tbuckley/cabot-search huggingface dataset:
Rehospitalization of advanced cancer patients in the year after diagnosis.
Authors: Robin L. Whitney, Janice Bell, Daniel J Tancredi, Patrick S. Romano, Richard J. Bold, Jill G. Joseph
Journal: Journal of Clinical Oncology (2016)

10 Background: Among individuals with advanced cancer (AC), frequent hospitalization is often at odds with patient preference and is increasingly viewed as a hallmark of poor quality care. Hospitalization contributes substantially to costs and regional spending variation in this population, but patterns and reasons are poorly described in the literature. Methods: California Cancer Registry data linked with hospital claims were used to quantify hospitalization in the year after diagnosis among individuals with AC [colorectal, pancreatic, prostate, breast, non-small cell lung cancer (NSCLC)] between 2009-2012 (n = 25, 032). Multi-state models and multilevel log-linear Poisson regression were used to model re-hospitalizations as a function of individual and hospital characteristics, accounting for the competing risk of mortality. Results: Among individuals with AC, 71% were hospitalized, 16% had at least 3 hospitalizations, and 64% of hospitalizations originated in the emergency department. Re-hospitalization rates were significantly higher for black, non-Hispanic (IRR 1.3; 95% CI: 1.1-1.4); Hispanic (IRR 1.1; 95% CI: 1.0-1.2); or Asian/Pacific Islander (IRR 1.1; 95% CI: 1.0-1.2) race/ethnicity vs. white, non-Hispanic; for public (IRR 1.4; 95% CI: 1.3-1.5) or no insurance (IRR 1.2; 95% CI: 1.0-1.5) vs. private; for lower SES quintiles (IRRs 1.1-1.3) vs. the highest; for 1 and 2 or more (IRR 1.1-1.6) comorbidities versus none, and for pancreatic cancer (IRR 2.1; 95% CI 1.9-2.2) and NSCLC (IRR 1.7; 95% CI 1.5-1.9) vs. colorectal cancer. Re-hospitalization rates were significantly lower after discharge from a hospital reporting an outpatient palliative care program (IRR 0.90; 95% CI 0.84-0.96). Conclusions: Individuals with AC experience a heavy burden of hospitalizations, many of which originate in the ED. Discharge from a hospital reporting an outpatient palliative care program appears to protect against re-hospitalization. Efforts to reduce hospitalization and provide care congruent with patient preferences might focus on improving access to outpatient palliative care, particularly among subgroups at greater risk, including racial/ethnic minority groups, those with lower SES, comorbidities and pancreatic or NSCLC.
A randomized trial of cytarabine with high-dose mitoxantrone compared to a standard vincristine/prednisone-based regimen as induction therapy for adult patients with ALL
Authors: M. A. Weiss, L. Heffner, N. Lamanna, M. Kalaycio, G. Schiller, S. Coutre, P. Maslak, J. Jurcic, K. Panageas, D. A. Scheinberg
Journal: Journal of Clinical Oncology (2005)

6516 Background: Induction therapy for adult ALL is similar across most regimens, typically comprised of vincristine, prednisone, and an anthracycline intensified with cyclophosphamide, asparaginase or both. Given the lack of randomized data, no program has emerged as standard. Previously we evaluated cytarabine 3g/m2/d x5d with mitoxantrone 80mg/m2 on day 3 (ALL-2 regimen) as a novel induction regimen (JCO 1996). Compared to historical controls, the ALL-2 was superior in terms of incidence of CR, failure with resistant disease, and activity in Ph+ ALL. Methods: We conducted a national, multicenter, prospective, randomized trial of this regimen compared to a standard regimen that utilized a 4-drug induction (vincristine, prednisone, cyclophosphamide, and doxorubicin; the L-20 regimen). Patients also received consolidation, maintenance therapy, and CNS prophylaxis. BMT was recommended in first CR only for Ph+ patients. Results: Accrual began 8/96 (completed 