tbuckley/cabot-search huggingface dataset:
Reductions in exercise behavior and tumor progression in newly diagnosed glioblastoma (GBM) patients.
Authors: Katherine B. Peters, Stevie Threatt, Patrick Healy, James Emmett Herndon, Eric S Lipp, Sujata Panta, Dina Randazzo, Gordana Vlahovic, Henry S. Friedman, Annick Desjardins
Journal: Journal of Clinical Oncology (2017)

e21636 Background: At diagnosis, GBM patients face the immediate challenge of significant morbidity and mortality. In this population, we have shown that better exercise behavior is an independent prognostic factor for improved survival. The association between tumor progression and exercise behavior in newly diagnosed GBM patients was explored within a clinical study investigating the use of bevacizumab (BV) with concurrent chemoradiation, followed by BV and temozolomide with the continuation of BV following progression. Methods: In this prospective single-center study, exercise behavior was evaluated using the Modified Godin Leisure Questionnaire at time of study enrollment (before chemoradiation), after chemoradiation, and then every 6 mos until study discontinuation or subject demise. Physical activity was defined as MET-hr/wk with higher number equaling a better exercise behavior. Results: 68 newly diagnosed GBM patients were initially included with a mean age of 55.4 yrs (sd = 10.7 yrs). KPS range was 70-100 with the following being 70 (n = 4), 80 (n = 28), 90 (n = 34), and 100 (n = 2). Subjects who continued study participation 6 mos after the completion of chemoradiation were divided into two groups: subjects with (n = 13) and without (n = 34) tumor progression 6 mos after chemoradiation completion. Subjects that experience tumor progression &lt; 6 mos after chemoradiation had a lower exercise behavior at baseline in comparison to their counterparts that did not experience progression &lt; 6 mos after chemoradiation (mean = 12.8 MET-hr/wk (sd = 22.2) vs. mean = 22.4 MET-hr/wk (sd = 28.9). Moreover, this exercise behavior decreased in subjects that had tumor progression to mean = 6.6 MET-hr/wk (sd = 7.6) and remained relatively stable in subjects that did not progress with mean = 23.9 MET-hr/wk (sd = 44.9). Conclusions: Our observations of exercise behavior over time suggest that poorer baseline exercise behavior is associated with a disease progression within 6 mos of chemoradiation completion in newly diagnosed GBM patients. Moreover, this exercise behavior continues to decline after progression. Based on these observations, a greater understanding of the role of physical functioning is merited in GBM patients. Clinical trial information: NCT01740258.
Effect of Mycophenolate Mofetil Dose on BK Virus Infection in Kidney Transplant Recipients
Authors: Vedran Pasara, Danica Galešić Ljubanović, Mladen Knotek
Journal: Journal of the American Society of Nephrology (2015)

Background: Intensity of overall immunosuppression is a risk factor for BK virus infection (BKVI). However, the exact impact of exposure to tacrolimus and mycophenolate mofetil (MMF) to BKVI is unclear. The aim of this study was to determine if BKVI in kidney transplant (KT) recipients (KTR) is associated with drug exposure to MMF. Methods: This prospective randomised controlled clinical trial (NCT01860183) included 36 KTR who underwent KT from May 2013 to February 2015 at Clinical Hospital Merkur. Immunosuppression consisted of basiliximab induction, with tacrolimus, MMF ±steroid maintenance. KTR were randomized in two groups, with respect to MMF dose (2g or 3 g daily). Urine cytology for decoy cells was performed at prespecified time-points posttransplant. KTR were followed up to 12 months post KT. Graft biopsy was performed per protocol at 2, 6 and 12 months, or in case of graft dysfunction. Kaplan-Meier analysis with log-rank test was used to assess graft survival. A Cox regression was used to determine variables associated with graft survival. Results: 13 (37.1%) KTR had decoy cells in urine, 4 (11.4%) KTR had biopsy-proven BK virus-associated nephropathy (BKVAN). The mean time-to-occurrence was 4.8 months for decoy cells and 4.3 months for BKVAN. Cumulative one-year overall graft survival was 93.5%. Incidence of decoy cells, BKVAN, or acute rejection was similar in the two MMF groups. Rejection was not a risk factor for decoy cell positivity or for BKVAN. Conclusions: MMF dose may not increase risk for BKVI after kidney transplantation.
