Phase II study to determine the anti-tumor activity and safety of simlukafusp alfa (FAP-IL2v) combined with atezolizumab in esophageal cancer.

PURPOSE: Reported here are results from the esophageal squamous cell carcinoma (SCC) cohort of a Phase II, non-comparative, basket study, evaluating the anti-tumor activity and safety of FAP-IL2v plus atezolizumab in patients with advanced/metastatic solid tumors (NCT03386721). EXPERIMENTAL DESIGN: Eligible patients had an Eastern Cooperative Oncology Group performance status of 0-1; measurable metastatic, persistent, or recurrent esophageal SCC; progression on ≥1 prior therapy; and were checkpoint inhibitor naive. Patients received FAP-IL2v 10 mg plus atezolizumab 1200 mg intravenously every 3 weeks, or FAP-IL2v weekly for 4 weeks, then every 2 weeks, plus atezolizumab 840 mg intravenously every 2 weeks. Primary endpoint was investigator-assessed objective response rate (ORR). RESULTS: In the response-evaluable population (N=34), best confirmed ORR was 20.6% (95% confidence interval [CI]: 10.4-36.8) with a complete response (CR) seen in one patient and partial responses (PR) in six patients. Disease control rate was 44.1% (CR=2.9%; PR=17.6%; stable disease [SD]=23.5%) and median duration of response was 10.1 months (95% CI: 5.6-26.7). Median progression-free survival was 1.9 months (95% CI: 1.8-3.7). Analysis of response by PD-L1 expression (Ventana SP263) resulted in an ORR of 26.7 % for patients with PD-L1-positive tumors (tumor area positivity [TAP] cut-off ≥1%; n=15) and 7.1% for patients with PD-L1-negative tumors (TAP cut-off <1%; n=14). Overall, the treatment combination was tolerable and adverse events were consistent with the known safety profiles of each drug. CONCLUSIONS: FAP-IL2v plus atezolizumab demonstrated clinical activity and was tolerable in patients with previously treated esophageal SCC.

Ready-to-Use Multichamber Bags in Home Parenteral Nutrition for Patients with Advanced Cancer: A Single-Center Prospective Study.

Home parenteral nutrition (HPN) is increasingly prescribed for patients with advanced cancer. This therapy improves free-fat mass, quality of life and survival, but it is not free from complications, especially catheter-related bloodstream infections (CRBSIs). The use of commercial multichamber bags in HPN has not been extensively explored in oncologic patients and their association with complications is not well known. In this prospective cohort study, we included 130 patients with advanced cancer and HPN. We compared the effects of individual compounded bags (n = 87) vs. commercial multichamber bags (n = 43) on complications. There were no differences in any complication, including thrombosis (p > 0.05). There were 0.28 episodes of CRBSI per 1000 catheter days in the individual compounded bag group and 0.21 in the multichamber bag group (p > 0.05). A total of 34 patients were weaned off HPN, 22 with individual bags and 12 with multichamber bags (p = 0.749). Regarding survival when on HPN, the group with individual bags showed a median of 98 days (95% CI of 49-147), whereas those with multichamber bags showed a median of 88 days (95% CI of 43-133 (p = 0.913)). In conclusion, commercial multichamber bags for HPN in patients with advanced cancer are non-inferior when compared to individual compounded bags in terms of complications.

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.

Outcome and Complications following Stabilization of Coxofemoral Luxations in Cats Using a Modified Hip Toggle Stabilization-A Retrospective Multicentre Study.

