tbuckley/cabot-search huggingface dataset:
Association of the diversity and composition of the gut microbiome with responses and survival (PFS) in metastatic melanoma (MM) patients (pts) on anti-PD-1 therapy.
Authors: Jennifer Ann Wargo, Vancheswaran Gopalakrishnan, Christine Spencer, Tatiana Karpinets, Alexandre Reuben, Miles Cameron Andrews, Michael T. Tetzlaff, Alexander Lazar, Patrick Hwu, Wen-Jen Hwu, Isabella Claudia Glitza, Hussein Abdul-Hassan Tawbi, Sapna Pradyuman Patel, Jeffrey Edwin Lee, Michael A. Davies, Jeffrey E. Gershenwald, Andrew Futreal, Padmanee Sharma, James Patrick Allison, Robert R. Jenq
Journal: Journal of Clinical Oncology (2017)

3008 Background: Significant advances have been made in cancer therapy with immune checkpoint blockade. However, responses in pts with MM are variable, and insights are needed to identify biomarkers of response and strategies to overcome resistance. There is a growing appreciation of the role of the microbiome in cancer, and evidence in murine models that modulation of the gut microbiome may enhance responses to immune checkpoint blockade, though this has not been well studied in pts. Thus we evaluated the microbiome in a large cohort of pts with MM, focusing on responses to anti-PD-1. Methods: We collected oral (n = 234) and gut microbiome samples (n = 120) on a large cohort of of MM patients (n = 221). Of note, the majority of pts were treated with PD-1 based therapy (n = 105). Pts on anti-PD1 were classified as either responders (R) or non-responders (NR) based on RECIST criteria, and 16S rRNA and whole genome shotgun (WGS) sequencing were performed. Immune profiling (via immunohistochemistry, flow cytometry, cytokines and gene expression profiling) was also done in available pre-treatment tumors at baseline. Results: Significant differences in diversity and composition of the gut microbiome were noted in R vs NR to anti-PD-1, with a higher diversity of bacteria in R vs NR (p = 0.03). Differences were also noted in the composition of gut bacteria, with a higher abundance of Clostridiales in R and of Bacteroidales in NR. Immune profiling demonstrated increased tumor immune infiltrates in R pts , with a higher density of CD8+T cells; this correlated with abundance of specific bacteria enriched in the gut microbiome (r = 0.59, 0.014). Other features of enhanced immunity were also noted, and WGS revealed differential metabolic signatures in R vs NR. Furthermore, diversity (p = 0.009; HR = 7.67) and abundance of specific bacteria in R (p = 0.007; HR = 3.88) was associated with improved PFS to anti-PD-1 therapy. Conclusions: Diversity and composition of the gut microbiome differ in R vs NR pts with MM receiving anti-PD-1 therapy. These have potentially far-reaching implications, though results need to be validated in larger cohorts across cancer types.
Knowledge, attitudes, and intentions toward fertility preservation awareness among oncologists in China.
Authors: Qing Li, Chuan Huang, Dan Gong, Qingyu Lan, Guangjin Liu, Anwen Liu
Journal: Journal of Clinical Oncology (2018)

e18537 Background: Fertility is a key aspect of quality of life for cancer patients of childbearing age. Some patients may benefit from preserve fertility before treatment. However, the issue of fertility preservation for cancer patients has not been taken seriously by oncologists. Currently, no studies of oncologists exist that question their Knowledge and attitudes toward discussing fertility preservation with cancer patients in China. This is the first study to examine these issues in a sample of China oncologists. Methods: A 20-items questionnaire was administered via paper questionnaire at Chinese society of clinical oncology (CSCO) annual meeting or administered web questionnaire via mobile phone software to oncologists in China. The survey was divided into three sections: demographics, fertility awareness, and attitudes toward discussing fertility preservation options with patients. Descriptive and inferential statistics were conducted. Results: Participants included 1,023 physician of China. 94% of physicians acknowledge that radiotherapy and chemotherapy can affect the patient's fertility. 62% oncologists aware male fertility preservation, 40.1% of them aware the fertility preservation methods. However, only 9.4% of the oncologists realize the correct institution for the preservation of male fertility. 65.3% of oncologists have some knowledge of the female fertility preservation, 43.14% of them are aware of the method of female fertility preservation. Only 5.1% of them realize the correct institution for the preservation of female fertility. Although 92% of physicians believed it is advisable to recommend fertility preservation to patients, 35.8% of physicians actually initiate discussions about it with their patients. Among those oncologists who did not recommend fertility to patients, 36% of them thought that the patient is not suitable for childbearing, 26.3% of them because they have few knowledge about it. Conclusions: Most of oncologists never informed their patients about fertility preservation, only a few know the correct methods and institutions for that in China. There appears to be a critical need for given more attention and improve education on fertility preservation.
