tbuckley/cabot-search huggingface dataset:
Measuring compliance to oral antineoplastic agents: A comparison between administrative data and medical records.
Authors: Winson Y. Cheung, Adam Amlani, Aalok Kumar
Journal: Journal of Clinical Oncology (2014)

6505 Background: With increasing use of oral drugs in oncology, recent studies of administrative data indicate that compliance with these agents is suboptimal. Using a population-based cohort of colon cancer to test our hypothesis, our aim was to evaluate the proportion of patients deemed non-compliant that actually had a reasonable indication for not adhering to their prescribed oral systemic therapy regimen. Methods: Consecutive patients diagnosed with stage III colon cancer from 2008 to 2010, referred to any 1 of 5 regional cancer centers in British Columbia, and who initiated at least 1 cycle of oral adjuvant capecitabine within 12 weeks of curative resection were included. Administrative data from the provincial oncology pharmacy were analyzed to assess for non-compliance, which was defined as any prescription refill delays of >/= 1 week from the end date of the preceding cycle. Electronic medical record abstraction was conducted to examine the factors, if any, which contributed to non-compliance. We compared administrative vs. medical record data to determine the level of concordance. Results: We included 752 patients: median age was 70 years (IQR 35-87), 56% were men, and 86% had ECOG 0/1. Administrative data showed that 413 patients were non-compliant: 230 (56%) and 183 (44%) had 1 and >/=2 late refills, respectively. In this group, a total of 2095 cycles of capecitabine were delivered among which 688 (33%) treatment deviations occurred. No differences in baseline characteristics were observed between individuals who were compliant and those who were not (all p>0.05). Of the 688 prescription delays that were ascertained from administrative data, medical records demonstrated that 30 (4%) were misclassified. From the remainder, the majority were attributable to valid reasons, including: 340 (50%) toxicities necessitating time off therapy; 171 (25%) physician discretion; 23 (3%) patient refusal; and 41 (6%) travel requiring adjustment to treatment schedule. Only 83 (12%) cases were considered as true non-compliance. Conclusions: Using administrative data alone to measure oral oncology drug compliance without corroborating with clinical records may overestimate the degree of non-adherence.
A 51 year old woman with leg weakness after falling
Authors: Shlok Gupta
Journal: BMJ (2019)

A 51 year old woman presented to the emergency department after being found on the floor beside her bed—she had fallen and was unable to get up. She had no angina, palpitations, dyspnoea, nausea, diaphoresis, or loss of consciousness before, during, or after the fall. She reported difficulty passing urine for 4-6 weeks. Her history included hypercholestrolaemia, generalised anxiety disorder, and gastroesophageal reflux. 

She had facial bruising and was unable to walk. Cardiopulmonary examinations were normal. Table 1 shows her strength examination results. Reflexes were 3+at the biceps, triceps, brachioradialis, patella, and Achilles tendons. Ankle plantar responses were upgoing bilaterally (Babinski sign) with spasticity in the legs and sustained clonus at the ankle. Hoffman sign was negative. Digital rectal examination revealed normal tone. Proprioception testing at the big toe was normal. Sensory examination was normal to light touch. Magnetic resonance imaging (MRI) was performed (fig 1).



Fig 1 
T2 weighted MRI of the spine



View this table:

Table 1 
Strength examination results according to …
Multivitamins in breast, prostate, and lung cancer: Is the case closed?
Authors: Danny Landau, Michael Landis, Ian Landis
Journal: Journal of Clinical Oncology (2014)

