tbuckley/cabot-search huggingface dataset:
Is there a benefit of adding surveillance imaging to frequent history and physical exams in patients treated definitively for head and neck squamous cell carcinoma?
Authors: Jeffrey Chi, Ryan Sugarman, Matthew C. Lee, Dev Kamdar, Douglas K. Frank, Lucio Pereira, Edward Z. Gabalski, Priscila Hermont Goncalves, Bhupesh Parashar, Sewit Teckie, Maged Ghaly, Nagashree Seetharamu
Journal: Journal of Clinical Oncology (2019)

6074 Background: In head and neck squamous cell carcinoma (HNSCC) patients (pts) who completed curative-intent definitive treatment (tx), close surveillance is important. Across all centers, pts are closely monitored for symptoms and undergo frequent dedicated head and neck evaluation. Role of surveillance imaging after the initial 12 week post-treatment PET/CT however is less clear. Our institutional practice is to follow pts with regular interval imaging for two years after treatment. However this carries a financial cost, and risk for false positives and unnecessary biopsies. Methods: This is a retrospective chart review of pts treated definitively for HNSCC at our institution from 2012 to 2016. Pts who had a biopsy (bx) post-tx due to suspicion for recurrence were included. Pts belonged to 3 groups: In the first group (A), biopsy was prompted by findings on surveillance imaging (SI); in the second (B), biopsy was prompted by symptom triggered imaging (STI) and in the third (C), biopsy was based on physical exam (PE). We recorded the aggregate results of bx in each group and calculated the positive predictive value (PPV) for each. Results: Of 353 HNSCC pts, 66 underwent post-tx bx for suspected recurrence of which 46 were positive. Of the 30 pts in group A, 21 had positive bx (PPV = 70%). Within this group, PPV was highest with PET/CT (81.82%) followed by magnetic resonance imaging (66.67%) and CT (62.5%). 20 out of 20 pts in group B had bx-proven recurrence (PPV = 100%). 27 out of 36 pts in group C had positive bx (PPV = 75%). While there was no overlap between groups A and B, there was some overlap between groups A and C; and B and C. 45.45% of all recurrences were captured because of SI. When both imaging and PE conducted were positive simultaneously, 54.35% of recurrences were detected first by PE and 45.65% by imaging. Conclusions: Bx triggered by STI has the highest PPV. SI has the lowest PPV, but 45.65% of recurrences were diagnosed because of SI alone. Our study suggests that routine SI for at least two years post treatment for HNSCC patients may add to the surveillance value of frequent PE but larger studies are needed to determine the optimal frequency and type of SI modality.
Predictive value of baseline clinicopathological factors in non-small cell lung cancer (NSCLC) patients on checkpoint inhibitors (CPI).
Authors: James Newman, Isabel Ruth Preeshagul, Kevin M. Sullivan, Nina Kohn, Nagashree Seetharamu
Journal: Journal of Clinical Oncology (2019)

e14119 Background: Tumor PD-L1 expression and tumor mutational burden currently serve as primary predictive markers for CPI efficacy in NSCLC. However, these markers are imperfect due to tumor heterogeneity, changes over time, and lab variations. These challenges highlight importance of developing dynamic, readily available predictive biomarkers. We evaluated predictive value of pre-treatment Neutrophil-to-Lymphocyte Ratio (NLR), smoking history (SH), body mass index (BMI) and smoking intensity (SI) in NSCLC patients (pts) on CPIs. Methods: Retrospective analysis of NSCLC pts treated with CPIs July 2015 to November 2017. Pt demographics, tumor PD-L1 status positive (pos) or negative (neg) (PD-L1 &gt; 0% or 0% respectively), SH, SI (heavy smokers (HS) or non-heavy smokers (NHS) [ = / &gt; 20 pack-year (PY) and &lt; 20 PY respectively], NLR and BMI high or low based on cutoffs of 5 and 25, respectively were captured. Disease Control Rate (DCR) was defined as objective response or stable disease per RECIST 1.1 at 3 months (m). Median overall survival (OS) and time to progression (TTP) were