Analysis of a United States observational registry of gastrointestinal stromal tumor (GIST) patients (pts): reGISTry

20508 Background: Most data on treatment of GIST pts were derived from clinical studies, reflecting practice at academic referral centers. The reGISTry, an observational, internet-based database initiated in 2004, was designed to characterize evolving patterns of care for pts with GIST in both community and university practice settings. It also provides site feedback to allow comparison of site management practices to the aggregate reGISTry data. Methods: Physicians may serially enter data on any enrolled pt with confirmed GIST. Pts must give written informed consent. Collected data include pt demographics, clinical characteristics, clinical/economic outcomes and therapy provided for GIST. Analyses are performed every 6 months. Results: As of Oct 2006, there were 353 pts enrolled from 78 centers. 228 pts (65%) were from community-based practices; 184 pts (52%) were male, and 283 pts (80%) were Caucasian, with a median age of 65 years (range 18–92). Median time from diagnosis to enrollment was 1.1 years (range 0–11.7). At diagnosis, 282 pts (80%) had a localized tumor and 71 (20%) presented with metastatic disease. 335 pts (95%) had immunohistochemical KIT testing, and 1% had genotyping. 274 pts had surgery as first-line treatment (78%), including 84% of pts with primary disease and 52% with metastatic cancer. 14 % and 42% of pts with localized and metastatic disease respectively had systemic therapy as initial treatment. Of the 202 pts with follow-up, 170 (82%) retained the same primary decision-maker, usually the medical oncologist and/or surgeon (57%, 56% respectively). 3 patients reported missing days from work or school due to GIST in their first year since diagnosis. Therapeutic efficacy was assessed by tumor size on CT (53%), tumor size and radiodensity on CT (33%), clinical assessment only (14%) and PET (9%). 161 pts (46%) had been treated with imatinib mesylate and 20 pts (6%) sunitinib malate. Conclusions: The reGISTry remains a useful tool for determining evolving patterns in the management of GIST, and it points out important differences in official practice guidelines and community standards. KIT testing is common in the community, but mutational analysis is rare. Assessment by CT is customary, but PET imaging is rarely utilized in clinical practice. [Table: see text]

Download Full-text

Pathological significance of deletions involving codons 557 and 558 of KIT gene in localized resected gastrointestinal stromal tumors (GIST) of intermediate and high risk: A study by the Spanish Group for Sarcoma Research (GEIS)

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.10051 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 10051-10051

Author(s):

I. Romero ◽

A. Poveda ◽

J. Martin ◽

A. Lopez-Pousa ◽

C. Gomez ◽

...

Keyword(s):

Tumor Size ◽

Mutational Analysis ◽

Mitotic Count ◽

Proliferative Potential ◽

Activating Mutations ◽

R1 Resection ◽

Kit Gene ◽

Central Pathology ◽

Pathology Review

10051 Background: Approximately 60 to 85% of GISTs harbour activating mutations of the KIT or PDGFRA tyrosine kinase genes. Deletions affecting codons 557–558 of KIT are relevant to prognosis of resected GIST (Martin J, et al. J Clin Oncol. 2005, 23:6190). Methods: GIST of high or intermediate malignant risk according to Fletcher classification (Hum Pathol. 2002;33; 459) with a complete (R0) or microscopic residual (R1) resection were prospectively evaluated. Central pathology review was carried out. The mutational analysis of exons 9, 11, 13 and 17 of KIT and exons 12 and 18 of PDGFRA was undertaken from DNA extracted from paraffin-embedded tissue. The purpose of this study was to explore the correlation between deletion mutation involving 557–558 codons within KIT gene and known prognostic factors in GIST: mitotic count and size. Results: Of the 33 GIST, 19 were gastric, 13 of small bowell and one of other location. Median tumor size was 10.4 cm (1.9–22 cm), and median mitotic count was 2 (1–32). All cases showed an immunostaining with diffuse cytoplasmic pattern of c-kit (CD117). An 82% (27) presented either a KIT (23) or a PDGFRA (4) mutation. Eleven deletions affecting codons 557–558 of KIT were observed. KIT mutations were associated to spindle type histology and PDGFRA mutations to epithelioid histology. No statistical association between tumor size and KIT mutations, including patients with deletions 557–558, was found. Tumors carrying a deletion of codons 557–558 of KIT presented a different median of mitotic count (8 mit × 50 hpf) than the rest (2 mit × 50 hpf), this difference was statistically significant (p = 0,029) in the Mann-Whitney U test. Conclusions: Deletions affecting codons 557–558 of KIT define a group of cases with a high proliferative potential. The prognostic and predictive significance of these findings are waiting for a longer follow-up. No significant financial relationships to disclose.