e20696 Background: Despite being a billion dollar industry, the role of multivitamin and supplement use in different cancers is largely unknown. A publication in the Annals of Internal Medicine declared that the “case is closed” on the general population benefiting from vitamin supplements, as no benefit was seen in mortality. We opted to do a Pubmed search to look at previous trials assessing general vitamin use in breast, lung, and prostate cancers. Methods: In December 2013, a search was conducted in Pubmed using the search term “multivitamin” and either “breast cancer,” “prostate cancer,” or “lung cancer.” The results were analyzed. Results: In total, 96 results were looked at; 40 for breast, 33 for prostate, and 23 for lung. Of these, the numbers that were suitable for evaluation were 29 in breast, 16 in lung, and 24 in prostate. 6 of the breast papers showed potential benefit, all other showed no benefit or potential harm. 2 prostate showed potential benefit, others increased harm no benefit. 2 lung papers showed potential benefit, others potential harm or no benefit. The estimated numbers of patients taking multivitamins was between 30-68% of patients in the papers. Of the ten trials showing potential benefit, seven were in the non Caucasian or in a population at risk for nutritional deficiencies. Conclusions: These results mostly confirm the notion that multivitamins do not provide significant protection or benefit in patients with breast, prostate, or lung cancer in the general population. Patients with nutritional deficiencies may have some benefit. That was not the primary population considered in the Annals of Internal Medicine publication.
Alpha/Beta T-Cell and B-Cell Depletion HLA-Haploidentical Hematopoietic Stem Cell Transplantation Is an Effective Treatment for Children/Young Adults with Acute Leukemia
Authors: Pietro Merli, Mattia Algeri, Giuseppina Li Pira, Michela Falco, Daniela Pende, Valentina Bertaina, Daria Pagliara, Federica Galaverna, Annalisa Ruggeri, Concetta Quintarelli, Lorenzo Moretta, Alice Bertaina, Franco Locatelli
Journal: Blood (2018)
Applying the Cutaneous Lupus Erythematosus Disease Area and Severity Index to paediatric cutaneous lupus erythematosus
Authors: B.F. Chong
Journal: British Journal of Dermatology (2019)

Linked Article: Kushner et al. Br J Dermatol 2019; 180:165–171. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Molecular profiling of bile duct and gallbladder cancer to identify different therapeutic options.
Authors: Randall F. Holcombe, Joanne Xiu, Zoran Gatalica, Michael A. Morse
Journal: Journal of Clinical Oncology (2014)

4097 Background: Biliary tree carcinomas arising in different anatomic locations (intrahepatic IHBC; extrahepatic, EHBC) and gallbladder (GBC) are rare tumors with a poor prognosis. An unmet medical need exists in identifying biomarkers of drug response. We interrogated biomarkers from a large cohort of patient samples with a multiplatform approach and considered associated therapeutic options. Methods: 643 cases (291 IHBC, 115 EHBC, 237 GBC) were evaluated using a commercial multiplatform profiling service (Caris Life Sciences, Phoenix, AZ). Specific testing performed included a combination of gene sequencing (Sanger, NGS), protein expression (IHC) and gene amplification (CISH or FISH). Results: OverallIHC showed high TOP2A (51%), TOPO1 (43%), SPARC (39%) and low RRM1 (76%), ERCC1 (72%) and TS (70%), indicating potential benefit from anthracycline, irinotecan, nab-paclitaxel, gemcitabine, platinum and fluoropyrimidine, respectively. 16 of 45 genes had mutations, with the highest rates seen in TP53 (29%), KRAS (19%), SMAD4 (9%) and IDH1 (9%). When comparing IHBC, EHBC and GBC, a number of statistically significant differences were observed (p values ranged from <0.0001 to 0.03). IHBC was characterized by the presence of IDH1 mutation (18% vs. 0% vs. 0%), low TP53 mutation (15% vs. 40% vs. 46%), and low HER2 amplification (2% vs.17% vs. 16%); IDH1 and TP53 mutations were mutually exclusive, and IDH1 was associated with high Pgp IHC (89% vs. 47%). EHBC had the highest KRAS mutation rate (EHBC 32% vs. IHBC 18% vs. GBC 13%). GBC had higher TOP2A IHC than IHBC and EHBC (71% vs. 36% vs. 46%) and higher RRM1 IHC (34% vs. 17% vs. 15%). Further, SMAD4 mutation was found in 20% (6/30) of metastatic tumors and 2.3% (1/44) of primary tumors (p=0.02). Conclusions: Multiplatform cancer profiling revealsdifferentbiomarker characteristics of biliary tree carcinomas arising in different locations, suggesting a different biology and the need for different therapeutic approaches. Biomarker differences detected by IHC and ISH prompt considerations of HER2-targeted therapies in EHBC and GBC, and anthracylines in GBC, highlighting the need for individualizing patient treatment based on tumor profiling in biliary tree carcinomas.
Effect of intervention on a quality measure of advance directives and end-of-life care at Medstar Washington Cancer Institute.
Authors: Irina Veytsman, Jaylon Harkness, Stephani Heller, Lynn Wood, Sekwon Jang
Journal: Journal of Clinical Oncology (2014)

