tbuckley/cabot-search huggingface dataset:
Unequal pupils and ptosis
Authors: Andrew Malem
Journal: BMJ (2017)

A 69 year old woman was referred by her primary care doctor to the eye emergency department with a dilated left pupil and ptosis of her right upper lid. She had visited her primary care doctor because of an upper respiratory tract infection and was unconcerned about her unequal pupil size (anisocoria), stating that she “has had odd pupils and a droopy right lid since being a teenager.” She had no ocular or medical history and was not taking any oral or topical medication. She denied any history of trauma, neck pain, weight loss, diplopia, or anhydrosis. On examination she had a partial right upper lid ptosis (fig 1⇓) and her right pupil, which was the abnormal one, was constricted and showed a dilatation lag. Both pupils constricted to light and accommodation and there was no relative afferent pupillary defect. Iris colour was equal on both sides. Visual acuity was 6/9 in both eyes and intraocular pressures were 12 mm Hg and 14 mm Hg in the right and left, respectively. Ocular motility was full and funduscopy showed healthy optic discs. She had no other neurological signs. One drop of apraclonidine 1% was applied to both eyes. After one hour there was dilation of the constricted pupil and improvement in the ptosis.



Fig 1  Photograph of patient in room light and distance fixation showing right upper lid ptosis ( A ) and right miosis ( B )



### Short answer

Right Horner’s syndrome. …
Evaluation of the association of matrix metalloproteinase-1 (MMP-1) and matrix metalloproteinase-2 (MMP-2) expression with KRAS and BRAF mutational status or survival outcomes in colorectal cancer (CRC) patients.
Authors: J. Ho, R. Woods, H. F. Kennecke, I. Tai, H. J. Lim
Journal: Journal of Clinical Oncology (2011)

452 Background: MMP-1 and MMP-2 proteins are felt to be involved in tumor growth, invasion and metastasis and may be regulated by the KRAS pathway. Methods: A tissue microarray was constructed from archival formalin-fixed paraffin-embedded primary tumor tissue samples of 96 patients with metastatic CRC. MMP-1 and MMP-2 expression was measured semiquantitatively by immunohistochemistry and graded 0 to 2. Mutation analysis was done for KRAS in codons 12 and 13, and patients without KRAS mutations were tested for BRAF V600E mutation. Chi-squared test, Fisher's exact test and Cox-proportionate hazard ratios were used for statistical analysis. Results: 96 patients had samples available for analysis (median age at diagnosis 60, 57% male, 46% stage IV at diagnosis, 33/93 (35%) KRAS mutated, 7/51 (14%) BRAF mutated, 22% received anti-EGFR therapy). No significant association was identified between MMP-1 and KRAS (p=0.88) or BRAF (p=0.54), or between MMP-2 and KRAS (p=0.08) or BRAF (p=0.41). Neither overall survival nor survival from diagnosis of metastatic disease were affected by MMP-1 or MMP-2 expression. Conclusions: MMP-1 and MMP-2 expression is not associated with KRAS or BRAF mutational status and is not a prognostic factor in our cohort of CRC patients. No significant financial relationships to disclose.
Adoption of adjuvant chemotherapy (ACT) for non-small cell lung cancer (NSCLC) in the elderly: A population-based outcomes study.
Authors: S. Cuffe, C. M. Booth, Y. Peng, G. E. Darling, G. Li, W. Kong, W. J. Mackillop, F. A. Shepherd
Journal: Journal of Clinical Oncology (2011)

