tbuckley/cabot-search huggingface dataset:
Safety and efficacy of accelerated hypofractionation and stereotactic body radiotherapy for hepatocellular carcinoma in the setting of advanced liver dysfunction.
Authors: Nima Nabavizadeh, Joseph Waller, Robert Fain, Yiyi Chen, Catherine Degnin, David Elliott, Brandon T Mullins, Ishan Patel, Brandon Alan Dyer, Willscott E Naugler, Khashayar Farsad, James Tanyi, Martin Fuss, Charles R. Thomas, Arthur Hung
Journal: Journal of Clinical Oncology (2017)

403 Background: To report toxicities and outcomes for stereotactic body radiotherapy (SBRT) and accelerated hypofractionated radiotherapy (AHRT) in patients with Child-Pugh (CP) A/B/C and Albumin-Bilirubin (ALBI) score 1/2/3 hepatocellular carcinoma (HCC). Methods: We retrospectively reviewed 151 patients with HCC treated with SBRT (50 Gy in 5 fractions) or AHRT (45 Gy in 18 fractions) between 2007 and 2015. Primary endpoint was incidence of grade 3 or higher toxicities within 6 months of radiotherapy (RT). Patients were censored for toxicity upon local progression, further liver-directed therapy, or if they exhibited grade 3 or higher toxicities prior to RT, unless RT elevated the grading or a new toxicity class was observed. Secondary endpoints of overall survival and local control were calculated. Results: Median follow-up was 11 months (1 – 90 months). Most received SBRT (72%), while 28% received AHRT due to size criteria ( &gt; 5 cm) or proximity to a critical organ-at-risk. Grade 3 or higher hyperbilirubinemia and hypoalbuminemia was greater in the CP-B8/B9/C patients (42% and 22%) or ALBI-3 patients (45% and 31%) compared to patients with CP-A/B7 (11% and 4%, p &lt; 0.001) or ALBI-1/2 (14% and 4%, p &lt; 0.001). For all other toxicity classes, no difference between liver functionality groups was seen. Eleven grade 4 and no grade 5 toxicities were observed. For all pts, 1- and 2-year treated-lesion local control (LC) rates were greater for SBRT as compared to AHRT (2-year LC 95% vs. 66%, p &lt; 0.0001). When excluding patients with planning treatment volumes &gt; 115 cc (equivalent to a 6 cm sphere), SBRT still yielded superior outcomes. Conclusions: Other than higher rates of grade 3+ hypoalbuminemia and hyperbilirubinemia, highly conformal RT appears to be a potentially safe and effective treatment option for HCC patients with advanced liver dysfunction. Compared to AHRT, SBRT is associated with superior local control.
Neck dissection for oral mucosal melanoma: Caution of nodular lesion.
Authors: Wei Guo, Yue He, Yunteng WU, Guoxin Ren
Journal: Journal of Clinical Oncology (2014)

6058 Background: Oral mucosal melanoma (OMM) often metastasizes to cervical nodes. A great number of studies have been conducted to evaluate the efficacy of neck dissection in the treatment of OMM, but considerable controversy remains in this field. Methods: The clinical features, treatments, and outcomes of 254 OMM patients were retrospectively analyzed from Jan. 1998 to Jul. 2012. Multivariate analysis was performed to identify the variables related to overall survival (OS). Results: Tumor size greater than 4 cm (p=0.01) and nodular types (p<0.0001) were independent prognostic factors for OS. Patients with nodular melanomas were more likely to have distant metastases than those with macular melanomas (p<0.0001). 164 patients (65%) had CLN metastases. The multivariate analysis revealed that prophylactic neck dissection was an independent favorable factor for OS (p=0.0016) in patients with cN0 nodular melanomas; whereas radical neck dissection (p=0.03) in patients with positive CLN. Patients undergoing functional neck dissection were more likely to have neck recurrence (p <0.001). Conclusions: Nodular type is a dangerous signal to OMM. It is advisable for patients with cN0 nodular melanomas to have prophylactic neck dissection, close observation is recommended for patients with cN0 macular melanomas, and patients with positive CLN should undergo radical neck resection.
Frequency of PIK3CA mutations in HER2+ surgically resected breast cancers in a Hispanic cohort.
Authors: Carlos Munive, Aly Gallo, Silvia P. Neciosup, Franco Doimi, Richard Dyer, Joseph Pinto, Marco Lopez-Ilasaca, Henry Gomez
Journal: Journal of Clinical Oncology (2012)