Download Full-text

Growth kinetics and outcomes of cT1b renal masses under active surveillance.

Journal of Clinical Oncology ◽

10.1200/jco.2014.32.4_suppl.440 ◽

2014 ◽

Vol 32 (4_suppl) ◽

pp. 440-440

Author(s):

Reza Mehrazin ◽

Marc C. Smaldone ◽

Alexander Kutikov ◽

Jeffrey J. Tomaszewski ◽

Tianyu Li ◽

...

Keyword(s):

Growth Rate ◽

Tumor Growth ◽

Metastatic Disease ◽

Growth Kinetics ◽

Tumor Size ◽

Renal Tumors ◽

Tumor Growth Rate ◽

Renal Masses ◽

Delayed Intervention

440 Background: The natural history of untreated T1b renal masses is poorly understood. We assessed the growth kinetics and outcomes of ≥cT1b cortical renal tumors which continue to remain on radiographic AS compared to those who underwent definitive surgery after a period of AS. Methods: Prospectively maintained, renal tumor database was reviewed to identify enhancing solid and cystic masses managed expectantly from 2000-2012. cT1a masses, transitional cell carcinoma or those suspected for metastatic disease were excluded from analysis. Localized tumors > 4.0 cm (≥T1b) that were radiographically followed for > 6 months were included for analysis. Clinical and pathological records were reviewed to determine tumor growth rate and clinical outcomes in those remained on AS or those who underwent delayed intervention. Mean for tumor size on presentation, annual linear tumor growth rate (LGR), Charlson comorbidity index (CCI), and follow-up (FU) were calculated. Chi−square test & Logistic regression were used for uni- and multi-variable analyses. Results: Of 457 pts managed with AS, 67 cT1b tumors (in 63 patients) were identified. 43 pts (67%) were managed solely with AS, while 21 pts (33%) progressed to intervention. The median age at presentation pts managed with AS and intervention was 77 and 60 yrs respectively (p=0.0002), while no difference was observed in median CCI (3 vs. 2, p=0.6). No difference was observed in tumor size at presentation between pts managed with AS and those undergoing delayed intervention (5.9 vs. 5.4 cm, p=0.8). In contrast, the mean LGR significantly differed between pts managed expectantly and pts progressed to intervention (0.37 vs. 0.73 cm/yr; p=0.02). On MVA, age (OR=0.9,CI:0.8−0.98) and LGR (OR=11,CI:1.8−60) were significant predictors of surgical intervention. With a mean FU period of 38.9 ± 24.0 months (6−105), 9 pts died (14%) from other cause and no pt progressed to metastatic disease. Conclusions: Localized cT1b≥ renal masses show comparable growth rates to small tumors managed expectantly with low rates of progression to metastatic disease with short term follow up. An initial period of AS to determine tumor growth kinetics is a reasonable option in select pts with significant competing risks and limited life expectancy.

Download Full-text

Incremental oncology workload generated by immunotherapy in the first-year of treatment.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e14143 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e14143-e14143

Author(s):

Marika Cinausero ◽

Silvio Ken Garattini ◽

Alessandro Marco Minisini ◽

Francesca Valent ◽

Chiara Riosa ◽

...

Keyword(s):