7012 Background: Subgroup analyses of JBR.10 and the LACE meta-analysis suggest that the elderly benefit from ACT with acceptable toxicity. Here we evaluate uptake of ACT and its impact on outcome by age group in the general population of Ontario. Methods: All NSCLC cases surgically resected in Ontario 2001-2006 were identified from the population-based Ontario Cancer Registry. Electronic treatment records were linked to the registry. Uptake of ACT was compared across age groups: <70, 70-74, 75-79, 80+ years. As a proxy of benefit from ACT, we compared survival of cases diagnosed in 2004-2006 to 2001-2003 (ACT trials reported in 2004). Hospitalization rates within 6 months of surgery served as a proxy of treatment related toxicity. Results: 2763/6304 (44%) eligible cases were elderly (≥70 yrs). The elderly were more often male, had more co-morbidities and longer postoperative stays. They were less likely to have adenocarcinoma, undergo pneumonectomy or be treated at a regional cancer center. Uptake of ACT in the elderly increased from 3.3% in 2001-2003 to 16.2% in 2004-2006 (p<0.001). Adoption of ACT declined with age: 43% in <70yrs, 23% in 70-74yrs, 13% in 75-79yrs and 5% in 80+yrs (p<0.001). Among evaluable elderly cases 70% received cisplatin, 28% carboplatin (versus 85% and 14% of cases <70yrs [p=0.005]). Dose modifications and drug substitutions were similar across age groups. In the elderly, 4-yr survival increased from 47.1% in 2001-2003 to 49.9% in 2004-2006 (p=0.01). Hospitalization rates within 6-24 weeks of surgery were similar across the age groups (p=0.54). Age, pathological stage, and geographical region were independently associated with receipt of ACT in the elderly. Conclusions: Adoption of ACT in the elderly was associated with significant improvement in overall survival without apparent increase in severe toxicity as judged by hospital admission. Our findings confirm that the benefits of ACT in the elderly, suggested by the relevant clinical trials, are being realized in the general population. Efforts to understand and improve underutilization of ACT in the elderly in clinical practice are needed.
Retrospective observational study of sunitinib administered on schedule 2/1 in patients with metastatic renal cell carcinoma (mRCC): The rainbow study.
Authors: Sergio Bracarda, Roberto Iacovelli, Mimma Rizzo, Marta Rossi, Luca Galli, Giuseppe Procopio, Flavia Longo, Matteo Santoni, Franco Morelli, Giuseppe di Lorenzo, Camillo Porta, Andrea Camerini, Sara Di Bella, Angelo Martignetti, Donatello Gasparro, Roberto Sabbatini, Giovanni Luca Ceresoli, Alessandra Mosca, Daniele Santini, Luca Boni
Journal: Journal of Clinical Oncology (2014)

471 Background: Sunitinib is a standard of care in first line mRCC; however, an increasing percentage of treatment-related adverse events are observed in the last 2 treatment weeks of the standard schedule 4/2 (4-weeks-on/2-weeks-off). In a multicenter, retrospective study, we evaluated the efficacy and safety of a modified 2/1 schedule (2-weeks-on/1-week-off), largely used in Italy based on a favorable initial experience. Methods: Data from all consecutive patients (pts) treated in 24 Italian centers with sunitinib on schedule 2/1 were analyzed according to the following groups: Group A, pts moved to schedule 2/1 because of treatment-related toxicities during initial therapy using schedule 4/2; Group B, pts treated ab initio with schedule 2/1, mainly because of poorer clinical conditions. A small group of pts treated with schedule 4/2 served as a control (Group C). Results: 276 consecutive pts treated from November 2005 to August 2013 were analyzed, including 249 treated with schedule 2/1 (Group A, n=208; Group B, n=41; respectively, median age 62 and 61 years; clear cell 94.7% and 87.8%; MSKCC good/intermediate/poor 47.1%/46.6%/6.3% and 36.5%/53.7%/9.8%; brain metastases 3.8% and 9.8%) and 27 pts in Group C (median age 59 years; clear cell 96.3%; MSKCC good/intermediate/poor 22.2%/70.4%/7.4%; no brain metastases). In Group A, the median treatment duration (TD) was 28.2 months (m) (with a median of 4.3 on the initial schedule 4/2 and 19.7 on the following schedule 2/1); median progression-free survival (PFS) was 38.6 m (95% CI, 24.0-58.6). In Group B (with less clear cell cases and more pts of intermediate risk or with brain metastases) median TD was 7.8 m and median PFS was 9.6 m (95% CI, 6.3-14.2). Median TD in Group C was 10.4 m. Maximum toxicity grade (≥3) and specific toxicities such as fatigue and hypertension were significantly reduced on schedule 2/1 in Group A compared with the initial schedule 4/2 (respectively, 8% vs 46% and 0% vs 10%, p &lt; .001, and 2% vs 9%, p = .007). Conclusions: In our experience, sunitinib on a modified schedule 2/1 has an improved safety profile and increased efficacy compared with schedule 4/2. Prospective evaluation of this schedule is warranted.
Effect of asymptomatic recurrence detection after nephroureterectomy on prognosis in patients with upper urinary tract urothelial carcinoma.
Authors: Shingo Hatakeyama, Takahiro Yoneyama, Yasuhiro Hashimoto, Takuya Koie, Chikara Ohyama
Journal: Journal of Clinical Oncology (2016)