e11066 Background: PI3K signaling pathway is responsible for balancing cell survival and apoptosis, and plays an important role in the pathogenesis and progression of human breast cancers. Alterations in this pathway could influence the response to targeted therapy. Our aim is to know the frequency of mutations in the PIK3CA gene in HER2+, operable breast tumors in an Andean population. Methods: We include a cohort of 59 patients with HER2+ surgically resected breast cancer that received adjuvant anti-HER2 targeted therapy at the Instituto Nacional de Enfermedades Neoplásicas. Genomic DNA was extracted from Paraffin embedded-formalin fixed tumor samples and mutational status of PIK3CA gene was using PCR-based DNA sequencing Results: At the current date, the median of follow-up in our cohort is 2.4 years and two recurrences have been registered. Four samples were not evaluable for molecular analysis. Mutation in PIK3CA gene was detected in 12 cases (20.3%). In cases where PIK3CA mutation was detected, eight cases (66.7%) had mutations in exon 9 (A1634C/E545A in 6 cases; G1624A/E542K in 1 case and G1633A/E545K in 1 case). Four cases (33.3%) had exon 20 mutated (A3140G/H1047R in all cases). There was not coexistence of mutations in both exons. One case of tumor recurrence had mutation in exon 9. Conclusions: We found similar rates of PIK3CA mutations as described previously to HER2+, breast tumors. A longest follow upwill show the prognostic value of PIK3CA status in our cohort treated with targeted anti-HER2 therapy. [Table: see text]
Cryotherapy and thermal ablation for renal malignancy over 3cm: Comparative analysis of survival with small renal masses.
Authors: Alex Jones, Megan Dinino, Mark Wakefield, Katie Murray, Naveen Pokala
Journal: Journal of Clinical Oncology (2017)

531 Background: Ablative treatments achieve good oncological outcome for renal parenchymal tumors 3 cm or smaller. Larger renal malignancies are increasingly being treated with ablation. This comparative study determines the survival following ablation in these large renal masses. Methods: Patients undergoing cryotherapy or thermal ablation (Procedure codes 13, 15, or 23) for renal tumors were identified from SEER database (1998-2013). Exclusions: T stage not recorded, more than one primary, metastatic, or node positive disease. Demographics, stage, and overall (OS) and cancer specific survival (CSS) were analyzed. T1a tumors were compared to T1b or T2 tumors. Tumors 3 cm or less were compared to greater than 3 cm. Results: 4886 patients were identified, and 2340 patients met inclusion criteria. The mean age was 66.5 years, 1943 were white, 243 were black, and 1419 were male. The stage distribution included T1a (n=2159), T1b (n=172), and T2 (n=9). 1186 tumors had right sided, 1149 had left ,and the others were bilateral or not specified. 2326 patients had the size recorded and 1637 patients had 3 cm or smaller tumors and 689 tumors were larger than 3 cm. The OS in T1a tumors was 84.4% at 5 years and 69.2% at 9 years. The patients with T1b tumors had 62% at 5 years and 38% at 9 years. The T2 tumors had an OS of 64.8% at 57 months. The 5 yr CSS was 97.4% in the whole group, 97.9% in T1a, and 97.4% in the T1b group. The corresponding 9 yr CSS was 96.9, 97.5, and 96.9%. Comparative CSS in patients with T1a tumors was 98% at 5 years and 97.5% at 9 years. In T1b or greater tumors the 5 and 9 year survival was 90.2%. All patients that survived beyond 5 years were alive at 9 years of follow-up. On analysis by size, tumors 3 cm or less had a 98.4 5-yr and a 98.2 9-yr CSS and tumors that were greater than 3 cm had 95% 5-yr and a 93.9 9-yr survival. On univariate analysis both T1a tumors and tumors smaller than 3 cm had significantly better survival (p=0.001). Conclusions: Ablative therapies for small renal masses can achieve excellent CSS at 97% at 9 years. This study demonstrates that reasonable CSS can be achieved in masses larger than 3 cm and patients with T1b or larger tumors. Further studies are required to address the role of ablative therapies for larger renal masses.
Outcome of isolated limb infusion (ILI) treatment for Chinese acral melanoma patients with/without gene mutations.
Authors: Zhihong Chi, Li Li Mao, Si Ming Li, Lu Si, Xi Nan Sheng, Chuan Liang Cui, Yan Kong, Jie Dai, Xuan Wang, Bi Xia Tang, Jun Guo
Journal: Journal of Clinical Oncology (2014)