calculated. Fisher’s exact test and chi-square test were used to compare DCR for each group. Kaplan-Meier curves were used to estimate OS and TTP for each factor. Results: 140 pts were included. NLR was associated with DCR, OS, and TTP. 62/90 (68.9%) pts in the low NLR group and 18/47 (38.3%) in the high NLR group had DCR (p &lt; 0.0006). Median OS for low NLR was 15 m (95% CI: 11.75, 22.25) vs. 5.25 m for high NLR (95% CI: 2.75, 9.75) (p &lt; 0.0005). Median TTP for low NLR was 8 m (95% CI: 6.00, 11.25) vs 3 m for the high (95% CI, 2.00, 4.00) (p &lt; 0.0001). SH was not associated with DCR or survival, but was predictive of TTP. SI was predictive of DCR, but not OS or TTP. 65/100 (65.0%) HS and 15/34 (44.1%) NHS had DCR (p &lt; 0.0320). BMI and PD-L1 (n = 55) were not associated with any outcome. There was association between high BMI and low NLR (P &lt; 0.0381). There were no other associations between factors. Conclusions: NLR &lt; 5 was associated with improvement in all measures of outcome while smoking was associated with some. Neither BMI nor PD-L1 were predictive of any outcome. A score incorporating NLR and smoking status may be beneficial in choosing patients for CPIs.
Impact of a regular exercise program on amount of exercise and QOL metrics in patients on immune therapy.
Authors: Nicole Brenna Quenelle, Kathryn Blount Bollin
Journal: Journal of Clinical Oncology (2019)

TPS11636 Background: Studies show physical activity has a positive impact on fatigue and quality of life both during cancer treatment with chemotherapy and radiation and post-treatment (1, 2). There may also be a survival benefit to increasing physical activity both during and after treatment (3). To date there is no published research on the role of exercise in ameliorating the fatigue patients can experience during treatment with immune therapy. Our study proposes to use the existing framework of the LIVESTRONG at the YMCA program to objectively measure improvement in activity level and objective quality of life measurements. Methods: Randomized controlled prospective study evaluating patient participation in LIVESTRONG at YMCA program during active cancer treatment to assess change in minutes per week of self-reported physical activity over 12 weeks. Assessments will be done based on attendance of 12 week program, activity log, functional assessments of physical activity pre- and post- program (6 min walk test, % change in weight, % change in max weight lifted and flexibility), and questionnaires evaluating fatigue (PROMIS 13a FACIT-F), pain (PROMIS pain intensity scale, ASCQ-Me short form), quality of life (FACT-G), Godin Leisure Time Activity Questionnaire, and inflammatory markers (ESR, CRP). Data will be analyzed on an intention-to-treat analysis. A sample size of 100 participants per group will achieve 80% power to detect a 60 minute difference with a standard deviation of 150 minutes 1 and with a significance level (alpha) of 0.050 using a two-sided two-sample t-test. Enrollment is targeted at 108 participants per arm to allow for 8% attrition, 216 total. Secondary endpoints will be assessed at a baseline functional assessment session for all participants and a follow up session after 12 weeks, including administration of questionnaires at both sessions. For physical activity measurements and survey completions, percent change in baseline and completion measurements will be calculated for each patient, then comparison using a chi-square test will be done to determine statistical significance.(Tomlinson et al. Effect of exercise on cancer-related fatigue: a meta-analysis. Am J Phys Med Rehabil. 2014;93:675-686; Irwin et al. Effect of the LIVESTRONG at the YMCA Exercise Program on Physical Activity, Fitness, Quality of Life, and Fatigue in Cancer Survivors. 2016 (published online October 28, 2016); Li T et al. The dose–response effect of physical activity on cancer mortality: findings from 71 prospective cohort studies . Br J Sports Med. 2016;50:339-345).
Trends in case-control allocation in phase III randomized cancer clinical trials.