364 Background: It is unknown whether routine follow up with body computed tomography (CT) to detect asymptomatic visceral recurrence after nephroureterectomy improves patient survival. We accessed the impact of follow up with body CT on patient survival after nephroureterectomy. Methods: A total 212 nephroureterectomy for upper urinary tract urothelial carcinoma were performed at our hospital between Feb 1995 and Oct 2015. All patients had regular follow up with chest x-ray, urine cytology and cystoscopy every 3 to 6 months, blood biochemical test, and CT of the chest and abdomen every 6 to 12 months. Additional examinations were required for symptomatic recurrence. We investigated the first site and date of tumor recurrence. Overall survival in patients with recurrence stratified by the mode of diagnosis (asymptomatic vs. symptomatic) was estimated using the Kaplan-Meier methods and compared with the log rank test. Cox proportional hazard regression models were used to evaluate the impact of the mode of diagnosing recurrence on survival. Results: A total 43 patients (20%) experienced recurrence after surgery, of whom 31 (72%) were asymptomatic and 12 (28%) were symptomatic. The most common symptoms at recurrence were pain in 7, hematuria in 2 , appetite loss in 1 , edema in 1 , palpable mass in 1, general malaise in 1 patients. Overall survival was not significantly different between in patients with asymptomatic vs. symptomatic recurrence; however, survival after tumor recurrence were better in patients with asymptomatic recurrence (P = 0.033). Moreover, multivariate analysis showed symptomatic recurrence was selected as a risk factor for overall survival after recurrence. Conclusions: Routine oncological follow up after nephroureterectomy for early detection of asymptomatic visceral recurrence was associated with patient survival. Further study is necessary to establish the optimal follow up regimen balancing the benefit of asymptomatic detection with the increased cost of routine surveillance.
Acid-suppressive medications and risk of esophageal adenocarcinoma in patients with Barrett’s esophagus: A systematic review and meta-analysis.
Authors: Preet Paul Singh, Siddharth Singh, Sushil Kumar Garg, Prasad G. Iyer, Hashem El-Serag
Journal: Journal of Clinical Oncology (2014)

