Efficacy and safety of pembrolizumab monotherapy in patients with advanced thyroid cancer in the phase 2 KEYNOTE-158 study.

BACKGROUND: The authors report results from the thyroid carcinoma cohort of the multicohort phase 2 KEYNOTE-158 study (NCT02628067), which evaluated pembrolizumab monotherapy in patients with previously treated cancers. METHODS: Eligible patients had histologically and/or cytologically confirmed papillary or follicular thyroid carcinoma, failure of or intolerance to prior therapy, and measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Patients received pembrolizumab (200 mg) every 3 weeks for up to 35 cycles. The primary end point was objective response rate (ORR) per RECIST v1.1 by independent central review. RESULTS: A total of 103 patients were enrolled and received pembrolizumab. Median duration from first dose to data cutoff (October 5, 2020) was 49.4 (range, 43.9-54.9) months. ORR was 6.8% (95% confidence interval [CI], 2.8%-13.5%), and median duration of response was 18.4 (range, 4.2-47.2+) months. ORR was 8.7% (95% CI, 2.4%-20.8%) among patients with programmed cell death ligand 1 (PD-L1) combined positive score (CPS) ≥1 (n = 46) and 5.7% (95% CI, 1.2%-15.7%) among patients with PD-L1 CPS <1 (n = 53). Median overall survival and progression-free survival were 34.5 (95% CI, 21.2 to not reached) and 4.2 (95% CI, 3.9-6.2) months, respectively. Treatment-related adverse events occurred in 69.9% of patients (grade 3-5, 14.6%). CONCLUSIONS: Pembrolizumab demonstrated manageable toxicity and durable antitumor activity in a small subset of patients with advanced thyroid cancer. These results provide evidence of modest antitumor activity in this setting regardless of tumor PD-L1 expression. Future studies evaluating immune checkpoint inhibitors in patients with differentiated thyroid cancer should focus on biomarker-driven patient selection or combination of immune checkpoint inhibitors with other agents, in order to achieve higher response rates than observed in this study.

Computed tomographic measurements of the femoral trochlea in dogs with and without medial patellar luxation.

OBJECTIVES: To determine cutoff values in small (SB) and medium/large (MLB) breed dogs with and without medial patellar luxation (MPL) for identifying abnormal femoral trochlea morphology. STUDY DESIGN: Original research. ANIMALS: A total of 80 computed tomographic (CT) scans from client-owned dogs METHODS: Four groups of 20 dogs were created: (1) control SB, (2) control MLB, (3) MPL-SB, and (4) MPL-MLB. Two authors measured the femoral trochlear groove angle (FTGA), femoral trochlear angle (FTA), and femoral trochlear ridge inclination angle (FTRIA) in two points with CT. ANOVA and ROC-analysis were tested to the control and MPL groups to assess sensitivity, specificity, and cutoff values. Statistical significance was set to p < .05. Intraclass correlation coefficients evaluated the inter-rater agreement. RESULTS: FTGA (± SD) in control SB (128.8° ± 4.7°) and control MLB (119.2° ± 5.6°), was smaller (p < .0001) than in MPL-SB (139.4° ± 4.4°) and MPL-MLB (133.7° ± 5.1°). FTA and FTRIA were decreased (p = .12, p = .23) in MPL-SB (2.1° ± 6.8; -0.3° ± 3.3°) and MPL-MLB (3.8° ± 5.6°; 1.7° ± 4.5°) compared to control SB (0.2° ±4.1; -0.1° ± 2.6°) and control MLB (5.3° ± 2.8°; 3.1° ± 1.3°). Cutoff values for FTGA, FTA, and FTRIA were > 134°, < -5.9°, < -2 ° (SB), and > 128.3°, < -0.4°, < -0.4° (MLB). Sensitivity, specificity, and inter-rater agreement were superior for FTGA than FTA and FTRIA. CONCLUSIONS: Dogs without MPL had a deeper femoral trochlear groove than MPL dogs. SB had a shallower groove than MLB. The measurement of FTA and FTRIA was not reliable. CLINICAL RELEVANCE: A FTGA <134° (SB) and < 128° (MLB) may be considered as a cutoff for trochleoplasty decision-making.

