tbuckley/cabot-search huggingface dataset:
Feasibility and long-term utility of a psychosocial support group for patients with Lynch syndrome.
Authors: Christina Tran, Jada G Hamilton, Anne Lincoln, Marina Corines, Jacob Musinsky, Pragna Gaddam, Lauren M Jacobs, Emily Glogowski, Christopher Anrig, Rachael Goldberg, Asad Ashraf, Erin E. Salo-Mullen, Megan Harlan Fleischut, Margaret Sheehan, Magan Trottier, Kenneth Offit, Zsofia Kinga Stadler
Journal: Journal of Clinical Oncology (2016)

e21545 Background: Lynch Syndrome (LS), an inherited cancer predisposition syndrome, is associated with a high risk of multiple cancers and requires lifelong multi-organ cancer surveillance and, in many patients, risk-reducing surgery. Formalized psychosocial support services for LS are limited, despite data in other cancer predisposition syndromes suggesting a need for such interventions. Methods: In 2012, the Memorial Sloan Kettering (MSK) Clinical Genetics Service implemented a quarterly LS patient Advocacy Network (LSPAN) support group led by a social worker (SW). Attendance and participant feedback through a post-support group survey (Post-SGS) assessing patient satisfaction, perceived benefit, desired topics, suggestions for improvement, and emotional needs were retrospectively analyzed and summarized using descriptive statistics. Results: From 2012-2015, nine support meetings were conducted with the mean number of participants being 7 (range: 3-12). By sessions 6-9, 52% of participants had previously attended a prior LSPAN meeting. Post-SGS (n = 67) indicated that participants perceived the meetings to be very helpful (59%) or helpful (35%). For 32% of participants, the meeting exceeded and in 57% met expectations. The information presented was clear (100%) with 77% stating that the group leader (SW) was excellent. The aspect of the support group liked most by participants, as assessed by an open-ended question, was the opportunity to discuss personal experiences with others. Specific topics identified by attendees for future support groups included: family planning, coping with stress and anxiety, genetic testing for at-risk family members, and development of a support network. Attendees also expressed a desire for the development of an online group for communication between LS patients. Conclusions: Psychosocial support for LS via a quarterly support group is feasible and perceived as beneficial by patients. Continued participation suggests the utility of such a resource over the long-term. This support group addresses patient’s needs for both reliable information and peer support, and by collecting direct participant feedback, it is possible to adapt to the changing needs of the group.
Treatment patterns of metastatic melanoma in five European countries.
Authors: Chakkarin Burudpakdee, Zhongyun Zhao, Arpamas Seetasith, Qiufei Ma, Ignasi Campos Tapias, Beth L. Barber
Journal: Journal of Clinical Oncology (2016)

e21024 Background: To describe treatment patterns by BRAF status, stage, and line of therapy among patients with metastatic melanoma in five European countries. Methods: Patients with metastatic melanoma (stage IIIB-IV M1c) from France, Germany, Italy, Spain, and the UK were identified from the IMS Oncology Advantage Database that was collected from Q2 2014 to Q1 2015. Treatment patterns were examined by BRAF status, stage, and line of therapy in each country. Results: The study included 2,532 patients with unresectable metastatic melanoma (50.0% BRAF mutated; 10.5% stage IIIB-IV M1a, 37.8% ≤ 55 years, 52.6% female). Monotherapy accounted for 94.9% of all drug therapies. In patients with BRAF mutated disease, vemurafenib was the most common first-line treatment in both stage IIIB-IV M1a and stage IV M1b-M1c (France: 63.0% and 61.4%, Germany: 65.2% and 56.3%, Italy: 88.9% and 75.0%, Spain: 38.1% and 52.8%, UK: 61.5% and 84.6%). In patients with BRAF wild-type disease, the most common first-line treatment in stage IIIB-IV M1a was ipilimumab in France (34.5%), Italy (38.9%), and the UK (76.5%), and dacarbazine in Germany (40.0%) and Spain(37.5%); while the most common first-line treatments in stage IV M1b-M1c were dacarbazine and ipilimumab in France (36.6% and 30.5%), Germany (31.3% and 40.7%), Italy (37.9% and 19.8%), and the UK (55.3% and 36.6%), and dacarbazine and fotemustine (44.9% and 17.7%) in Spain. In second-line, ipilimumab was the most commonly used agent regardless of BRAF status (BRAF mutated: 27.0%-85.7%, BRAF wild-type: 39.5%-90.9%). Conclusions: In the five Western European countries, the most commonly used first-line treatment for patients with BRAF mutated disease was vemurafenib in all stages; whereas dacarbazine and ipilimumab were most frequently used for patients with BRAF wild-type disease. The high prevalence of dacarbazine use, an older agent, suggests a need for more effective and less toxic treatments for patients with unresectable metastatic melanoma.
