tbuckley/cabot-search huggingface dataset:
Evaluation of hematology/oncology patient and physician opinions on medical office outpatient services in an ethnically diverse population.
Authors: Dallas Sheinberg, Neil Mohile, Jeremy Ramdial, Farooq Faheem, Jorge Antunez de Mayolo, Eugene Ahn, Rakesh Singal, Damien Mikael Hansra
Journal: Journal of Clinical Oncology (2016)

e18182 Background: We aim to compare how various medical office outpatient services are valued between hem/onc physicians (MD) & patients (pts). Methods: Pts & MDs were enrolled to complete a survey. Survey had 13 questions asking: “Is important that my MDs office…” smells nice, is clean, looks nice, serves coffee, serves beverages, has TV in waiting room, has accessible parking, has info pamphlets regarding my illness, good waiting times, friendly support staff, staff that speaks my language, reminds me about my appointments, has fast checkout. Answers recorded on a 5 point scale (1 = highly disagree 2 = disagree 3 = neutral 4 = agree 5 = highly agree) & converted into 2 categories (1,2,3 = neutral/disagree vs 4,5 = agree). Fisher’s exact test with 2 sided p-value used to compare significance b/w MD & pt responses. Results: 1008 pts & 55 MDs enrolled from 06/2013 to 10/2015. Pt mean age 55, range 18-88 w/ 45% male & 55% female. 62% of pts were Hispanic vs. 38% not Hispanic. 16% white, 14% black, 2% Asian/Pacific Islander, & 6% other. 21% of pts had hematologic disorders vs. 79% of pts had solid malignancies. Significance disparities were demonstrated: 71% of pts agree that TV in waiting room important vs 41% of MD p < 0.0001; 57% of pt agree that serving beverages are important vs MD p = 0.0018; 57% of pt agree that serving coffee is important vs 31% of MD p < 0.0001. No significant disparities seen for looks of physical location: 83% pt vs 84% MD p = 1.00; cleanliness 94% pt vs 93% MD p = 0.56; nice smell 83% pt vs 72% MD p = 0.07; parking 86% pt vs 83% MD p = 0.54; pamphlets 88% pt vs 87% MD p = 0.67; short waiting times 88% pt vs 92% MD p = 0.39; friendly staff 92% pt vs 95% MD p = 0.79; staff speaks same language 91% pt vs 90% MD p = 0.60; appt reminders 91% pt vs 86% MD p = 0.32; fast check out 87% pt vs 91% MD p = 0.53. Conclusions: Majority of pts value all outpatient medical office services. Hem/onc practices who do not offer such services may enhance patient satisfaction and customer care by doing so. Also pts want TVs in waiting room, coffee, & other beverages served significantly more than MDs. Addressing these disparities could enhance pt satisfaction and customer service in the outpatient hematology/oncology office setting.
A randomized phase II trial of abiraterone, olaparib or abiraterone + olaparib in patients with metastatic castration-resistant prostate cancer with DNA repair defects.