Authors: Shruti Gupta, Swathi Gopishetty, Srishti Malhotra, Vamsi Kota, Anand P. Jillella, Achuta Kumar Guddati
Journal: Journal of Clinical Oncology (2019)

e14582 Background: Patients enrollment in cancer clinical trials has traditionally been limited to an equal distribution between cases and controls. Some clinical trials have an unequal distribution between the case and control arm. Although such unequal allocation is uncommon it has certain advantages and disadvantages to it. The trend and proportion of cancer clinical trials that have an unequal allocation has not been studied. Methods: Data about cancer clinical trials was extracted from clinical trials.gov. The query included phase 3 trials which included adults and were conducted between 2010 to 2017. Only clinical trials that were either completed or active – but not recruiting were included. T test was used to determine statistical difference between different subgroups. Results: 601 clinical trials were identified of which 356 trials with two arms and 47 trials with 3+ arms were identified. Amongst the eligible 298 trials with two arms, there were 216 trials with equal allocation (1:1) and 82 trials with unequal allocation. Amongst the eligible 29 trials with 3+ arms; there were 21 trials with equal allocation (1:1:1) and 8 trials with unequal allocation. There was no significant difference in the proportion of trials with unequal allocation over the time period from 2010 to 2017. The categories of cancer which had the highest number of two arm clinical trials with unequal allotment were: genitourinary, breast and hematological malignancies (Table). Conclusions: Cancer clinical trials with unequal allocation between case and control arms have been common in the past decade. This may represent a new trend in clinical trial design to help enhance closer monitoring of adverse events despite higher costs attached to this method.[Table: see text]
Sequential assessments of <i><i>KRAS-</i></i>mutated circulating tumor DNA in longitudinal monitoring enable the prediction of prognosis and therapeutic responses in patients with pancreatic cancer.
Authors: Fumiaki Watanabe, Koichi Suzuki, Sawako Tamaki, Hideki Ishikawa, Nao Kakizawa, Hiroshi Noda, Toshiki Rikiyama
Journal: Journal of Clinical Oncology (2019)

e15712 Background: Liquid biopsy enables the detection of circulating tumor DNA (ctDNA) levels, including KRAS-mutated ctDNA, which is considered a predictive biomarker for pancreatic cancer. This study aimed to evaluate the significance of sequential KRAS ctDNA assessments in longitudinal monitoring. Methods: A total of 422 blood samples were collected from 78 patients undergoing treatments for localized and metastatic pancreatic ductal adenocarcinoma. KRAS ctDNA levels was determined by droplet digital polymerase chain reaction. Longitudinal monitoring of KRAS ctDNA was performed to assess its significance for predicting recurrence and prognosis and evaluating therapeutic responses to chemotherapy. Results: In 39 patients who underwent surgery for potentially resectable tumors, sequential assessments of KRAS ctDNA in longitudinal monitoring was significantly associated with prognosis ( P &lt; 0.001). In 39 patients who did not undergo surgery, sequential assessments of KRAS ctDNA was a predictive factor for prognosis ( P = 0.005). Multivariate analysis revealed that detection of KRAS ctDNA in longitudinal monitoring was the only independent prognostic factor regardless of tumor resection ( P&lt; 0.001). Longitudinal monitoring revealed the significance of sequential assessments of KRAS ctDNA within a short period. The presence of KRAS ctDNA in sequential assessments within 1 year after surgery showed significant association with prognosis irrespective of recurrence ( P&lt; 0.001). The presence of KRAS ctDNA in sequential assessments within 6 months was significantly correlated with therapeutic responses in the first line chemotherapy ( P&lt; 0.001). Conclusions: Our study showed for the first time that sequential assessments of KRAS ctDNA levels within a short period enabled the prediction of prognosis and therapeutic response in patients with pancreatic cancer.
Identifying predictors of pathologic complete response to neoadjuvant chemotherapy for muscle invasive bladder cancer.