e20014 Background: Chinese melanoma patients had high incidence of limb in-transit metastasis because acral melanoma accounts for about 50% of melanoma in China. So far, isolated limb infusion (ILI) with melphalan and dactinomycin was used to treat patients with in-transit metastases in extremity. While many new targeted drugs were proved to be very effective to selected patients, for those patients with gene mutation, whether they can benefit from ILI or not is really confusing. Methods: Eighty-five stage III or IV acral melanoma patients with limb in-transit metastasis have been treated with isolated limb infusion from July 2009 to August 2013 in Peking University Cancer Hospital. ILI was performed using melphalan and dactinomycin (7.5mg/L and 75ug/L, respectively). Fifty-one of them had available gene mutation test results(C-KIT, BRAF, PDGFRA, NRAS). Objective response rate(ORR) and progression-free survival (PFS) was observed. Results: Of all the 51 patients. the mean age was 52 years old (24-79yr).Thirty-eight patients were male, 13 were female; 35 patients had stage III disease and 16 were stage IV. Fifteen (15/51, 29%) patients had gene mutation detected, including 9(18%) c-kit mutations, 3(6%) BRAF mutations, 3(6%) PDGFRA mutations, and 3(6%) NRAS mutations. Among which 4 patients had multiple gene mutations. In the gene mutation negative cohort, 17 (47%) of them achieved partial response and 16 (46%) had a stable disease, while in gene mutation positive cohort, 5 (33%) of them achieved partial response and 9(60%) had stable disease, no statistical significance were detected (P=0.7). The median PFS in the gene mutation positive cohort was 3 months (1-17m), while in the gene mutation negative cohort was 3 months (1-38m) as well. Conclusions: The outcome of isolated limb infusion treatment for Chinese acral melanoma patients seems worse than the result of the Caucasian, regardless of the status of gene mutation. Gene mutations don’t seem to affect the response of ILI-treated patients, for which gene mutation guided targeted therapy should be considered. Larger sample prospective trial is needed to confirm this result.
Rebiopsy rate for non-small cell lung cancer patients after EGFR-TKI failure in clinical setting: Toward the third-generation EGFR-TKI era.
Authors: Takahisa Kawamura, Hirotsugu Kenmotsu, Kazushige Wakuda, Akira Ono, Tetsuhiko Taira, Tateaki Naito, Haruyasu Murakami, Yasuhisa Ohde, Masahiro Endo, Toshiaki Takahashi
Journal: Journal of Clinical Oncology (2015)

e19080 Background: The secondary epidermal growth factor receptor (EGFR) mutation Thr790Met (T790M) accounts for approximately half of acquired resistances to EGFR-tyrosine kinase inhibitors (TKIs). Third-generation EGFR-TKIs can overcome T790M-mediated resistance in non-small cell lung cancer (NSCLC), and recently we can access these third-generation EGFR-TKIs in clinical trials. However, performing rebiopsy to confirm T790M status is sometimes impossible. We aimed to evaluate the rebiopsy rate for subsequent therapy in clinical setting. Methods: We screened NSCLC patients harboring EGFR sensitive mutations who had experienced disease progression (PD) after EGFR-TKI treatment at our institution in 2014. We retrospectively evaluated patient characteristics, tumor progression sites and rebiopsy procedure from medical records. Scorpion Amplification Refractory Mutation System was used in EGFR mutational analyses. Results: Among 116 patients who had experienced PD after EGFR-TKI treatment, 62 (53%) patients underwent rebiopsy. Anatomical sites of rebiopsy were as follows: 27 pleural effusion, 23 thoracic lesions, 4 bone lesions, 2 hepatic lesions, and 6 other lesions. Rebiopsy procedures were 27 pleural punctures, 18 transbronchial biopsies, 10 CT-guided needle biopsies and 7 other procedures. Among rebiopsy samples from 62 patients who had undergone rebiopsy, 59 (95%) patients were pathologically diagnosed with malignancy. Although EGFR mutational analyses were performed in 48 (81%) of 59 patients, T790M mutation was identified in only 18 (38%) of 48 patients. Fifty-four patients did not undergo rebiopsy due to inaccessible tumor sites (n = 15: 13 with brain metastasis and 2 with small lung lesion), ineligibility for clinical trials (n = 19), patient refusal (n = 4), or decision of physician (n = 10). Conclusions: In clinical setting, 53% of the patients harboring EGFR mutations who had PD after EGFR-TKI treatment underwent rebiopsy, and most rebiopsy samples were diagnosed with malignancy. Skill and experience with rebiopsy will be increasingly important to bring the benefits of third-generation EGFR-TKIs to NSCLC patients.
Association Between a Virtual Glucose Management Service and Glycemic Control in Hospitalized Adult Patients
Authors: Robert J. Rushakoff, Mary M. Sullivan, Heidemarie Windham MacMaster, Arti D. Shah, Alvin Rajkomar, David V. Glidden, Michael A. Kohn
Journal: Annals of Internal Medicine (2017)