10/04). Median f/u for survivors is 22 months (range up to 88 months) and to date we have evaluated responses in 161 (77 on ALL-2 and 84 on L-20) patients. Median age-39 years (range 18–72), 60% men, 71% B lineage disease, and 17% Ph+ disease. Allogeneic BMT in first CR was performed in 9%. The arms were balanced in terms of pre-treatment characteristics. Frequency of CR by arm (ALL-2 vs L-20) was 83% vs 70%, P=0.05 (Chi-square). More patients on L-20 failed with resistant disease 21% vs 8%, P=0.02 (Chi-square). Induction deaths were comparable at 9% (ALL-2) vs 8% (L-20). Median survival was similar at 24 months (ALL-2) vs 23 months (L-20) but thereafter the survival curves diverge and overall survival appears superior for ALL-2 treated patients compared to L-20 at both 4 years (40% vs 22%) and 5 years (35% vs 22%). Patients with Ph+ ALL also appeared to have superior outcomes with ALL-2 therapy, including improved frequency of CR (85% vs 47%, P=0.04(Chi-square)) and superior survival at 5 years (26% vs 16%). Conclusions: Therapy with ALL-2 appears superior to L-20 in terms of frequency of CR, failure with resistant disease, activity in Ph+ disease, and 5-year survival. No significant financial relationships to disclose.
Small volume versus standard volume radiotherapy in invasive carcinoma of urinary bladder
Authors: T. Hashem, N. Mobarek, K. Kamal El-Deen, M. Aboulfetouh, T. El-Sayed, A. Gamal El-Deen, K. El-Ghamrawy
Journal: Journal of Clinical Oncology (2005)

4590 Background: Reducing the volume of irradiation may minimize the incidence of acute and late radiation effects on normal tissue and subsequently improve the quality of life. In this trial we evaluated the impact of reducing the irradiated volume on disease free survival (DFS), overall survival (OS) and quality of life (QOL) in patients with bladder cancer. Methods: This trial included 61 consecutive patients with invasive bladder cancer (T2-T4a). All patients received 3 cycles neo-adjuvant chemotherapy (Gemcitabine 1250 mg/m2 D1 + D8 and cisplatin 70 mg/m2 D1), then patients were randomized into two arms: arm I: 30 patients received standard volume radiotherapy (45 Gy to the whole pelvis + 20 Gy boost to the bladder to a total dose of 65 Gy), arm II: 31 patients received small volume radiotherapy by conformal technique (65 Gy to the tumor plus 2 cm around). Both arms received cisplatin 20 mg/m2 hours before each radiation fraction on days 1–5 and 29–33. QOL was assessed in all patients included using QOL questionnaire. Results: The CR rate to neoadjuvant chemotherapy was 32.8% in the whole group of patients (33.3% in arm I and 32.3% in arm II) and the PR rate was 29.5% (23.3% in arm I and 35.5% in arm II) p=0.56. The CR rate after concurrent chemo-radiotherapy was 62.3% in the whole group of patients (60% in arm I and 64.5% in arm II) and the PR rate was 18% (13.3% in arm I and 22.6% in arm II) p=0.52. Acute toxicities that occurred with concurrent chemo-radiotherapy mainly affected the bladder and GIT. Acute diarrhea was higher in arm I (G1 33.3%, G2 20%, and G3 10%) than in arm II (G1 19.4%, G2 3.2%, and G3 0%) p=0.006. Also acute proctitis was higher in arm I (G1 36.7%, and G2 13.3%) than in arm II (G1 19.4 and G2 0%) p=0.019. There was no significant difference in OS and DFS between the two treatment arms. The mean OS in arm 1 was 20.38 months and in arm II it was 22.19 P=0.88. The mean DFS in arm 1 was 19.96 months and in arm II it was 22.93 P=0.73. There was a statistically significant difference in the rectal and physical subscales of the quality of life questionnaire P=0.004 and 0.037 respectively. Conclusions: Reduction of the treatment volume resulted in decrease in the rate of acute GIT toxicities but did not have negative impact on tumor control or survival. No significant financial relationships to disclose.