Effect of pretreatment steroids on the development of immune related adverse events.
Authors: Philip Margiotta, Mario Caldararo, Daniel Altman, Sheel A. Patel, Sharon Li, Sean Clark-Garvey, Reetu Mukherji, Thomas Holden, Jennifer Maria Johnson, Marlana M. Orloff, Ryan Michael Weight
Journal: Journal of Clinical Oncology (2018)

e15095 Background: Immune checkpoint blockade is being used with increasing frequency across a variety of tumor types. Corticosteroids are used in diverse clinical scenarios and can have immune-modulatory effects. The administration of steroids with immune checkpoint blockade in combination with cytotoxic chemotherapy has not diminished treatment efficacy in select patient populations1. However, the effect of steroids on the development of immune-related adverse events (irAEs) across tumor types is unknown. We hypothesized that pretreatment with corticosteroids reduces treatment-limiting irAEs. Methods: A single institution registry of patients (n = 163) receiving immune checkpoint blockade, including anti-CTLA-4 antibody (n = 51) or anti-PD-1 antibody (n = 112), was reviewed. Various primary tumor types were included (33% melanoma, 31% non-small cell lung, 36% other). Patients were determined to have discontinued treatment because of irAEs versus any other cause (disease progression, infection, comorbidity, or death). Results: None of the 17 patients (0%) who were receiving corticosteroids prior to starting immunotherapy experienced treatment-limiting irAEs (average dose 34mg/day prednisone or equivalent, only one patient taking < 10mg/day prednisone). This is compared to 29 of 146 patients (19.9%) who were not taking steroids at the start of treatment (p = 0.045). Interestingly, pretreatment steroids were not associated with an increase in disease progression or death. Conclusions: Incidence of treatment-limiting immune-related adverse events was significantly decreased, regardless of tumor type, in patients receiving corticosteroids prior to initiation of immunotherapy. An associated decrease in treatment efficacy was not seen. Table: Incidence of treatment-limiting adverse events in patients undergoing immunotherapy Treatment-Limiting Adverse Events - n (%) Immune Infection or Comorbidity Disease Progression or Death Ongoing Treatment Total On Steroids When Immunotherapy Initiated? Yes 0 (0) 7 (41.1) 8 (47.1) 2 (11.8) 17 (100) No 29 (19.9) 19 (13.0) 71 (48.6) 27 (18.5) 146 (100) Total 29 (17.8) 26 (16.0) 79 (48.4) 29 (17.8) 163 (100)
Prevalence and survival of smoldering multiple myeloma in the US: Analysis using a national dataset.
Authors: Aishwarya Ravindran, Adam C. Bartley, Aneel A. Ashrani, Wilson I. Gonsalves, Shahrukh K. Hashmi, Prashant Kapoor, Ariela L. Marshall, Mustaqeem Ahmad Siddiqui, Angela Dispenzieri, Robert A. Kyle, S.Vincent Rajkumar, Ronald S. Go
Journal: Journal of Clinical Oncology (2016)

8035 Background: Epidemiologic studies of smoldering multiple myeloma (SMM) are not available due to the lack of International Classification of Diseases (ICD) codes specific for smoldering status. Methods: The National Cancer Database (NCDB) represents approximately 70% of cancer cases in the US. Using the NCDB, we estimated the overall proportion of new adult MM cases that are smoldering and analyzed outcomes according to socio-geo-demographic subgroups and type of treatment facility. Overall survival (OS) of SMM was compared to active MM. We included new MM patients from 2003-2011. NCDB records the time to initial treatment or reasons for not receiving treatment. Those who did not require treatment ≤ 120 days of MM diagnosis were considered to have SMM. Results: 86,327 patients were diagnosed with MM. Of these, 13.8% were SMM. Median age at diagnosis was 67 years. Median age and proportion of SMM did not change significantly during the study period (P = 0.23 and 0.34, respectively). The