e20506 Background: Medstar Washington Cancer Institute (MWCI) has participated in Quality Oncology Practice Initiative (QOPI) since 2008. According to our survey, aggressive treatment continues at the end of life. We have done preliminary analysis and found that only 4% of patients had advance directives discussion on the first visit. We hypothesized that the use of advance directives brochure, forms and detail explanation provided during first visit can improve the communication and documentation of the end of life care. Methods: MWCI created a team of physicians, nurses, quality resources, and administrative staff in March 2013. We used data for quarter 1 as a baseline. Nurse navigators provided education and information package on advance directives during first visit. Discussion was recorded in the special design form on the computer system available to physicians for review. Results: The total number of charts evaluated, advance directives documentation at the end of the second quarter 24% (19/79), end of third quarter 51% (40/79), end of 4th quarter 57%(60/105). Our results show significant improvement in documentation of advance directives. Conclusions: Our study demonstrates that information package about advance directives that includes detail explanation, forms and communication between patient and nurses during first visit improved documentation of advance directives in the chart.
Minimally invasive surgery for simple bone cysts using hydroxyapatite cannulated pin: A long-term follow-up.
Authors: Takashi Higuchi, Norio Yamamoto, Hideji Nishida, Hiroaki Kimura, Akihiko Takeuchi, Shingo Shimozaki, Takashi Kato, Yu Aoki, Subhadrabandhu Saran, Hiroyuki Tsuchiya
Journal: Journal of Clinical Oncology (2014)

e21501 Background: Simple bone cysts (SBCs) are benign tumor-like lesions of unknown etiology which sometimes need a long period treatment and restriction on activities in children because of its high recurrency. Despite various treatment modalities with variable outcomes have been described in the literature, there is still no commonly accepted treatment. This study evaluated the outcome of minimally invasive technique using a ceramic hydroxyapatite cannulated pin (HA pin) for SBCs. Methods: Since 1998, sixty-two patients with SBCs have been treated in our hospital with continuous decompression by inserting HA pin after curettage and multiple drilling (Group 1, 36 patients) or with artificial bone filling after curettage (Group 2, 26 patients). Among these patients, a retrospective analysis was performed for factors implicated in the recurrence using log-rank test and COX proportional hazards analysis. Results: Sixty-two patients (44 males, 18 females) with a mean age of 16.6±10.4 years and with histopathologically confirmed diagnosis of SBCs were included. Mean follow-up was 31 months. Remaining or developing of the cysts was seen in 8 patients after the surgery and seven of them underwent additional surgery. Recurrence-free survivals (RFS) were 89% at one year and 84% at two years. Overall RFS was 84%. Recurrence rate was significantly lower when the cysts seen in the bone out of long bone, in the place distant from epiphysis, and in the patients with 12 years of age or more (log-rank test). Multivariate analysis indicated that the age under 12 years was independent risk factor for the recurrence. Furthermore, all of the 8 patients who underwent the recurrence had walls in the cyst. There was no significant difference between Group1 and 2 in the recurrence rate, however, mean operating time was significantly short in Group 1. (57.5 minutes vs 94.5 minutes) Conclusions: Our results suggest that cannulation using HA pin is a less invasive technique compared to artificial bone filling with a high cure rate. However, the recurrence rate was still high if the cysts were located in long bone, remained adjacent to epiphysis or occurred in children younger than 12 years. Further analyses including its etiology are crucial.
Hypertension Development, Management, and Cardiovascular Events Following Ibrutinib Initiation for Hematologic Malignancies
Authors: Tyler Dickerson, Tracy Wiczer, Allyson Waller, Jennifer Philippon, Devin Haddad, Avirup Guha, Kyle Porter, Kerry A. Rogers, Jennifer A. Woyach, John C. Byrd, Daniel Addison, Farrukh T. Awan
Journal: Blood (2018)
A comparison between 5-fluorouracil/mitomycin (FM) and capecitabine/mitomycin (CM) in combination with radiation (RT) for squamous cell carcinoma (SCC) of the anal canal.
Authors: Dante D.C. Wan, Devin Schellenberg, John Hay, Howard John Lim, Renata D'Alpino Peixoto
Journal: Journal of Clinical Oncology (2014)