Efficacy and safety of trifluridine/tipiracil in older and younger patients with metastatic gastric or gastroesophageal junction cancer: subgroup analysis of a randomized phase 3 study (TAGS).

BACKGROUND: Trifluridine and tipiracil (FTD/TPI) demonstrated survival benefit vs placebo and manageable safety in previously treated patients with metastatic gastric/gastroesophageal junction cancer (mGC/GEJC) in the randomized, placebo-controlled, phase 3 TAGS study. This subgroup analysis of TAGS examined efficacy/safety outcomes by age. METHODS: In TAGS, patients with mGC/GEJC and ≥ 2 prior therapies were randomized (2:1) to receive FTD/TPI 35 mg/m2 or placebo, plus best supportive care. A preplanned subgroup analysis was performed to evaluate efficacy and safety outcomes in patients aged < 65, ≥ 65, and ≥ 75 years. RESULTS: Among 507 randomized patients (n = 337 FTD/TPI; n = 170 placebo), 55%, 45%, and 14% were aged < 65, ≥ 65, and ≥ 75 years, respectively. Overall survival hazard ratios for FTD/TPI vs placebo were 0.67 (95% CI 0.51-0.89), 0.73 (95% CI 0.52-1.02), and 0.67 (95% CI 0.33-1.37) in patients aged < 65, ≥ 65, and ≥ 75 years, respectively. Regardless of age, patients receiving FTD/TPI experienced improved progression-free survival and stayed longer on treatment than those receiving placebo. Among FTD/TPI-treated patients, frequencies of any-cause grade ≥ 3 adverse events (AEs) were similar across age subgroups (80% each), although grade ≥ 3 neutropenia was more frequent in older patients [40% (≥ 65 and ≥ 75 years); 29% (< 65 years)]; AE-related discontinuation rates did not increase with age [14% (< 65 years), 12% (≥ 65 years), and 12% (≥ 75 years)]. CONCLUSIONS: The results of this subgroup analysis show the efficacy and tolerability of FTD/TPI treatment regardless of age in patients with mGC/GEJC who had received 2 or more prior treatments.

Three-dimensional volume rendering planning, surgical treatment, and clinical outcomes for femoral and tibial detorsional osteotomies in dogs.

OBJECTIVES: To describe a computed tomographic (CT) methodology for planning the correction of femoral and tibial torsion and report the clinical outcomes after femoral (FDO) and tibial (TDO) detorsional osteotomy in dogs affected by torsion malalignment and patellar luxation (PL). STUDY DESIGN: Multicenter retrospective study. ANIMALS: Eighteen client-owned dogs. METHODS: Dogs underwent CT to measure femoral (FTA) and tibial torsion angle (TTA). Abnormal femoral external torsion was defined when FTA <20°, abnormal femoral internal torsion if FTA >35°; abnormal tibial external torsion was defined when TTA < -10°, and abnormal tibial internal torsion when TTA >2°. The cortical arch length (CAL) was measured with CT and used intraoperatively to determine the magnitude of correction. The medical records and radiographs were reviewed and used to report clinical and radiographic outcomes. Radiographs were reviewed to evaluate postoperative limb alignment, patellar position, and bone healing. RESULTS: Twenty-two detorsional osteotomies were performed. Mean preoperative FTA was 14° for medial-PL and 45.2° for lateral-PL. Mean preoperative TTA was 11° for medial-PL. Physiological patellar tracking was restored in 22/22 of cases. CAL measurement allowed for correction of abnormal torsion in 19/22 of cases. Seventeen out 18 dogs had full or acceptable functional outcome. The median radiographic follow-up was 3 months. Major complications occurred in 2/22 cases, which suffered an iatrogenic abnormal femoral internal torsion and a persistent hindlimb lameness. CONCLUSIONS: CAL can be measured with CT and used intraoperatively to guide the correction of abnormal torsion in dogs. CLINICAL RELEVANCE: Abnormal femoral and tibial torsion are predisposing factors for PL. A higher complication rate is expected when FDO and TDO are performed in the same hindlimb.