Lymph node evaluation and long term survival in colon cancer stage II using NCDB.
Authors: Ahmed I Tahseen, Aabra Ahmed, Ryan W Walters, Peter T. Silberstein
Journal: Journal of Clinical Oncology (2016)

e15125 Background: Retrieving 12 lymph nodes (LN) is a quality indicator in colon cancer, supported by the National Comprehensive Cancer Network and the American College of Surgeons. Previous studies have shown 38% of patients with stage II are estimated to have 12 LN checked. Methods: 35,261 Patients with stage II colon cancer were identified from 2004-2014 using the National Cancer Database (NCDB), which has 70% of newly diagnosed cancer patients. We analyzed differences in survival in patients with stage II colon cancer, based on having at least 12 LN examined, which are stratified by age, race, gender, and type of facility providing care. Community Programs (CCP) receive 100-500 newly diagnosed cancer cases per year. Among those receiving 500+ patients, hospitals are either Academic Comprehensive Programs (ACP) or Comprehensive Community Programs (CCCP). Median survival is estimated by Kaplan Meier analysis and differences were shown by log-rank test. Results: CCP has less 12 LN examination than other hospitals at only 18% of patients, while ACP met the quality measure in 27% of patients and CCCP in 25% of patients (p < .01). Survival decreases markedly as age increases, from 114 in ages 51-60 to 84 months in ages 71-80 when < 12 LN are examined. If ≥ 12 LN are examined, survival rate increases by 3% in ages 51-60, but jumps to a 12% increase in ages 71-80. Women survive longer than men. Survival rates in blacks and whites are very similar. When comparing survival of those with < 12 and ≥ 12 LN examined, p < .05 in all categories. Conclusions: This largest, most recent analysis of stage II colon cancer reinforces the association between examining ≥ 12 LN and a better prognosis in stage II colon cancer. A greater survival when ≥ 12 LN are examined is a consistent finding across the board, but the difference is even more apparent as age increases and survival decreases. Survival between hospital types is comparable, but CCP had fewer patients with 12 LN examined. Only 25% of patients have ≥ 12 LN examined; thus, this quality measure is only achieved in a minority of patients. < 12 LN Median Survival (mo) ≥ 12 LN Median Survival (mo) % ≥ 12 LN examined CCP 92 104 18 ACP 94 103 27 CCCP 92 102 25 Ages 51-60 114 117 26 Ages 61-70 103 112 26 Ages 71-80 84 94 26 Male 91 101 23 Female 94 104 27
Metastatic Breast Cancer Collateral Damage (MBCCD) project: Addressing unique needs and identifying patients at highest risk.
