tbuckley/cabot-search huggingface dataset:
The role of chronic disease in the costs of potentially preventable emergency department use during treatment: A regional study.
Authors: Laura Elizabeth Panattoni, Catherine R. Fedorenko, Karma L. Kreizenbeck, Stuart Greenlee, Julia Rose Walker, Mikael Anne Greenwood-Hickman, Sarah Barger, John Whitelaw Rieke, Ted Conklin, Thomas D. Brown, Sharon Chance, Keith D. Eaton, Rose Guerrero, Mary Gunkel, Renato G. Martins, Marilyn Moorhouse, Bruce Smith, Gary H. Lyman, Scott David Ramsey
Journal: Journal of Clinical Oncology (2017)

6505 Background: The Centers for Medicare and Medicaid Services (CMS) released a quality metric for potentially preventable chemotherapy-associated emergency department (ED) use, effective in 2020. This metric excludes diagnoses with emerging evidence for outpatient management, such as proactive symptom management (PSM) and those for ambulatory care sensitive chronic conditions. Little is known about the intersection between potentially preventable ED visits due to cancer vs. other chronic disease. This study characterized the number and costs of ED visits during treatment. Methods: Western Washington cancer registry records from 2011- 2015 were linked with claims from two commercial insurers. Patients with newly diagnosed solid tumors undergoing initial treatment with chemotherapy or radiation were eligible. ED use was tracked one year post treatment initiation. ED diagnosis codes for fields 1-10 from the CMS metric and the PSM literature were labeled “Potentially Preventable” (Pp). Codes from the Agency for Healthcare Research and Quality’s Prevention Quality Indicators (PQI) for Chronic Conditions were labeled “Potentially Preventable-Chronic Disease” (PpChronic). Costs were adjusted to $2016. Results: Of the 7,053 eligible patients, 2,543 (36.1%) visited the ED (median # visits [IQR]: 1 [1-2]). The most commonly listed codes included Pain (1,054 visits) and Dyspnea (279 visits) for Pp, Hypertension-PQI (652 visits) and COPD-PQI (206 visits) for PpChronic, and Diabetes (247 visits) and Hyperlipidemia (181 visits) for the other codes. Spending on ED visits including both potentially preventable cancer and chronic disease diagnoses totalled $706,552 (20% of ED costs). Conclusions: One fifth of ED costs potentially resulted from simultaneous poor cancer symptom and chronic disease management. Future research should explore the role of chronic illness in categorizing which ED visits are potentially preventable during cancer treatment. [Table: see text]
Prognostic impact of kinetics of circulating plasma cells before and after induction therapy in newly diagnosed multiple myeloma patients undergoing early transplantation.
Authors: Rajshekhar Chakraborty, Eli Muchtar, Angela Dispenzieri, Martha Lacy, Francis Buadi, David Dingli, William J. Hogan, Shaji Kumar, Dragan Jevremovic, Suzanne R. Hayman, Prashant Kapoor, Nelson Leung, Morie A. Gertz
Journal: Journal of Clinical Oncology (2017)

8020 Background: Circulating plasma cells (CPCs) at diagnosis, prior to transplant and at relapse have a negative prognostic impact on survival in multiple myeloma (MM). However, the impact of changes in CPCs along the course of illness has not been defined. Methods: We evaluated 247 patients with newly diagnosed MM (NDMM) undergoing early autologous stem cell transplantation (ASCT) in the era of novel agents (2007 to 2015), who had serial evaluation of CPCs at diagnosis and pre-ASCT by 6-color flow cytometry. Results: The median age at transplant was 62 years.A total of 117 (47%) patients had no detectable CPCs at both time points (CPC-/-), 82 (33%) had CPCs at diagnosis followed by complete eradication after induction therapy (CPC+/-) and 48 (19%) had detectable clonal CPCs at transplant, with persistence of cells (CPC+/+; n=45) or emergence of new CPCs (CPC-/+; n=3) after induction. The incidence of t(11;14) by iFISH was lower in the CPC-/- group (19%) compared to CPC+/- (29%) and CPC +/+ or -/+ (39%) groups ( p=0.033). Conversely, the incidence of hyperdiploidy was significantly higher in patients with CPC-/-, compared to those with CPC+/- and CPC+/+ or -/+ (64%, 44% and 39% respectively; p=0.005). The rate of post-ASCT stringent complete response was 32% in the CPC-/- group, 30% in CPC+/- group and 12% in CPC+/+ or -/+ group ( p=0.018). At a median follow-up of 58 months from ASCT, the median progression-free survival (PFS) from transplant in the 3 respective groups was 30, 24 and 14 months and the 5-year overall survival (OS) rates were 83%, 70% and 43% ( p&lt;0.001 for both comparisons). On a multivariate analysis, using CPC-/- group as the comparator, PFS and OS was significantly inferior in CPC+/- (RR 1.6; p=0.020 and RR 2.7; p=0.008 for PFS and OS respectively) and CPC +/+ or -/+ groups (RR 2.9; p&lt;0.001 and RR 5.8; p&lt;0.001 for PFS and OS respectively). Conclusions: Clonal CPCs are detectable in more than 50% of newly diagnosed MM patients undergoing upfront ASCT. Monitoring for CPCs before initiation of induction therapy and before ASCT by 6-color flow cytometry is highly predictive of outcome in NDMM and should be incorporated into prospective clinical trials.