Dose-escalated neoadjuvant chemoradiotherapy for locally advanced oesophageal or oesophagogastric junctional adenocarcinoma.

Background: Neoadjuvant chemoradiotherapy with CROSS-protocol is the standard of care for locally advanced esophageal cancer. The purpose of this study was to demonstrate an improvement in complete pathological response (ypCR) after a dose-escalation neoadjuvant protocol compared to standard treatment. Secondary endpoints were disease-free survival (DFS) and acute gastrointestinal toxicity. Material and methods: We prospectively evaluated patients with locally advanced esophageal adenocarcinoma who received neoadjuvant chemoradiotherapy. The radiation dose was 41.4 Gy in 23 fractions or 50.4 Gy in 28 fractions with weekly administration of six intravenous cycles of carboplatin AUC 2 mg/mL and intravenous paclitaxel 50 mg/m2 followed by surgery. Results: Between December 2015 and July 2020, 21 patients were treated according to the reported radiation schedules. Median age was 61 years (57-67). 20 (95.2%) tumors were located at the esophagogastric junction and 1 (4.8%) in the middle esophagus. Five (23.8%) were stage II and 16 (76.2%) stage III. Twelve (57.1%) patients received 41.4 Gy (standard group) and 9 (42.9%) received 50.4 Gy (intensification group), with 5 (41.67%) and 5 (55.6%) presenting ypCR in the standard and intensification group, respectively (p = 0.67). After a median follow-up of 17 months (8-30), DFS in the standard group was 17.78 months [95% (CI, confidence interval): 12.9-22.6] and 45.5 months (95% CI: 24.4-66.05) in the intensification group (p = 0.299). Grade III acute gastrointestinal toxicity was 16% and 33.33%, respectively (p = 0.552). Postoperative toxicity events ≥ Grade III were 5 (41.7%) and 4 (44.4%), respectively (p = 0.623). Conclusions: In our study we found a trend towards a higher complete pathological response-rate and disease-free survival in the intensification group compared to the standard group, with no differences in gastrointestinal toxicity. Well-designed randomized and controlled trials are needed to obtain conclusive data.

External validity of docetaxel triplet trials in advanced gastric cancer: are there patients who still benefit?

BACKGROUND: The purpose of our study was to develop an online calculator to estimate the effect of docetaxel triplets (DPF) in first line of advanced gastric cancer (AGC), and to assess the external validity of docetaxel trials in individual patients. METHODS: The study includes patients with HER2(-) AGC treated with platin and fluoropyrimidine (PF) or with DPF in first line. Treatment effect and interactions were assessed using Bayesian accelerated failure time models. RESULT: The series comprises 1376 patients; 238 treated with DPF and 1138 with PF between 2008 and 2019. DPF was associated with increased progression-free survival (PFS) and overall survival (OS) with time ratio (TR) 1.27 (95% credible interval [CrI], 1.15-1.40), and TR 1.19 (95% CrI, 1.09-1.27), respectively. Serious adverse events were more common with DPF, particularly hematological effects (32% vs 22%). Younger participants received greater DPF dose density without achieving greater disease control, while severe toxicity was likewise higher. DPF yielded superior OS in Lauren intestinal (TR 1.27, 95% CrI, 1.08-1.11) vs diffuse subtype (TR 1.17, 95% CrI, 1.09-1.24) and the probability of increasing OS > 15% was 90% vs 67% in each subtype, respectively. The effect dwindles over time, which can be attributed to pathological changes and clinical practice changes. CONCLUSION: Our study confirms the effect of DPF is highly dependent on several clinical-pathological variables, with discreet and gradually declining benefit over platinum doublets in later years, at the expense of increased toxicity. These results may help to underpin the idea that external validity of AGC trials should be revised regularly.

Real-life use of ramucirumab in gastric cancer in Spain: the RAMIS study.