OBJECTIVES: The main aim of this study was to report the surgical technique, the complications and the clinical outcomes of the mini-Tight Rope system (mini-TR) for a modified hip toggle stabilization of coxofemoral luxation in cats. STUDY DESIGN: A multicentre retrospective study. ANIMALS: Thirty-two client-owned cats. METHODS: Medical records (2009-2017) of cats, which underwent stabilization of a coxofemoral luxation with the mini-TR and had at least a 3-month follow-up, were reviewed. The femoral tunnel diameter, the use of one or two FiberWire loops, perioperative complications and clinical outcomes were recorded. Follow-up information was obtained through clinical and radiographic examinations and an owner questionnaire. RESULTS: Thirty-two cats met the inclusion criteria. Concurrent injuries were present in 16 cats. A single or double loop mini-TR was used in 21 and 12 cats respectively. One double loop (1/12 cats) and four single loop (4/16 cats) sutures failed. Moderate-to-severe coxofemoral osteoarthritis developed in 14/27 cats. Owner questionnaires revealed excellent clinical outcomes. CLINICAL SIGNIFICANCE: Mini-TR with a double-stranded implant is recommended to decrease the risk of suture failure. Osteoarthritis is common after open reduction of hip luxations.

Discordant Humoral and T-Cell Response to mRNA SARS-CoV-2 Vaccine and the Risk of Breakthrough Infections in Women with Breast Cancer, Receiving Cyclin-Dependent Kinase 4 and 6 Inhibitors.

Few data are available about the immune response to mRNA SARS-CoV-2 vaccines in patients with breast cancer receiving cyclin-dependent kinase 4/6 inhibitors (CDK4/6i). We conducted a prospective, single-center study of patients with breast cancer treated with CDK4/6i who received mRNA-1273 vaccination, as well as a comparative group of healthcare workers. The primary endpoint was to compare the rate and magnitude of humoral and T-cell response after full vaccination. A better neutralizing antibody and anti-S IgG level was observed after vaccination in the subgroup of women receiving CDK4/6i, but a trend toward a reduced CD4 and CD8 T-cell response in the CDK4/6i group was not statistically significant. There were no differences in the rate of COVID-19 after vaccination (19% vs. 12%), but breakthrough infections were observed in those with lower levels of anti-S IgG and neutralizing antibodies after the first dose. A lower rate of CD4 T-cell response was also found in those individuals with breakthrough infections, although a non-significant and similar level of CD8 T-cell response was also observed, regardless of breakthrough infections. The rate of adverse events was higher in patients treated with CDK4/6i, without serious adverse events. In conclusion, there was a robust humoral response, but a blunted T-cell response to mRNA vaccine in women receiving CDK4/6i, suggesting a reduced trend of the adaptative immune response.

Impact of the COVID-19 Pandemic on Cancer Diagnosis in Madrid (Spain) Based on the RTMAD Tumor Registry (2019-2021).

The coronavirus disease 2019 (COVID-19) pandemic has caused a significant disruption to cancer diagnosis, treatment and prevention worldwide that could have serious consequences in the near future. We intend to evaluate the weight of this backlog on a community-wide scale in Madrid during the period 2020-2021, and whether a stage shift towards the advanced stage has occurred. Cancer diagnoses in the Madrid tumor registry (RTMAD) from 2019-2021 were evaluated. Absolute and percentage differences in annual volume and observed-to-expected (O/E) volume ratios were calculated. Standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) were calculated using the O/E ratio. The SIR for 2020-2021 compared to 2019 was 94.5% (95% CI 93.8-95.3), with unequal gender-specific cancer diagnosis recovery (88.5% for males and 102.1% for females). Most cancer types were underdiagnosed in 2020. The tendency worsened in 2021 for colorectal and prostate cancers (87.8%), but lung cancer recovered (102.1%) and breast cancer was over-diagnosed (114.4%) compared with reference pre-COVID-19 data. These changes have modified the ranking of the most frequent malignancies diagnosed in Madrid. Breast cancer has overtaken colorectal and prostate cancers, displaced to second and third position, respectively. Not only was colorectal cancer diagnosis affected more as a consequence of the COVID-19 pandemic but diagnosis of this malignancy at the advance stage also increased by 3.6% in 2020 and 4.2% in 2021 compared to the reference period of 2019. In summary, there is a large volume of undetected cancer in Madrid caused by the reduced access to care secondary to the COVID-19 pandemic, especially regarding colorectal and prostate cancer. Strategies are needed to recover the backlog of diagnoses and effectively treat these cases in the future and solve the negative impact that will be caused by the diagnostic delay. Analyzing the impact of new diagnoses suffered by each different malignancy and their recovery will help to understand how the future allocation of resources should look.