TCT-47 Longitudinal adaption of high-risk patients surviving five years after successful MitraClip implantation
Authors: Eike Tigges, Daniel Kalbacher, Nicole Rübsamen, Daniel Reichart, Florian Deuschl, Lenard Conradi, Johannes Schirmer, Hermann Reichenspurner, Ulrich Schäfer, Stefan Blankenberg, Edith Lubos
Journal: Journal of the American College of Cardiology (2018)
Confirmatory trial of non-amputative digit preservation surgery in subungual melanoma: JCOG1602 (J-NAIL study).
Authors: Yasuhiro Nakamura, Kiyo Tanaka, Taro Shibata, Junki Mizusawa, Tomonori Mizutani, Haruhiko Fukuda, Arata Tsutsumida, Kenjiro Namikawa, Akira Takahashi, Yasuhiro Fujisawa, Shusuke Yoshikawa, Shigeto Matsushita, Naoya Yamazaki
Journal: Journal of Clinical Oncology (2018)

TPS9607 Background: Subungual melanomas (SUMs) are rare, comprising only 2–3% of all cutaneous melanomas in the Caucasian population and 8.7–20% of all cutaneous melanomas in the Asian and African populations. The excision margin for SUM remains controversial, and although amputations at various bone levels have been proposed, more proximal amputation levels have not improved prognoses. In addition, the prognosis for patients with SUM does not depend on the amputation level, but rather on the time from initial diagnosis to surgery. Furthermore, non-amputative digit-preservation surgery has been performed for SUMs in situ and < = 0.5 mm-thick. A recent study has indicated that not all patients with invasive SUMs histologically showed invasion to the underlying distal phalanx, and digit-preservation surgery can be applied to such patients without compromising prognosis. This trial is designed to investigate the efficacy and safety of digit preservation surgery in SUMs without bone invasion. Methods: Eligible patients are less than 80 years old, with stage I, II, or III SUM without evidence of tumor invasion to the underlying distal phalanx on preoperative radiograph. Eligible patients receive digit preservation surgery. Sentinel node biopsy is performed for patients without regional lymph node enlargement. Regional lymph node dissection is performed for patients with regional lymph node enlargement. The primary endpoint is major relapse-free survival (major RFS), which do not include local recurrence as an event; and the secondary endpoints are overall survival, digit-preservation survival, relapse-free survival, local relapse-free survival, partial relapse-free survival, and incidence of adverse events. We anticipate that the expected 5-year major RFS of historical control of amputation surgery is 77%, and that of non-amputative digit preservation surgery will decrease the major RFS by less than 10%. The planned sample size is 85 patients to provide power of 70% and on-sided alpha of 10%. Planned accrual period is 5.5 years and a follow-up period is 5 years. The trial began in November 2017 and two patients have been enrolled as of January 2018. Clinical trial information: UMIN000029997.
Refill patterns with oral oncolytic medications.