Aims: To obtain real-world data on ramucirumab use and effectiveness for the treatment of advanced gastric cancer (AGC) or gastroesophageal junction adenocarcinoma (GEJ). Methods: Observational, retrospective study carried out in 20 Spanish hospitals, in patients who started ramucirumab treatment between December 2015 and December 2018. Descriptive analysis was conducted for patient characteristics, treatment patterns and effectiveness outcomes. Results: Three hundred seventeen patients were included (93.7% treated with ramucirumab-paclitaxel and 6.3% with ramucirumab); age 62.5 (11.3) years; 66.9% male. Median progression-free survival and overall survival were 3.9 months (95% CI: 3.4-4.3) and 7.4 (95% CI: 6.4-8.9) in combination regimen and 2.0 (1.1-2.8) and 4.3 (95% CI: 1.9-7.3) in monotherapy, respectively. Conclusion: The study findings were consistent with available real-world studies and randomized clinical trials.

A review of minimally invasive fracture stabilization in dogs and cats.

OBJECTIVE: To summarize and discuss peer-reviewed studies on minimally invasive osteosynthesis (MIO) of long bone, physeal, and articular fractures in dogs and cats. STUDY DESIGN: Invited review. METHODS: A critique of literature was performed to assess MIO feasibility, outcomes, and complications through PubMed, Scopus, and CAB abstracts research databases (2000-2020). RESULTS: More than 40 MIO articles have been published in the last 15 years, but most studies had small numbers, lacked control groups, and used limited outcome measures. Studies generally showed that MIO was feasible in dogs and cats with low complication rates. The current evidence does not demonstrate superior bone healing or functional outcomes with MIO when compared to standard methods. Although treatment principles, case selection, and techniques varied depending on the anatomical location, there were no salient differences in complication rates among long bones, physeal, and articular fractures treated by MIO. CONCLUSION: The current available evidence and the personal experience of the authors support MIO as a promising fracture management modality. MIO can yield excellent outcomes when applied in carefully selected cases, performed by surgeons experienced in the technique. We cannot, however, conclude that MIO is superior to open fracture stabilization based on the available evidence in veterinary literature. Randomized controlled studies are warranted to prospectively compare MIO with other osteosynthesis techniques and thereby validate its role in fracture management for dogs and cats.

A three-dimensional computed tomographic volume rendering methodology to measure the tibial torsion angle in dogs.

OBJECTIVE: To describe a three-dimensional (3D) computed tomographic (CT) methodology to measure the tibial torsion angle (TTa) and to evaluate intrarater and interrater agreements and accuracy through comparison with anatomic measurements. STUDY DESIGN: Ex vivo cadaveric study. SAMPLE POPULATION: Thirty-six tibiae from 18 dogs. METHODS: Tibial torsion angle of each tibia was measured by using two CT techniques (axial and 3D volume rendering) by three raters who blindly measured TTa in duplicate. A semitransparent bone filter was used to enhance the visibility of the target anatomical landmarks for the 3D volume rendering CT technique. Tibial torsion angle was also quantitated in tibial specimens. Intrarater and interrater agreements were analyzed by using intraclass coefficients (ICC). Accuracy was evaluated by using adjusted R2 coefficients (R2 > 80% was considered acceptable). RESULTS: The 3D volume rendering CT technique had excellent intrarater and interrater agreements (ICC > 0.94) and an R2 value of 97%. The axial CT technique had good to excellent intrarater and interrater agreements (0.8 < ICC < 0.95) and an R2 of 86%. No difference was found between axial and 3D CT techniques. A mean internal TT angle of approximately -6° was found with CT and anatomic measurements. CONCLUSION: The 3D volume rendering and axial CT techniques were precise and accurate for measuring TTa in dogs unaffected by patellar luxation. CLINICAL RELEVANCE: Combining 3D bone manipulation with application of a semitransparent filter allows simultaneous visualization of anatomic landmarks, which may facilitate the evaluation of complex bone deformations. Internal tibial torsion may be present in nonchondrodystrophic dogs without patella luxation.

Computed tomographic localization of the deepest portion of the femoral trochlear groove in healthy dogs.

