth-line. Median age was 39 (IQR: 33 to 48). Three out of five had failed high-dose chemotherapy (HDCT), two had an extragonadal primary, all pts had at least one elevated STM at baseline, the sole parameter in one patient, two had liver metastases, four pts had a retroperitoneal relapse. Four had elevation of alfafetoprotein (AFP), one of human choriogonadotropin (HCG). Four were nonseminomas, one a pure seminoma. After the first month of treatment, four out of five pts had a decrease in marker levels, one patient had disease progression (PD). Two of the responding pts had a necrotic evolution of disease at computed tomography corresponding to a RECIST and metabolic (PET/CT) progression, two had a stable disease. Two-month follow up is available for three out of four responders: one interrupted PZP for toxicity and had a marker PD, another an increase to baseline levels and the last one a further reduction (pure seminoma, one out of five confirmed response at two months). There were two cases of hepatic toxicities (one G2 and one G3-4 with dose interruption). Conclusions: PZP is endowed with preliminary activity in extensively pretreated patients with GCT. The unique availability of STM in interpreting densitometric and metabolic response might provide insights into response assessment of solid tumors under antiangiogenic therapy. Clinical trial information: NCT01743482.
Risk of renal cell cancer in people immunodepressed after solid organ transplant: Results from an Italian multicenter cohort study.
Authors: Piselli Pierluca , Busnach Ghil , Citterio Franco , Burra Patrizia , Ettorre Giuseppe Maria , Segoloni Giuseppe Paolo , Messa Piergiorgio , Sandrini Silvio , Rigotti Paolo , Scolari Maria Piera , Piredda Gian Benedetto , Donati Donato , Maresca Maria Cristina , Tisone Giuseppe , Sparacino Vito , Vizzini Giovanni Battista , Cimaglia Claudia , Fratino Lucia , Serraino Diego , Grandaliano Giuseppe ,   The Immunosuppression and Cancer Study Group
Published: February 2017

422 Background: The etiology of renal cell cancer (RCC) is poorly understood, and data from immunosuppressed population may help to highlights risk factors unknown in the immune competent population. To assess incidence and risk factors for renal cell cancer (RCC) after kidney and liver transplant (KT and LT, respectively), we carried out a cohort investigation in 24 Italian transplant centers. Methods: This study is part of an ongoing cohort investigation conducted in 24 transplant centers in all of Italy. Two cohorts have been implemented, including 7,217 KT recipients (64.2% men) and 2,770 LT recipients (74.7% men) transplanted between 1997 and 2009—and followed-up until 2010. Person years (PY) at risk of cancer were computed from 30 days after transplant to cancer diagnosis, death, return to dialysis (for KT) or to study closure. The number of observed cancers was compared to that expected in the general population through standardized incidence ratios (SIR) and 95% confidence intervals (CI). To identify risk factors, incidence rate ratios (IRR) were computed through Poisson regression. Results: Overall, 581 cancers were diagnosed during 61,817 PYs of follow-up, with Kaposi’s sarcoma, non-Hodgkin lymphoma, lung, RCC, and prostate as the most common types. Thirty-eight cases of RCC were diagnosed (36 in KT and 2 in LT). As compared to the general population, the risk of RCC was 4.9-fold significantly higher in KT recipients than expected (95% CI: 3.4-6.8). The increased risk was restricted to the native kidney (31 native kidney OR=4.2, 95% CI:2.9-6.0), and no risk elevation was found in LT recipients (SIR=0.5 95% CI: 0.1-1.9). Use of mTOR inhibitors seemed to exert a 40% reduced risk (IRR=0.6, 95% CI: 0.2–1.4) of RCC, but the difference was not statistically significant. Conclusions: Our study findings confirmed, in Italy, the increased risks for RCC following KT, and they also suggested a possible protective effect of mTORi. The magnitude of the excess risk documented in this cohort study was higher than reported for potential risk factors described in immune competent people—or in people under dialysis—thus suggesting a role for the immune system in the etiology of RCC.
The role of obesity in the incidence of lymphatic spread, disease-free, and overall survival: Data from the ARISER clinical trial.