Authors: Jessica Noelle Clague DeHart, Annette Stanton, Leah Eshraghi, Heather Cooper Ortner, Timothy Williamson, Alexandra Jorge, Nwamaka Obidegwu, Susan M. Love
Journal: Journal of Clinical Oncology (2017)

e21592 Background: From The Health of Women (HOW) Study™, we found that participants living with metastatic breast cancer (MBC) had a considerably diminished quality of life (QoL) compared to those with less advanced breast cancer. When faced with MBC, managing and minimizing collateral damage (CD) resulting from sequential and often continuous treatments is crucial to improving QoL. The aim of the MBCCD Project was to characterize the unique experience of MBC in order to identify and address potential areas of need in this underserved population. Methods: We crowdsourced input and gathered free-text data from 353 MBC patients to document the breadth of CD affecting QoL. We then developed a new questionnaire using validated QoL scales and PROMIS measures, along with a novel assessment of Living with MBC derived from the crowdsourcing data, which, in some cases, included verbatim statements from patients. Results: Among the 515 MBC respondents, the median age was 57 years (28-86 years), and the majority was female (99%) and non-Hispanic White (91%). Patients retrospectively reported a significant decline in overall QoL after MBC diagnosis (Before MBC: 51% excellent and1% poor/extremely poor; After MBC diagnosis: 12% excellent and15% poor/extremely poor; p &lt; 0.05). As expected, considerable CD was reported in every aspect of the patients’ lives—physical, social, financial and psychological. MBC patients who were younger ( &lt; 50 years), had lower financial status, and/or reported having children under the age of 18 years living at home were identified as being at highest risk of significant CD in every category (p &lt; 0.05). Contrary to common belief in the clinical setting, CD did not vary as a function of treatment type or metastatic location. Conclusions: Findings illustrate the need for dynamic and personalized strategies targeting CD to improve the health and well-being of MBC patients. Within each area of CD, critical needs and subsets of patients at highest risk were identified. Next steps include increasing diversity and working with MBC advocates and provider-survivor collaborators to develop recommendations that maximize benefit to MBC patients while remaining feasible for providers.
Risk-adjusted survival for melanoma brain metastases in the era of checkpoint blockade immunotherapies: Results from a national cohort.
Authors: Bryan Iorgulescu, Maya Harary, Cheryl Zogg, Keith L. Ligon, David A. Reardon, F. Stephen Hodi, Ayal Aaron Aizer, Timothy Smith
Journal: Journal of Clinical Oncology (2018)

2011 Background: The recent successes of checkpoint blockade immunotherapy (CBI) and BRAFV600-targeted therapy trials have generated exciting promise for revolutionizing the management of patients with advanced melanoma. However, because early clinical trials of CBIs and BRAFV600-targeted therapy either excluded or included disproportionately fewer cases of melanoma brain metastases (MBM), the survival benefit of these novel therapies for MBM remains unknown. Methods: The characteristics, management, and overall survival (OS) outcomes of patients who presented with cutaneous MBMs during 2010-2015 were evaluated using the National Cancer Database, which comprises approximately 70% of all newly diagnosed cancers in the U.S. OS was analyzed with risk-adjusted Cox proportional hazards and compared by Kaplan-Meier techniques. Results: 2,753 (36%) of patients presenting with stage 4 melanoma had MBMs. MBM patients who presented after the 2011 FDA approvals for CBI and BRAFV600-targeted therapy demonstrated a 91% relative increase in 4-yr OS to 14.1% (95CI: 12.2-16.1) from 7.4% pre-approval (95CI: 5.3-10.0, p < 0.001). In the post-approval era, the proportion of MBM patients that received CBI rose from 10.5% in 2011 to 34.0% in 2015 (p < 0.001). Initial CBI in MBM patients displayed a 2.4x improved median and 4-yr OS of 12.4 mos (95CI: 10.4-15.8; vs. 5.2 mos, 95CI: 4.7-5.9, p < 0.001) and 28.1% (95CI: 22.1-34.4; vs. 11.1%, 95CI: 9.3-13.1). These benefits were particularly pronounced in MBM patients without extracranial metastases, in which CBI demonstrated improved median and 4-yr OS of 56.4 mos (95CI: 25.0-not reached; vs. 7.7 mos, 95CI: 6.7-8.7, p < 0.001) and 51.5% (95CI: 38.9-62.8; vs. 16.9%, 95CI: 13.5-20.6) that persisted in MBMs that underwent resection or SRS. Conclusions: Using a large national cohort comprised of a “real-life” treatment population of MBMs, we demonstrate the dramatic improvements in OS associated with novel checkpoint blockade immunotherapies.