Authors: Zachery Reichert, Benedito A. Carneiro, Stephanie Daignault-Newton, Amanda Sullivan, Felix Yi-Chung Feng, Todd Matthew Morgan, Scott A. Tomlins, Arul M. Chinnaiyan, Maha Hussain
Journal: Journal of Clinical Oncology (2017)

TPS5086 Background: Approximately 20% of patients with metastatic castration-resistant prostate cancer (mCRPC) harbor mutations in genes encoding DNA repair proteins (e.g. ATM, BRCA1, BRCA2, PALB2, RAD51, CHEK2, FANCA). These mutations impact base excision repair and alternative end-joining, which rely on the activity of poly(ADP-ribose) polymerase (PARP). Olaparib (olap) inhibits PARP and showed activity in a post hoc analysis in mCRPC patients with DNA repair defects (DRD). In a subgroup analysis of the NCI 9012 trial evaluating abiraterone (abi) +/- veliparib (a PARP inhibitor), patients with DRD in both treatment groups had a &gt; 80% prostate-specific antigen (PSA) response rate and prolonged progression free survival (PFS) (13.8 mos vs. 7.8 mos; P = 0.01). Preclinical data suggests interactions between androgen signaling and PARP activity. These observations provide the rationale to evaluate the efficacy of olap, abi or the combination in patients with DRD. Methods: This is a prospective, randomized, open-label phase 2 clinical trial with a primary endpoint of objective PFS (radiographic + clinical). Secondary endpoints: objective disease and PSA response rates. Analysis of tumor specimens, circulating tumor cells/DNA will be performed. Eligible patients with progressive mCRPC, no prior mCRPC therapy with tumor loss of ATM, BRCA1 or BRCA2 (based on known germline loss, prior CLIA certified tumor analysis or new metastatic biopsy) will be stratified by germline vs. somatic mutational status and randomized 1:1:1 to abi (1000 mg daily) + prednisone (5 mg bid), olap (300 mg daily) or olap + abi + prednisone (same doses). Patients in single agent arms may cross over to opposite single agent therapy at progression. An exploratory cohort of patients with DNA repair defects besides ATM, BRCA1, BRCA2 may receive olap. Statistical analysis will provide median, 12-month, and 24-month product-limit estimates of PFS by treatment arm. The study is recruiting 60 randomized patients at sites in the US. The trial is coordinated by the Prostate Cancer Clinical Trials Consortium, LLC and funded by AstraZeneca. Clinical trial information: NCT03012321.
Retrospective analysis of activity of pembrolizumab (pembro) in melanoma patients (pts) with brain metastasis (BM).
Authors: Ibiayi Dagogo-Jack, Anita Giobbie-Hurder, Justin F. Gainor, Donald P. Lawrence, Alice Tsang Shaw, Ryan J. Sullivan
Journal: Journal of Clinical Oncology (2016)

2071 Background: Approximately 50% of pts with metastatic melanoma (MM) develop BM. Among MM pts, pembro, a humanized antibody against PD-1, is associated with objective response rates of 32-35% in the first line setting and 20-30% in ipilimumab-refractory pts. Median progression-free survival on pembro ranges from 4-6 months (mos). However, only 10% of pts included in these studies had BM. We, therefore, performed a retrospective analysis of MM pts treated at our institution to assess the activity of pembro in BM. Methods: We reviewed records of 113 consecutive pts with MM treated with pembro at Massachusetts General Hospital from May 1, 2014 to October 31, 2015. Twenty-four pts were excluded due to absence of available imaging for response evaluation. We evaluated time to progression (TTP) on pembro based on investigator assessment for the remaining 89 patients. Results: Thirty-six (40%) pts had BM prior to initiation of pembro, of whom 72% had received prior treatment for BM [SRS (50%), WBRT (3%), surgery (8%), or a combination of radiation and surgery (38%)]. With a median follow-up of 8.5 mos, 49 pts (55.1%) had disease progression (PD) on pembro. Intracranial (IC)-only PD was observed in 9 (10%) pts, one of whom developed BM on pembro. Median overall TTP at any site was 4 mos (90% CI: 2.7 to 7.8 mos). Median TTP at any site was 5.4 mos for those without BM (n = 53), 6.8 mos for those with treated BM (n = 26), and 1.2 mos for pts with untreated BM (n = 10). Based on Cox regression analysis adjusting for baseline factors, there was a significant (Wald chi-squared p-value = 0.003) reduction in risk of PD in pts without BM (HR 0.18, 90%CI: 0.08 to 0.41) and in patients with treated BM (HR 0.25, 90% CI: 0.11 to 0.61) compared with those with untreated BM. Thirty-two (36%) pts were treated beyond PD (duration 21 days to 365+ days); half received local therapies. The 6-mos estimate of overall survival (OS) for the study population was 86% (90%CI: 77% to 91%). Median OS was not reached. Conclusions: Pembro has clinical activity in MM pts with BM, particularly those with previously treated BM. Prospective trials evaluating activity of pembro in MM patients with untreated BM are ongoing (NCT02085070).
