Scheduled and Breakthrough Opioid Use for Cancer Pain in an Inpatient Setting at a Tertiary Cancer Hospital.

Background: Our aim was to examine the frequency and prescription pattern of breakthrough (BTO) and scheduled (SCH) opioids and their ratio (BTO/SCH ratio) of use, prior to and after referral to an inpatient supportive care consult (SCC) for cancer pain management (CPM). Methods and Materials: Patients admitted at the MD Anderson Cancer Center and referred to a SCC were retrospectively reviewed. Cancer patients receiving SCH and BTO opioids for ≥24 h were eligible for inclusion. Patient demographics and clinical characteristics, including the type and route of SCH and BTO opioids, daily opioid doses (MEDDs) of SCH and BTO, and BTO/SCH ratios were reviewed in patients seen prior to a SCC (pre-SCC) and during a SCC. A normal BTO ratio was defined as 0.5-0.2. Results: A total of 665/728 (91%) patients were evaluable. Median pain scores (p < 0.001), BTO MEDDs (p < 0.001), scheduled opioid MEDDs (p < 0.0001), and total MEDDs (p < 0.0001) were higher, but the median number of BTO doses was fewer (2 vs. 4, p < 0.001), among patients seen at SCC compared to pre-SCC. A BTO/SCH ratio over the recommended ratio (>0.2) was seen in 37.5% of patients. The BTO/SCH ratios in the pre-SCC and SCC groups were 0.10 (0.04, 0.21) and 0.17 (0.10, 0.30), respectively, p < 0.001. Hydromorphone and Morphine were the most common BTO and SCH opioids prescribed, respectively. Patients in the early supportive care group had higher pain scores and MEDDs. Conclusions: BTO/SCH ratios are frequently prescribed higher than the recommended dose. Daily pain scores, BTO MEDDs, scheduled opioid MEDDs, and total MEDDs were higher among the SCC group than the pre-SCC group, but the number of BTO doses/day was lower.

Survival of TP53-mutated acute myeloid leukemia patients receiving allogeneic stem cell transplantation after first induction or salvage therapy: results from the Consortium on Myeloid Malignancies and Neoplastic Diseases (COMMAND).

We conducted a multi-center study to analyze factors predicting survival among patients with TP53-mutated (m) AML receiving allogeneic hematopoietic stem cell transplant (allo-HSCT) in the recent era. Out of 370 TP53m AML patients, 68 (18%) patients were bridged to allo-HSCT. The median age of the patients was 63 years (range, 33-75), 82% of patients had complex cytogenetics and 66% of patients had multi-hit TP53m. Forty three percent received myeloablative conditioning and 57% received reduced intensity conditioning. The incidence of acute graft versus host disease (GVHD) was 37% and chronic GVHD was 44%. The median event-free survival (EFS) from the time of allo-HSCT was 12.4 months (95% CI: 6.24-18.55) and median overall survival (OS) was 24.5 months (95% CI: 21.80-27.25). In multivariate analysis utilizing variables that showed significance in univariate analysis, complete remission at day 100 post allo-HSCT retained significance for EFS (HR: 0.24, 95% CI: 0.10-0.57, p = 0.001) and OS (HR: 0.22, 95% CI: 0.10-0.50, p ≤ 0.001). Similarly, occurrence of chronic GVHD retained significance for EFS (HR: 0.21, 95% CI: 0.09-0.46, p ≤ 0.001) and OS (HR: 0.34, 95% CI: 0.15-0.75, p = 0.007). Our report suggests that allo-HSCT offers the best opportunity to improve long-term outcome among patients with TP53m AML.

Bryozoan carbonate skeletal geochemical composition in the White Sea compared with neighbouring seas.

A fundamental question underlying skeletal mineral secretion in marine invertebrates is the extent to which the physico-chemical parameters of seawater (e.g., salinity, temperature) and animal physiology influence their skeletal mineralogy and chemistry. Groups with more complex mineralogies, such as bryozoans, have the ability to actively control their own skeletal composition in response to environmental conditions and could be considered indicators of global environmental change. Thus, this study aims to reveal how the unique environmental conditions of low salinity (circa 24-26), prominent seasonality and semi-isolation of the White Sea (WS) subarctic region caused by the last glaciation (12,000 ya) affect the carbonate skeletal geochemical composition of bryozoans. X-ray diffraction analysis of 27 bryozoan taxa (92 specimens) revealed a completely monomineral calcite composition of skeletons with a mean value of 6.9 ± 1.8 mol% MgCO3 and moderate variability at the species and family levels. Most specimens (43.5%) precipitated skeletal magnesium within the range of 7-8 mol% MgCO3. Regional analysis of the mineralogical profile of the White Sea bryozoans shows that they differ statistically from bryozoan species living in the neighbouring Arctic and temperate Scotland regions in terms of magnesium content in calcite (approximately 7 mol% MgCO3 in the White Sea versus 5 mol% MgCO3 in other regions). We suggest that the effect of low salinity on magnesium content was compensated by relatively high summer temperature causing rapid growth and calcification and possibly resulted in the increased Mg contents in the White Sea (WS) bryozoans. However, on a local scale (between sampling locations), the influence of temperature and salinity could be excluded as a source of observed intraspecific variability. The concentration of MgCO3 in skeletons of the studied bryozoans is controlled by other environmental variables or is species-specific and depends on the physiological processes of the organisms.