Combined FDG and NaF PET/CT study in patients (pts) with metastatic genitourinary tumors (mGU) treated with cabozantinib + nivolumab +/- ipilimumab (CaboNivo+/-Ipi).
Authors: Jeffrey Lin, Amir Mortazavi, Mark N. Stein, Sumanta K. Pal, Nicole N. Davarpanah, Rosa Maria Nadal, Deneise C Francis, Marilise Anne Berniger, Paul Monk, Jeffrey Kempf, Murray Becker, Levi Sokol, Yolanda McKinney, Michael V. Knopp, Chadwick Wright, Alex Jung, Peter L. Choyke, Esther Mena, Liza Lindenberg, Andrea B. Apolo
Journal: Journal of Clinical Oncology (2017)

e16017 Background: The primary objective of the study is to assess the feasibility of obtaining combined FDG and NaF PET/CT in detecting soft-tissue and bone metastatic disease in mGU pts treated with CaboNivo+/-Ipi. Methods: Pts in this single-arm, multicenter, phase I trial had FDG PET/CT followed by NaF PET/CT within 1 hour, at baseline and 8 weeks. The number and location of metastatic lesions on FDG PET/CT and on NaF PET/CT were captured. Lesions were considered positive when there was focal abnormal radiotracer uptake with CT correlation. We analyzed soft tissue and bone lesions distribution and the concordance of baseline metastatic bone disease. Results: From 7/14/15 to 9/9/16, 27 pts (urothelial carcinoma N = 11, bladder squamous cell carcinoma N = 2, sarcomatoid renal cancer N = 1, sertoli cell N = 1, germ cell tumor N = 4, trophoblastic testicular cancer N = 1, urachal N = 4, castrate-resistant prostate cancer N = 2, prostate neuroendocrine N = 1) had scans. Median age was 55 (range 35-75 yr), 24 (89%) were male. Pts completed the dual PET/CTs on the same day (imaging time 3-4 hours) without complications. On FDG, the distribution of 340 lesions were lymph node 41%, bone 35%, lung 18%, liver 11%, soft tissue 4%, kidney 0.6%, adrenal 0.3%, spleen 0.3%, pancreas 0.3%. On NaF, the distribution of 130 lesions was spine 33%, rib 16%, pelvis 13%, femur 10%, scapula 9%, sacrum 8%, skull 5%, humerus 4%, sternum 3%, manubrium 2%, clavicle 2%. Of the 130 lesions on FDG/NaF PET/CT, 38% were not seen on initial FDG. The combination of the two tracers did not affect the quality of the PET/CTs given distinct radiotracer uptake in the anatomical locations with no distortions. Residual FDG activity on combined FDG-NaF images required background intensity to be adjusted to delineate focal radiotracer uptake. There was no difficulty in identifying metastatic lesions, and no instances of prior FDG uptake affecting the determination of metastatic disease. Conclusions: Combination FDG-NaF PET/CT is a feasible imaging modality that offers convenience to pts without compromising detection of metastatic disease in mGU pts. FDG alone detected fewer bone lesions than combined FDG-NaF PET/CT. Clinical trial information: NCT02496208.
Age as a determinant of overall survival (OS) and progression free survival (PFS) in patients with stage III lung carcinoma: A Cleveland Clinic experience.