Tale of two vaccines: differences in response to herpes zoster vaccines
Authors: Anne A. Gershon
Journal: Journal of Clinical Investigation (2018)

About one-third of the US population will develop herpes zoster (HZ, commonly known as shingles) over a lifetime, while two-thirds will not. It is not clear exactly why certain people are susceptible to HZ; however, we may be coming closer to an answer. In this issue of the JCI, a study by Levin et al. provides important details concerning pathogenesis of and protection from HZ. The authors characterized differences in the immunologic responses induced by two HZ vaccines, the live attenuated zoster vaccine (ZV) and the more recently developed adjuvanted varicella-zoster virus (VZV) glycoprotein E (gE) subunit herpes zoster vaccine (HZ/su), in vaccine-naive subjects and those previously vaccinated with HZ. The observed differences in responses paralleled the observed clinical protection of the two zoster vaccines, with HZ/su being superior to HZ. Together, these results seem to explain immunologically why the new subunit vaccine outperforms the live vaccine. These differences may also provide clues as to why HZ develops in the first place.
Pazopanib exposure-response assessment as adjuvant therapy for patients with localized or locally advanced renal cell carcinoma (RCC) following nephrectomy.
Authors: Cora N. Sternberg, Frede Donskov, Naomi B. Haas, Christian Doehn, Paul Russo, Mohamed Elmeliegy, Hiya Banerjee, Paola Aimone, Maurizio Voi, Robert J. Motzer
Journal: Journal of Clinical Oncology (2017)

4564 Background: PROTECT was a Phase 3 randomized placebo-controlled study to evaluate pazopanib efficacy and safety as adjuvant RCC treatment. The starting dose was 800 mg daily, which was reduced to 600 mg in an attempt to improve tolerability. Pazopanib trough concentrations (Ctrough) were collected from 358 patients at the 600-mg starting dose at two timepoints (Week 3/ 5 and Week 16/20). This analysis characterized the relationship between Ctrough and efficacy and safety endpoints. Methods: The relationship between pazopanib Ctrough and disease-free survival (DFS) was explored by Cox regression analysis. DFS of pazopanib Ctrough quartiles was explored using Kaplan-Meier plots. Exposure-safety relationship was explored via summaries of all grade adverse events (AEs), grade 3/4 (G3/4) AEs, and AE-related treatment discontinuation by Ctrough quartiles. Results: The geometric mean (geo-CV%) of Ctrough at 600-mg dose was 31.4 (57%) µg/mL and 25.3 (70%) µg/mL for Week 3/5 and Week 16/20, respectively. At Week 16/20, Ctrough values overlapped among patients receiving 400-, 600-, and 800-mg doses. Cox regression analysis showed pazopanib Ctrough at Week 3/5 as a significant covariate for DFS after adjusting for TNM staging and Fuhrman Nuclear grading (HR: 0.58, 95% CI, 0.42, 0.82; p = 0.002). Longer DFS was observed in higher Week 3/5 Ctrough quartiles (median DFS by quartile—Q1: 41.89 months, Q2-Q4: median DFS not reached). Incidence of all-grade AEs, as well as G3/4 hypertension, increased as Ctrough increased. Treatment discontinuation due to hypertension among pazopanib-treated subjects was low (3.1% vs &lt; 1% in the placebo group). Ctrough was not correlated to G3/4 ALT increase. Incidence of other G3/4 AEs plateaued at higher Ctrough. No relationship was observed between Ctrough and treatment discontinuation due to AEs. Conclusions: Pazopanib Ctrough levels in PROTECT were consistent with levels associated with efficacy in the advanced setting. Higher pazopanib Ctrough correlated with longer DFS. Higher pazopanib exposure did not increase the incidence of G3/4 AEs, with the exception of hypertension, which was adequately controlled and managed. Clinical trial information: NCT01235962.
