Evaluation of response from axitinib per response evaluation criteria in solid tumors versus Choi criteria in previously treated patients with metastatic renal cell carcinoma

Background: Axitinib, a selective and potent tyrosine kinase inhibitor of vascular endothelial growth factor receptors, was available to patients from Canada and Australia, prior to regulatory approval of axitinib in these countries, for treatment of clear-cell metastatic renal cell carcinoma (mRCC) after failure of one prior systemic regimen. Methods: This single-arm, open-label study of axitinib evaluated the efficacy, safety, and quality of life (QoL) in patients with mRCC whose disease progressed after one prior systemic first-line regimen. Primary objective was objective response rate evaluated per Response Evaluation Criteria in Solid Tumors (RECIST) and Choi criteria. Progression-free survival, overall survival, safety, and QoL were secondary end points. Due to the small study size, analyses comprised of descriptive statistics. Results: Fifteen patients were recruited, five from Canada and ten from Australia, over a limited recruitment period. Thirteen patients received sunitinib as prior therapy. All patients had clear-cell carcinoma, eleven had prior nephrectomy. Liver, lung, and lymph nodes were the most frequent sites of metastases; one patient had brain metastasis. Median time on axitinib was 118.0 days (range: 3.5-645.0 days); estimated survival probability at 12 months was 57.8%. Two (13.3%) patients had objective responses per RECIST versus nine (60.0%) per Choi criteria. Six patients had progressive disease based on RECIST versus three per Choi criteria. Nine (60.0%) events of progression or death occurred by the end of study, and three patients continued to receive the study drug. Fatigue (33%) and diarrhea (20%) were the most common grade >= 3 all-causality, treatment-emergent adverse events. The mean change in European Quality of Life-5 Dimensions score from baseline to end of treatment was -0.0837. Conclusion: The small number of patients and lack of a comparator arm limit the ability to draw definitive conclusions; however, safety and efficacy profiles of axitinib were consistent with reports from previous studies in patients with mRCC, and patients generally maintained QoL. The sizeable difference observed in objective response rate by RECIST versus Choi criteria merits further research

Systemic inflammation, nutritional status and survival in patients with cancer

Systemic inflammation, nutritional status and survival in patients with cance

Ebp1 expression in benign and malignant prostate

<p>Abstract</p> <p>Background</p> <p>ErbB3-binding protein 1 (Ebp1) is a member of the <it>PA2G4 </it>family of proliferation-regulated proteins that is expressed in multiple malignant and non-malignant cells. ErbB3 and other members of the EGFR family have been implicated in cancer progression, it however remains unknown whether Ebp1 participate in prostate cancer progression <it>in vivo</it>. Therefore, the present study examines Ebp1 expression in cancerous and non-cancerous prostates tissues. Ebp1 expression was also correlated to known Ebp1 regulated proteins (Androgen receptor (AR), Cyclin D1 & ErbB3) and the proliferation marker Ki67. Furthermore we evaluated whether Ebp1 expression correlated with biochemical recurrence (BCR) following radical prostatectomy.</p> <p>Methods</p> <p>The expression of Ebp1, AR, Cyclin D1, ErbB3 and Ki67 were evaluated by immunohistochemistry using three separate tissue micro-arrays containing normal prostate tissues, non-cancerous tissue adjacent to the primary tumor, hormone-sensitive and hormone-refractory cancerous tissues. Multivariate COX regression analysis was performed with four clinical parameters in order to correlate Ebp1 expression with PCa progression.</p> <p>Results</p> <p>The expression of Ebp1 significantly increased with the progression from normal to hormone sensitive and to hormone refractory PCa. Furthermore, we observed strong correlation between Ebp1 expression and the nuclear expression of AR, Cyclin D1 and ErbB3 in both normal adjacent and cancer tissues. The expression of AR, Cyclin D1 and ErbB3 in normal adjacent tissues correlated with PSA relapse, whereas Ebp1 on its own did not significantly predict PSA relapse. Finally, in a multivariate analysis with a base clinical model (Gleason, Pre-op PSA, surgical margins and P-stage) we identified the multi-marker combination of Ebp1+/Cyclin D1- as an independent predictor of PSA relapse with a hazard ratio of 4.79.</p> <p>Conclusion</p> <p>Although not related to disease recurrence, this is the first <it>in vivo </it>study to report that Ebp1 expression correlates with PCa progression.</p

