Higher Preimplantation Opioid Doses Associated With Long‐Term Spinal Cord Stimulation Failure in 211 Patients With Failed Back Surgery Syndrome

ObjectiveSpinal cord stimulation (SCS) is an effective treatment in failed back surgery syndrome (FBSS). We studied the effect of preimplantation opioid use on SCS outcome and the effect of SCS on opioid use during a two-year follow-up period.Materials and methodsThe study cohort included 211 consecutive FBSS patients who underwent an SCS trial from January 1997 to March 2014. Participants were divided into groups, which were as follows: 1) SCS trial only (n = 47), 2) successful SCS (implanted and in use throughout the two-year follow-up period, n = 131), and 3) unsuccessful SCS (implanted but later explanted or revised due to inadequate pain relief, n = 29). Patients who underwent explantation for other reasons (n = 4) were excluded. Opioid purchase data from January 1995 to March 2016 were retrieved from national registries.ResultsHigher preimplantation opioid doses associated with unsuccessful SCS (ROC: AUC = 0.66, p = 0.009), with 35 morphine milligram equivalents (MME)/day as the optimal cutoff value. All opioids were discontinued in 23% of patients with successful SCS, but in none of the patients with unsuccessful SCS (p = 0.004). Strong opioids were discontinued in 39% of patients with successful SCS, but in none of the patients with unsuccessful SCS (p = 0.04). Mean opioid dose escalated from 18 ± 4 MME/day to 36 ± 6 MME/day with successful SCS and from 22 ± 8 MME/day to 82 ± 21 MME/day with unsuccessful SCS (p < 0.001).ConclusionsHigher preimplantation opioid doses were associated with SCS failure, suggesting the need for opioid tapering before implantation. With continuous SCS therapy and no explantation or revision due to inadequate pain relief, 39% of FBSS patients discontinued strong opioids, and 23% discontinued all opioids. This indicates that SCS should be considered before detrimental dose escalation.     

Acute coronary syndrome following arteriovenous fistula creation in a post CABG patient: A steal phenomenon from coronary artery to subclavian artery

A 70‐year‐old man with a history of coronary artery bypass grafting 15 years back and arteriovenous (AV) fistula creation in the left arm 1 month back presented with acute coronary syndrome (ACS). He had not received dialysis before his referral. We felt the most likely etiology for these complaints was increased cardiac oxygen demand from an increased cardiac output related to the newly formed left AV fistula. Coronary angiography was done to detect any significant stenosis in the native or grafted vessels. This revealed that the left subclavian artery was totally occluded in the ostioproximal segment and the coronary arteries did not have occlusions to explain the ACS setting. CT angiography confirmed the angiographic findings of the totally occluded left subclavian artery followed by a well‐developed and patent left internal mammary artery to left anterior descending artery. This led to the consideration of a steal syndrome from the coronary artery by the subclavian artery distal to the occlusion. A successful percutaneous endovascular intervention on the left subclavian artery occlusion was performed. Subsequently, the patient became asymptomatic and experienced a dramatic increase in left ventricular ejection fraction.     

The impact of cytogenetic risk on the outcomes of allogeneic hematopoietic cell transplantation in patients with relapsed/refractory acute myeloid leukemia: On behalf of the acute leukemia working party (ALWP) of the European group for blood and marrow transplantation (EBMT)

Karyotypic analysis at time of diagnosis has an important value in determining initial response to treatment, remission duration and overall survival (OS) in acute myeloid leukemia (AML). Less is known about its value before allogeneic hematopoietic cell transplantation (allo‐HCT) in patients transplanted with active disease, either relapsed or primary refractory (Rel‐Ref) AML. We explored the impact of cytogenetic risk (stratification according to MRC‐UK) in 2089 patients with either Ref (n = 972) or Rel AML (n = 1117) transplanted during the period 2000‐2017. Overall, 154 patients had a favorable risk, 1283 had an intermediate risk and 652 had an adverse cytogenetic risk. Median follow‐up was 49 months. Compared to the favorable risk group, intermediate and adverse risk patients were associated with worse leukemia‐free survival and OS and also with a higher incidence of relapse. In a subgroup analysis of patients in the intermediate risk group harboring Fms‐like tyrosine kinase 3‐internal tandem duplication (FLT3‐ITD), this remained an important prognostic factor, being associated with worse outcomes. When analyzing patients according to the intensity of the conditioning regimen, no differences were observed for the main transplant outcomes. In conclusion, in patients diagnosed with AML and transplanted with active disease, karyotype remains an important prognostic factor, allowing splitting patients into different risk groups according to their cytogenetics. Similarly, FLT3‐ITD mutation also remains a negative prognostic factor in this population.     

Phase II Study of Panitumumab Monotherapy in Chemotherapy‐Naïve Frail or Elderly Patients with Unresectable RAS Wild‐Type Colorectal Cancer: OGSG 1602

Lessons Learned

• Panitumumab monotherapy showed favorable efficacy and feasibility in the treatment of frail or elderly patients with RAS wild‐type unresectable colorectal cancer.
• It is especially effective for left‐sided tumors; therefore, panitumumab as first‐line treatment could be an additional therapeutic option for frail elderly patients, particularly in those who are unsuitable for upfront oxaliplatin‐based or irinotecan‐based combination regimens.

BackgroundFirst‐line panitumumab monotherapy is expected to be well tolerated and improve survival in patients ineligible for intensive chemotherapy. However, its safety and efficacy in chemotherapy‐naïve frail or elderly patients with unresectable RAS wild‐type (WT) colorectal cancer (CRC) have not been studied. The aim of this phase II trial was to evaluate the efficacy and safety of panitumumab as first‐line treatment.MethodsWe conducted a multicenter phase II study on patients aged ≥76 years or ≥65 years considered unsuitable for intensive chemotherapy. Panitumumab 6 mg/kg of intravenous infusion was administered every 2 weeks. The primary endpoint was disease control rate (DCR). Secondary endpoints included progression‐free survival (PFS), overall survival (OS), response rate (RR), time to treatment failure (TTF), and incidence of grade 3 or 4 toxicities.ResultsThirty‐six patients (median age: 81 [range, 67–88] years) were enrolled between February 2017 and August 2018. Two patients were excluded from the analysis of efficacy: one from lack of image examination at baseline and the other from lack of a measurable lesion. Thirty‐three (91.6%) patients had a performance status (PS) of 0 or 1, whereas two (5.6%) patients and one (2.8%) patient had a PS of 2 and 3, respectively. Twenty‐eight patients (77.8%) had left‐sided CRC, whereas eight (22.2%) had right‐sided CRC. The RR was 50.0% (95% confidence interval [CI], 32.4–67.6), including three patients (8.8%) who had complete responses. A total of 26.5% had stable diseases, resulting in a DCR of 76.5% (90% CI, 61.5–87.7). The RR of patients with left‐ and right‐sided tumors was 65.4% (95% CI, 44.3–82.8) and 0.0% (95% CI, 0.0–36.9), respectively. Major grade 3 or 4 nonhematologic toxicities were rash (n = 6, 16.7%), hypomagnesemia (n = 4, 11.1%), fatigue (n = 3, 8.3%), paronychia (n = 2, 5.6%), and hyponatremia (n = 2, 5.6%). The only grade 3 hematologic toxicity was neutropenia (n = 1, 2.8%).ConclusionPanitumumab monotherapy showed favorable efficacy and feasibility in frail or elderly patients with RAS WT unresectable CRC. Survival analysis including OS, PFS, and TTF is currently in progress.