Background: Inpatient hyperglycemia is common and is linked to adverse patient outcomes. New methods to improve glycemic control are needed. Objective: To determine whether a virtual glucose management service (vGMS) is associated with improved inpatient glycemic control. Design: Cross-sectional analyses of three 12-month periods (pre-vGMS, transition, and vGMS) between 1 June 2012 and 31 May 2015. Setting: 3 University of California, San Francisco, hospitals. Patients: All nonobstetric adult inpatients who underwent point-of-care glucose testing. Intervention: Hospitalized adult patients with 2 or more glucose values of 12.5 mmol/L or greater (≥225 mg/dL) (hyperglycemic) and/or a glucose level less than 3.9 mmol/L (<70 mg/dL) (hypoglycemic) in the previous 24 hours were identified using a daily glucose report. Based on review of the insulin/glucose chart in the electronic medical record, recommendations for insulin changes were entered in a vGMS note, which could be seen by all clinicians. Measurements: Proportion of patient-days classified as hyperglycemic, hypoglycemic, and at-goal (all measurements ≥3.9 and ≤10 mmol/L [≥70 and ≤180 mg/dL] during the pre-vGMS, transition, and vGMS periods). Results: The proportion of hyperglycemic patients decreased by 39%, from 6.6 per 100 patient-days in the pre-vGMS period to 4.0 per 100 patient-days in the vGMS period (difference, −2.5 [95% CI, −2.7 to −2.4]). The hypoglycemic proportion in the vGMS period was 36% lower than in the pre-vGMS period (difference, −0.28 [CI, −0.35 to −0.22]). Forty severe hypoglycemic events (<2.2 mmol/L [<40 mg/dL]) occurred during the pre-vGMS period compared with 15 during the vGMS period. Limitation: Information was not collected on patients' concurrent illnesses and treatment or physicians' responses to the vGMS notes. Conclusion: Implementation of the vGMS was associated with decreases in hyperglycemia and hypoglycemia. Primary Funding Source: National Institutes of Health, the Wilsey Family Foundation, and the UCSF Clinical & Translational Science Institute.
Beyond classical risk adjustment: Socioeconomic status and hospital performance in urologic oncology.
Authors: Anobel Y. Odisho, John L. Gore, Ruth Douglas Etzioni
Journal: Journal of Clinical Oncology (2017)

526 Background: Safety-net hospitals care for more patients of lower socioeconomic status (SES) than non-safety-net hospitals and may be disproportionately punished under readmission risk adjustment models that do not incorporate (SES). We developed a readmission risk adjustment framework incorporating SES to assess impact of SES on safety-net hospital rankings for patients undergoing major surgery for urologic malignancies. Methods: Quasi-experimental design using California Office of Statewide Health Planning and Development data from 2007-2011. Subjects included all patients undergoing radical cystectomy for bladder cancer (n = 3,771), partial nephrectomy (n = 5,556), and radical nephrectomy (n = 13,136) for kidney cancer. Unadjusted hospital rankings and predicted rankings under a base model, which simulated the Medicare Hospital Readmissions Reduction Program model, were compared with predicted rankings under models incorporating socioeconomic status. Socioeconomic status was derived from a multifactorial neighborhood score at the ZIP code level calculated from US Census data. The main outcome measures were hospital rankings based on 30-day all-cause readmission rate and differences between model predicted rankings. Results: For all procedures, the addition of socioeconomic status, geographic, and hospital factors changed the overall hospital rankings significantly compared with the base model (p &lt; 0.01), with the exception of socioeconomic status in radical cystectomy (p = 0.07) and socioeconomic status and rural factors in partial nephrectomy (p = 0.12). For radical nephrectomy and partial nephrectomy, the addition of socioeconomic status and hospital factors significantly improved the mean ranking of safety-net hospitals and improved the ratio of observed relative to expected rankings (p &lt; 0.01). For radical cystectomy there was no significant change in rankings with the addition of socioeconomic status, rural status, or hospital factors. Conclusions: Adding socioeconomic status to existing Medicare readmission risk adjustment models leads to significant changes in hospital rankings, with a differential impact on safety-net hospitals.
Impact of exogenous female hormone use (EHU) on breast cancer (BC) recurrence as assessed by the 21-gene assay (Onco<i>type</i> DX).
Authors: Wendy M. Ledesma, Adedayo A. Onitilo, Chong Zhang, KyungMann Kim, Molly Andreason, John A. Charlson, Kimberly Ridolfi, Jessica Marie Engel, Kari Braun Wisinski, Robert Millholland, James T Dean, Amye Tevaarwerk
Journal: Journal of Clinical Oncology (2012)