Analysis of paclitaxel-based high-dose chemotherapy (Tax HD-VIP) in 18 patients (pts) with relapsed germ-cell tumors (GCT)
Authors: A. Lorch, A. Neubauer, R. Schirren, S. Hingott, M. Hoexter, K. Oechsle, J. Beyer
Journal: Journal of Clinical Oncology (2008)

16055 Background: Addition of paclitaxel to sequential high-dose chemotherapy has been suggested to improve treatment outcome in relapsed or refractory GCT. Methods: Single institution retrospective analysis of 18 consecutive pts with relapsed GCT treated between 11/04 and 03/06 with one cycle of cisplatin 100 mg/m2, etoposide 375 mg/m2 and ifosfamide 6 g/m2 (VIP) plus three cycles of paclitaxel 225 mg/m2, cisplatin 100 mg/m2 plus high-dose etoposide 750 mg/m2 and ifosfamide 10 g/m2 (Tax HD-VIP) followed by reinfusion of autologous peripheral blood progenitor cells. Residual tumor resection after Tax HD-VIP was performed whenever possible. Remission rates, progression-free survival (PFS) as well as toxicities were evaluated. Results: All 18 pts had nonseminomatous GCT histology. 10/18 (56%) pts were refractory, 2/18 (11%) pts absolute refractory and 6/18 (33%) pts sensitive to cisplatin combination treatment. According to the Einhorn score 4718 pts (22%) were “good”, 12/18 pts (67%) “intermediate” and 2/18 pts (11%) “poor” risk. Treatment was given as planned in 15/18 (83%) pts, 2/18 (11%) pts received only 2 cyles Tax HD-VIP due to nephrotoxicity and insufficient stem cell collection. 1/18 (6%) pt died due to pneumonia during the second Tax-HD VIP cycle. A complete remission to chemotherapy alone was achieved in 4/18 (22%) pts, 9/18 (50%) achieved a partial remission with negative markers. 5/18 (28%) pts became tumor-free after residual tumor resection. With a median follow-up of 27 months (range 18–76) 12/18 (69%) pts are still alive and progression-free. The estimated rate for PFS is 68% of patients. Apart from one treatment-related death, grade III nephrotoxicity occurred in 1/18 (6%) pt, grade III ototoxicity and polyneuropathy in 3/18 (17%) pts and 3/18 (17%) pts each. Polyneuropathy grade II occurred in 7/18 (39%) pts. Conclusions: Treatment with sequential Tax HD-VIP may salvage selected pts with relapsed or refractory GCT pts despite poor prognosis features. Nephrotoxicity, ototoxicity and peripheral neuropathy were the most relevant non- haematological side effects. No significant financial relationships to disclose.
Developing a conceptual framework of optimal spiritual care: Clergy perspectives.
Authors: Virginia T. LeBaron, Rebecca Quinones, Callie Nibecker, Gloria White-Hammond, Patrick T. Smith, Tracy A. Balboni, Michael Balboni
Journal: Journal of Clinical Oncology (2015)

234 Background: An intriguing finding from previous research is that spiritual support by clergy led to more aggressive care at the end-of-life (EOL), particularly for Black and Latino patients. A better understanding of this phenomenon is critical as aggressive EOL care results in poorer patient and caregiver quality of life, and can significantly impact the death experience. Methods: This was a qualitative, descriptive study. The purpose was to develop a conceptual framework regarding clergy perspectives of optimal spiritual care provision to inform an EOL educational curriculum for clergy. Clergy from varying spiritual backgrounds, geographical locations in the U.S., and race/ethnicities were recruited. Semi-structured interview guides were developed by an interdisciplinary panel of medical educators and religious experts. Interviews were audio-taped, transcribed verbatim, and de-identified. Following principles of grounded theory, a final set of themes and sub-themes were identified through an iterative process of constant comparison. Results: A total of 35 clergy participated in one-on-one interviews (N = 14) and two focus groups. 43% of clergy were Black/African-American, 50% Caucasian and 7% Asian. 7% self-identified as Latino/Hispanic; most reported affiliation with a Christian denomination (96%). Primary themes included Patient Spiritual Struggles, Who Clergy Are (‘Being’), What Clergy Do (‘Doing’) and What Clergy Believe (‘Believing’). Spiritual struggles focused on existential questions, practical questions and difficult emotions. ‘Being” was supported by subthemes related to various manifestations of Presence; “Doing” by subthemes of religious activities, pastoral support, meeting the needs of patient/families, and mistakes to avoid; “Believing” by subthemes of having a relationship with God, virtues, and eternal life. Conclusions: Understanding clergy perspectives regarding optimal spiritual care provision is crucial to improve EOL care, especially for patient populations highly engaged with faith communities. This conceptual framework can help inform the design of educational EOL care initiatives for clergy and foster productive dialogue among clergy, clinicians, and patients.