Body mass index and long-term outcomes in patients with colorectal cancer.
Authors: Dorin Colibaseanu, Faisal Shahjehan, Jordan Cochuyt, Zhuo Li, Amit Merchea, Pashtoon Murtaza Kasi
Journal: Journal of Clinical Oncology (2018)

e15631 Background: The association between body mass index (BMI) and colorectal cancer is unique. There are several patient- and tumor-related factors that affect this and associations are not entirely clear. The primary aim of this study is to examine the association between BMI and survival after colorectal cancer diagnosis. Methods: Among 28,006 Mayo Clinic patients diagnosed with colorectal cancer between 1972 and 2017, 4,056 patients had information on BMI within 6 months prior to cancer diagnosis. The international classification guideline for adult BMI was used to create the standard groups. Continuous variables were compared between BMI groups using Kruskal-Walis test and categorical using Chi-squared test. Overall survival rates after diagnosis at 5, 10, and 15- years were estimated using Kaplan-Meier method. Multivariable Cox regression models were used to assess the differences in overall survival between BMI groups in each cancer stage, controlling for age, gender, year of diagnosis and cancer location. Results: Among 4056 patients included in the study, there were 29% normal weight, 2% underweight, 36% overweight and 33% obese patients. With all stages combined together, the overall survival rates for underweight, normal weight, overweight and obese patients were 22.53%, 29.03% , 33.82% and 30.93% respectively (p < 0.001). The results show that, the difference in overall survival was not statistically significant when underweight, overweight and obese patients were compared to normal weight patients in stage 1 and stage 2, although there was a trend that overweight patients had better survival than normal weight group in stage 2 cancer patients (HR = 0.8, p = 0.086). In both stage 3 and 4 patients, underweight group demonstrated either a trend (in stage 3: HR = 2.1, p = 0.06) or a significant disadvantage (in stage 4: HR = 2.6, p = 0.002) for overall survival compared to the normal weight group. Conclusions: BMI is an important consideration in patients with colorectal cancer. Outcomes are stage-dependent where in some situations obesity is an advantage. Being underweight is a significant negative predictor of outcome.
An exploratory phase II clinical trial of apatinib in progressive radioiodine refractory differentiated thyroid cancer.
Authors: Yan-Song Lin, Xin Zhang, Yanqing Liu, Chen Wang, Teng Zhang
Journal: Journal of Clinical Oncology (2018)

e18094 Background: Anti-angiogenic TKI is the most potential effective strategy for patients (pts) with progressive radioiodine refractory differentiated thyroid cancer (RAIR-DTC). This phase II trial assessed apatinib, an oral TKI against VEGFR-2, in RAIR-DTC. Methods: Twenty pts were sequentially recruited to receive apatinib with two dosing schedules, 750 or 500 mg qd initially. Interruption and dose reduction to 500 and 250 mg qd were allowed. Results: Baseline data are shown in the Table. Data cut-off date was 12/15/2017. The median time for thyroglobulin (Tg) decline of ≥ 30% was 3.3 wks (750 mg: 4.0; 500 mg: 2.4). The best objective response rate was as high as 80% (750 mg: 90%; 500 mg: 70%), and the disease control rate reached 100%. Pts achieved the first partial response after 8.1 wks (750 mg: 8.1; 500 mg: 8.0). The median progression-free survival was 16.6 (95%CI, 7.4–18.5) mos (750 mg: 17.6; 500 mg: 13.8). The median overall survival had not reached. All pts had drug-related adverse events (DRAEs). Grade ≥3 DRAEs were reported in 17 (85%) pts: 10 (100%) and 7 (70%) pts in 750 and 500 mg schedule, causing a dose reduction of 100% pts receiving 750 mg schedule, but of 50% pts receiving 500 mg schedule, respectively. The most common Grade ≥3 DRAEs in pts with 750 mg schedule included hypertension, hand-foot-skin reaction (HFSR), hypocalcemia, diarrhea, stomach pain and anal mucositis, while those in pts with 500 mg schedule were hypertension and HFSR. The incidence of DRAEs of any grade and Grade ≥3 DRAEs within the first 8 wks following apatinib were comparable with those thereafter, as well as the safety profile. Conclusions: Apatinib represents a new treatment option for progressive RAIR-DTC with rapid response, good efficacy and acceptable tolerance. Clinical trial information: NCT02731352.Table 1. Table: Baseline data, n (%) 750 mg 500 mg Age (yrs), Median (IQR) 51.0 (46.0, 65.0) 56.0 (49.0, 65.0) Males 5 (50) 5 (50) ECOG PS 0/1 10 (100) 9 (90) 2 — 1 (10) Histologic subtype Papillary 10 (100) 6 (60) Mixed Papillary/ Poorly-differentiated — 2 (20) Follicular — 2 (20)
Decreased lymphocyte count at diagnosis as a marker for worse outcome in localized sarcoma.