Authors: Andrea Harzstark, Maqdooda Merchant
Journal: Journal of Clinical Oncology (2019)

e16015 Background: Pathologic complete response (pCR) to neoadjuvant chemotherapy is associated with improved outcome in patients (pts) with muscle invasive and/or lymph node positive (LN+) bladder cancer. Although molecular predictors are currently being evaluated, limited information is available regarding purely clinical parameters offering predictive information regarding pCR to neoadjuvant chemotherapy. Methods: We identified 189 unique pts within Kaiser Permanente Northern California diagnosed with bladder cancer during 1/1/10 through 12/31/17 who underwent chemotherapy with neoadjuvant intent with a plan for subsequent radical cystectomy. All pts had disease that was ≥cT2 and/or ≥cN1 and M0. Fourteen variables were examined for their association with pCR at radical cystectomy, using bivariate analysis and multivariate models. Results: Of the 189 pts in our cohort, 141 (74.6%) were male, 162 (85.7%) were white and the mean age was 66.4 years. 76 (40.2%) pts achieved pCR; of these, 59 (77.6%) had pre-treatment hemoglobin (hg) ≥ 13 g/dL (p = 0.0087), 69 (90.8%) did not have hydronephrosis (p &lt; 0.0001), 66 (86.8%) had no lymphovascular invasion (LVI) on transurethral resection of bladder tumor (TURBT) (p = 0.0506) and 69 (90.8%) had cT2 disease at time of diagnosis (p &lt; 0.0001). Logistic regression analysis showed that pCR was associated with hg ≥ 13 (OR 2.736, 95% CI 1.188-6.657), absence of hydronephrosis (OR 4.672, 95% CI 1.820-13.554), age ≤ 75 years (OR 3.410, 95% CI 1.263-10.057), absence of LVI on TURBT (OR 2.592, 95% CI 1.055-6.829), and clinical stage T2 vs. ≥T3 and/or N+ (OR 6.480, 95% CI 2.645-17.858). There was no statistically significant relationship between pCR and the following variables: cumulative cisplatin dose, split dose chemotherapy, chemotherapy regimen, history of tobacco use, race, gender, Charlson comorbidity score, baseline alkaline phosphatase, and percentage body weight loss during therapy. Conclusions: Pathologic CR was predicted by Hg &lt; 13 g/dL, absence of hydronephrosis, age ≤ 75 yrs, absence of LVI on TURBT specimen, and stage at diagnosis. These factors may influence selection of pts with muscle invasive and/or LN+ bladder cancer for neoadjuvant chemotherapy.
Venous thromboembolism in breast cancer patients receiving cyclin-dependent kinase inhibitors.
Authors: Lorenzo Gervaso, Alberto J. Montero, Xuefei Jia, Alok A. Khorana
Journal: Journal of Clinical Oncology (2019)

e18184 Background: Venous thromboembolism (VTE) complicates several anti-cancer regimens including chemotherapy and anti-angiogenic agents. Cyclin-dependent kinase 4/6 inhibitors (CDKIs) are a new approach for hormone receptor positive (HR+) metastatic breast cancer (mBC). Reported VTE rates in randomized trials range from 0.6% for ribociclib (MONALEESA-2) to 2% for palbociclib (PALOMA-3) and 5% for abemaciclib (MONARCH-3) but these may underestimate actual rates compared to patients in clinical practice who are generally older and have greater comorbidities. Little is known about real world incidence or prevalence of VTE with CDKIs in mBC. The aim of this study was to evaluate rates of VTE in clinical practice and association with outcomes in mBC patients on CDKIs. Methods: We conducted a retrospective cohort study at Cleveland Clinic Taussig Cancer Institute, approved by the institutional review board. We identified consecutive mBC patients who received any of three FDA-approved CDKIs (palbociclib, ribociclib, abemaciclib) from 1/2015 through 12/2017. VTE including deep venous thrombosis (DVT) and pulmonary embolism (PE) were identified by electronic medical record review. Overall survival (OS), progression free survival (PFS) and time to VTE were estimated by the Kaplan-Meier method and evaluated for association with VTE using Cox proportional hazard regression. Results: The study population included 424 patients, with a median age at diagnosis of 54.76 yrs, (range 27 -85). Palbociclib was the most commonly used CDKI (n = 390, 91.8%); 27 patients (6.3%) received more than one drug. VTE during CDKI therapy occurred in 9% of patients (n = 38), including DVT in 52.6% (n = 20), PE in 18.5% (n = 7) and visceral vein thrombosis (VVT) in 15.8% (n = 6). Median time to VTE was 314 days, and 6-months rate was 4.1%. VTE was associated with numerically worse PFS and OS, but this was not statistically significant (PFS [HR 1.25, 95% CI 0.73 – 2.14, p = 0.42], OS [HR 1.60, 95% CI 0.89 – 2.87, p = 0.12]). Conclusions: VTE affected nearly 10% of breast cancer patients receiving CDKIs, 2- to 5-fold greater than reported in registration trials. Further work is necessary to identify pathophysiology, risk factors and benefit of thromboprophylaxis.