4031 Background: There are no randomized phase III trials comparing 5FU versus capecitabine in combination with mitomycin and RT for locally advanced anal cancer. Capecitabine has been increasingly adopted in substitution for infusional 5FU, based on data from other disease sites as well as the easier administration. In this retrospective cohort analysis, we aim to evaluate the outcomes of patients treated with both regimens. Methods: Patients with new histologic diagnosis of SCC of the anal canal who initiated curative-intent RT (50-54 Gy) with CM or FM between 1998 and 2013 at one of 6 provincial cancer centers in British Columbia were included. Their characteristics and outcomes were retrospectively analyzed. Differences in proportions were analyzed using the Chi-square test. Disease free survival was estimated using the Kaplan Meier method with log rank test for comparison. Results: A total of 300 patients (195 females) were reviewed. Median age was 58.5 (range 18-85). 34% of the patients were T3 or above and 29% were N2 or above. Median tumor size was 4 cm. Only 4.3% were HIV positive. 194 pts (64.6%) were treated with FM and 106 (35.3%) with CM. The groups were balanced for age, gender, histology, HIV status, T and N status. Median follow-up was 61.7 months (75.2 for FM and 15.8 for CM). Median DFS was not reached in both groups (p 0.24, HR 0.774). The remainder of response and outcomes are included in the Table. Conclusions: There is no difference between the two cohorts in this retrospective study. Additionally, there is a trend towards lower recurrence rates favoring capecitabine that may be explored in larger phase III studies. Capecitabine can be considered an alternative to 5FU in the chemoradiation treatment of SCC of the anus. Total (n=300) Capecitabine (n=106) 5-FU (n=194) p value Complete response 97 (91.5%) 179 (92.2%) 0.817 Recurrence rates 15 (15.2%) 42 (23.3%) 0.105 Rates of APR 6 (5.6%) 14 (7.8%) 0.267 Rates of colostomy 7 (6.6%) 13 (6.7%) 0.974 DFS (1 year) 93.9% 91.1% 0.511
LEOPARD-II: A randomized phase II study of radiochemotherapy (RCT) with 5FU and cisplatin plus/minus cetuximab (Cet) in unresectable locally advanced esophageal cancer (LAEC).
Authors: Dirk Rades, Markus Hermann Moehler, Juergen Debus, Claus Belka, Nils Homann, Cordula Petersen, Karsten Ridwelski, Renato Reyes, Anne L. Kranich
Journal: Journal of Clinical Oncology (2014)