proportions of SMM according to socio-geo-demographic subgroups and treatment facility are shown in the Table. SMM was more likely to be diagnosed among those who were women, Black, older, less educated, had fewer medical co-morbidities, living closer to a treatment facility, and evaluated in the Northeast. The proportions of SMM diagnosed at academic and non-academic facilities were similar. The median OS for SMM and active MM were 62.9 and 33.0 months, respectively. The OS of SMM did not differ among the racial groups (P = 0.27). Conclusions: Approximately 1 in 7 MM cases in the US is smoldering at diagnosis. The prevalence, but not the OS, of SMM varied among various socio-geo-demographic subgroups. Our results can be used in the future to study the health care impact of SMM. Proportion of MM that were smoldering Sex Males : 13% Females : 14.7% Race White : 13.2% Black : 15.5% Asian: 14.8% Native American: 11.0% Age < 50 : 10.9% 50-64 : 11.9% 65-79 : 14.7% ≥ 80 : 16.6% Educational level low: 14.9% intermediate: 13.4% high: 13.7% Charlson/Deyo Score 0 : 14.5% 1 : 11.5% ≥ 2 : 11% Travel distance (miles) < 12.5 : 15% 12.5-49.9 : 12.8% ≥ 50 : 10.2% Facility location Northeast : 16% South : 14.2% Midwest : 11.8% West : 13.2% Facility type Academic: 13.6% Non-academic: 13.8%
Patterns of care in long term survivors (&gt;3 years) in metastatic NSCLC : A subset analysis of 30 patients from a single institute.
Authors: Y Indibor Singh, Ambika A, Sonia Hage, Chito Th
Journal: Journal of Clinical Oncology (2018)

e21185 Background: Long term survivors ( > 3years) in metastatic NSCLC is increasing from 5 % to 15 - 20%. It is becoming a chronic manageable disease. It is related with treatment given in an individualised manner with better understanding of tumour biology. Many factors are associated with the improved outcome. Institute’s data of > 3 years survivors during last 5 years is analysed in an attempt to find out the favorable factors Methods: Data of metastatic NSCLC treated at RCC, RIMS during Jan. 2012 to Dec. 2016 are retrieved from departmental record .Patients diagnosed and treated at RIMS who have survived > 3 years are included. Patient lost to F.U are contacted on phone for censoring. Patient characteristics, disease profile, treatment pattern, response and OS are analysed by using IBM corps SPSS ver.21. Results: : Out of 196 records retrievable Stage IV patients 160 patients were evaluable. Of these 30 (19%) patients survived > 3 years and analysed. The M: F ratio 2:3, mean age 66 yrs (range 32 to 82 ) . Histologically, SCC. 9 (30%) Adeno Ca. 21 (65%) and undifferentiated ( 5%). KPS ranges 50% to 90% . Treatment given: 25 (84%) received combo Chemo +/- RT to primary and metastatic sites and targeted agents when indicated as maintenance therapy with curative intent. And 5(16%) received palliative intent chemo (single agent) sequentially till P.D. +/- RT short course followed by targeted agents as maintenance. The M.S. of this cohort of 30 patients is 42 months . No significance in survival between palliative & curative intent[ log Rank (Mantel-cox) .525 chi-sq. Value df 1 sig. .469 ] Majority are smokers 26 (86.6%) but no co relation with survival due to study design. Age and PS are not significant factors . Histogically, Adenocarcinoma is found to be highly significant compared to SCC type ( at p-value .02 by log Rank (Mantel-cox) and at .005 by Breslow -Wilcoxon and .008 by Tarone ware). Conclusions: Females, Adenocarcinoma treated with combo Chemo + RT +/- targeted therapy with intent to treat are the favorable factors of long term survivors in this study. The study indicates that treatment should be given and all treatment options exercised in a sub set of patients with metastatic disease who are responders..
Analysis of the impact of body mass index in the treatment of metastatic melanoma with ipilimumab.