OBJECTIVE: To validate a computed tomographic (CT) method to measure the femoral trochlear groove depth (FTGD). STUDY DESIGN: Cadaveric study. SAMPLE POPULATION: Fifteen dogs, 26 femoral trochleae. METHODS: Five points were identified from proximal to distal (proximal point [PP], P25, P50, P75, and distal point [DP]) along the trochlea via three-dimensional volume-rendering function on the sagittal plane and measured on multiplanar reconstruction images. Each rater repeated measurements in duplicate, unaware of the identity of the joint. The FTGD was quantitated on the anatomical specimens and statistically compared with CT measurements. Intrarater and interrater agreements were analyzed by using intraclass coefficients. Accuracy was evaluated by using either adjusted R2 coefficients (R2 > 80% was considered acceptable) or Student's t test. The ratio of the patellar and the trochlear width and the ratio of the patellar craniocaudal thickness inside the trochlear groove were calculated at three different patellar locations. RESULTS: Good to excellent intrarater and interrater agreements were observed in four of five trochlear points (P25, P50, P75, and DP), and accuracy was acceptable for these points (R2 > 80%). Computed tomographic measurements differed from the mean anatomical measurements at three of five points (PP, P50, and P75; P < .01), overestimating the FTGD by an overall mean of 0.18 mm (range, 0.02-0.3). P25 and P50 were the deepest points measured. CONCLUSION: Computed tomography allowed precise measurements of trochlear groove depth except for the most proximal point. The deepest trochlear points were P25 and P50. P25 was the most precise and accurate point measured, while PP was the least consistent. CLINICAL SIGNIFICANCE: The deepest portion of the trochlea groove may be located between P25 and P50. Evaluation of this CT method in dogs with patellar luxation is recommended.

Impact of interval timing to surgery on tumor response after neoadjuvant treatment for gastric cancer.

INTRODUCTION: neoadjuvant chemotherapy (NACT) followed by radical surgery is the optimal approach for locally advanced gastric cancer (GC). Interval timing to surgery after NACT in GC is controversial. The aim of this study was to evaluate the impact of NACT interval time on tumor response and overall survival. MATERIAL AND METHODS: a retrospective analysis from a prospective database was performed at a single referral tertiary hospital, from January 2010 to October 2018. Patients were assigned to three groups according to the surgical interval time after NACT: < 4 weeks, 4-6 weeks and > 6 weeks. Univariate and multivariable analyses were performed in order to clarify the impact of NACT on post-neoadjuvant pathological complete response rate (ypCR), downstaging (DS) and overall survival (OS). RESULTS: of the 60 patients analyzed, 18 patients (30 %) had an interval time to surgery < 4 weeks, 26 (43.3 %) between 4-6 weeks and 16 (26.7 %) > 6 weeks. Two patients (3 %) had achieved ypCR and 37 patients (62 %) had achieved DS. There were no differences in DS rates among the interval time groups (p: 0.66). According to the multivariate analysis, only poorly differentiated carcinoma was significantly related to lower DS rates (p: 0.04). Cox regression analysis showed that the NACT interval time had no impact on OS. According to the multivariate analysis, > 25 lymph node harvested (HR: 0.35) and female sex (HR: 5.67) were OS independent predictors. CONCLUSIONS: the NACT interval time prior gastrectomy for locally advanced GC is not associated with ypCR or DS and has no impact on overall survival.

Clinical utility of ABCB1 genotyping for preventing toxicity in treatment with irinotecan.

Preventing severe irinotecan-induced adverse reactions would allow us to offer better treatment and improve patients' quality of life. Transporters, metabolizing enzymes, and genes involved in the folate pathway have been associated with irinotecan-induced toxicity. We analyzed 12 polymorphisms in UGT1A1, ABCB1, ABCG2, ABCC4, ABCC5, and MTHFR in 158 patients with metastatic colorectal cancer treated with irinotecan and studied the association with grade >2 adverse reactions (CTCAE). Among the most frequent ADRs, the SNPs rs1128503, rs2032582, and rs1045642 in ABCB1 and rs1801133 in MTHFR were associated with hematological toxicity and overall toxicity. The SNP rs11568678 in ABCC4 was also associated with overall toxicity. After correction of P values using a false discovery rate, only ABCB1 variants remained statistically significant. Haplotype analysis in ABCB1 showed an 11.3-fold and 4.6-fold increased risk of hematological toxicity (95% CI, 1.459-88.622) and overall toxicity (95% CI, 2.283-9.386), respectively. Consequently, genotyping of the three SNPs in ABCB1 can predict overall toxicity and hematological toxicity with a diagnostic odds ratio of 4.40 and 9.94, respectively. Genotyping of ABCB1 variants can help to prevent severe adverse reactions to irinotecan-based treatments in colorectal cancer.