Meta-Analysis of Pharmacological, Nutraceutical and Phytopharmaceutical Interventions for the Treatment of Cancer Related Fatigue.

Purpose: In this study we aimed to estimate the effectiveness of pharmacological, nutraceutical, and phytopharmaceutical treatments on CRF. Methods: Ovid MEDLINE, Ovid Embase, Ovid Psych info, CINHAHL and Cochrane Library databases were searched up to 30 September 2021. Randomized controlled trials of pharmacological, nutraceutical and phytopharmaceutical interventions for treatment of CRF for at least one week duration and have used valid tool to assess severity of CRF as a primary or secondary outcome were considered. Results: 32 eligible studies (4896 patients) were reviewed. For the overall meta-analysis, the random effect models yielded the treatment effect (95% CI) of −0.29 (−0.48,−0.09), p < 0.001. The meta-analysis did not show significant reduction of CRF with treatment with ginseng (n = 6), guarana (n = 3), megestrol (n = 2), mistletoe (n = 3), psychostimulants (n = 14), SSRI/antidepressants (n = 2). Corticosteroids (n = 2) showed significant reduction in CRF with treatment effects of 0.94 (−1.21, −0.67), p <0.0001, respectively. Conclusions: In this study, overall meta-analysis of all studies demonstrates significant reduction of CRF using Pharmacological, Nutraceutical and Phytopharmaceutical interventions with a pooled standardized treatment effect of −0.29. Metanalysis of Corticosteroids studies showed significant reduction in CRF. Further studies are needed.

Review of New-Generation Tyrosine Kinase Inhibitors for Chronic Myeloid Leukemia.

PURPOSE OF REVIEW: In this review, we analyzed the available data from clinical trials with new tyrosine kinase inhibitors (TKIs) under development and how to consider chronic myeloid leukemia (CML) patients who had either resistance or intolerance to current TKIs for treatment with such agents. RECENT FINDINGS: Nearly 50% of CML patients treated with TKIs frontline have required a change of therapy by 10 years. Second-line therapy is effective (by achievement of complete cytogenetic response) in only approximately 50% of patients, and available third-generation TKI has been marred by concerns of arterio-occlusive events. These facts highlight the need for additional treatment options. New TKIs have shown promising efficacy and tolerance in CML patients with resistance or intolerance to multiple available TKIs. Additional studies will determine their role in the management of CML.

Frequency of and Factors Associated With Nonmedical Opioid Use Behavior Among Patients With Cancer Receiving Opioids for Cancer Pain.