A randomized phase II trial of interleukin-2/interferon-α plus bevacizumab versus interleukin-2/interferon-α in metastatic renal cell carcinoma (mRCC): Results from the Danish Renal Cancer Group (DARENCA) study 1.
Authors: Frede Donskov, Niels Viggo Jensen, Torben Smidt-Hansen, Line Brondum, Poul F. Geertsen
Journal: Journal of Clinical Oncology (2016)

4563 Background: The potential benefit of combining the antiangiogenic agent bevacizumab (BEV) with Interleukin-2/Interferon-alpha (IL2/IFN) immunotherapy is unknown. This randomized, open-label, phase 2 study compared IL2/IFN/BEV with IL2/IFN in patients with clear-cell metastatic renal-cell carcinoma (mRCC). Methods: We randomly assigned 118 patients (1:1) after stratification by MSKCC risk group to receive IFN 3 MIU sc once daily and IL2 2.4 MIU/m2 sc twice daily, 5 days per week, weeks 1 and 2 every 28-day-cycle, for a maximum of 9 months; or supplemented with BEV 10 mg/kg, every two weeks iv until progression, unacceptable toxicity, withdrawal of consent or a maximum of 1 year following no evidence of disease (NED). The primary end point was progression-free survival. Secondary end points included objective response rate and overall survival. Results: Baseline characteristics were well balanced between the IL2/IFN/BEV (N = 59) and IL2/IFN (N = 59) arms; metastasis-free interval < 1 year, (75% vs 76%); prior nephrectomy, (85% vs 86%); MSKCC favourable/intermediate risk group, (51%/49% vs 52%/48%); three or more disease sites, (41% vs 44%), respectively. The median progression-free survival was 8.0 mo (95% CI, 4.2 to11.9) with IL2/IFN/BEV and 8.1 mo (95% CI, 5.1 to 11.0) with IL2/IFN, p = 0.47. There was no difference in secondary endpoints between IL2/IFN/BEV and IL2/IFN; median time to treatment failure, (8.3 mo vs 5.6 mo, p = 0.18), response rate (44.1% vs 28.8%, p = 0.13), surgery of residual disease (17.0% vs 17.0%, p = 1.0), patients achieving NED (8.5% vs 8.5%, p = 1.0), and median overall survival (27.8 mo vs 35.1 mo, p = 0.19), respectively. TKI following progression was well balanced between arms (80% vs 73%). No new or unexpected toxicity was observed. Most common grade 3/4 adverse events for IL2/IFN/BEV and IL2/IFN were fatigue (64.4% vs 61.1%), flu-like symptoms (37.3 vs 41%) and thrombosis (6.8% vs 18.6%, p = 0.01), respectively. Conclusions: The addition of bevacizumab to Interleukin-2/Interferon did not add efficacy in mRCC. No new or unexpected safety findings were identified. Clinical trial information: ClinicalTrials.gov, NCT01274273.