Authors: Joseph T. Dye, Sharanya Murty, Irene Nsiah, Kenneth Kennedy, Tyler Whisman, Karen Worley
Journal: Journal of Clinical Oncology (2016)

e18216 Background: Complexity of oral cancer treatments varies from continuous (CT) daily to cyclical (CY) dosing patterns (e.g., 3 weeks on treatment, 1 week off). CY dosing can cause confusion and use in the off period, which may lead to adverse outcomes. This study investigated oral oncolytic refill patterns and their association with rates of adverse drug events (ADEs). Methods: This exploratory retrospective study was conducted using data from a large national health plan of fully-insured commercial or Medicare Advantage Prescription Drug plan patients initiated on an oral oncolytic between 1/1/2011 and 3/31/2014 (identification period, ID). Continuous eligibility was required 6 months pre- and post- index date (1st oral oncolytic claim in ID period). Patients aged 19-89 years, with no oral oncolytic pre-index claims, use of a single post-index oncolytic agent no switching and at least 2 post-index refills were included. Regimens were categorized as CT or CY based on FDA labeling and quantity dispensed. For regimens, patients with at least one oncolytic agent refill > 7 days before expected refill date ( > 7 days early group) was compared to those who refilled within 7 days of expected refill date (±7 group). Expected refill dates were calculated using days’ supply (CT) or days’ supply plus off-therapy days (CY). Potential ADEs were identified from the day of first > 7 day refill or first ±7 refill until 90 days after. Differences in ADE rates by regimen were estimated using Chi-square tests. Results: Overall, 3,699 patients (CY = 2,015; CT = 1,684) were included. 16% of CY and 6% of CT patients refilled at least one prescription 7 days before estimated refill date. For patients on CY regimens, the > 7 days early group was more likely to have 2 ADEs (14% vs. 10%) and ≥ 3 ADEs (13% vs. 8%), compared to the ±7 group (p < 0.001). For CT regimens, there was no difference in ADE rate by refill pattern. Conclusions: Despite data limitations, cyclical regimens appear to create more opportunity for refilling prescriptions before 7 days from the recommended refill date. The presence of even one such refill for cyclical regimens was associated with significantly higher rates of ADEs. Care management and coordination for patients on cyclical oral oncolytics may be beneficial.
Response of advanced soft tissue sarcoma to apatinib: A retrospective analysis.
Authors: Wuwei Yang, Baorang Zhu, Jing Li, Qiaosheng Xie, Liyan Diao, Lvhua Gai
Journal: Journal of Clinical Oncology (2017)

e22502 Background: Soft tissue sarcomas (STSs) are rare but malignant tumors with high risks of local recurrence and distant metastasis. Promising efficacy of apatinib was reported in several subtypes of STSs (Dong et al. 2016, Medicine 95: e4368; Ji et al. 2016, OncoTargets and therapy 9:643-647). We aimed to preliminarily assess the short efficacy and safety of apatinib, an oral tyrosine kinase inhibitor targeting VEFGR-2, in patients with advanced STS. Methods: The medical records of 31 patients who received apatinib between September 2015 and August 2016 were retrospectively reviewed to evaluate the short efficacy, time to progression (TTP) and safety. Results: Nineteen (61.3%) patients taken apatinib after failing second or even more lines of cytotoxic chemotherapy, 8 (25.8%) patients received apatinib as second-line therapy, and 4 (12.9%) cases who refused chemotherapy was given apatinib as first-line therapy. In the study cohort, one patient was treated with apatinib as adjunctive therapy after ablation, while the remaining 30 as salvage therapy. Administration was stopped in 6 cases due to adverse events (n = 3) or personal reasons (n = 3). As a result, 24 patients were eligible for tumor response to apatinib evaluation, and 25 patients were available for survival analysis. The objective response rate was 33.3% and clinical benefit rate was as high as 75.0%. The median TTP was 4.3 months (range, 1.8–11.6 months). Most of the AEs were at grade 1 or 2. The grade 3 AEs were hypertension (n = 2, 6.5%), hand-foot syndrome (n = 2, 6.5%), and diarrhea (n = 1, 3.2%). No grade 4 AE or drug-related mortality occurred. Conclusions: Apatinib showed promising efficacy and acceptable safety profile in metastatic or recurrent STS, giving rationale clinical evidence to conduct clinical trials.