Lauren subtypes of advanced gastric cancer influence survival and response to chemotherapy: real-world data from the AGAMENON National Cancer Registry.

BACKGROUND: The choice of chemotherapy in HER2-negative gastric cancer is based on centre's preferences and adverse effects profile. No schedule is currently accepted as standard, nor are there any factors to predict response, other than HER2 status. We seek to evaluate whether Lauren type influences the efficacy of various chemotherapies and on patient overall survival (OS). METHODS: We have conducted a multicenter study in 31 hospitals. The eligibility criteria include diagnosis of stomach or gastroesophageal junction adenocarcinoma, HER2 negativity, and chemotherapy containing 2-3 drugs. Cox proportional hazards regression adjusted for confounding factors, with tests of 'treatment-by-histology' interaction, was used to estimate treatment effect. RESULTS: Our registry contains 1303 tumours analysable for OS end points and 730 evaluable for overall response rate (ORR). A decrease in ORR was detected in the presence of a diffuse component: odds ratio 0.719 (95% confidence interval (CI), 0.525-0.987), P=0.039. Anthracycline- or docetaxel-containing schedules increased ORR only in the intestinal type. The diffuse type displayed increased mortality with hazard ratio (HR) of 1.201 (95% CI, 1.054-1.368), P=0.0056. Patients receiving chemotherapy with docetaxel exhibited increased OS limited to the intestinal type: HR 0.65 (95% CI, 0.49-0.87), P=0.024, with no increment in OS for the subset having a diffuse component. With respect to progression-free survival (PFS), a significant interaction was seen in the effect of docetaxel-containing schedules, with better PFS limited to the intestinal type subgroup, in the comparison against any other schedule: HR 0.65 (95% CI, 0.50-0.85), P=0.015, and against anthracycline-based regimens: HR 0.64 (95% CI, 0.46-0.88), P=0.046. CONCLUSIONS: As a conclusion, in this registry, Lauren classification tumour subtypes predicted survival and responded differently to chemotherapy. Future clinical trials should stratify effect estimations based on histology.

Identification of new SNPs associated with severe toxicity to capecitabine.

Predicting individual risk of chemotherapy-induced severe adverse reaction is a critical issue when selecting the best treatment for cancer patients. SNPs have been identified in genes involved in the pharmacodynamics of fluoropyrimidines, and guidelines even recommend genotyping some DPYD variants in order to estimate the risk of toxicity. However, the predictive value of this approach remains insufficient, thus limiting its clinical implementation. The aim of the present study was to identify new genetic variants by selecting a group of tag SNPs in genes associated with the pharmacodynamics of fluoropyrimidines (CDA, DPYD, ENOSF1, CES1, TYMS, SLC22A7, TYMP, and UMPS). For this purpose, 23 selected SNPs were genotyped on an OpenArray™ platform in a cohort of 301 colorectal cancer patients receiving capecitabine-based chemotherapy. Univariate and multivariate statistical analysis by logistic regression revealed 10 SNPs associated with severe adverse reactions to capecitabine (P<0.05): rs1048977, rs12726436, and rs2072671 in CDA; rs12119882 in DPYD; rs2853741 in TYMS; rs699517 in TYMS/ENOSF1; rs2270860 and rs4149178 in SLC22A7; and rs2279199 and rs4678145 in UMPS. Except for rs2072671, no association had previously been reported between these SNPs and the risk of capecitabine-induced toxicity. The use of tag SNPs to find new polymorphisms related to adverse reactions to capecitabine was successful. These new variants could increase the predictive power of currently available tests and thus prevent severe adverse reactions to capecitabine.

Prognostic significance of performing universal HER2 testing in cases of advanced gastric cancer.