Authors: Jessica Ribeiro Gomes
Journal: Journal of Clinical Oncology (2017)

e21044 Background: Recently observational and retrospective studies have been observing a higher incidence of melanoma among patients with over normal body mass index (BMI), as well as a higher melanoma-specific mortality. However, no study has analyzed the impact of BMI in patients with metastatic melanoma treated with immunotherapy. We aim to evaluate whether BMI could influence the treatment of patients with metastatic melanoma receiving Ipilimumab. Methods: Patients diagnosed with metastatic melanoma treated with Ipilimumab at Centro Oncológico Antônio Ermírio de Moraes - Brazil were identified. Patients were stratified according to BMI value at the beginning of Ipilimumab therapy (BMI ≥ 25 and BMI &lt; 25). Progression free survival (PFS) was compared between the groups. Results: We evaluated 187 patients with metastatic melanoma treated with Ipilimumab. About fifty eight percent were male and median age was 58 years (range 27-89). About 88.8% had cutaneous melanoma (42.6% BRAF mutated), 5.3% mucosal melanoma, and 5.9% choroid melanoma. The overall PFS was 3.13 months (95% CI 2.84 – 3.41). Median BMI was 25.8% (range 15.2 - 47.9), and 37.4% of the patients had BMI &lt; 25. The group with BMI ≥ 25 had higher median PFS when compared to those with BMI &lt; 25 (3.5 versus 2.9 months, p = 0.037). In the group of BMI &lt; 25, 16 (22.8%) and 4 (5.7%) patients had PFS &gt; 6 months and 12 months, respectively, versus 35 (30%) and 16 (13.6%) patients in the group of BMI ≥ 25. Conclusions: We have observed a superior PFS on Ipilimumab among overweight patients with metastatic melanoma . Further studies are necessary to confirm whether activity of Ipilimumab is greater among patients with higher BMI.
Multi-spatial whole-lesion molecular heterogeneity of an immunotherapy-resistant metastatic melanoma.
Authors: Akash Mitra, Whijae Roh, Alexandre Reuben, Mariana Macedo, Fernando Cintra Lopes Carapeto, Curtis Gumbs, Jianhua Zhang, Scott Eric Woodman, Patrick Hwu, Wen-Jen Hwu, Alexander J. Lazar, Jennifer Ann Wargo, Phillip Andrew Futreal
Journal: Journal of Clinical Oncology (2018)

9568 Background: Genomic and immune intratumor heterogeneity (ITH) can be a major reason for therapy failure in patients undergoing checkpoint blockade immunotherapy. Here, we report comprehensive molecular and immune analysis of a sequential anti-CTLA-4- and anti-PD-1-resistant metastatic lesion, sampled and reconstructed in 3D, combined with a longitudinal view of a pre-immunotherapy lesion. Methods: We performed 3D reconstruction of a metastasis obtained at palliative surgery from a patient progressing on sequential anti-CTLA-4 and anti-PD-1 therapy utilizing genomic (gene expression, methylation, whole exome sequencing and neoantigen prediction) and immune (immunohistochemistry, RNA- and DNA-based T cell receptor sequencing) profiling of 67 spatially distinct regions. Results: Limited point-mutation heterogeneity was found in melanoma driver genes however, copy number alteration analysis revealed changes over time and space with gain of chromosome 7 and 13, and loss of chromosome 10 in spatially-distinct regions. Differences in immune signatures were observed across regions of the tumor with pockets of immune activation and suppression. TCR profiling revealed dominance of three T cell clonotypes distributed across the tumor, highlighting spatial patterns in tumor immunogenicity and T cell response. Neoantigen prediction and expression indicated the persistence of a neoantigen detectable prior to anti-CTLA-4 therapy enriched in different regions of the post-anti-PD-1 tumor. Gene expression correlated with the distribution and dominance of a specific T cell subclone. Conclusions: 3D-reconstruction of a sequential immune checkpoint blockade treated progressing tumor shows marked spatially-distinct genomic and immune ITH in the setting of a relatively homogenous somatic gene mutation landscape. As immune markers move into the mainstream for use as biomarkers, the use of single biopsies to inform treatment choice may be confounding. These data further impress the need for comprehensive, integrated molecular phenotyping approaches to unravel immunotherapy response and resistance in metastatic melanoma.