Authors: Nam Bui, Solomon Henry, Kristen N. Ganjoo
Journal: Journal of Clinical Oncology (2018)

e23537 Background: Increasing data has implicated the role of host-related immune factors in the development and progression of cancer. In this study, we investigated whether any routine immunologic laboratory parameters at diagnosis influenced the prognosis of localized bone and soft tissue sarcoma. Methods: We analyzed 531 localized bone and soft tissue sarcoma patients diagnosed and treated at Stanford Cancer Institute between 1991-2016, that had laboratory values within sixty days of diagnosis. Metastatic disease at diagnosis was excluded. Labs must have been drawn before the start of chemotherapy, if it was given. Total white blood cell count (WBC), absolute lymphocyte count (ALC), absolute neutrophil count (ANC), and age at diagnosis were fit into a Cox proportional hazards model to determine relationship with overall survival. Results: A diverse array of sarcomas was represented with the most common being undifferentiated pleomorphic sarcoma (n = 49), leiomyosarcoma (n = 48), chondrosarcoma (n = 39), sarcoma NOS (n = 36), and fibromyxosarcoma (n = 27). There was no significant correlation between low WBC (p = 0.65) and low ANC (p = 0.37) with survival. However, there was a clear significant relationship with low ALC, with patients with abnormally low lymphocyte count less than 1,000 cells/μL having a significantly worse prognosis (HR 1.9, p = 8.7e-6). This correlated with a 10-year survival of 39% versus 64% for normal ALC. Consistently lower lymphocyte count correlated with even worse prognosis with patients with grade 3/4 lymphopenia (ALC < 500) having a HR of 2.5 (p = 4.5e-6) while patients with grade 1/2 lymphopenia (500 < ALC < 1000) had a HR 1.7 (p = 0.0009). Conclusions: An abnormally low absolute lymphocyte count correlates with worse outcome in localized sarcoma and this trend worsens with lower ALC. Further research is needed to define whether this represents an immunologically suppressed state that allows cancer to grow. Laboratory Parameter # Patients (n = 531) Hazard Ratio P-Value Low WBC ( < 4) 100 (19%) 0.87 0.37 Low ANC ( < 1.5) 16 (3%) 1.7 0.37 Low ALC ( < 1) 278 (52%) 1.9 8.7e-6 ALC G1/2 ( < 1, > 0.5) 155 (29%) 1.7 0.0009 ALC G3/4 ( < 0.5) 16 (11%) 2.5 4.5e-6
Short course radiotherapy (SCRT) and delayed surgery by 8-10 weeks for MRI defined high-risk rectal cancer.