Authors: Chamie Karim , Kloepfer Pia , Fall Barbara , Said Jonathan W. , Störkel Stephan , Bevan Paul , Belldegrun Arie S. , Pantuck Allan J. ,   ASCO
Published: February 2017

435 Background: The role of obesity and the incidence of high-risk clear cell renal cell carcinoma (ccRCC) are poorly understood. We examined the association of obesity with lymphatic spread and survival using data from an international Phase III clinical trial testing the efficacy of adjuvant treatment with cG250 antibody in subjects with non-metastatic (ccRCC) at high risk for recurrence. Methods: We reviewed the clinical and pathologic records of 864 patients across three continents and 14 countries that were enrolled in a prospective, double blind, placebo controlled study of adjuvant cG250 Ab treatment for high-risk ccRCC. Clinical features analyzed included age, gender, race, body mass index (BMI), and performance status. A single pathologist centrally reviewed the specimens for TNM stage and nuclear grade. BMI was stratified into normal (<25 kg/m2), overweight (25.0–29.9 kg/m2), obese (30.0–34.9 kg/m2), and morbidly obese (≥35 kg/m2). We examined the association between BMI, disease severity, and survival using logistic and Cox regression analyses, respectively. Results: Mean BMI was 28.2 kg/m2. The vast majority of our cohort was overweight (43%) and an additional 29% were obese (or morbidly obese). The incidence of lymphatic spread decreased with rising BMI: normal was 11%; overweight was 8%; obese was 5%; and morbidly obese was 2%. Obesity was associated with improved disease-free and overall survival, log rank=0.01 and <0.01, respectively. When compared with those who were normal in weight, subjects who were obese (HR 0.50, p<0.01) and morbidly obese (HR 0.22, p<0.01) had significantly improved overall survival. A trend towards improved disease-free survival was found among subjects who were obese (HR 0.77, p=0.10) and morbidly obese (HR 0.69, p=0.09). Conclusions: While we cannot speak to the association between obesity and ccRCC, our study demonstrates that in a cohort of nephrectomized patients with high-risk disease, obesity is associated with a lower risk of lymphatic spread and improved overall survival.
Retrospective observational study of sunitinib administered on schedule 2/1 in patients with metastatic renal cell carcinoma (mRCC): The rainbow study.
Authors: Bracarda Sergio , Iacovelli Roberto , Rizzo Mimma , Rossi Marta , Galli Luca , Procopio Giuseppe , Longo Flavia , Santoni Matteo , Morelli Franco , di Lorenzo Giuseppe , Porta Camillo , Camerini Andrea , Di Bella Sara , Martignetti Angelo , Gasparro Donatello , Sabbatini Roberto , Ceresoli Giovanni Luca , Mosca Alessandra , Santini Daniele , Boni Luca 
Published: February 2017

471 Background: Sunitinib is a standard of care in first line mRCC; however, an increasing percentage of treatment-related adverse events are observed in the last 2 treatment weeks of the standard schedule 4/2 (4-weeks-on/2-weeks-off). In a multicenter, retrospective study, we evaluated the efficacy and safety of a modified 2/1 schedule (2-weeks-on/1-week-off), largely used in Italy based on a favorable initial experience. Methods: Data from all consecutive patients (pts) treated in 24 Italian centers with sunitinib on schedule 2/1 were analyzed according to the following groups: Group A, pts moved to schedule 2/1 because of treatment-related toxicities during initial therapy using schedule 4/2; Group B, pts treated ab initio with schedule 2/1, mainly because of poorer clinical conditions. A small group of pts treated with schedule 4/2 served as a control (Group C). Results: 276 consecutive pts treated from November 2005 to August 2013 were analyzed, including 249 treated with schedule 2/1 (Group A, n=208; Group B, n=41; respectively, median age 62 and 61 years; clear cell 94.7% and 87.8%; MSKCC good/intermediate/poor 47.1%/46.6%/6.3% and 36.5%/53.7%/9.8%; brain metastases 3.8% and 9.8%) and 27 pts in Group C (median age 59 years; clear cell 96.3%; MSKCC good/intermediate/poor 22.2%/70.4%/7.4%; no brain metastases). In Group A, the median treatment duration (TD) was 28.2 months (m) (with a median of 4.3 on the initial schedule 4/2 and 19.7 on the following schedule 2/1); median progression-free survival (PFS) was 38.6 m (95% CI, 24.0-58.6). In Group B (with less clear cell cases and more pts of intermediate risk or with brain metastases) median TD was 7.8 m and median PFS was 9.6 m (95% CI, 6.3-14.2). Median TD in Group C was 10.4 m. Maximum toxicity grade (≥3) and specific toxicities such as fatigue and hypertension were significantly reduced on schedule 2/1 in Group A compared with the initial schedule 4/2 (respectively, 8% vs 46% and 0% vs 10%, p < .001, and 2% vs 9%, p = .007). Conclusions: In our experience, sunitinib on a modified schedule 2/1 has an improved safety profile and increased efficacy compared with schedule 4/2. Prospective evaluation of this schedule is warranted.