11 Background: Acid-suppressive medications, particularly proton pump inhibitors (PPI), may modify risk of esophageal adenocarcinoma (EAC) in patients with Barrett’s esophagus (BE). We performed a systematic review and meta-analysis of studies evaluating the association between PPIs and histamine receptor antagonists (H2RA) and risk of EAC or high-grade dysplasia (BE-HGD) in patients with BE. Methods: Through a systematic search up to June 2013, we identified 7 observational studies (5 cohort studies and 2 case-control studies; 2,813 patients with BE, 317 cases of EAC and/or BE-HGD, 84.4% PPI users) reporting the association between PPIs or H2RA and EAC in patients with BE. Summary odds ratio (OR) with 95% confidence intervals (CI) was estimated using random effects model, and heterogeneity was measured using the inconsistency index (I 2 ). Results: On meta-analysis, PPI use was associated with 71% reduction in EAC risk in patients with BE (adjusted OR, 0.29; 95% CI, 0.12-0.71). There was a trend toward a dose-response relationship with PPI use for &gt;2 years protective against EAC [3 studies; PPI use &gt;2 years vs. &lt;2 years (as compared to no use): OR, 0.45 (0.19-1.06) vs. 1.09 (0.47-2.56)]. Considerable heterogeneity was observed in the overall analysis (I 2 =81%). On restricting analysis to 5 cohort studies, use of PPIs was consistently associated with a lower risk of EAC and/or BE-HGD (adjusted OR, 0.33; 95% CI, 0.19-0.58; I 2 =9%). H2RA use was not associated with decreased risk of EAC in patients with BE based on 2 studies (adjusted OR, 1.15; 95% CI, 0.77-1.72). Using a 67% summary risk reduction (derived from cohort studies) of EAC and/or BE-HGD with PPI use in patients with BE, and observed cumulative incidence rates of EAC and/or BE-HGD in patients with BE overall as 10.2 per 1,000 patient years, we estimate the number needed to treat with PPIs to prevent 1 case of EAC or BE-HGD in BE patients at 147. Conclusions: Based on meta-analysis of observational studies, the use of PPI, but not H2RA appears to be associated with a decreased risk of EAC and/or BE-HGD in patients with BE. PPI use should be considered in BE, and chemopreventive trials of PPIs in patients with BE are warranted.
Attitudes toward and use of cancer management guidelines in a national sample of medical oncologists and surgeons.
Authors: Grace Huang, Sarah T. Hawley, Brian Zikmund-Fisher, Nancy K. Janz, Kent A. Griffith, Jennifer J. Griggs, Steven J. Katz, Reshma Jagsi
Journal: Journal of Clinical Oncology (2012)

163 Background: Previous studies have assessed physician perceptions of practice guidelines and identified barriers to adherence, including lack of knowledge, attitudes, and other factors. Little is known about attitudes toward and use of cancer management guidelines specifically. Methods: We surveyed a random sample of 750 medical oncologists and 750 surgeons drawn from the AMA Masterfile between January and June 2012. 896 responded; 130 of these reported that they had not seen breast cancer patients in the previous year and were asked not to complete the remainder of the survey. We analyzed responses from the remaining 766 (403 surgeons and 363 medical oncologists). Results: Mean participant age was 52; 36% worked in a practice with an academic affiliation. Attitudes towards clinical practice guidelines were generally favorable. Few (&lt;3%) disagreed that guidelines were good educational tools or convenient, and only 12% felt that they were biased, although 24% felt they were oversimplified, 20% found them too rigid, and 20% perceived them as a challenge to physician autonomy. Most agreed that guidelines were intended to improve the quality of care (98%) but opinion split about whether they were intended to decrease costs (51% felt they were). NCCN guidelines were reported to influence the cancer management decisions of 96% of medical oncologists and 70% of surgeons (p&lt;0.001), and ASCO guidelines influenced 65% of medical oncologists and 45% of surgeons (p&lt;0.001). Many respondents looked at the NCCN guidelines at least every few months (93% of medical oncologists, 48% of surgeons, p&lt;0.001). Most respondents reported they made guideline-concordant decisions in the majority of their cancer cases. Yet most respondents reported that they rarely refer patients to the patient versions of the NCCN guidelines (76% refer ¼ or fewer of their patients). When making a guideline-inconsistent recommendation, 17% do not routinely discuss the inconsistency with patients. Conclusions: Attitudes toward physician-directed cancer management guidelines are generally positive, and they are frequently used. However, physicians infrequently advise use of patient versions.
Y<sup>90</sup> ibritumomab tiuxetan with maintenance rituximab as initial therapy for high tumor burden follicular lymphoma: A Wisconsin Oncology Network study.
Authors: K. Thorhildur, J. E. Chang, J. C. Eickhoff, J. E. Werndli, R. A. Kirby, C. G. Peterson, C. E. Cole, R. S. Go, B. S. Kahl
Journal: Journal of Clinical Oncology (2011)