Authors: Thuraiya Nasser Al-Hajri, Lucy Wells, Leslie M. Samuel
Journal: Journal of Clinical Oncology (2017)

e15145 Background: Pelvic MRI can identify rectal cancer patients at risk of an incomplete (R1) resection, allowing pre-operative treatment, usually with pelvic chemo-radiotherapy (CRT) over 5 weeks. Co-morbidities (eg IHD) may make CRT high risk, &amp; SCRT with delayed surgery 8-10 weeks later may be an option, but with relatively little published data on efficacy. Methods: Between 2004 &amp; 2016 our database identified 573 patients with MRI defined high risk rectal adenocarcinomas, and 55 (9.6%) had SCRT &amp; delayed surgery. Results: Patient characteristics: m 35, F 20, mean age 75 years (55- 90). Main co-morbidities were active IHD &amp; frailty. Major post-operative complications were an anastomic leak in 1 (1.8%) patient &amp; septicaemia/shock in 1 (1.8%) patient, with the latter being the only 30 day post-operative death (1.8%). The R1 resection rate was 7 (12.7%), affecting the circumferential resection margin (CRM) in 6, with 2 subsequently developing local recurrence. 4 CRM +ve patients are dead, all of systemic relapse. Distal margin involved in 1 patient, alive with no recurrence on follow up. Local recurrence (with systemic relapse) occurred in 1 patent with a clear CRM, 4 years after SCRT/surgery. Overall local recurrence rate was 5.4%. Pathology response was minimal 4 (7.3%), partial 28 (51%), good partial 15 (27%), &amp; complete (pCR) 8 (14.5%). The 5 year disease specific survival rates, accepting small numbers in each group, were 60% for minimal, 96% for partial, 93% for good partial &amp; 100% for pCR patients respectively. Systemic relapse occurred in 12 (22%) patients, with liver surgery &amp; liver ablation in 2 patients respectively. 18 (33%) patients have died, 10 of infection, 2 of IHD, 2 of progressive disease, 2 of separate cancers, &amp; 2 unknown. Conclusions: In a MRI defined high risk rectal cancer population &amp; co-morbidities, the outcomes from SCRT with delayed surgery 8-10 weeks later are similar to CRT, &amp; a reasonable option to consider.
EGFR-TKI rechallenged treatment combined with apatinib in non-small cell lung cancer with EGFR-TKI resistance.
Authors: Li Liang, Fang Li, Baoshan Cao, Zhaohui Zhang, Xiang Zhu, Jiadong Wang
Journal: Journal of Clinical Oncology (2017)

e20529 Background: Acquired resistance to EGFR-TKIs frequently occurs in non-small cell lung cancer (NSCLC) patients (pts) with sensitizing EGFR mutations. EGFR-TKIs rechallenged therapy is one of the recommended strategies. This study aimed to explore the efficacy and safety of EGFR-TKI combined with apatinib (a TKI against VEGFR-2) in EGFR-TKIs resistant pts. Methods: From Aug 2015 to Nov 2016, we retrospectively screened 16 NSCLC pts who acquired resistance to the EGFR-TKI therapy and chose apatinib plus EGFR-TKI as the second-line treatment in our hospital. All pts signed informed consent before treatment. Results: Pts characteristics and efficacy are shown in the table below. Two pts discontinued on the 4 th and 10 th day due to side effects, respectively, and thus were excluded from short efficacy analysis. No CR, 4 PR and 10 SD were confirmed, resulting in an objective response rate of 28.6% and a disease control rate of 100%, respectively. At the cut-off date on Feb 7, 2017, 6 pts were still being treated. The median progression-free survival was 4.60 months (95%CI, 2.23–12.52 months). The main adverse events were hypertension, hand-foot skin reaction (HFSR) and diarrhea. Five (31.3%) grade 3 hypertension, 1 (6.3%) grade 3 HFSR and 1 (6.3%) grade 3 diarrhea were observed. Conclusions: EGFR-TKI combined with apatinib may stand for a new option for NSCLC pts with acquired EGFR-TKIs resistance. [Table: see text]