Alpha-fetoprotein (AFP) as tumor marker in a patient with urothelial cancer with exceptional response to anti-PD-1 therapy and an escape lesion mimic
Authors: Johannes C. Melms, Rohit Thummalapalli, Kristin Shaw, Huihui Ye, Leo Tsai, Rupal S. Bhatt, Benjamin Izar
Journal: Journal for ImmunoTherapy of Cancer (2018)

The development of a new lesion in a patient with a complete remission to anti-PD-1 therapy is highly concerning for a drug resistant escape lesion. Here, we present a case of a 62-year-old patient with chemotherapy-resistant metastatic urothelial cancer who had a complete remission to pembrolizumab. The patient's disease burden tracked closely to serum levels of alpha-fetoprotein (AFP) expressed by the tumor and served as an accurate tumor marker. Surveillance imaging revealed a solitary growing pulmonary nodule mimicking an escape lesion in the absence of an increase in AFP levels. Biopsy of this lesion revealed a benign intraparenchymal lymph node with no evidence of metastatic carcinoma. This case indicates that in some patients, biomarkers aberrantly expressed by their tumors, such as AFP in this patient, may be used as a tumor marker for response to anti-PD-1 therapy and emphasizes the importance of confirming potential escape lesions by pathologic examination.
Challenges and guidelines toward 4D nucleome data and model standards
Authors: Marc A. Marti-Renom, Genevieve Almouzni, Wendy A. Bickmore, Kerstin Bystricky, Giacomo Cavalli, Peter Fraser, Susan M. Gasser, Luca Giorgetti, Edith Heard, Mario Nicodemi, Marcelo Nollmann, Modesto Orozco, Ana Pombo, Maria-Elena Torres-Padilla
Journal: Nature Genetics (2018)
The mutational landscape of gastrointestinal malignancies as reflected by circulating tumor DNA.
Authors: Paul Riviere, Paul T. Fanta, Sadakatsu Ikeda, Joel Micah Baumgartner, Gregory M. Heestand, Razelle Kurzrock
Journal: Journal of Clinical Oncology (2017)

11574 Background: Liquid biopsy of circulating tumor DNA (ctDNA) is a novel method of detecting genetic alterations in cancer patients without tissue acquisition. Methods: Our analysis surveyed the genomic landscape of 213 patients with various gastrointestinal malignancies using next generation sequencing of plasma ctDNA across a 68 gene panel (www.guardanthealth.com/guardant360/). Data analysis was performed following UCSD IRB guidelines for de-identified database (NCT02478931). Results: The most common cancer types were colorectal adenocarcinoma (N = 55 (26%)), appendiceal adenocarcinoma (N = 46 (22%)), hepatocellular carcinoma (N = 31 (15%)), and pancreatic ductal adenocarcinoma (N = 25 (12%)). 70% of patients had discernible alteration(s), and 58% of patients had ≥1 characterized alterations. The median number of characterized alterations per patient was 1 (range 0-13). The number of detected alterations per patient varied between cancer types: in hepatocellular carcinoma, 74% of patients (23/31) had &gt; 1 characterized alteration(s), whereas 76% of patients (35/46) with appendiceal adenocarcinoma had no characterized alterations. Overall, of 123 patients with characterized alterations, &gt; 99% (122/123) had ≥1 hypothetical (experimental or approved) treatment options available. Potentially targetable alterations varied between cancer types, proportionally to the detection rate of characterized alterations. The median percent ctDNA of characterized alterations was 2.50% (IQR 0.76-8.96%). Of interest, 95% of patients (117/123) had distinct molecular portfolios. Altogether, there were 143 unique characterized alterations within 56 genes. Overall concordance rates of 96%, 94%, 95%, and 91%, respectively, were found between ctDNA and tissue biopsy (105 patients) (https://www.foundationmedicine.com/) in the four most common alterations ( KRAS amplification, MYC amplification, KRAS G12V, and EGFR amplification). Conclusions: Our observations suggest that many patients with gastrointestinal tumors have discernible and pharmacologically tractable ctDNA alterations. Hence, ctDNA assessment through non-invasive liquid biopsy may have an important role in clinical practice.
PSA doubling time (PSADT) and proximal PSA value predict metastasis-free survival (MFS) in men with biochemically recurrent prostate cancer (BRPC) after radical prostatectomy (RP).