IMPORTANCE: One of the main aims of research on nonmedical opioid use (NMOU) is to reduce the frequency of NMOU behaviors through interventions such as universal screening, reduced opioid exposure, and more intense follow-up of patients with elevated risk. The absence of data on the frequency of NMOU behavior is the major barrier to conducting research on NMOU. OBJECTIVE: To determine the overall frequency of and the independent predictors for NMOU behavior. DESIGN, SETTING, AND PARTICIPANTS: In this prognostic study, 3615 patients with cancer were referred to the supportive care center at MD Anderson Cancer Center from March 18, 2016, to June 6, 2018. Patients were eligible for inclusion if they had cancer and were taking opioids for cancer pain for at least 1 week. Patients were excluded if they had no follow-up within 3 months of initial consultation, did not complete the appropriate questionnaire, or did not have scheduled opioid treatments. After exclusion, a total of 1554 consecutive patients were assessed for NMOU behavior using established diagnostic criteria. All patients were assessed using the Edmonton Symptom Assessment Scale, the Screener and Opioid Assessment for Patients with Pain (SOAPP), and the Cut Down, Annoyed, Guilty, Eye Opener-Adapted to Include Drugs (CAGE-AID) survey. Data were analyzed from January 6 to September 25, 2020. RESULTS: A total of 1554 patients (median [interquartile range (IQR)] age, 61 [IQR, 52-69] years; 816 women [52.5%]; 1124 White patients [72.3%]) were evaluable for the study, and 299 patients (19.2%) had 1 or more NMOU behaviors. The median (IQR) number of NMOU behaviors per patient was 1 (IQR, 1-3). A total of 576 of 745 NMOU behaviors (77%) occurred by the first 2 follow-up visits. The most frequent NMOU behavior was unscheduled clinic visits for inappropriate refills (218 of 745 [29%]). Eighty-eight of 299 patients (29.4%) scored 7 or higher on SOAPP, and 48 (16.6%) scored at least 2 out of 4 points on the CAGE-AID survey. Results from the multivariate model suggest that marital status (single, hazard ratio [HR], 1.58; 95% CI, 1.15-2.18; P = .005; divorced, HR, 1.43; 95% CI, 1.01-2.03; P = .04), SOAPP score (positive vs negative, HR, 1.35; 95% CI, 1.04-1.74; P = .02), morphine equivalent daily dose (MEDD) (HR, 1.003; 95% CI, 1.002-1.004; P < .001), and Edmonton Symptom Assessment Scale pain level (HR, 1.11; 95% CI, 1.06-1.16; P < .001) were independently associated with the presence of NMOU behavior. In recursive partition analysis, single marital status, MEDD greater than 50 mg, and SOAPP scores greater than 7 were associated with a higher risk (56%) for the presence of NMOU behavior. CONCLUSIONS AND RELEVANCE: This prognostic study of patients with cancer taking opioids for cancer pain found that 19% of patients developed NMOU behavior within a median duration of 8 weeks after initial supportive care clinic consultation. Marital status (single or divorced), SOAPP score greater than 7, higher levels of pain severity, and MEDD level were independently associated with NMOU behavior. This information will assist clinicians and investigators designing clinical and research programs in this important field.

Calcifying Fibrous Tumor Complicated by Empyema.

Calcifying fibrous tumor (CFT) is a rare, benign proliferation of fibroblasts and inflammatory cells that is non-invasive and usually arises in deep tissue structures. Due to its overall paucity, no accurate incidence has been reported yet. We understand this disease via a handful of case studies published in the medical literature, first of them being from 1988. Earlier known as 'pseudotumor', it was recently given its name due to the potential of recurrence and multifocal involvement. We describe the case of a 43-year-old Hispanic male who presented with a large symptomatic pleural-based mass which turned out to be CFT and was later complicated by empyema. Our aim is to increase awareness about this rare disease and throw light upon its benign nature, despite an alarming and suspicious appearance on imaging. Due to the large size of our patient's mass (largest reported yet), he needed extensive chest wall reconstruction, leading to complications requiring additional invasive procedures. This underscores the importance of early diagnosis and treatment which can reduce the need for aggressive surgical manipulation and avoid postoperative complications, thereby providing high-value care. Treating physicians should be mindful of this, in order to prompt early recognition to ensure effective patient care.

Existing and Emerging Biomarkers for Immune Checkpoint Immunotherapy in Solid Tumors.

In the last few years, immunotherapy has transformed the way we treat solid tumors, including melanoma, lung, head neck, breast, renal, and bladder cancers. Durable responses and long-term survival benefit has been experienced by many cancer patients, with favorable toxicity profiles of immunotherapeutic agents relative to chemotherapy. Cures have become possible in some patients with metastatic disease. Additional approvals of immunotherapy drugs and in combination with other agents are anticipated in the near future. Multiple additional immunotherapy drugs are in earlier stages of clinical development, and their testing in additional tumor types is under way. Despite considerable early success and relatively fewer side effects, the majority of cancer patients do not respond to checkpoint inhibitors. Additionally, while the drugs are generally well tolerated, there is still the potential for significant, unpredictable and even fatal toxicity with these agents. Improved biomarkers may help to better select patients who are more likely to respond to these drugs. Two key biologically important predictive tissue biomarkers, specifically, PD-L1 and mismatch repair deficiency, have been FDA-approved in conjunction with the checkpoint inhibitor, pembrolizumab. Tumor mutation burden, another promising biomarker, is emerging in several tumor types, and may also soon receive approval. Finally, several other tissue and liquid biomarkers are emerging that could help guide single-agent immunotherapy and in combination with other agents. Of these, one promising investigational biomarker is alteration or deficiency in DNA damage response (DDR) pathways, with altered DDR observed in a broad spectrum of tumors. Here, we provide a critical overview of current, emerging, and investigational biomarkers in the context of response to immunotherapy in solid tumors.