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.

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.

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.

Health-related quality of life in patients treated with pembrolizumab for microsatellite instability-high/mismatch repair-deficient advanced solid tumours: Results from the KEYNOTE-158 study.

BACKGROUND: In the KEYNOTE-158 study (NCT02628067), pembrolizumab showed a high objective response rate and durable clinical benefit for patients with previously treated, unresectable/metastatic microsatellite instability-high (MSI-H)/mismatch repair‒deficient (dMMR) non-colorectal solid tumours. We present health-related quality of life (HRQoL) results from the MSI-H/dMMR population (cohort K). PATIENTS AND METHODS: Eligible patients had previously treated MSI-H/dMMR advanced non-colorectal solid tumours, measurable disease per RECIST v1.1, and ECOG performance status ≤1. Patients received pembrolizumab 200 mg Q3W for 35 cycles (2 years). The EORTC Quality of Life Questionnaire (QLQ-C30) and EQ-5D-3L were administered at baseline, at regular intervals throughout treatment, and 30 days after treatment discontinuation. Prespecified analyses (exploratory endpoints) included the magnitude of change from baseline to post-baseline timepoints in all patients and by the best overall response for QLQ-C30 global health status (GHS)/QoL, QLQ-C30 functional/symptom scales/items, and EQ-5D-3L visual analogue scale (VAS) score. RESULTS: At data cutoff (October 5, 2020), 351 patients were enrolled, of whom 311 and 315 completed baseline QLQ-C30 and EQ-5D-3L questionnaires, respectively. QLQ-C30 GHS/QoL scores improved from baseline to week 9 (mean [95% CI] change, 3.07 [0.19-5.94]), then remained stable or improved by week 111, with greater improvements observed in patients with a best response of complete response (CR) or partial response (PR) (10.85 [6.36-15.35]). Patients with CR/PR showed improvements in physical (5.58 [1.91-9.25]), role (9.88 [3.80-15.97]), emotional (5.62 [1.56-9.68]), and social (8.33 [2.70-13.97]) functioning, and stable cognitive functioning (1.74 [-1.45 to 4.94]). CONCLUSIONS: Pembrolizumab generally improved or preserved HRQoL in patients with previously treated MSI-H/dMMR advanced non-colorectal solid tumours.

SEOM—GECOD clinical guideline for unknown primary cancer (2021)

Cancer of unknown primary site (CUP) is defined as a heterogeneous group of tumors that appear as metastases, and of which standard diagnostic work-up fails to identify the origin. It is considered a separate entity with a specific biology, and nowadays molecular characteristics and the determination of actionable mutations may be important in a significant group of patients. In this guide, we summarize the diagnostic, therapeutic, and possible new developments in molecular medicine that may help us in the management of this unique disease entity.

SEOM-GECOD clinical guideline for unknown primary cancer (2021).

Cancer of unknown primary site (CUP) is defined as a heterogeneous group of tumors that appear as metastases, and of which standard diagnostic work-up fails to identify the origin. It is considered a separate entity with a specific biology, and nowadays molecular characteristics and the determination of actionable mutations may be important in a significant group of patients. In this guide, we summarize the diagnostic, therapeutic, and possible new developments in molecular medicine that may help us in the management of this unique disease entity.

Limited T cell response to SARS-CoV-2 mRNA vaccine among patients with cancer receiving different cancer treatments.