Pilot study (SWOG S0429) of weekly cetuximab and chest radiotherapy (RT) for poor-risk stage III non-small cell lung cancer (NSCLC).
Authors: Y. Chen, J. Moon, K. J. Pandya, K. Kelly, L. E. Gaspar, D. Lau, F. R. Hirsch, D. R. Gandara
Journal: Journal of Clinical Oncology (2011)

7040 Background: Stage III NSCLC patients (pts) with poor performance status (PS) or co-morbidities are not good candidates for standard chemoradiation (chemoRT) due to toxicity or uncertainty of benefit from treatment. SWOG previously published 2 studies of pts with poor-risk features. S9429 applied concurrent carboplatin/etoposide/RT, and yielded 13 mos median survival (MS). S9712 applied concurrent carboplatin/etoposide/RT and consolidative paclitaxel yielding MS of 10.3 mos, which was attributed to 7% treatment related deaths. To avoid cytotoxic chemotherapy, a pilot study S0429 applied concurrent cetuximab, a chimeric monoclonal antibody targeting EFGR, and concurrent RT to treat poor-risk stage III NSCLC. Methods: Stage III NSCLC pts with Zubrod PS 0-1, poor pulmonary function (FEV 1 <2L), and/or co-morbidities prohibiting chemoRT, or Zubrod PS 2 were eligible. A loading dose of cetuximab (400 mg/m2) was given 1st week, followed by weekly cetuximab (250 mg/m2) and Chest RT to 64.5 Gy in 1.8 Gy fractions, and maintenance weekly cetuximab (250 mg/m2) for 2 years or until evidence of disease progression. Results: From 07/2006 to 12/2009, 24 pts were enrolled. One pt remains on protocol treatment as of 01/2011. Median age was 72.9 y/o. Male: female ratio = 1:1. IIIA: IIIB ratio = 55%:45%. Two pts were excluded from analysis due to FEV1 >2 L without major co-morbidities. Estimated overall survival (OS) at 1 year was 61% (95% C.I. 40%-82%) and estimated MS was 14 mos (95 % C.I. 8-17 mos). Median progression-free survival was 8 mos (95% C.I. 5-9 mos). Response rate was 47% (95% C.I. 24%-71 %) in 19 evaluable pts. Toxicity was assessed in 22 pts. There were no grade 5 adverse events (AEs). 14% (3/22) had grade 4 AEs: one of elevated cardiac tromponin I and pulmonary embolism, the other two of hypomagnesemia. 4/22 had grade 1-2 skin rash and no ≥ grade 3 skin rashes. Conclusions: Concurrent weekly cetuximab and chest RT followed by maintenance cetuximab was well tolerated by pts with poor-risk stage III NSCLC. Toxicities were low. MS was encouraging at 14 mos for pts who were not candidates for standard chemoRT. Support: NCI CA32102, CA38926 and Bristol-Myers Squibb, ImCone Systems, Inc. and Response Genetics.