Adaptability of urban grids : patterns of morphological change and persistence in Midtown Manhattan, 1884-2011

Urban grid, as an open framework and an adaptable form of spatial organisation, has a capacity to produce infinite complexity and variety through time. This research is about the morphological conditions that affect the generative capacity of urban grids. Arguing that there could be distinctive morphological settings and conditions that may hinder or facilitate further adaptation and change, the research aims to develop an analytical framework to identify possible morphological variables affecting the patterns of change and persistence in the built environment. The study focuses on the Midtown Manhattan, the central part of Manhattan's extensive grid, and traces the morphological changes and continuities between 1884 and 2011 by relying on a comprehensive spatial database. The longitudinal analysis of the site reveals that different characteristic areas in the grid (in terms of plot compositions, syntactic values of the streets, diversity of land uses) show different patterns of change and levels of adaptation to emerging disturbances through time. Identification of the reliable morphological parameters explaining the capacity of spatial change and persistence will contribute to the emerging discussions on the resilience and adaptability of urban form

The role of nephrectomy in metastatic renal cell carcinoma in the immuno-oncology era

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Concomitant Carcinoma in situ in Cystectomy Specimens Is Not Associated with Clinical Outcomes after Surgery

Objective: The aim of this study was to externally validate the prognostic value of concomitant urothelial carcinoma in situ (CIS) in radical cystectomy (RC) specimens using a large international cohort of bladder cancer patients. Methods: The records of 3,973 patients treated with RC and bilateral lymphadenectomy for urothelial carcinoma of the bladder (UCB) at nine centers worldwide were reviewed. Surgical specimens were evaluated by a genitourinary pathologist at each center. Uni- and multivariable Cox regression models addressed time to recurrence and cancer-specific mortality after RC. Results: 1,741 (43.8%) patients had concomitant CIS in their RC specimens. Concomitant CIS was more common in organ-confined UCB and was associated with lymphovascular invasion (p < 0.001). Concomitant CIS was not associated with either disease recurrence or cancer-specific death regardless of pathologic stage. The presence of concomitant CIS did not improve the predictive accuracy of standard predictors for either disease recurrence or cancer-specific death in any of the subgroups. Conclusions: We could not confirm the prognostic value of concomitant CIS in RC specimens. This, together with the discrepancy between pathologists in determining the presence of concomitant CIS at the morphologic level, limits the clinical utility of concomitant CIS in RC specimens for clinical decision-making. Copyright (C) 2011 S. Karger AG, Base

Disparities in selective referral for cancer surgeries: implications for the current healthcare delivery system

Objectives: Among considerable efforts to improve quality of surgical care, expedited measures such as a selective referral to high-volume institutions have been advocated. Our objective was to examine whether racial, insurance and/or socioeconomic disparities exist in the use of high-volume hospitals for complex surgical oncological procedures within the USA. Design, setting and participants Patients undergoing colectomy, cystectomy, oesophagectomy, gastrectomy, hysterectomy, lung resection, pancreatectomy or prostatectomy were identified retrospectively, using the Nationwide Inpatient Sample, between years 1999 and 2009. This resulted in a weighted estimate of 2 508 916 patients. Primary outcome measures Distribution of patients according to race, insurance and income characteristics was examined according to low-volume and high-volume hospitals (highest 20% of patients according to the procedure-specific mean annual volume). Generalised linear regression models for prediction of access to high-volume hospitals were performed. Results: Insurance providers and county income levels varied differently according to patients’ race. Most Caucasians resided in wealthier counties, regardless of insurance types (private/Medicare), while most African Americans resided in less wealthy counties (≤$24 999), despite being privately insured. In general, Caucasians, privately insured, and those residing in wealthier counties (≥$45 000) were more likely to receive surgery at high-volume hospitals, even after adjustment for all other patient-specific characteristics. Depending on the procedure, some disparities were more prominent, but the overall trend suggests a collinear effect for race, insurance type and county income levels. Conclusions: Prevailing disparities exist according to several patient and sociodemographic characteristics for utilisation of high-volume hospitals. Efforts should be made to directly reduce such disparities and ensure equal healthcare delivery