Medical cannabis in cancer patients: Prevalence, efficacy, and safety.
Authors: David Macari, Bolanle Gbadamosi, MD., Daniel Ezekwudo, John Khoury, Ishmael A. Jaiyesimi, Susanna S. Gaikazian
Journal: Journal of Clinical Oncology (2019)

e23099 Background: Cancer patients are using medical cannabis (MC) to address symptoms, however, little data exists to guide clinicians when counseling patients regarding use. We seek to define the patterns of MC use among oncology patients as well as efficacy and safety of MC. Methods: Cancer patients attending oncology office visits at Beaumont Hospital, Michigan from July – Dec 2018 were anonymously surveyed. The survey included data regarding demographics, diagnosis, treatment, symptom burden, and MC use. Patients who reported MC since their cancer diagnosis completed a section on patterns of use, efficacy, and safety. Results: Response rate was 188 of 327 (57.1%). Ages ranged from 18 to &gt; 71, 59% were 61 or older. Early stage solid malignancy was 38%, metastatic was 41%, and hematologic malignancy was 21%. Cancer treatment was active in 80%. MC use was reported in 46 of 188 (24.5%). Median composite baseline symptom score ranging from 8 (best) to 32 (worst) was higher in patients using MC vs non-users; 17.5 vs 14.4 (p &lt; 0.001). Pain was the symptom with the highest frequency of improvement 34/42 (81%), followed by appetite 34/44 (77%), and anxiety 32/44 (73%). MC improved ability to tolerate treatment in 24/44 (54%). The most frequent adverse effects were cloudy thinking 7/42 (17%), and decreased energy 4/41 (10%) Use of cannabis prior to cancer had no impact on median composite efficacy score (p = 0.43). Age &gt; 61 was not associated with higher toxicity (p = 0.077). Conclusions: This data confirms MC is being utilized by a significant portion of cancer patients, across age, diagnosis, stage, and treatment. Patients with a higher severity of baseline symptoms are more likely to use MC, and report a favorable efficacy profile of MC with no increased risk of adverse effects in older population and similar efficacy in novel MC users. Minimal toxicity was reported in this cohort. Prospective studies are needed to define the efficacy and safety of MC. [Table: see text]
Analysis of proportion of geriatric patients in phase III cancer clinical trials.