4081 Background: Patients (pts) with LAEC have a poor prognosis; new therapies are required. A study showed the addition of Cet to RCT to be safe and effective for resectable EC [Ruhstaller et al, J Clin Oncol 29;2011:626-31]. A phase II/III trial showed increased grade ≥3 acute toxicity and worse OS if Cet was added for localized EC [Crosby et al, J Clin Oncol 30;2012(suppl 34;abstr LBA3)]. However, increased toxicity in the Cet-arm was due to skin and metabolic toxicity, which usually can be easily managed. Furtermore, capecitabine (Cap) was used; Cap+Cet is less effective than 5-FU+Cet. More trials are required investigating RCT+Cet for LAEC, particularly unresectable EC. Methods: This is an open-label, randomized (1:1) multicenter phase II study. Pts with unresectable non-metastatic EC, age 18-75 yrs, + KPS ≥70 are eligible. Pts receive RCT+Cet (Arm A) or RCT alone (Arm B). RCT included 5-FU (1000 mg/m²/d iv, d 1-4 + 29-32, and 750 mg/m²/d, d 64-67 + 92-95), cisplatin (20 mg/m²/d iv, same days as 5-FU) and RT (59.4 Gy/6.5 wks). If resectability is achieved at 45 Gy, surgery is performed. In Arm A, Cet starts 1 wk pre RCT (400 mg/m² iv), followed by 250 mg/m² weekly for a total of 14 wks. Endpoints of this planned interim analysis (20/134 pts) are toxicity, response (RECIST 1.1), and PFS. Results: GI toxicity occurred in all pts of both arms (9 arm A, 11 arm B). Skin toxicity was more frequent in arm A (100% vs. 36%). All skin toxicities were gr. 1-2. Regarding all toxicities, in arm A, 19 gr. 3 + 4 gr. 4 events occurred; in arm B, 20 gr. 3 + 2 gr. 4 events. 1 Cet-related SAE (nail toxicity) occurred. 2 fatal SAEs occurred in arm B. Response rates were 67% (95%CI [30-90]) in Arm A and 27% in arm B (95%CI [8-61]) (p=0.051). 5 (56%) pts in arm A and 1 (9%) pt in arm B had CR (p=0.01), 1 (11%) pt and 2 (18%) pts PR, and 0 pt (0%) and 3 (27%) pts PD. Median PFS was 15.5 mos (95%CI [3.6-19.3]) in arm A and 4.1 mos (95%CI [1,0]) in arm B. 6-mos PFS was 78% in arm A and 48% in arm B. Conclusions: Treatment was similarly tolerated in both groups. Most adverse events were mild to moderate. This interim analysis showed a trend towards higher response for RCT+Cet than for RCT. CR was significantly higher in the RCT+Cet group. Clinical trial information: NCT01787006.
VEGF and VEGFRs polymorphisms analysis in advanced renal cell carcinoma tissues: Is heterogeneity ever the answer?
Authors: Maristella Bianconi, Mario Scartozzi, Luca Faloppi, Marco D'Anzeo, Antonio Zizzi, Matteo Santoni, Alessandro Bittoni, Michela Del Prete, Riccardo Giampieri, Luciano Burattini, Rodolfo Montironi, Stefano Cascinu
Journal: Journal of Clinical Oncology (2014)

4533 Background: Metastatic renal cell carcinoma (mRCC) ever represented a challenge in patients’ treatment, even with the new generation drugs. In fact there is a wide variability in the amount and duration of response among patients. Sunitinib a drug mainly targeting the angiogenic pathway, is commonly used in mRCC treatment. We previously reported how VEGF and VEGFRs SNPs could predict response to treatment with either sunitinib or pazopanib. Tumour heterogeinity and its possible correlation with response is matter of debate in mRCC. The aim of our study is to assess the expression of VEGF and VEGFRs polymorphisms in tumour, metastatic and normal renal tissues. Methods: We enrolled 123 patients treated at our Institution. We collected histologic samples of tumour, metastatic and normal renal tissue of 84 patients with mRCC treated with first-line sunitinib. For 61 patients samples of tumour, metastatic and normal renal tissue were available. Histologic samples were tested for VEGF-A, VEGF-C and VEGFR-1,2,3 single nucleotide polymorphisms (SNPs). Polymorphisms were correlated with PFS and OS. We then analysed concordance in SPNs expression among tissues. Results: The VEGF A rs833061 resulted significant in PFS (C>T, 17 vs 4 months; p<0.0001) and OS (C>T, 38 vs 10 months; p<0.0001). The VEGF A rs699947 was significant for PFS (A>C, 18 vs 4 months; p=0.0001) and OS (A>C, 37 vs 16 months; p<0.0001). The VEGF A rs2010963 was significant in PFS (G>C, 18 2 months; p=0.0001) and OS (G>C, 36 vs 9 months; p=0.0045). The VEGR3 rs6877011 was significant in PFS (C>G, 12 vs 4 months; p=0.0075) and OS (C>G, 36 vs 17 months; p=0.0001).59 out of 61 patients presented concordance between tumour, metastatic and normal renal tissue (97%). Conclusions: Preliminary data fromour analysis show how angiogenic polymorphisms are significantly correlated with either PFS and OS. These polymorphisms genotypes are preserved between tumour, its metastatic sites and the normal renal tissue. Further analyses will be presented at the Meeting.
Requiring Human Papillomavirus Vaccination for School Entry
Authors: Michelle J. Bayefsky, Lawrence O. Gostin
Journal: JAMA Pediatrics (2018)

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