BACKGROUND: Trastuzumab significantly improves overall survival (OS) when added to cisplatin and fluoropyrimidine as a treatment for HER2-positive advanced gastric cancers (AGC). The aim of this study was to evaluate the impact of the gradual implementation of HER2 testing on patient prognosis in a national registry of AGC. METHODS: This Spanish National Cancer Registry includes cases who were consecutively recruited at 28 centers from January 2008 to January 2016. The effect of missing HER2 status was assessed using stratified Cox proportional hazards (PH) regression. RESULTS: The rate of HER2 testing increased steadily over time, from 58.3 % in 2008 to 92.9 % in 2016. HER2 was positive in 194 tumors (21.3 %). In the stratified Cox PH regression, each 1 % increase in patients who were not tested for HER2 at the institutions was associated with an approximately 0.3 % increase in the risk of death: hazard ratio, 1.0035 (CI 95 %, 1.001-1.005), P = 0.0019. Median OS was significantly lower at institutions with the highest proportions of patients who were not tested for HER2. CONCLUSION: Patients treated at centers that took longer to implement HER2 testing exhibited worse clinical outcomes. The speed of implementation behaves as a quality-of-care indicator. Reviewed guidelines on HER2 testing should be used to achieve this goal in a timely manner.

Supracutaneous plating using a locking plate for the treatment of a tibial fracture in a cat.

Radiographs revealed a slightly displaced long oblique diaphyseal tibial fracture with bone fissures running distally in a 2-year-old, 4.5 kg cat that had been hit by a car. An angle stable implant was applied in a supracutaneous fashion. The patient tolerated the external implant and had a satisfactory functional recovery. Radiographic follow-up after 60 days revealed sign of osseous union; therefore, the plate was removed.

Plaque supracutanée à l'aide d'une plaque de fixation pour le traitement d'une fracture tibiale chez un chat. Des radiographies ont révélé une fracture tibiale diaphyséale longue et oblique légèrement déplacée avec des os fissurés distalement chez un chat de 4,5 kg âgé de 2 ans qui avait été heurté par une automobile. Un implant à angle stable a été appliqué d'une manière supracutanée. Le patient a toléré l'implant externe et a connu un rétablissement fonctionnel satisfaisant. Un suivi radiographique après 60 jours a révélé des signes d'union osseuse. Par conséquent, la plaque a été retirée.(Traduit par Isabelle Vallières).

Epigenetic profiling to classify cancer of unknown primary: a multicentre, retrospective analysis.

BACKGROUND: Cancer of unknown primary ranks in the top ten cancer presentations and has an extremely poor prognosis. Identification of the primary tumour and development of a tailored site-specific therapy could improve the survival of these patients. We examined the feasability of using DNA methylation profiles to determine the occult original cancer in cases of cancer of unknown primary. METHODS: We established a classifier of cancer type based on the microarray DNA methylation signatures (EPICUP) in a training set of 2790 tumour samples of known origin representing 38 tumour types and including 85 metastases. To validate the classifier, we used an independent set of 7691 known tumour samples from the same tumour types that included 534 metastases. We applied the developed diagnostic test to predict the tumour type of 216 well-characterised cases of cancer of unknown primary. We validated the accuracy of the predictions from the EPICUP assay using autopsy examination, follow-up for subsequent clinical detection of the primary sites months after the initial presentation, light microscopy, and comprehensive immunohistochemistry profiling. FINDINGS: The tumour type classifier based on the DNA methylation profiles showed a 99·6% specificity (95% CI 99·5-99·7), 97·7% sensitivity (96·1-99·2), 88·6% positive predictive value (85·8-91·3), and 99·9% negative predictive value (99·9-100·0) in the validation set of 7691 tumours. DNA methylation profiling predicted a primary cancer of origin in 188 (87%) of 216 patients with cancer with unknown primary. Patients with EPICUP diagnoses who received a tumour type-specific therapy showed improved overall survival compared with that in patients who received empiric therapy (hazard ratio [HR] 3·24, p=0·0051 [95% CI 1·42-7·38]; log-rank p=0·0029). INTERPRETATION: We show that the development of a DNA methylation based assay can significantly improve diagnoses of cancer of unknown primary and guide more precise therapies associated with better outcomes. Epigenetic profiling could be a useful approach to unmask the original primary tumour site of cancer of unknown primary cases and a step towards the improvement of the clinical management of these patients. FUNDING: European Research Council (ERC), Cellex Foundation, the Institute of Health Carlos III (ISCIII), Cancer Australia, Victorian Cancer Agency, Samuel Waxman Cancer Research Foundation, the Health and Science Departments of the Generalitat de Catalunya, and Ferrer.