Ocena jakości życia u pacjentów z chorobą Gravesa-Basedowa i postępującą naciekową oftalmopatią tarczycową w trakcie skojarzonego leczenia metyloprednizolonem i radioterapią przestrzeni pozagałkowych

Wstęp: Celem pracy była ocena jakości życia u chorych z naciekową postacią oftalmopatii tarczycowej (GO, Graves&#8217; opthalmopathy) w trakcie pulsacyjnego leczenia metylprednizolonem w połączeniu z radioterapią oczodołów oraz próba odniesienia wyników leczenia oftalamopatii do zmian w jakości życia. Materiał i metody: Badaniem objęto grupę 29 pacjentów w wieku 25-74 lat (śr. wieku: 52 &#177; 6 lat) z naciekową GO. Podstawą kwalifikacji chorych do leczenia oftalmopatii było uzyskanie eutyreozy, postępujący charakter zmian ocznych, stopień zaawansowania zmian ocznych oceniany w oparciu o klasyfikację NO SPECS mieszczący się przynajmniej w klasie 3c, indeks oftalmopatii według Donaldson &#8805; 4 punktów. Za aktywną postać GO przyjmowano wartości klinicznego wskaźnika aktywności (CAS, clinical activity score) &#8805; 4. Podczas leczenia, u chorych zastosowano 6 cykli soli sodowej metyloprednizolonu w dawce 1,0 g/dobę podczas jednogodzinnych wlewów dożylnych, przez kolejne trzy dni w tygodniu. Między 2. a 4. cyklem Solu-Medrolu prowadzono radioterapię tkanek pozagałkowych promieniami X o energii 10 MeV. Grupę kontrolną utworzono ze zdrowych ochotników, dobranych w stosunku do grupy badanej pod względem płci, wieku, posiadanego wykształcenia i uzależnienia od nikotyny. Składała się ona z 53 osób, w wieku 21-75 lat (śr. wieku: 52,4 &#177; 14 lat). Badania jakości życia przeprowadzano, opierając się na kwestionariuszu MOS SF-36. Wyniki: Pacjenci z GO gorzej oceniali jakość życia w stosunku do osób zdrowych w zakresie ogólnej sprawności, ograniczeń fizycznych i emocjonalnych w pełnieniu funkcji, stanu zdrowia, witalności, funkcjonowania społecznego, zdrowia psychicznego oraz występowania i nasilenia bólu. Nie wykazano korelacji pomiędzy jakością życia a wiekiem, płcią, czasem trwania choroby Gravesa-Basedowa i oftalmopatii. Podobnie nie stwierdzono zależności pomiędzy aktywnością i zaawansowaniem klinicznym zmian ocznych a jakością życia. Zastosowanie skojarzonej terapii GO spowodowało znamienne zmniejszenie stopnia zaawansowania zmian ocznych i obniżenie aktywności choroby. Po leczeniu pacjenci wskazali na poprawę jakości życia w zakresie ograniczeń fizycznych w odgrywaniu ról, występowania i nasilenia bólu oraz witalności. Pozostałe parametry jakości życia nie różniły się istotnie statystycznie. Wnioski: Oftalamopatia tarczycowa powoduje znaczne pogorszenie jakości życia. Stopień zaawansowania klinicznego i aktywność oftalmopatii nie wykazują związku z jakością życia. Skuteczności leczenia oftalmopatii nie można oceniać, kierując się zmianami w jakości życia pacjentów.Introduction: The aim of the study was to assess quality of life (QoL) in patients with infiltrative form of Graves&#8217; ophthalmopathy (GO) during the combined pulse treatment with methylprednisolone and orbital radiotherapy, and also to search for the relation between the results of ophthalmopathy treatment and changes in QoL. Material and methods: The study involved 29 patients aged 25-74 (the mean age: 52 &#177; 6 years) with infiltrative form of GO. They were classified for ophthalmopathy treatment on the basis of the following factors: the obtained euthyreosis, progressive character of eye changes, the level of eye changes determined on the basis of NO SPECS classification (at least class 3c), ophthalmopathy index (OI) according to Donaldson &#8805; 4. GO was diagnosed as active if CAS (clinical activity score) &#8805; 4. During the treatment, the patients received 6 cycles of methylprednisolone sodium succinate in doses of 1,0 g/24 h given as one-hour-long intravenous infusions for three successive days in a week. Between the 2nd and 4th cycle of Solu-Medrol, orbital radiotherapy with 10 MeV X-rays was performed. The control group was made up of healthy volunteers selected with regard to sex, age, educational background and nicotine addiction so as they corresponded with the study group. It involved 53 individuals aged 21-75 (the mean age: 52,4 &#177; 14 years). QoL was assessed by means of the MOS SF-36 questionnaire. Results: Patients with GO evaluated their QoL lower than healthy individuals, which referred to physical functioning, physical and emotional role functioning, general health, vitality, social functioning, mental health and bodily pain. No correlation was found between quality of life and such factors as age, sex, or duration time of Graves disease and ophthalmopathy. Analogically, no relation was observed between the activity and stage of clinical development of eye changes and QoL. The use of the combined GO therapy contributed to a considerable decrease in the development of eye changes and the disease activity. After treatment, the patients&#8217; QoL improved which referred to physical role functioning, bodily pain, and vitality. Other QoL parameters did not statistically significantly differ. Conclusions: GO causes a considerable worsening of QoL. The stage of clinical development and activity of GO find no reflection in QoL. Effectiveness of treatment for GO cannot be evaluated on the basis of changes in QoL