Metastatic Cancer ◽

Rapid Development ◽

Cancer Center ◽

First Year ◽

Number Of Patients ◽

Clinical Episode ◽

Student’S T ◽

Few Data ◽

New Diagnosis

e14143 Background: The rapid development of immunotherapy (IO) has transformed the cancer therapy landscape with growing impact on oncology workload. Given the few data on this topic, we conducted a study to estimate the shift in workload generated by any new metastatic cancer patient treated with IO and referred to the Oncology Department of the Academic Academic Cancer Center of Udine, Italy, within the 12 months of first consultation. Methods: We collected from our “Data Warehouse” electronic accountability system all new diagnosis of metastatic cancer between 01.01.2017 and 31.12.2018, resulting in a first consultation and leading to a second clinical episode during the following year, in order to assess the oncology workload. The population was divided into patients that received IO (anti-CTLA-4/PD-1/PDL1) versus patients treated with “other treatments”. Mean number per patient and standard deviation were calculated for clinical episodes (first consultations, treatment sessions, unplanned presentations, hospitalizations, re-evaluations, follow-up and inpatient oncology advices). The total number of patients treated and the number of episodes were recorded. Mean numbers of episodes in the IO group and “other treatments” group were compared using Student’s t-test (significance p < 0.005). Follow-up data was collected up to 31.12.2019. Results: A total number of 969 patients were considered (854 “other treatments” group and 115 IO group), resulting in a total of 12407 clinical episodes over the period of 12 months (first consultations excluded). Compared to “other treatments” group, patients in the IO group generated a greater workload in terms of treatment sessions (9.59 vs 6.83 per patient, p < 0.0001), re-evaluations (2.55 vs 1.88, p = 0.0002), and unplanned presentations (2.19 vs 1.51, p = 0.08). On the other hand, follow-up visits workload was greater for “other treatments” group (0.83 vs 0.63, p = 0.0002). No differences were found regarding hospitalizations and inpatient oncology advices. Further analysis will be presented. Conclusions: IO represents a new frontier in oncology landscape, leading to outcome’s improvement and longer lasting treatment periods. The estimate of oncology workload generated by new diagnosis of metastatic cancer requiring IO, is crucial for implementing more sustainable systems and for planning clinical activities.

Download Full-text

A Case of Hyperimmunoglobulinemia D Syndrome Successfully Treated with Canakinumab

Case Reports in Rheumatology ◽

10.1155/2013/795027 ◽

2013 ◽

Vol 2013 ◽

pp. 1-4 ◽

Cited By ~ 2

Author(s):

Elena Tsitsami ◽

Charis Papadopoulou ◽

Matthaios Speletas

Keyword(s):

Autosomal Recessive ◽

Mutational Analysis ◽

First Year ◽

Kinase Gene ◽

Inflammatory Drugs ◽

First Year Of Life ◽

Length Analysis ◽

Mevalonate Kinase Gene

Hyperimmunoglobulinemia D syndrome is a rare autosomal recessive autoinflammatory disorder caused by mutations in the mevalonate kinase gene (MVK). In a proportion of patients, however, noMVKmutations are detected. Although various standard anti-inflammatory drugs have been tried, until now there is no consensus about how HIDS should be treated. We present a case of HIDS in an 8-year-old girl whose clinical picture had started before the end of the first year of life. The patient had consistently elevated IgD levels but no mutations were found after a full-length analysis of theMVKgene. The method ofMVKmutational analysis is presented in details. Treatment with canakinumab in a final single dose of 4 mg/kg every 4 weeks resulted in the disappearance of febrile attacks and a considerable improvement of patients’ quality of life during a 12-month follow-up period. The drug has been well tolerated, and no side effects were observed.

Download Full-text

Symptomatic and Incidental Venous Thromboembolic Disease Are Both Associated With Mortality In Patients With Prostate Cancer

Blood ◽

10.1182/blood.v122.21.3626.3626 ◽

2013 ◽

Vol 122 (21) ◽

pp. 3626-3626

Author(s):

Shruti Chaturvedi ◽

Surbhi Sidana ◽

Alok A. Khorana ◽

Keith R. McCrae

Keyword(s):