Persistent pain in the Achilles mid-portion? Consider the plantaris tendon as a possible culprit!
Authors: Hakan Alfredson
Journal: British Journal of Sports Medicine (2017)

The plantaris tendon can contribute to persistent pain in patients who present with what seems at first glance to be mid-portion Achilles tendinopathy.1–8 Clinicians should consider the plantaris tendon when evaluating painful Achilles tendon conditions, particularly those that are not responding to treatment. Below are typical findings related to the history, clinical examination and imaging. A short treatment guide follows. A patient presents with mid-portion Achilles tendon pain. Here are features that point to plantaris tendon involvement. ### History
The Candidate Tumor Suppressor p29ING4 Is Down-Regulated in Human Myeloma Cells and Involved in Their Pro-Angiogenic Properties.
Authors: Nicola Giuliani, Francesca Morandi, Simona Colla, Sara Tagliaferri, Mirca Lazzaretti, Gabriella Sammarelli, Cristina Mancini, Sabrina Bonomini, Vittorio Rizzoli
Journal: Blood (2005)
High-fidelity DNA polymerase-based PNA-PCR plus pyrosequencing: Is it a sensitive and accurate assay for genotyping and quantifying plasma KRAS mutations?
Authors: S. Yu, B. Liu, J. Wei, L. Xie
Journal: Journal of Clinical Oncology (2011)

e21006 Background: Plasma DNA may harbor tumor-specific genetic alternations and could be used as surrogate tumor tissues for nonivasive examination of tumor-specific gene mutation. Peptide nucleic acid (PNA)-PCR is reported to be a high sensitivity method to screen KRAS mutation from plasma/serum of cancer patients. However, since DNA polymerase errors could affect the performance of PNA-PCR and most of PNA-PCR reports didn’t take this into consideration, it’s necessary to compare the mutation status between plasma and tumor tissue to evaluate the effect of DNA polymerase errors during PNA-PCR. Methods: High-fidelity DNA polymerase based PNA-PCR plus pyroquencing assay was developed and its detection limit was assessed by dilutions of the KRAS mutant DNA. Using this assay, we investigated KRAS mutations on cell-free DNA from 19 (15 pre-operations and 4 post-operations) pancreatic cancer patients. KRAS mutation status of these 19 patients was also screened on formalin-fixed paraffin-embedded (FFPE) tumor specimens and compared with results from plasma. Results: PNA-PCR plus pyrosequencing assay could detect as little as 20 pg of mutant DNA (1:5000 mutant to wild-type ratio) and could completely suppress the amplification of wild-type DNA, which enabled the quantification of mutant DNA simultaneously. Overall incidences of KRAS mutation at FFPE samples was 16 out of 19 (84.2%), and 14 corresponding plasma specimens was also found the existence of KRAS mutations. The plasma mutation type was identical to tumor tissue in 13 out of 14 subjects (92.9%) except for one subject whose plasma was gathered after operation and a serial of chemotherapy. Conclusions: High-fidelity DNA polymerase based PNA-PCR plus pyrosequencing is a sensitive, fast and accurate assay to screen plasma KRAS mutations and has potential to quantify KRAS mutant DNA in order to predict treatment response and monitor disease progression.
Combining next-gen sequencing of TP53 and FGFR3 for detecting bladder cancer-related mutations.