Authors: Mark Christopher Markowski, Daniel Suzman, Yongmei Chen, Bruce J. Trock, Jennifer Cullen, Zhaoyong Feng, Emmanuel S. Antonarakis, Channing Judith Paller, Misop Han, Alan W. Partin, Mario A. Eisenberger
Journal: Journal of Clinical Oncology (2017)

5075 Background: We previously reported a relationship between PSADT and MFS in BRPC post RP (Pound 1999; Freedland 2007; Antonarakis 2012). In men with PSADT&lt;12 months, who are at high risk of lethal PCa, we sought to identify a PSA cutpoint (proximal PSA; PP) that indicates the imminent emergence of metastasis (M+). In this report we combined Center for Prostate Disease Research and Johns Hopkins (CPDR/JHU) databases to investigate the association of the PP value on MFS in men with BRPC and PSADT &lt;12 mos. Methods: In the CPDR/JHU RP database (31,296), 513 men with BCR (&gt;0.2ng/ml) with PSADT &lt;12 mos who received no adjuvant/salvage ADT/RT were prospectively followed until radiological evidence of M+ are included in this analysis. All patients were evaluated yearly with &gt;1 PSA and scans at regular intervals until M+. Associations with MFS were compared using logrank test and Cox regression. The PP is the most recent value &gt;6 months prior to M+/censor. Results: M+ occurred in 218 of 513 patients with BRPC (median follow up 9 years). Risk of M+ increased successively for PSADT 6.0-7.5, 4.5-6, 3.0-4.5, and &lt;3.0 months, adjusted for pT stage and Gleason score. PP ≥10ng/ml significantly increased risk of M+ in pts with PSADT &lt;12 mos, regardless of PSADT subgroup, hazard ratio=2.95, p&lt;.0001. Median MFS was 4.0 years at PP &gt;10ng/ml vs 20 years at PP &lt;10ng/ml. Table 1 shows median MFS and 3, 5, and 7 year MFS rates in subgroups with PSADT &lt;3 and 3.01-6 months representing the highest risk groups. Conclusions: In men with PSADT&lt;12 months, PSADT subgroups &lt;7.5 months and PP &gt;10ng/ml are independent predictors of MFS, adjusted for pT stage and Gleason score. PP ≥10ng/ml further define risk of M+ in BRPC with PSADT&lt;12 months. These data can assist physicians in patient counseling and clinical trial design. [Table: see text]
UGT1A1 gene polymorphisms and clinical outcomes in small cell lung cancer (SCLC) patients treated with irinotecan-platinum chemotherapy: The first study from north India.
Authors: Navneet Singh, Ankan Bandyopadhyay, Siddharth Sharma, Digambar Behera
Journal: Journal of Clinical Oncology (2017)

e20024 Background: Irinotecan(CPT11) is an important drug for SCLC chemotherapy(CTx). UDP-glucuronosyl-transferase1A1(UGT1A1) polymorphisms can influence CPT11-related toxicity. This study aimed to assess incidence of UGT1A1 polymorphisms and their association with clinical outcomes in SCLC patients on CPT11-CTx. Methods: Observational cohort of treatment-naïve SCLC patients given CPT11-platinum doublet at a referral centre in North India over 3-yrs(January 2013-December 2015). Clinical outcomes assessed were hematological &amp; gastrointestinal toxicity(CTC-AE v3.0), response rates by RECIST &amp; overall survival(OS). Peripheral blood was drawn from all enrolled patients just prior to CPT11-CTx initiation &amp; genomic DNA isolated. Genotyping was done by PCR-RFLP for UGT1A1*7, UGT1A1*6 &amp; UGT1A1*27 &amp; by PCR-DNA sequencing for UGT1A1*28. Patients were classified as homozygous wild-type(WT/WT), heterozygous-mutant(WT/M) or homozygous-mutant(M/M) for each polymorphism assessed. Results: Of 140 patients enrolled, no mutant alleles were found for UGT1A1*27 or UGT1A1*7. Frequency of UGT1A1*6 polymorphisms(n = 