Impact of obesity on outcomes after definitive dose escalated intensity modulated radiation therapy for localized prostate cancer.
Authors: Wang Lora S , Ruth Karen J. , Smaldone Marc C. , Kutikov Alexander , Sobczak Mark L. , Viterbo Rosalia , Horwitz Eric M. 
Published: February 2017

50 Background: Multiple retrospective studies have investigated the association between body mass index (BMI) and biochemical failure (BF) after definitive external beam radiotherapy (EBRT) of localized prostate cancer (CaP) prior to the dose escalation era, with conflicting results. The purpose of this study is to determine whether increasing BMI is associated with CaP outcomes in patients treated with dose escalated radiotherapy. Methods: From 2000 to 2010, we identified 1,291 patients with localized (T1b-T4N0M0) CaP who were treated with definitive intensity modulated radiation therapy (IMRT). BMI was categorized using World Health Organization classification. Multivariable competing risk and Cox proportional hazards regression models were used to assess the risk of BF, distant metastasis (DM), cause-specific mortality (CSM) and overall mortality (OM). BF was defined as prostate-specific antigen (PSA) greater than or equal to nadir + 2 ng/mL. Covariates included age, androgen deprivation therapy (ADT), pre-treatment PSA (iPSA), Gleason score, and T stage. For OM, self-reported history of diabetes, heart disease, and hypertension were included. Results: Of the 1,291 patients identified, there were 20% normal (BMI<25 kg/m2), 47% overweight (BMI 25-29.9), 23% obese class I (BMI 30-34.9), 6% obese class II (BMI 35-39.9), and 4% obese class III (BMI >40). Median follow-up was 43.7 months (range 1.1-127) with median age of 68 (range 36 to 88). Median dose was 78 Gy (range 76-80) and 33% of patients received ADT. Increasing BMI was inversely associated with age (p<0.0001) and iPSA (p=0.047). There were 128 BF, 51 DM, 15 CSM, and 119 OM. Risk of BF, CSM, and OM were increased for obese class II and III compared to normal (all p<0.05). On multivariable analysis, for BF, HR was 2.1(p=0.057) for obese class II and 2.5 (p=0.043) for class III. For CSM, HR was 5.1 (p=0 .028) for class II and 5.15 (p=0.014) for class III. For OM, HR was 2.3 (p=0.022) for class II and 2.6(p=0.023) for class III. There was a trend toward increased DM for class III (p=0.057). Conclusions: For CaP patients receiving IMRT, those with higher levels of obesity may be at increased risk of BF and prostate cancer mortality, and should be considered for more aggressive treatment.
Treatment pattern and prognosis in Japanese patients with metastatic renal cell carcinoma (mRCC) with favorable or intermediate MSKCC risk factors in the era of molecular targeted therapy.
Authors: Shinohara Nobuo , Maruyama Satoru , Obara Wataru , Tatsugami Katsunori , Naito Sei , Kamba Tomomi , Naito Seiji ,   Japanese Collaboration Group
Published: February 2017

532 Background: We investigated the prognosis of Japanese mRCC patients with favorable or intermediate MSKCC risk factors in the era of molecular targeted therapy Methods: Data on patients who started systemic therapies including cytokine and molecular targeted therapies at 18 hospitals between 2008 and 2010 was analyzed. Of these, 269 patients classified as favorable or intermediate prognosis according to MSKCC risk classification were the subject of this analysis. The endpoints of the present study were progression-free survival (PFS) and overall survival (OS). Relationships between PFS or OS and clinical variables were assessed using the Cox-proportional hazard model. Results: The median OS of all 268 patients was 38 month, and 3-year OS rate was 51% (95%CI 45-58). Regarding the first-line therapy, IFN-alfa (IFN), sunitinib (SU), sorafenib (SO), and others were administered in 89 (33%), 104 (39%), 40 (15%), and 35 (13%). There were more patients without nephrectomy and with multiple organ metastases in patients received SU or SO compared to patients received IFN. Median PFS (mPFS) and 1-year PFS rate in patients who received IFN, SU, and SO were 5 months and 38%, 12 months and 50%, and 11 months and 48% (p=0.556), respectively. Second-line therapy was performed in 69 patients of first IFN group (mPFS: 9 months), 67 of first SU group (mPFS: 7 months), and 24 of first SO group (mPFS: 3 months). Third-line therapy was performed in 47 patients of first IFN group (mPFS: 11months), 35 of first SU group (mPFS: 5 months) and 12 of first SO group (mPFS 3 months). Median OS in patients who received IFN, SU, and SO as first-line therapy were 45, 29 and 27 months (p=0.093), respectively. Multivariate analysis demonstrated that lower value of serum C-reactive protein and first IFN therapy were associated with more favorable OS (p<0.05). Conclusions: In Japanese mRCC patients with favorable or intermediate MSKCC risk factors, first IFN therapy would still be appropriate even in the era of molecular targeted therapy. Furthermore, more potent sequential strategy after first molecular targeted therapy should be established for the improvement of OS.