INTRODUCTION: Patients with cancer (PC) are at high risk of acquiring COVID-19 and can develop more serious complications. Deeper understanding of vaccines immunogenicity in this population is crucial for adequately planning vaccines programs. The ONCOVac study aimed to comprehensively assess the immunogenicity of mRNA-1273 vaccine in terms of humoral and cellular response. METHODS: We conducted a prospective, single-center study including patients with solid tumours treated with cyclin-dependent kinases 4 and 6 inhibitors (CDK4/6i), immunotherapy (IT) or chemotherapy (CT). Patients were enrolled previously to vaccination with mRNA-1273. We also involved health care workers (HCW) to serve as a control group. We took blood samples before first dose administration (BL), after first dose (1D), and after second dose (2D). The primary objective was to compare the rate and magnitude of T cell response after second dose whereas safety and humoral response were defined as secondary objectives. We also collected patient reported outcomes after both the first and second vaccine dose and a six-month follow-up period to diagnose incident COVID-19 cases was planned. RESULTS: The rate of specific anti-S serologic positivity (anti-S IgG cut-off point at 7,14 BAU/mL) was significantly higher in HCW compared to PC after 1D (100% versus 83.8%; p = 0.04), but similar after 2D (100% versus 95.8%; p = 0.5). This difference after 1D was driven by PC treated with CT (100% versus 64.5%; p = 0.001). Cellular response after 2D was significantly lower in PC than in HCW for both CD4+ (91.7% versus 59.7%; p = 0.001) and CD8+ (94.4% versus 55.6%; p < 0.001) T cells. We found a difference on pre-existing CD4+ T cell response in HCW comparing to PC (36% and 17%, p = 0.03); without difference in pre-existing CD8+ T cell response (31% and 23%, p = 0.5). After excluding patients with pre-existing T cell response, PC achieved even lower CD4+ (50.9% versus 95.5%, p < 0.001) and CD8+ (45.5% versus 95.5%, p < 0.001) T cell response compared with HCW. Regarding safety, PC reported notably more adverse events than HCW (96.6% versus 69.2%, p < 0.001). CONCLUSION: We demonstrated that PC showed a similar humoral response but a lower T cell response following two doses of mRNA-1273 vaccination. Further studies are needed to complement our results and determine the implication of low T cell response on clinical protection of PC against COVID-19.

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.

External validity of clinical trials with diverse trastuzumab-based chemotherapy regimens in advanced gastroesophageal adenocarcinoma: data from the AGAMENON-SEOM registry.

BACKGROUND: Trastuzumab combined with cisplatin and fluoropyrimidines, either capecitabine or 5-fluorouracile (XP/FP), is the standard first-line treatment for advanced, HER2-positive, gastric cancer patients based on the ToGA trial. Despite the lack of phase III trials, many clinicians administer trastuzumab with alternative regimens. One meta-analysis suggests that substituting cisplatin for oxaliplatin might lead to greater efficacy and less toxicity. METHODS: 594 patients with HER2-positive gastroesophageal adenocarcinoma were recruited from the AGAMENON-SEOM registry. The objective was to evaluate the external validity of clinical trials with chemotherapy and trastuzumab. RESULTS: The regimens used in at least 5% of the patients were XP (27%), oxaliplatin and capecitabine (CAPOX) (26%), oxaliplatin and 5-fluorouracil (FOLFOX) (14%), FP (14%), triplet with anthracycline/docetaxel (7%), and carboplatin-FU (5%). Median exposure to trastuzumab was longer with FOLFOX (11.4 months, 95% CI, 9.1-21.0) versus ToGA regimens (7.5, 6.4-8.5), p < 0.001. Patients with HER2-IHC 3+ cancers had higher response rates than those with IHC 2+/FISH+, odds-ratio 1.97 (95% CI, 1.25-3.09). The results achieved with CAPOX-trastuzumab were comparable to those attained with ToGA regimens. FOLFOX-trastuzumab was superior to ToGA schemes in terms of overall survival (OS), with a greater magnitude of effect in IHC 2+/FISH+ tumors (HR 0.47, 0.24-0.92) compared with IHC 3+ (HR 0.69, 0.49-0.96), and in diffuse (HR 0.37, 0.20-0.69) versus intestinal-type tumors (HR 0.76, 0.54-1.06). CONCLUSION: We have updated the external validity of clinical trials with trastuzumab in first-line treatment of gastric cancer. Our data confirm the comparable outcomes of ToGA regimens and CAPOX-trastuzumab in clinical practice and point toward a possible benefit of FOLFOX-trastuzumab, contingent on the subtypes typically less sensitive to trastuzumab, to be confirmed in 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.

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.