563 Background: Observational studies suggest that EHU, such as oral contraceptive (OCPs) or postmenopausal hormone replacement therapy (HRT), increases the risk of developing BC. However, the prognosis of women taking EHU compared to nonusers remains controversial. The Oncotype Dx 21-gene assay RS predicts the distant recurrence risk for early stage, HR+ BC. We assessed RS in patients (pts) on EHU at diagnosis (users) vs nonusers. Methods: Retrospective chart review was conducted on BC pts with a RS, diagnosed 2005–2010. Stage, grade, estrogen (ER), progesterone (PR) and HER2 receptor status were abstracted. Manual review of medications, as well as electronic data pull within ≤5yrs of diagnosis, defined users as pts on EHU within 1 yr of diagnosis for ≥1 yr. Nonusers had been on EHU &gt; 5 yrs before diagnosis or never. Comparisons between EHU users and nonusers were made using two-sample tests; chi-square or Fisher’s exact test for discrete data such as stage and ER status and t-test or Wilcoxon rank sum test for continuous data such as RS. All tests were at a two-sided significance level of 0.05. Results: 495 pts had RS. EHU was documentable for 475, 77 were using exogenous hormone at diagnosis. Type of hormone use included systemic HRT (48%), OCPs (36%), other (4%), and unknown (12%). For users vs nonusers, mean RS was 17 vs 19, (p=0.007, t-test). See table for other predictors. Conclusions: Prior study shows21-gene assay predict distant recurrence risk for HR+BC. In our study, an association existed between EHU and lower RS, suggesting that BC developing on EHU may have less risk of recurrence. Prospective evaluation is warranted. [Table: see text]
Clinical trial enrollment and follow-up visit rates among survivors of childhood cancer.
Authors: Kelley Kennedy Hutchins, Sureyya Savasan, Ronald Thomas, Laura Strathdee, Jeffrey Warren Taub
Journal: Journal of Clinical Oncology (2017)

22 Background: Childhood cancer treatment outcomes have improved substantially with five-year overall survival rates reaching greater than 80%. However, survivors are at increased risk of long-term complications, and long-term follow-up (LTFU) is critical. Distance from a cancer treatment center and increased time from completion of therapy have been associated with decreased LTFU rates. We studied whether lack of enrollment in a therapeutic clinical trial may be an additional barrier to receiving LTFU care. Methods: We conducted a retrospective review of 353 patient records at the Children’s Hospital of Michigan enrolled in our Children’s Oncology Group (COG) registry between 1/1/05-12/31/10. All patients were ≤ 25 years of age at diagnosis.Sixty-seven patients were excluded (died prior to follow-up, n = 61; still on therapy, n = 5; insufficient information, n = 1). A total of 286 patient charts were available for analysis after exclusion. One hundred sixty-two (57%) patients were enrolled in a therapeutic clinical trial, and 124 (43%) were enrolled in a biology study alone due to lack of an open therapeutic clinical trial at the time of diagnosis. One hundred eighty-six (65%) patients were &lt; 10 years of age at diagnosis. Results: Follow-up rates at one-, two- and five-years following completion of therapy for patients enrolled in a therapeutic clinical trial were 94.5%, 91.9% and 74%, respectively, compared to 82.9% (p = 0.002), 74% (p &lt; 0.001) and 66% (p = 0.029) for patients not enrolled. The follow-up rate at five-years for patients who were &lt; 10 years of age was 77.5% compared to 70.7% (p = 0.007) for patients &gt; 10 years. There was no significant difference at one- or two-years based on age at diagnosis. Conclusions: Our findings demonstrate that patients enrolled in a therapeutic clinical trial have significantly superior LTFU rates compared to patients enrolled in biology studies alone. Younger age at diagnosis demonstrated a superior rate at five-years of follow-up. Our findings suggest that additional resources/strategies must be utilized to ensure better LTFU for patients not enrolled in therapeutic clinical trials.