Computation of Femoral Canine Morphometric Parameters in Three-Dimensional Geometrical Models.

OBJECTIVE: To define and validate a method for the measurement of 3-dimensional (3D) morphometric parameters in polygonal mesh models of canine femora. STUDY DESIGN: Ex vivo/computerized model. SAMPLE POPULATION: Sixteen femora from 8 medium to large-breed canine cadavers (mean body weight 28.3 kg, mean age 5.3 years). METHODS: Femora were measured with a 3D scanner, obtaining 3D meshes. A computer-aided design-based (CAD) software tool was purposely developed, which allowed automatic calculation of morphometric parameters on a mesh model. Anatomic and mechanical lateral proximal femoral angles (aLPFA and mLPFA), anatomic and mechanical lateral distal femoral angles (aLDFA and mLDFA), femoral neck angle (FNA), femoral torsion angle (FTA), and femoral varus angle (FVA) were measured in 3D space. Angles were also measured onto projected planes and radiographic images. RESULTS: Mean (SD) femoral angles (degrees) measured in 3D space were: aLPFA 115.2 (3.9), mLPFA 105.5 (4.2), aLDFA 88.6 (4.5), mLDFA 93.4 (3.9), FNA 129.6 (4.3), FTA 45 (4.5), and FVA -1.4 (4.5). Onto projection planes, aLPFA was 103.7 (5.9), mLPFA 98.4 (5.3), aLDFA 88.3 (5.5), mLDFA 93.6 (4.2), FNA 132.1 (3.5), FTA 19.1 (5.7), and FVA -1.7 (5.5). With radiographic imaging, aLPFA was 109.6 (5.9), mLPFA 105.3 (5.2), aLDFA 92.6 (3.8), mLDFA 96.9 (2.9), FNA 120.2 (8.0), FTA 30.2 (5.7), and FVA 2.6 (3.8). CONCLUSION: The proposed method gives reliable and consistent information about 3D bone conformation. Results are obtained automatically and depend only on femur morphology, avoiding any operator-related bias. Angles in 3D space are different from those measured with standard radiographic methods, mainly due to the different definition of femoral axes.

Trochlear Ridge Prostheses for Reshaping Femoral Trochlear Ridges in Dogs with Patellar Luxation.

OBJECTIVES: To describe the implant characteristics and surgical application of a custom-made trochlear ridge prosthesis (TRP) and to report clinical outcomes in dogs affected by patellar luxation treated with TRP. STUDY DESIGN: Dogs affected by patellar luxation underwent computed tomography. A specific canine bone anatomical replica, a cutting guide, and a TRP were designed and provided for surgery. Surgical records, clinical and radiographic reassessments, complications, pre- and postoperative lameness, type and degree of patellar luxation, and TRP and patellar position after surgery were reviewed. Clinical outcomes were defined as full, acceptable, or unacceptable function. RESULTS: The TRP was implanted in 60 femoral trochleae: 48 unilateral and 12 bilateral. Successful correction of patellar luxation was achieved in 59/60 cases. TRP was applied with other surgical techniques in 36/60 of the cases and as the only surgical procedure in 24/60 cases. Overall, three complications were observed: two minor and one major (patellar luxation recurrence). Neither implant loosening nor infection was observed. The mean radiographic follow-up was 3.8 months. At the time of the final follow-up, 57/60 cases were scored as fully functional. CONCLUSION: The TRP application either alone or in combination with other surgical techniques allowed for correction of patellar luxation and improvement in preoperative lameness with nominal complications. TRP could represent a potentially reliable alternative to trochleoplasty.