Safety and clinical activity results from a phase Ib study of alectinib plus atezolizumab in <i>ALK</i>+ advanced NSCLC (aNSCLC).
Authors: Dong-Wan Kim, Shirish M. Gadgeel, Scott N. Gettinger, Gregory J. Riely, Geoffrey R. Oxnard, Tarek Mekhail, Peter Schmid, Afshin Dowlati, Rebecca Suk Heist, Antoinette J. Wozniak, Genevive Hernandez, Indrani Sarkar, Emmanuel Mitry, Paul Foster, Carol O'Hear, Jessica Spahn, Sai-Hong Ignatius Ou
Journal: Journal of Clinical Oncology (2018)

9009 Background: Alectinib has proven systemic and CNS efficacy in patients (pts) with ALK+ aNSCLC (ALEX study). Tumor cell death caused by alectinib may release antigens broadening the potential anti-tumor T cell response. The monoclonal antibody atezolizumab (atezo) releases T cell suppression by inhibiting PD-L1 binding and improves OS in second-line NSCLC treatment. We hypothesized atezo in combination with alectinib would lead to enhanced efficacy. Methods: This phase Ib enrolled treatment-naïve pts with ALK+ aNSCLC regardless of PD-L1 status, including pts with untreated asymptomatic brain metastases. Pts received alectinib 600 mg PO BID for 7 days (safety evaluation), followed by alectinib 600 mg PO BID with atezo 1200 mg IV q3w (expansion stage) until progression or unacceptable toxicity. The primary objective was to evaluate the safety and tolerability of the combination. Secondary objectives included evaluation of tumor response (ORR) per RECIST v1.1. Results: At cut-off (18 August 2017) 21 pts (safety stage n = 7; expansion stage n = 14) who received ≥1 dose of alectinib or atezo were considered safety evaluable. Median age was 53 years. Incidence of grade 3 and serious adverse events (AEs) were 62% (52.4% treatment-related) and 33%, respectively. No grade 4–5 AEs were reported. Four pts (19%) discontinued atezo and 2 pts (10%) discontinued alectinib due to AEs. 14 pts (67%) had alectinib dose interruptions/modifications. No dose-limiting toxicities were observed. At a median follow up of 13 months, (1–22), ORR was 81% (95% CI 58.1–94.6); median progression-free survival was 21.7 months (95% CI 10.3–21.7), median duration of response was 20.3 months (95% CI 11.5–20.3), however, only 6 pts had progressed at the time of data cut-off. On-treatment CD8+ T-cell increase was observed post-alectinib run-in. Conclusions: Combination of full dose alectinib and atezo appears to have an acceptable safety profile with no new safety findings for either agent. Early efficacy results are encouraging but further follow-up is needed to define the role of this combination in pts with treatment-naïve ALK+ NSCLC.
Cabozantinib (Cabo) in advanced non-clear cell renal cell carcinoma (nccRCC): A retrospective multicenter analysis.
Authors: Nieves Martinez Chanza, Dominick Bossé, Mehmet Asim Bilen, Daniel M. Geynisman, Archana Balakrishnan, Rohit K. Jain, I. Alex Bowman, Yousef Zakharia, Vivek Narayan, Benoit Beuselinck, Neeraj Agarwal, Rana R. McKay, Joann Hsu, Sumit Shah, Abhishek Tripathi, Elaine Tat Lam, Tracy Lynn Rose, Benedito A. Carneiro, Nicholas J. Vogelzang, Lauren Christine Harshman
Journal: Journal of Clinical Oncology (2018)

4579 Background: Cabo shows robust clinical activity in advanced clear cell RCC. nccRCC, a heterogeneous mix of diseases, have been underrepresented in clinical trials and effective systemic therapy is lacking. We retrospectively characterized the clinical activity and toxicity of cabo in nccRCC. Methods: Medical records from advanced nccRCC patients (pts) treated with cabo across 18 institutions were reviewed. We captured baseline characteristics, clinical outcomes and genomic alterations by next-generation sequencing (NGS). Objective response rate (ORR) was assessed by RECIST. Clinical benefit (CB) included ORR or stable disease. Time to treatment failure (TTF) and overall survival (OS) were estimated by Kaplan-Meier. Results: We identified 80 pts with nccRCC: papillary (59%), chromophobe (10%), collecting duct (5%), Xp11.2 translocation (15%) or unclassified (11%). The majority were IMDC intermediate/poor risk (88%) and received cabo ≥3rd line (53%). Median exposure was 4 months(mos) (range: < 1-23). 