e18503 Background: Yttrium90 ibritumomab tiuxetan (Y90IT) radio-immunotherapy has proved to be an effective therapy in relapsed follicular lymphoma (FL). The Wisconsin Oncology Network conducted a clinical trial in which Y90IT followed by maintenance rituximab (MR) was evaluated as initial therapy for high tumor burden FL. Methods: Eligible patients had histologically confirmed follicular lymphoma and met GELF criteria for high tumor burden. All patients received a single dose of Y90IT. At 6 months, patients without PD received 4 weekly doses of rituximab 375 mg/m² followed by MR consisting of a single dose every 3 months for a planned duration of 5 years. Results: Sixteen eligible patients were enrolled from 1/05-11/07. The protocol was closed in 5/08 secondary to slow accrual (planned N = 36). Baseline characteristics include median age of 55 years (37-75) and FLIPI distribution of 19% low, 44% int, and 37% high. The major toxicities from Y90IT were expected myelosuppression with 88% and 31% experiencing grade 3 and 4 heme toxicity, respectively. Median nadir was 752/mm³ for ANC, 46k/ mm³ for platelets, and 11.5 g/dL for hemoglobin. Median duration of grade 3 and grade 4 toxicities was 2.5 weeks (1-7) and 1 week (1-2), respectively. One patient developed MDS/AML and has since expired. Response to Y90IT induction therapy included 7 CR/CRu, 4 PR, 3 SD, and 2 PD. All 4 PR patients converted to CR/CRu during MR therapy. We identified 6 patients with early PD (range 4-16 months) and 10 patients with prolonged remissions (range 37-71+ months). All patients with baseline masses over 9 cm experienced early PD, while 7/9 patients with masses less than 9 cm are experiencing prolonged remissions ranging from 39+ to 71+ months. With a median follow up of 48 months, the 3 year PFS and OS were 63% and 94% respectively. Conclusions: The ORR to Y90IT was 69% in previously untreated, high tumor burden FL patients, which is lower than what is observed with contemporary rituximab-chemotherapy combinations. FL patients with large nodal masses (> 9cm) should be considered for alternative therapies while patients with intermediate size masses (3-9 cm) have the potential for durable responses.
Predictors and prognostic importance of weight change in adult solid tumors.
Authors: Shiva Shrotriya, Declan Walsh, Aynur Aktas, Bassam N. Estfan
Journal: Journal of Clinical Oncology (2015)