Authors: Jyothirmai Seepana, Suryanarayan Mohapatra, Sidra Khalid, Subanandhini Subramaniam, Timothy Peter Spiro, Hamed Daw, Abdo S. Haddad
Journal: Journal of Clinical Oncology (2017)

e20036 Background: Stage III NSCLC is defined as loco-regionally advanced disease due to primary tumor extension into the extra-pulmonary structures(T3 or T 4 ) or mediastinal lymph node involvement without evidence of distant metastasis. Methods: Retrospective study with 561 patients during study period 2003-2014. The most common method used for staging was contrast enhanced CT (97.5%) followed by PET(94.1%). The patients were further stratified into three subgroups &lt; 65 years, 65-75 years and &gt; 75 years. The overall median age was 66, and the median age for the groups was 57, 69and 79 years respectively. 33.9% patients received surgery; 43% patients received concurrent/sequential chemo-radiation, 7.8% patients received chemotherapy only, and 10.1% received radiotherapy only. In terms of type of chemotherapy, 21.4% had adjuvant chemotherapy, 8.8% had neo-adjuvant chemotherapy and 12.9% had both. 24.7% patients had target therapy and 3.7% had immunotherapy. The median survival was 57 months (95% CI). The two-year survival rate was 98% ± 0.7%, and the five-year survival rate was 47.3% ± 4.0%. 387 patients had relapsed. Relapse and death were both treated as PFS events, and the median PFS was 14 months (95%CI). The two-year PFS was 40% ± 0.23%, and the five-year PFS was 14.2% ± 1.7%. Results: see table. Conclusions: No difference was found for OS between &lt; 65 versus 65-75 age groups, neither between 65-75 versus ≥75 age groups. PFS was not different between &lt; 65 versus 65-75 age group. However PFS was marginally significantly different between 65-75 versus &gt; 75 age groups (p = 0.088). [Table: see text]
Pacritinib (PAC) vs best available therapy (BAT) in myelofibrosis (MF): 60 week follow-up of the phase III PERSIST-1 trial.
Authors: Ruben A. Mesa, Miklos Egyed, Anita Szoke, Aleksandr Suvorov, Andrew Perkins, Jiri Mayer, Peter Ganly, Harry C. Schouten, Patrizia Tosi, Charles Michael Farber, Pierre Zachee, Christof Scheid, James P. Dean, Tanya Granston, Jean-Jacques Kiladjian, Alessandro M. Vannucchi, Jyoti Nangalia, Adam Mead, Claire N. Harrison
Journal: Journal of Clinical Oncology (2016)

7065 Background: Effective treatment (Tx) options for patients (pts) with MF that do not induce myelosuppression are limited. PAC, an oral kinase inhibitor with specificity for JAK2, FLT3, IRAK1, and CSF1R, was not associated with clinically significant myelosuppression in early trials. PERSIST-1 compares PAC vs BAT, excluding JAK2 inhibitors, in intermediate (Int)- to high-risk pts with MF, regardless of baseline (BL) platelets (plt). At wk 24, a significantly greater proportion of PAC- vs BAT-treated pts achieved ≥ 35% spleen volume reduction (SVR; ITT: 19.1% vs 4.7%, p = 0.0003, 1º endpoint). This analysis examines outcomes at wk 60. Methods: JAK inhibitor naïve pts (N = 327) were randomized 2:1 to PAC 400 mg qd or BAT. Eligibility criteria included: DIPSS Int-1, Int-2, or high-risk MF; ANC > 500/µL; no restriction on BL plt or hemoglobin; palpable splenomegaly ≥ 5 cm; and BL Total Symptom Score (TSS) ≥ 13 (MPN-SAF). Pts could cross over from BAT to PAC after wk 24 or upon disease progression prior to wk 24. Results: Median duration of Tx with PAC was 15.1 mo (range, 0.1-31.8); 133 (60%) 103 (96%) PAC- vs BAT-treated pts discontinued, most commonly due to AEs for PAC (21%) and physician decision for BAT (78%). At wk 60, 24% of evaluable PAC-treated pts achieved SVR ≥ 35% (mean % change in spleen volume stable from wk 24 at ~ -22%). 90/107 (84%) BAT-treated pts crossed over to PAC, with median duration of 10.9 mo (range, 0.1-24.2); 19% of evaluable pts achieved SVR ≥ 35% at wk 36 after crossover and mean % change in spleen volume was -17% and -16% at wks 24 and 36 after crossover, respectively. Incidence of Tx-emergent diarrhea with initial PAC Tx was highest in wks 1-8 (All Gr = 51%; Gr 3/4 = 2.7%), followed by 12% in wks 8-16 (Gr 3/4 = 1.4%), 9% in wks 16-24 (Gr 3/4 = 1.5%), and lower in other time intervals. For pts who crossed over from BAT, a similar trend was seen. Anemia, thrombocytopenia, and neutropenia were reported in 29% vs 22%, 23% vs 14%, and 5% vs 2% of PAC- vs BAT-treated pts, respectively; peripheral neuropathy was 1% vs 4%. Conclusions: In pts with MF, responses to PAC were durable and there was no evidence of cumulative toxicities. Pts who crossed over to PAC were able to achieve similar responses to those receiving initial PAC Tx. Clinical trial information: NCT01773187.