48% remained on cabo while 42% had discontinued for progression and 5% for toxicity. Most common adverse events were fatigue (51%) and rash (33%). In 66 pts on cabo ≥8 weeks, ORR was 27.3%. 71% had CB; with 64% durable CB ≥6 mos. Median OS was 11 mos (95%CI 9-NR). TTF was 6.9 mos (95%CI 4.8-9.9). Subset analyses in Table. Most frequently altered genes in 43 pts with NGS were MET (21%) and CDKN2A (19%). Of the 7 evaluable papillary RCCs with MET alterations, 5 (71%) achieved CB. Conclusions: Cabo is safe and active in nccRCC. Support of ongoing (e.g.NCT02761057) and future prospective studies in nccRCC encompassing all histologies is warranted. ORR (%) N = 66 CB (%) N = 66 Median TTF (mos) N = 80 Median OS (mos) N = 80 HISTOLOGY(n)* -Papillary(38) 11(28.9) 24(63.2) 6 11 -Chromophobe(7) 3(42.9) 5(71.4) 5.8 8 -Collecting(3) 1(33.3) 2(66.7) 10.6 NR -Xp11.2(10) 2(20) 9(90) 8.3 16 -Unclassified(8) 1(12.5) 7(87.5) 6.7 11 IMDC RISK GROUP(n)* -Good(6) 4(66.7) 5(83.3) NR NR -Intermediate(41) 8(19.5) 27(65.9) 6 11.2 -Poor(16) 5(31.3) 13(81.3) 5.8 8 TREATMENT LINE(n)* -1ST(13) 1(7.7) 10(76.9) 6.7 11.2 -2ND(17) 4(23.5) 11(64.7) 4.8 9 -≥3RD(36) 13(36.1) 26(72.2) 8.1 11 (n)* for ORR/CB
Phase III trial of first-line treatment with gemcitabine plus docetaxel versus gemcitabine plus paclitaxel in women with metastatic breast cancer (MBC): A comparison of different schedules and treatment.
Authors: Lucia Del Mastro, Alessandra Fabi, Mauro Mansutti, Michele De Laurentiis, Antonio Durando, Giuseppe Colantuoni, Alberto Zaniboni, Sandro Barni, Domenico Franco Merlo, Paolo Bruzzi, Ignazia La Torre, Matteo Ceccarelli, Gbenga Kazeem, Paolo Marchi, Davide Boy, Marco Venturini, Sabino De Placido, Francesco Cognetti
Journal: Journal of Clinical Oncology (2012)

1073 Background: Weekly (W) administration of Gemcitabine+Docetaxel (G+D) or Gemcitabine+Paclitaxel (G+P) at low doses may be associated with greater efficacy and/or lower toxicity compared to the standard 3-weekly (3W) schedule. Methods: Patients (pts) (360) with MBC, that relapsed after one adjuvant/neoadjuvant regimen containing an anthracycline (unless contraindicated) that was completed for at least 12 months, were to be randomized equally to a) D 75mg/m 2 on Day1 + G 1000mg/m 2 on Days1/8 q3W ; b) P 175mg/m 2 on Day1 + G 1250mg/m 2 on Days1/8 q3W ; c) D 30mg/m 2 + G 800mg/m 2 on Days1/8/15 qW; or d) P 80mg/m 2 + G 800mg/m 2 on Days1/8/15 qW. Primary endpoint was time to progression (TTP). Secondary endpoints were overall survival (OS), overall response rate (ORR) and overall toxicity (T). Results: Due to slow accrual rate, a futility analysis was performed to evaluate the chance of observing a significant result in favour of the alternative hypothesis. The results from this led to early study termination. 241 pts [median age (range) 57.0(31-77) years] were enrolled and randomized to: 3W G+D 60(24.9%); 3W G+P 64(26.6%); W G+D 58(24.1%); W G+P 59(24.5%), of which 18(30.0%), 24(37.5%), 14(24.1%) and 19(32.2%) pts respectively completed the study protocol (i.e. received 6 cycles, extended up to 10 for partial/complete responders). Median TTP [months(95%CIs)] was 8.33 (6.19-10.16) in W and 7.51 (5.93-8.33) in 3W, with 86.3% of pts progressed in each schedule. OS did not significantly differ between treatments and schedules. ORR was comparable between D and P, while it was higher in W than in 3W (50.4% vs. 33.1%; odds ratio 0.44 [95%CI: 0.26-0.75], p=0.003). Grade 3/4 Ts were 69.2% and 71.9% of pts in D and P and showed a higher trend in 3W (75.2%) than in W (65.8%). Neutropenia was the most frequent grade 3/4 T (51.7% and 44.7% in D and P; 39.3% and 56.5% in W and 3W). Conclusions: No substantial differences between treatments were observed in safety and efficacy. W might be associated with lower grade 3/4 Ts and possibly with a better tumour response compared to 3W. These results should be interpreted with caution due to early termination of the study.