SENTICOL III: International validation study of sentinel node biopsy in early cervical cancer: A GINECO, ENGOT and GCIG study.
Authors: Fabrice Lecuru, Mary McCormack, Peter Hillemanns, Amelie Anota, Mario M. Leitao, Patrice Mathevet, Ronald P. Zweemer, Keiichi Fujiwara, Vanna Zanagnolo, Ane Gerda Zahl Eriksson, Emma Hudson, Gwenael Ferron, Marie Plante
Journal: Journal of Clinical Oncology (2018)

TPS5602 Background: Sentinel node biopsy (SLN) is an alternative to pelvic lymphadenectomy (PLN). The false negative rate is < 1%) when “MSKCC Algorithm” is fulfilled. The technique can detect isolated tumor cells (ITC) or micrometastases in 15 – 20 % of N0 patients, reveal SLN in unexpected areas in up 30% of cases and reduce short term lymphatic morbidity. However, the long-term prognosis of SLN negative patients is unknown. In 2014, the GCIG brainstorming on cervical cancer pointed out the need for a validation study, taking survival into account, giving birth to SENTICOL III. Methods: SENTICOL III is an international prospective multicenter randomized trial. We use a « co-primary » objective regarding Disease Free Survival (DFS) and Health Related Quality of Life. The hypothesis is that SLN biopsy alone provides similar DFS and better quality of life. Secondary objectives are outcome of patients with ITC and micrometastases, evaluation of mapping with indocyanine green (ICG), overall survival, recurrence free survival. A cost analysis will be undertaken and a tumor tissue bank will be established. Patients with an early stage cervical cancer defined as FIGO stage Ia1 with lymphovascular invasion to IIa1, maximum diameter ≤40mm on MRI and node negative on imaging will be eligible to participate. SLN biopsy will be performed using isotopic detection +/- blue dye or ICG. SLN of patients with an “optimal” mapping will be analyzed by frozen section. SLN negative patients will be randomized intraoperatively 1:1 to SLN only or SLN + PLN. All SLN will be submitted to ultrastaging (200 microns levels). All centers will follow a quality assurance program to ensure surgical competency and a standardized pathological evaluation 900 patients will be recruited in 3 years, with 4 years of follow-up. (3 years-disease free survival of 85%, with a non-inferiority margin of 5% (80 vs 85%, HR = 1.373), a unilateral alpha error of 5%, and a power of 80%) The trial has started in France, and an international collaboration has been developed through GCIG and ENGOT. (NCT03386734). CHU Besançon is the sponsor for France Clinical trial information: ID-RCB : 2017-A00945-48.
Effect of duration from initial diagnosis on the frequency of T790M secondary mutation after EGFR-TKI failure in EGFR-mutant lung adenocarcinomas.
Authors: Kosuke Tanaka, Yuko Oya, Tatsuya Yoshida, Junichi Shimizu, Yoshitsugu Horio, Toyoaki Hida, Yukinori Sakao, Yasushi Yatabe
Journal: Journal of Clinical Oncology (2016)

9048 Background: The resistance mechanism after EGFR-TKI failure is reportedly EGFR T790M secondary mutation in about half of EGFR-mutant NSCLC. However, the predictive marker for T790M mutation remains unknown. Methods: We retrospectively screened 135 EGFR-mutant adenocarcinoma patients who received re-biopsy after EGFR-TKI failure between 2009 and 2015. We examined clinical correlative factors associated with T790M secondary mutation among them. Results: Among 135 patients, 90 (67%) were female and 89 (66%) were never-smokers, with the age range 35-84 years (median, 62 years). Nine, 95, 31 patients were stage III, stage IV, recurrence after surgery, respectively. Seventy patients were exon 19 deletion, and 65 were L858R point mutation. Re-biopsy site was primary lesion in 25 patients, pleural effusion in 44 patients, lymph nodes in 11 patients, pulmonary metastasis in 18 patients, and distant metastases in 37 patients. T790M mutation was identified in 68 re-biopsy cases (50%) after EGFR-TKI failure. Although no clinical patient characteristics were associated with acquiring T790M mutation, the duration from initial diagnosis to re-biopsy significantly affected the frequency of T790M mutation: T790M mutation was identified in 36 % (10/28), 37% (14/38), 45% (10/22), 60% (9/15), 62% (8/13) and 89% (17/19) among those patients whose duration was < 1 year, 1-2 years, 2-3 years, 3-4 years, 4-5 years and > 5years, respectively. Interestingly, five out of nine patients who received repeated re-biopsies showed reverse T790M mutation status, and four out of those five patients were turned out to be T790M-positive, despite T790M-negative results in previous re-biopsy. The overall survival time after EGFR-TKI was significantly longer in T790M-positive patients, compared with T790M-negative patients (47.1[95%CI: 37.3-NA] vs.31.7 [24.0-37.8] months, p= 0.002). Conclusions: T790M secondary mutation is more frequently detected, as the duration from initial diagnosis is longer. Repeated re-biopsy may be important after some interval, despite T790M-negative status in earlier biopsy.