Prostate Cancer ◽

Metastatic Disease ◽

Advanced Disease ◽

Metastatic Cancer ◽

Clinical Care ◽

Locally Advanced ◽

Cleveland Clinic ◽

Categorical Variables ◽

Significant Difference

Abstract Introduction The association between malignancy and venous thromboembolism (VTE) is well established. Less is known about the independent impact of VTE, both symptomatic and incidental, on survival in patients with prostate cancer. Methods We conducted a retrospective cohort study of 457 consecutive patients with prostate cancer who received outpatient clinical care at the Cleveland Clinic from January 2006 to June 2006. Data were collected regarding clinical characteristics, treatment and outcomes. Fisher exact (for categorical variables) and t-test (continuous variables) were utilized to test associations with VTE and mortality. Survival functions were estimated using the Kaplan Meier method and a Cox regression model was used to model the mortality hazard ratio (HR) with date of diagnosis as time origin. Results The mean age of our cohort of patients was 65.86 ± 8.64 years. Three hundred and fifty eight (78.3%) had clinically localized disease, 76 (16.7%) had locally advanced disease and 41 (8.9%) had metastatic cancer at diagnosis. One hundred twenty four (27.1%) men underwent surgery, 315 (68.9%) received radiotherapy, 201 (44%) received hormonal therapy and 71 (15.5%) received chemotherapy. Complete follow up was available on 403 patients of which 109 (27%) died during the period of follow up. VTE occurred in 42 (9.2%) patients (33 deep vein thrombosis, 5 pulmonary embolism, and 4 patients with both DVT and PE), of which 27 (64.3%) were symptomatic and 15 (35.7%) were incidentally diagnosed. Twenty-three were outpatients and 17 were hospitalized when VTE was diagnosed. Metastatic disease (p<0.0021), and chemotherapy (p=0.002) were associated with VTE. There was no association of VTE with more traditional risk factors such as obesity, renal disease, rheumatologic disease, hip fracture, COPD, and smoking. Metastatic disease (p=0.002), ECOG score of 3 or 4 (p<0.001), and VTE (p<0.001) were predictors of mortality. Adjustment for stage of disease was included in the multivariate analysis. Mean survival of patients with and without VTE was 91.8±11.3 months and 144.8±3.6 months respectively (p<0.01). Five-year survival rates were also significantly lower for patients with VTE compared to those without (45.2% vs. 87.8%, p<0.001). Patients with both symptomatic and incidental VTE had significantly poorer survival than those without however there was no significant difference in survival between patients with symptomatic or incidental VTE (70.78±44.82 years versus 77.87±63.07, p=0.674). Conclusion VTE, both symptomatic and incidental, is a predictor of poor survival in patients with prostate cancer, especially those with advanced disease. This finding has implications for the clinical care of patients with prostate cancer. Further studies are needed to evaluate the benefit of prophylactic and therapeutic anticoagulation in this population. Disclosures: No relevant conflicts of interest to declare.

Download Full-text

Impact of 12 months of immunotherapy for metastatic cancer patients on oncology workload.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.29_suppl.279 ◽

2020 ◽

Vol 38 (29_suppl) ◽

pp. 279-279

Author(s):

Victoria Andreotti ◽

Marika Cinausero ◽

Silvio Ken Garattini ◽

Lucia Bortot ◽

Lorenza Palmero ◽

...

Keyword(s):

Standard Deviation ◽

Checkpoint Inhibitors ◽

Metastatic Cancer ◽

Mean Value ◽

First Year ◽

Clinical Episode ◽

System Data ◽

Student’S T ◽

Number Of Treatment

279 Background: In the last years, the introduction of immune checkpoint inhibitors (ICI) in clinical practice translated into major changes in oncology workload. We conducted a study aimed to estimate the shift in workload generated, within 1 year of first consultation, by any new metastatic cancer patient receiving ICI at the Oncology Department of the Academic Hospital of Udine, Italy. Methods: We collected from our electronic accountability system data all new cases of metastatic cancer between 01.01.2017 and 31.12.2018, leading to at least a second clinical episode (treatment sessions, unplanned presentations, hospitalizations, re-evaluations, follow-up, and inpatient oncology advices) during the following year. Patients (pts) were divided into those receiving ICI (anti-CTLA4/PD1/PDL1) versus pts receiving other treatments. Mean number per patient and standard deviation were calculated for clinical episodes, and the mean numbers in each group were compared using Student’s t-test (significance p<0.05). Follow-up continued until 31.12.2019. Results: 969 pts were included: 115 were treated with ICI, 854 received other treatments. In the first group a greater number of treatment sessions, re-evaluations and unplanned presentations was generated, with a statistically significant increased workload. On the other hand, pts receiving other treatments generated a greater workload in terms of follow-up. In detail, data are reported in Table. Conclusions: ICI have transformed the oncology landscape, leading to longer lasting treatment period with emerging toxicities. Estimating the workload generated by ICI is crucial for the implementation of more sustainable systems and for planning clinical activities. Mean number of clinical episodes in the first year of treatment with ICI for metastatic disease. Mean number per patient is represented by mean value and standard deviation (SD). Total number of clinical episodes is shown (N=). Data are reported for ICI versus other treatments group. [Table: see text]

Download Full-text