Authors: Swathi Gopishetty, Vamsi Kota, Achuta Kumar Guddati
Journal: Journal of Clinical Oncology (2019)

e23032 Background: Geriatric patients are often under-represented in cancer clinical trials. The presence of multiple comorbidities makes geriatric patients ineligible for most clinical trials. However, the increase in cancer incidence in geriatric patients raises the question of applicability of the results is such clinical trials. Methods: Data about Phase 3 trials was extracted from the clinical trials.gov for 3 common solid organs and 3 hematological malignancies [breast, colon, lung, diffuse large B-cell lymphoma (DLBCL), acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL)]. The time period studied was for the past 10 years and included only adult patients (≥ 18 years). The age distribution of the patient population in these trials were extracted and analyzed. Results: Geriatric patients are heavily under-represented in all phase 3 cancer clinical trials. Table shows the proportion of patients below 65 years, above 65 years and older in clinical trials for each organ specific malignancy. The range of the proportion of geriatric patients varied from 10% to 40%. Conclusions: The results of phase 3 clinical trials that are currently conducted on non-geriatric patient population may not meaningfully be applicable to geriatric patients. This study highlights the disparity of age for patients enrolled in clinical trials as against the patients seen in the real world.[Table: see text]
Everolimus treatment of subependymal giant cell astrocytomas (SEGA's) associated with tuberous sclerosis complex (TSC): the EXIST-I trial.
Authors: S. Sparagana, Elena Belousova, Sergiusz Jozwiak, Bruce Korf, M. Frost, Rachel Kuperman, M. Kohrman, Olaf Witt, J. Wu, Robert Flamini, Anna Jansen, P. Curtalolo, Elizabeth Thiele, V. Whittemore, Petrus De Vries, James Ford, Gaurav Shah, H. Cauwel, Pascal Edrich, T. Sahmoud, David Franz
Journal: Neuro-Oncology (2011)
A phase I study of pazopanib with weekly paclitaxel and carboplatin in advanced solid tumors.
Authors: Nancy Chan, Daniella E. Portal, Rebecca Anne Moss, Ann W. Silk, Mark N. Stein, Joseph Aisner, Jyoti Malhotra, Weichung Shih, Hongxia Lin, Michael P. Kane, Janice M. Mehnert, Antoinette R. Tan
Journal: Journal of Clinical Oncology (2019)

3021 Background: Pazopanib (pazo) is an oral tyrosine kinase inhibitor of VEGFR, PDGFR and c-Kit. It is a weak inhibitor of CYP3A4 and CYP2C8 and may decrease paclitaxel (P) clearance. Daily pazo with P and carboplatin (C) every 21 days was not feasible on a previous study. We hypothesized that pazo dosed intermittently and on a different day from P and C may be tolerable. We sought to determine the maximum tolerated dose (MTD), dose-limiting toxicity (DLT), and pharmacokinetics (PK) of pazo with weekly P and C. Methods: Using a 3+3 standard design, a schedule of P 60-80 mg/m 2 and C AUC2 on days 1, 8, and 15 with pazo 400-800 mg on days 2-5, 9-12, and 16-26 on a 28-day cycle was evaluated. Pazo alone could be continued if P and C were omitted due to maximal benefit or toxicity. PK was collected during cycles 1 and 2. Results: 34 patients (pts) were treated over 6 dose levels (Table). Mean age 57 (37-79). Tumor types: breast (22), lung (3) and other (9); 27 had prior platinum. Delay in starting cycle 2 due to grade 3 neutropenia was a DLT at dose level 2 and 5. Pts on 5A missed dosing during C1 and C2 due to neutropenia and required subsequent growth factor, and this was deemed unlikely to be sustainable long-term. All grade toxicities included anemia (62%), neutropenia (59%), and thrombocytopenia (56%). Protocol-defined MTD was not determined. PK analysis showed a dose proportional increase in pazo concentration, consistent with previous reports. Pazo did not alter the PK of C. C max of P was higher C2D1 vs C1D1; mean C max ratio between C2D1:C1D1 was 1.63 (95% CI:1.29-1.96). There were 11 objective responses (3 CRs, 8 PRs). Five breast pts were on pazo alone for a median of 9 cycles (2-52) with CR (2), PR (2) and SD (1); a squamous cell of unknown primary in CR received 22 cycles. Clinical trial information: NCT01407562. Conclusions: PK confirm that pazo is a weak inhibitor of CYP3A4 and CYP2C8. Myelosuppression was a major adverse event at all dose levels. MTD was not determined. Antitumor activity was achieved with this alternate combination schedule and sustained responses from sequential pazo monotherapy was observed.[Table: see text]