Assessing clinical outcomes following liver transplantation in intrahepatic cholangiocarcinoma and mixed hepatocellular carcinoma-cholangiocarcinoma patients: The Mayo Clinic experience.
Authors: Thomas DeLeon, David D. Lee, Marcela Salomao, Marlene E. Girardo, Charles Burke Rosen, Julie Heimbach, Adyr A Moss, Amit Mathur, Denise M Harnois, Bashar A. Aqel, Sumera H. Rizvi, Kabir Mody, Mohamad Bassam Sonbol, Heidi E. Kosiorek, Mitesh J. Borad
Journal: Journal of Clinical Oncology (2018)

e16114 Background: Historically, intrahepatic cholangiocarcinoma (iCCA) and mixed hepatocellular carcinoma-cholangiocarcinoma (HCC/CCA) patients who undergo liver transplantation (LT) have poorer outcomes compared to HCC patients. The objective of this study is to determine clinical and pathological factors that predict clinical outcomes in these patients. Methods: A retrospective study was performed at Mayo Clinic. Patients who underwent LT and were found to either have iCCA, gallbladder cancer or HCC/CCA were included. Outcomes of interest included overall survival (OS) and recurrence free survival (RFS). Characteristics assessed included pathologic grade, lymphovascular invasion (LVI), tumor histology, clinical stage, lymph node positivity, total number of hepatic lesions, size of largest lesion and whether Milan Criteria was met. Results: A total of 69 patients were identified with iCCA or HCC/CCA who underwent LT (19 iCCA, 12 HCC & iCCA, 1 HCC & gallbladder cancer, 37 HCC/iCCA). The 5-year OS for the iCCA, HCC/CCA and synchronous HCC & iCCA tumors were 42%, 61% and 41% respectively. The 5-year RFS for the iCCA, HCC/CCA and synchronous HCC & iCCA tumors were 32%, 56% and 41% respectively. Stage III-IV disease (HR 3.81 [95% CI 1.39 – 10.46], p = 0.011) and lymph node involvement (HR 6.41 [95% CI 1.86 – 22.09], p = 0.0007) were the only characteristics that met statistical significance for impacting OS. Grade 4 tumors (HR 5.44 [95% CI 1.50 – 19.73], p = 0.0088), stage III-IV disease (HR 5.01 [95% CI 1.61 – 15.64], p = 0.0025), largest tumor size > 3 cm (HR 2.99 [95% CI 1.20 – 7.45], p = 0.014), presence of LVI (HR 2.74 [95% CI 1.06 – 7.09], p = 0.03), lymph node involvement (HR 5.82 [95% CI 1.68 – 20.20], p = 0.0017) and meeting Milan criteria (HR 0.37 [95% CI 0.17 – 0.84], p = 0.014) all met statistical significance for impacting RFS. Conclusions: Careful consideration of pathologic and clinical characteristics such as tumor grade, size of largest tumor, stage, LVI, lymph node involvement and meeting Milan criteria may predict improved outcomes and result in improved selection of iCCA and HCC/CCA patients considered for LT.