111) was 89.2% WT/WT, 8.1% WT/M &amp; 2.7% M/M. For UGT1A1*28(n = 102), this was 41.2% WT/WT, 43.1% WT/M &amp; 15.7% M/M. For UGT1A1*6, 60% WT/WT patients tolerated &gt; 95% predicted CPT11 dose (vs. 25% in WT/M-M/M combined group;p = 0.026). Severe(grade≥3) diarrhea was more common in WT/M-M/M group (44.4% vs. 17.9% in WT/WT,p = 0.06) as was any grade mucositis (55.6% vs. 9.5% in WT/WT,p = 0.002). On multivariate logistic regression analysis, UGT1A1*6 WT/M-M/M status was the only variable associated with(a/w) occurrence of both mucositis[OR = 10.4] &amp; severe(grade≥3) diarrhea[OR = 4.8]. UGT1A1*28 WT/M-M/M patients had better OS[338 days(95% CI = 190-486) vs. 216 days(95% CI = 136-296) in WT/WT group;p = 0.045]. On multivariate Cox proportional hazards analysis, better OS was independently a/w number of CTx cycles, UGT1A1*28 WT/M-M/M status, maximum % dose of CPT11 delivered &amp; inversely with age. Conclusions: UGT1A1*6 &amp; UGT1A1*28 polymorphisms are a/w increased toxicity &amp; improved OS respectively in North Indian SCLC patients receiving CPT11-CTx.
Local consolidation therapy (LCT) after first line tyrosine kinase inhibitor (TKI) for patients with <i>EGFR</i> mutant metastatic non-small cell lung cancer (NSCLC).
Authors: Yasir Elamin, Daniel Richard Gomez, Vassiliki Papadimitrakopoulou, Hai T. Tran, Waree Rinsurongkawong, Jeff Lewis, Lara Lacerda, Emily Roarty, J. Jack Lee, Jack A. Roth, Stephen Swisher, Jianjun Zhang, John Heymach
Journal: Journal of Clinical Oncology (2017)

e20654 Background: Although most NSCLC patients with sensitizing EGFR mutations (L858R, Exon 19 deletion) have an impressive initial response, the vast majority develop acquired resistance after 9-14 months of EGFR TKI therapy. Clearly, more effective strategies to prevent resistance emergence are needed. We recently reported a randomized phase 2 trial that showed that LCT with surgery or radiation, for molecularly unselected patients with oligometastatic NSCLC who did not progress after initial systemic therapy, improved progression-free survival (PFS) compared to maintenance therapy alone (Gomez, et al., 2016). Herein, we aim to determine the outcomes of LCT after first line TKI in patients with metastatic EGFR mutant NSCLC. Methods: This is a post-hoc analysis of our recently published phase 2 clinical trial and a retrospective review of MD Anderson Cancer Center GEMINI database. Eligible patients had metastatic EGFR mutant NSCLC, had first line TKI without progression followed by LCT with surgery or radiation. Results:In GEMINI database, 129 EGFR (L858R/Exon 19 deletion) mutant NSCLC patients were treated with first line TKI (erlotinib, gefitinib or afatinib) and 12 were treated with TKI followed by LCT (3 treated within our published clinical trial and 9 at the discretion of their physician). Among the 12 patients treated with TKI plus LCT, 8 patients had oligometastatic disease (defined as ≤3 metastases) and 4 patients had &gt; 3 metastases. LCT regimens were hypofractionated radiotherapy or stereotactic ablative body radiotherapy for 11 patients and surgery for one patient. Patients treated with TKI followed by LCT had a significantly longer PFS (36 months) compared to patients treated with first line TKI alone (PFS 14 months, p = 0.0024, log-rank). Conclusions:Our retrospective data suggests that first line TKI plus LCT is a promising therapeutic strategy that led to a significant outcome improvement for patients with EGFR mutant NSCLC. A multicenter phase 2 clinical trial comparing TKI plus LCT to TKI alone is planned.