103 Background: Body weight change in adults with solid tumors was examined in outpatients. Objective was to determine if demographics, clinical and biochemical characteristics were associated with change in weight between visit 1 and visit 2. Examine if weight change and related parameters were associated with survival. Methods: Electronic medical records (EMR) from a tertiary cancer center retrospectively reviewed from 2009-2011. Body weight and other clinical parameters on visit 1 - within a year post diagnosis; visit 2 ≥3 weeks after visit 1. Weight change categorized as: weight gain, 0-5%, 5.01-10%, &gt;10%. Ordinal logistic regression and Cox proportional hazards utilized for WL predictors and prognostic factors respectively. Results: N = 5,901; Mean age (±SD): 61 ± 12 years; 82% were Caucasians; 16% African Americans. Common cancers were prostate 19%; breast 15%; lung 15%; head and neck 6%; colorectal 6%; others 12%. Metastatic disease was present in 18%. Bone, brain, lymph nodes – were common metastatic sites. 45% had radiotherapy; 41% chemotherapy. Median weight change from visit 1 to visit 2 = -1 (-48, 66) kgs. Weight loss (WL) in 57% (≤5%: 30%, 5.01-10%: 13%, &gt;10%: 14%). Different primary cancer sites, number of metastatic sites, radiotherapy/chemotherapy/hormonal therapies, older age, body mass index (BMI), and albumin predicted weight change. Median survival in 5.01-10.0% WL= 9.4 months, &gt;10.0% = 5.3 months, and not observed ≤ 5%. Conclusions: 1. Majority lost ≤5% of body weight by visit 2. 2. Esophagus, head and neck, and pancreas (primary) - the greatest risk of WL; prostate – lowest. 3. High BMI predicted greater WL compared to normal or underweight. 4. ≤5% WL had a survival advantage compared to 5.01-10% and &gt;10%. 5. WL remained prognostic for survival after adjusting for other prognostic factors.
The Incidence of BCR-ABL Mutations and Their Impact on Outcome in Patients with Newly Diagnosed Chronic Myeloid Leukemia in Chronic Phase (CML-CP) Treated with Nilotinib or Imatinib in ENESTnd: 36-Month Follow-up
Authors: Timothy P. Hughes, Dong-Wook Kim, Gabriel Etienne, Carmino De Souza, Mineo Kurokawa, Matt Kalaycio, Giuseppe Saglio, Richard A. Larson, Hagop M. Kantarjian, Albert Hoenekopp, Yaping Shou, Richard Yu, Rick E. Blakesley, Gianantonio Rosti, Andreas Hochhaus
Journal: Blood (2011)
Utility of the proximal margin frozen section for resection of gastric adenocarcinoma: A 7-institution study of the U.S. gastric cancer collaborative.
Authors: Malcolm Hart Squires, David A. Kooby, Timothy M. Pawlik, Sharon M. Weber, George A. Poultsides, Carl Richard Schmidt, Konstantinos I. Votanopoulos, Ryan C. Fields, Aslam Ejaz, Alexandra W. Acher, David J. Worhunsky, Neil Saunders, Doug S. Swords, Linda X. Jin, Clifford Suhyun Cho, Mark Bloomston, Emily Winslow, Kenneth Cardona, Charles A. Staley, Shishir K. Maithel
Journal: Journal of Clinical Oncology (2014)

103 Background: The proximal gastric margin dictates the extent of resection for gastric adenocarcinoma (GAC). The value of achieving negative margins by additional gastric resection after a positive proximal margin frozen section (FS) is unknown. Methods: The US Gastric Cancer Collaborative includes all patients who had resection of GAC at 7 institutions by oncologic surgeons from 2000-2012. Intraoperative proximal margin FS data were classified as R0 or R1 based on final permanent section (PS); positive distal margins were excluded. Primary aim was to evaluate the impact on local recurrence (LR) of converting a positive proximal margin FS to an R0 final margin by additional resection. Secondary endpoints were recurrence-free (RFS) and overall survival (OS). Results: Of 860 pts, 520 had a proximal margin FS; 67 were positive. Of these 67, 48 were converted to R0 on PS by additional resection. R0 proximal margin was achieved in 447 pts (86%), R1 in 25 (5%), and R1 converted to R0 in 48 (9%). Median FU was 44 mos. Although LR was decreased in the converted R1 to R0 group compared to the R1 group (10% vs 32%, p=0.01), when accounting for other pathologic variables on multivariate (MV) analysis, R1 to R0 conversion was not associated with decreased LR. Median RFS was similar between the R1 to R0 and R1 cohort (37 vs 31 mos; p=0.6) compared to 110 mos for the R0 group. Median OS was similar between the R1 to R0 conversion and R1 groups (36 vs 26 mos; p=0.14) compared to 50 mos for the R0 group. On MV analysis, increasing T-stage and positive lymph nodes were associated with worse OS; R1 to R0 conversion of the proximal margin was not associated with improved OS (p=0.5; Table). Conclusions: Conversion of a positive intraoperative proximal margin frozen section during gastric cancer resection does not decrease local recurrence or improve recurrence-free or overall survival. This may guide decisions regarding the extent of resection. [Table: see text]