Results of a phase II trial of novel carbonic anhydrase IX radiotracer 18F-VM4-037 in renal cell carcinoma.
Authors: Metwalli Adam R. , Turkbey Baris , McKinney Yolanda , Weaver Juanita , Yaqub-Ogun Nana , Merino Maria , Lindenberg Maria Liza , Linehan W. Marston , Choyke Peter L. 
Published: February 2017

LBA400 Background: Carbonic Anydrase IX (CAIX) has been identified as a potential marker for clear cell renal cell carcinoma (ccRCC). We report the results of a phase II clinical trial of a novel small molecule radiotracer that binds to CAIX in clinically localized kidney tumors or biopsy proven metastases. Methods: Between October 2012 and May 2013, patients with kidney tumors underwent imaging with the 18F-VM4-037 radiotracer within 4 weeks of biopsy or surgery for kidney tumors. Imaging characteristics with the radiotracer were collected. All H&E pathology was centrally reviewed by a single pathologist. Immunohistochemistry of the surgical specimens for CAIX and Carbonic Anhydrase XII (CAXII) was reviewed by two experienced pathologists. Primary objectives were to evaluate the biodistribution of the radiotracer within tumor and non-tumor tissues as well to assess the safety of the radiotracer in patients. Results: 12 patients were enrolled and 11 received radiotracer and images were obtained. All patients tolerated the radiotracer well with no significant adverse events. 10 of the 11 patients had histologically confirmed malignancy. 1 patient had a complex cyst with no tumor found at surgery. Two patients had extrarenal disease and 9 had tumors in the kidney only. 100% had ccRCC and 4/11 had germline VHL mutations. Mean SUV for the entire group as 5.44 in the index lesions; in patients with histologically confirmed ccRCC the mean SUV was 5.91. 12 samples were stained for CAIX and CAXII including a biopsy obtained from a lung metastasis in one patient. The concordance between pathologists for CAIX IHC was 75%, for CAXII was 67%. Of the CAIX IHC slides, 67% had 3+ staining, 25% had 2+ and one specimen did not demonstrate CAIX staining. Only one specimen demonstrated 3+ staining for CAXII; 2 specimens had no detectable staining for CAXII and the remainder stained 1-2+ for CAXII. Conclusions: The 18F-VM4-037 was well tolerated and demonstrated modest signal uptake in tumors within the kidney. Immunohistochemistry staining for CAIX and CAXII was robust in nearly all tumors making correlation with radiotracer signal difficult. Larger studies are needed to evaluate the diagnostic performance of this radiotracer. Clinical trial information: NCT01712685.
Reduction in late mortality among 5-year survivors of childhood cancer: A report from the Childhood Cancer Survivor Study (CCSS).
Authors: Armstrong Gregory T. , Yasui Yutaka , Chen Yan , Leisenring Wendy M. , Gibson Todd M. , Mertens Ann , Stovall Marilyn , Hudson Melissa M. , Oeffinger Kevin C. , Bhatia Smita , Krull Kevin R. , Nathan Paul C. , Neglia Joseph Philip , Green Daniel M. , Robison Leslie L. 