Multiplex germline testing in selected melanomas presenting to oncology clinic.
Authors: Pauline Funchain, Brandie Heald, Jung Min Song, Emily Nizialek, Jessica Marquard, Michael J. McNamara, Ahmad A. Tarhini, Brian Gastman, Joshua Arbesman
Journal: Journal of Clinical Oncology (2018)

1588 Background: A recent twin study found melanoma to be the most heritable cancer with high twin-twin concordance (Mucci et al., JAMA 2016). Of melanoma patients presenting to oncology, 29% had a family history of ≥3 cancers, 59% had cancer in a 1st degree relative, and 17% had a family history of melanoma (Sussman et al., SMR 2017). The clinical utility of multiplex germline testing in the oncologic melanoma population has not yet been established. Methods: Consecutive patients who met criteria were offered germline testing with a multiplex panel (Invitae, San Francisco, CA) comprised of 12 genes related to melanoma and 69 additional cancer-related genes not known to be related to melanoma. Eligibility criteria included ≥ 2 melanomas in an individual or family; melanoma and other cancer(s) in an individual; melanoma and at least 2 other cancers in 1st- or 2nd-degree relatives, including a 1st-degree relative; age ≤35 at diagnosis; and limited family structure. Results: Of 81 patients with completed testing, 15 (18.5%) had a pathogenic/likely pathogenic mutation. 8 (53%) mutations were in genes previously associated with melanoma (CDKN2A, BRCA1/2, BAP1, TP53), and 7 (47%) were in genes from an extended pan-cancer panel (CHEK2,PMS2,RAD51C, BLM, MUTYH). Study eligibility met by mutation-positive individuals included 9 (60%) with a personal history of multiple cancers, 6 (40%) with multiple relatives with cancer, 4 (33%) with family history of ≥2 melanomas, 3 (20%) age ≤35 years, 2 (13%) with personal history of ≥3 melanomas, and 1 (7%) with limited family history. Melanoma subtypes of mutation-positive probands included 12 cutaneous, 1 mucosal, and 2 uveal. Other cancers observed in probands/families: bladder, brain, renal, pancreatic, carcinoid, thyroid, lymphoma, colon, breast, and ovarian cancers. Conclusions: Multiplex germline testing in a melanoma cohort selected by family or personal history of multiple cancers resulted in an 18.5% mutation-positive rate, nearly half identified in genes not previously associated with melanoma. Patients with melanoma, particularly with a personal or family history of other cancers, may benefit from germline testing. More data will be required to further refine testing guidelines for melanoma.
TCT-26 Recanalization of Chronic Total Occlusions in Patients with vs. without Chronic Kidney Disease: the Impact of Contrast-Induced Acute Kidney Injury
Authors: Lorenzo Azzalini, Soledad Ojeda, Ozan Demir, Joseph Dens, Masaki Tanabe, Alessio La Manna, Susanna Benincasa, Barbara Bellini, Enrico Poletti, Davide Maccagni, Francisco Hidalgo, Joren Maeremans, Giacomo Gravina, Corrado Tamburino, Manuel Pan, Mauro Carlino, Antonio Colombo
Journal: Journal of the American College of Cardiology (2018)