ACTR-43. OPEN-LABEL PHASE 1 CLINICAL TRIAL TESTING PERSONALIZED AND TARGETED SKULL REMODELING SURGERY TO MAXIMIZE TTFIELDS INTENSITY FOR RECURRENT GLIOBLASTOMA – INTERIM ANALYSIS AND SAFETY ASSESSMENT (OPTIMALTTF-1)
Authors: Anders Korshoej, Slavka Lukacova, Jens Christian Sørensen, Frederik Lundgaard Hansen, Nikola Mikic, Axel Thielscher, Søren Ole Stigaard Cortnum, Trine Lignell Guldberg, Yasmin Ramshad-Lassen, Christian Rahbek, Kåre Eg Severinsen, Gorm von Oettingen
Journal: Neuro-Oncology (2018)

We present a pre-specified interim analysis of an ongoing open-label, phase-1 IST (NCT02893137) testing safety/efficacy of a new rGBM treatment. The intervention combines personalized skull-remodeling (SR) surgery with TTFields and best-choice chemotherapy. SR-surgery involves minor craniectomy or burr-holes personalized to enhance TTFields intensity focally in the tumor. Accrual began Dec 2016 (planned total 15 patients). Eligibility: Age > 18 years, first recurrence focal supratentorial GBM (RANO), and KPS 70. Patients were excluded upon progression, death, SUSARs, or unacceptable AEs. Primary endpoints: Toxicity (CTCAEv4.0). Secondary endpoints: OS, PFS, PFS6, ORR (iRANO). Interim analysis was based on data prior to April 1, 2018. 16 patients were screened, 1 declined, and 2 had KPS < 70. 3 patients were excluded prior to TTFields (radionecrosis/non-recurrence, post-op infection, and neurodeficit, respectively). All included patients (10, M/F 9:1) had GBM IDH-wt tumors (4 MGMT-methylated). Median baseline variables were KPS 90 (range 70–100), age 55 years (range 49 to 67), skull-defect area 10.5 cm2 (range 7 to 24), field enhancement 37 % (range 25 to 61), and TTFields compliance 91% (range 61 to 95). All patients received maximum safe resection (4 had non-measurable and 2 measurable disease). 8 patients received adjuvant bevacizumab and 2 temozolomide rechallenge. 5 patients had progression, 3 died, 5 were censored for PFS and 7 for OS. We observed no SUSARs, no grade 4/5 SAEs, 5 grade 3 SAEs (2 generalized seizures, 1 post-op infection, 1 diarrhea, and 1 DVT). 2 patients had grade 1–2 skin rash, and 1 had grade 1–2 headaches. Median outcome estimates: OS 15.5 months, 95%-CI: 5.9-NA, PFS 9.5 months, 95%-CI: 3.7-NA, and PFS6 58%, 95%-CI: 0.27–0.90. 1 patient had complete response. SR-surgery with TTFields is non-toxic and holds promising potential for improving rGBM outcome. A future phase 2/3 trial is being planned.