Published: February 2017

LBA2 Background: Over the past four decades, treatment of many childhood cancers has been modified with the aim of achieving high survival rates while reducing the risk of life-threatening late-effects, and promoting risk-based follow-up care of survivors. Methods: Late mortality was evaluated in 34,033 5-year survivors (diagnosed < 21 years of age from 1970-1999, median follow-up 21 years, range 5-38) using cumulative incidence and Poisson regression models adjusted for demographic and disease factors to calculate relative risk (RR) and 95% confidence intervals (CI). Mortality due to non-recurrence/non-external (NR/NE) causes, which includes deaths that reflect late-effects of cancer therapy, was evaluated. Results: 1,622 (41%) of the 3,958 deaths were attributable to NR/NE causes, including 751 subsequent neoplasm (SN), 243 cardiac, and 136 pulmonary deaths. Changes in therapy by decade included reduced rates of: cranial radiotherapy (RT) for acute lymphoblastic leukemia (ALL, 86%, 54%, 22%), RT for Wilms tumor (WT, 77%, 54%, 49%) and RT for Hodgkin lymphoma (HL, 96%, 88%, 77%). Reductions in 15 year cumulative NR/NE mortality were observed across treatment eras for ALL (p < .001), HL (p = .005), and WT (p = .005). Cardiac deaths decreased in ALL (p = .002), HL (p = .06), and WT (p = .04), and SN deaths decreased in WT (p < .001). Year of diagnosis (adjusted for age, sex, diagnosis, follow-up time) was significantly associated with a reduced risk of all-cause mortality (RR = 0.85, CI 0.83-0.87), NR/NE death (RR = 0.87, CI 0.84-0.91), death from SN (RR = 0.84, CI 0.80-0.89), cardiac death (RR = 0.78, CI 0.69-0.87) and pulmonary death (RR = 0.79, CI 0.68-0.91). Conclusions: The CCSS cohort provides evidence that the strategy of modifying therapy to reduce the occurrence of late-effects, and promotion of early detection, is successfully translating into a significant reduction in observed late mortality. [Table: see text]
Ibrutinib combined with bendamustine and rituximab (BR) in previously treated chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL): First results from a randomized, double-blind, placebo-controlled, phase III study.
Authors: Chanan-Khan Asher Alban Akmal , Cramer Paula , Demirkan Fatih , Fraser Graeme , Silva Rodrigo Santucci , Pylypenko Halyna , Grosicki Sebastian , Janssens Ann , Pristupa Alexander , Mayer Jiri , Dilhuydy Marie-Sarah , Loscertales Javier , Bartlett Nancy L. , Avigdor Abraham , Rule Simon , Sun Steven , Mahler Michelle , Salman Mariya , Howes Angela J. , Hallek Michael J. 
Published: February 2017

LBA7005 Background: The phase III HELIOS study evaluated the first-in-class, oral covalent BTK inhibitor ibrutinib in combination with BR (BR+ibr) vs BR plus placebo (BR+plb) in patients (pts) with previously treated CLL/SLL. The preplanned interim analysis reported here showed that the primary end point was met, upon which the IDMC recommended unblinding the study. Methods: Pts received BR ( ≤ 6 cycles) and were randomized 1:1 to ibr (420 mg daily) or plb. Purine analog refractoriness was a stratification factor. Pts with del17p ( > 20% of cells) were excluded. Primary end point was independent review committee (IRC)-assessed progression-free survival (PFS). Secondary end points included overall survival (OS) and overall response rate (ORR) per IRC. Results: 578 pts were randomized (289 per arm); median age 64 yrs; 38% Rai Stage III/IV; median 2 prior therapies. 6 cycles of BR were completed in 83% and 78% of pts in the ibr and plb arms, respectively. At a median follow-up of 17.2 months, IRC-assessed PFS was significantly longer with BR+ibr vs BR+plb (median not reached vs 13.3 months; HR: 0.203, 95% CI: 0.150-0.276, P< 0.0001); PFS results were consistent across high-risk subgroups. ORR and CR/CRi rates were 82.7% vs 67.8% (P< 0.0001) and 10.4% vs 2.8%. Median OS was not reached. 90 pts (31%) in the BR+plb arm with confirmed PD crossed over to receive ibr, as permitted per the protocol. Incidence of most AEs was similar between arms. The most common all-grade AEs with BR+ibr and BR+plb were neutropenia (58.2% vs 54.7%) and nausea (36.9% vs 35.2%); most common grade 3/4 AEs were neutropenia (53.7% vs 50.5%) and thrombocytopenia (15.0% each arm). Rates of grade 3/4 atrial fibrillation were 2.8% and 0.7%, and major hemorrhage were 2.1% and 1.7%. Fatigue (FACIT-Fatigue) was improved with BR+ibr vs BR+plb. Conclusions: The addition of ibr to BR reduced the risk of progression or death by 80% compared with BR+plb. ORR was also significantly improved. Safety of BR+ibr was consistent with the known profiles for BR and ibr. The data further support ibr as an important treatment option for pts with previously treated CLL/SLL. Clinical trial information: EudraCT No. 2012-000600-15; UTN No. U1111-1135-3745.