Abstract 19486: Does the Association Between Adherence to Statin Medications and Mortality Depend on the Measurement Approach? A Retrospective Cohort Study
Authors: MHD Wasem Alsabbagh, Dean Eurich, Lisa Lix, Thomas Wislon, David F Blackburn
Journal: Circulation (2015)

Background: Optimal adherence to statin medications is associated with reduced mortality rates. However, it is not clear if the estimated benefits of statin adherence are influenced by the method used to measure adherence. Objective: To contrast the association between all-cause mortality and statin adherence when two different measurement approaches are used: (i.e., fixed summary measurement versus repeated measurement). Methods: A retrospective cohort study was conducted using administrative data from Saskatchewan, Canada between 1994 and 2008. Eligible individuals received a statin prescription following discharge from a hospitalization for acute coronary syndrome (ACS). Adherence was measured using proportion of days covered (PDC) expressed either as: 1) a fixed summary measure, or 2) as a repeatedly measured covariate. Cox proportional hazards models were used to test the association between each adherence measure and mortality after covariate adjustment. Results: Among 9,051 eligible individuals, optimal adherence (≥80%) modeled with a fixed summary measure was not associated with mortality (adjusted HR 0.97, 95% CI 0.86 to 1.09). In contrast, optimal adherence defined by the repeated measures approach was associated with a 25% reduction in the risk of death (adjusted HR 0.75, 95% CI 0.67 to 0.85). Conclusions: Unlike summary measure, the repeated measures approach appears to provide a significant reduction of all-cause mortality of adherence to statins. This effect may be a result of the repeated measures approach being more sensitive, or more prone to survival bias. Therefore, we recommend comparing different measurement approaches whenever possible.
Delayed subspecialist referral in diffuse large B-cell lymphoma: Predictive factors and impact on disease status and mortality.
Authors: Joanna Zurko, Raymond Chad Wade, Amitkumar N. Mehta
Journal: Journal of Clinical Oncology (2018)

e19524 Background: Several societies recommend time based targets for cancer evaluation in an attempt to reduce cancer-related mortality. There is scarce data on the reasons for and impact of delays in the evaluation of lymphoid malignancies. In this study we aimed to determine whether structural factors predicted delayed referral at a tertiary care center (TCC) in diffuse large B-cell lymphoma (DLBCL) and whether delays had an impact on disease status and mortality. Methods: Using a retrospective cohort design, we included patients with a new pathologic diagnosis of DLBCL seen at our institution from 2009-13. The primary measure of interest was time from symptom onset to subspecialist referral at TCC. ≥3 months was considered delayed referral (DR) and < 3 months timely referral (TR). Differences between groups were analyzed using t-test and chi-square testing. Logistic regression was done to determine factors predictive of delayed referral and mortality. A p-value < 0.05 was considered significant. Results: 103 patients met inclusion criteria. Age, ethnicity, comorbidities, B symptoms, bone marrow involvement, bulky disease, and time from referral to diagnosis were similar between groups. Female sex (OR 2.29, p = 0.04) and increased distance from TCC (OR 1.009, p = 0.01) predicted an increased likelihood of DR, whereas higher stage (OR 0.58, p = 0.005) and IPI (OR 0.69, p = 0.02) predicted decreased likelihood of DR. Rural county residence, absence of a primary care physician and uninsured status did not predict DR. DR did not affect likelihood of disease progression (OR 0.74, p = 0.65). Neither DR (OR 0.96, p = 0.92) nor time from symptoms to diagnosis (OR = 0.105, p = 0.19) predicted mortality. Charlson Comorbidity Index (OR 1.53, p = 0.002), IPI (OR 2.86, p < 0.0001), and stage (OR 2.12, p = 0.0025) were the only factors associated with increased mortality. Conclusions: In this study, female sex and increased distance from referral center predicted DR whereas higher stage and IPI predicted TR. DR at a TCC was not associated with an increase in mortality or disease progression.