Authors: John M. Millholland, Maria F. Campo, Cecilia A. Fernandez, Anthony P. Shuber
Journal: Journal of Clinical Oncology (2013)

304 Background: We have recently described an ultra-deep amplicon sequencing method for FGFR3 in urine that closely replicates the sensitivity found in tissue. While FGFR3 mutations are present in a large fraction of non-invasive tumors, these mutations are rarely detected in invasive bladder tumors. To complement our existing FGFR3 deep sequencing assay, we have developed a sequencing assay for TP53. Mutations in TP53 are commonly found in advanced bladder cancer, and show little overlap with FGFR3 mutations. This proof of concept study demonstrates detection of FGFR3 and TP53 in bladder cancer tissue. Methods: The FGFR3 sequencing assay was performed as described previously, permitting the detection of 9 mutations associated with bladder cancer. Similarly, amplicons were designed against TP53 exons 5-8 using, permitting the detection of 133 unique TP53 mutations previously detected in bladder cancer. Primary amplification was performed on DNA isolated from 3 10µ tissue sections. The resulting PCR products were used as template for emulsion PCR and sequenced using the Ion Torrent PGM. Samples were analyzed for total DNA reads and number of mutant sequencing reads to determine percent mutation. Results: Previously we analyzed 151 non-invasive bladder tumor samples for the presence of FGFR3 mutations. Of these samples, 93 out of 151 (61.5%) were positive for FGFR3 mutations. An additional set of 10 high stage bladder tumor samples were analyzed for mutations in TP53. Of these samples, 5 out of 10 (50.0%) were positive for TP53 mutations, while a separate sample was found to be positive for FGFR3 only. Importantly, a TP53 mutation was detected in a Tis carcinoma in situ sample. These studies will be expanded to a larger set of bladder cancer tissues and urine samples to more accurately assess clinical performance of this FGFR3/TP53 deep sequencing assay. Conclusions: We have developed a multiplexed FGFR3 and TP53 sequencing assay that can detect mutations in a broad range of bladder cancer stages. The complementarity of mutations found in these two genes may allow for the detection of a larger fraction of patients with undiagnosed bladder cancer.
Variation in sex steroid methyl transferases associated with androgen deprivation therapy (ADT) efficacy in advanced prostate cancer.
Authors: M. Kohli, D. W. Mahoney, H. S. Chai, D. W. Hillman, D. R. Rider, B. A. Costello, J. R. Cerhan
Journal: Journal of Clinical Oncology (2011)

4647 Background: The association of germline variation in genes regulating hormonal pathways with duration of treatment response in advanced prostate cancer patients receiving ADT was evaluated, focusing on genes in the androgen biosynthesis (the C4 Δ; C5 Δ; C21 CYP pathways and the alternate “backdoor pathway”) and metabolism pathways. Methods: We successfully genotyped 747 single nucleotide polymorphisms (SNPs) from 84 genes in a cohort of 304 patients with advanced prostate cancer who progressed on ADT. Tagging SNPs with a minor allele frequency (MAF) of >5% and r2 ≥0.8 were selected from HapMap, NIEHS and Seattle SNP databases. The primary endpoint was time to ADT failure, and we conducted a gene-level test (principal components), along with individual SNP level tests adjusted for patient age and Gleason score. To account for multiple testing, we calculated the false discovery rate (FDR), and FDRs of 0.10 were considered noteworthy. Results: The median age of the cohort at ADT failure was 72 years (range 65-78 years), and the overall median time to ADT failure was 3.21 years (IQ (25-75): 1.54-6.20 years). At the gene level, TRMT11 (tRNA methyltransferase 11 homologue) showed the strongest association with time to ADT failure (p<0.0008; adjusted p-value for FDR-0.068). Two of four TRMT11 tag SNPs were associated with time to ADT failure. The first was the intronic SNP rs1268121 (A>G) with a MAF of 15%, for which there was a positive association of median time to ADT failure with the number of variant alleles (p=0.023): 3.1 years for 0, 4.1 years for 1, and 5.9 years for 2 variant alleles. The second was the SNP rs6900796 (A>G) in the 3’ untranscribed region with a MAF of 49%, for which the median time to ADT failure was 2.6 years for 0, 2.5 years for 1, and 3.8 years for 2 variant alleles (p=0.023). Four additional genes showed an association with ADT response at the p<0.10 level, including LOC390956, PRMT3, SLC7A6OS, and WBSCR22, although all FDRs were >0.95. Conclusions: Variation in TRMT11 was associated with time to ADT failure. Confirmation of these findings in an independent cohort is needed.