Low CAIX expression and absence of VHL gene mutation are associated with tumor aggressiveness and poor survival of clear cell renal cell carcinoma.

International audienceWe attempted to describe, in a series of clear cell renal cell carcinoma (RCC), the relationship between CAIX expression, VHL gene mutations, tumor characteristics and outcome. Radical nephrectomy was performed in 100 patients. Genomic DNA was extracted from frozen tumor samples. Four amplimers covering the whole coding sequence of the VHL gene were synthesized by PCR and sequenced. The monoclonal antibody M75 was used to evaluate CAIX protein expression immunohistochemically. VHL mutations were identified in 58 patients (58%) and high CAIX expression (>85%) was observed in 78 (78%). Tumors with VHL mutation showed higher CAIX expression than those without (p = 0.02). Low CAIX expression and absence of VHL mutation were associated with a more advanced tumors e.g., higher T stages and presence of metastases. VHL mutation and high CAIX expression predicted longer progression-free survival (p = 0.037) and disease-specific survival (p = 0.001), respectively. In combination, they defined three prognostic groups (p = 0.002): (i) good prognosis, defined as VHL mutation and high CAIX (2-year survival: 86%), (ii) intermediate prognosis with either VHL mutation or high CAIX (69%), and (iii) poor prognosis with no VHL mutation and low CAIX (45%, median survival 18 months). CAIX expression, but not VHL mutational status, was an independent prognostic factor in multivariate analysis. Taken together, CAIX expression and VHL mutational status are able to stratify patients with clear cell RCC into distinct groups with regards to clinicopathological variables and prognosis, with low CAIX expression and absence of VHL mutation being associated with a poor clinicopathological phenotype and diminished survival