AbstractOpioids are commonly used in the context of oncology to treat cancer‐related pain. In the context of increased awareness of nonmedical use of opioids, including misuse and opioid use disorder among individuals with cancer, oncologists may find themselves having difficult conversations with patients regarding the use of opioids. We offer a review of pertinent literature and a conversation framework for providers to use, as well as key communication strategies for clinicians. Building on the therapeutic alliance between provider and patient, emphasizing the importance of nonabandonment, and using a benefit‐to‐harm framework, we hope clinicians find they are more able to navigate these challenging but important conversations with patients.Implications for Practice.Providers may find it difficult and uncomfortable to discuss nonmedical use of opioids with patients. To the authors’ knowledge, no previous articles discuss ways to communicate about nonmedical use of opioids in the oncology setting. This work borrows from other specialties and offers a communication framework and key communication strategies to help clinications communicate more effectively with patients who may have an opioid use disorder or may be using their prescribed opioids for reasons other than their pain.
Phase II, Multicenter, Randomized Trial of Docetaxel plus Prednisone with or Without Cediranib in Men with Chemotherapy‐Naive Metastatic Castrate‐Resistant Prostate Cancer
AbstractLessons Learned. The negative results are consistent with the negative results of large phase III trials in which docetaxel plus antiangiogenic agents were used in patients with metastatic castrate‐resistant prostate cancer (mCRPC).The negative data underscore that, despite a sound biological rationale and supportive early‐phase clinical results, adding antiangiogenic agents to docetaxel for mCRPC is a great challenge.Background.Inhibition of vascular endothelial growth factor (VEGF) signaling abrogates tumor‐induced angiogenesis to constrain tumor growth, and can be exploited therapeutically by using cediranib, an oral tyrosine kinase inhibitor of VEGF receptor signaling. Our preliminary phase I trial data showed that adding cediranib to docetaxel plus prednisone (DP) was safe and feasible, with early evidence for efficacy in patients with metastatic castrate‐resistant prostate cancer (mCRPC).Methods.This multicenter phase II trial assessed whether adding cediranib to DP improves efficacy of DP in patients with mCRPC. Chemotherapy‐naive patients with mCRPC were randomly assigned to receive either docetaxel (75 mg/m2 intravenously every 3 weeks) with prednisone (5 mg twice daily) plus cediranib (30 mg once daily; the DP+C arm) or DP only (the DP arm). The primary endpoint was to compare 6‐month progression‐free survival (PFS) rate between the two arms. Secondary endpoints included 6‐month overall survival (OS), objective tumor and prostate‐specific antigen (PSA) response rates, biomarkers, and adverse events.Results.The 6‐month PFS rate in a total of 58 patients was only numerically higher in the DP+C arm (61%) compared with the DP arm (57%). Similarly, the 6‐month OS rate, objective tumor and PSA response rates, and biomarkers were not significantly different between the two arms. Increased baseline levels of interleukin 6 (IL‐6), however, were significantly associated with increased risk of progression. Neutropenia was the only grade 4 toxicity (38% in the DP+C arm vs. 18% in the DP arm).Conclusion.Combining cediranib with docetaxel + prednisone failed to demonstrate superior efficacy, compared with docetaxel + prednisone, and added toxicity. Our data do not support pursuing the combination further in patients with mCRPC.
The Development of an International Oncofertility Competency Framework: A Model to Increase Oncofertility Implementation
AbstractBackground.Despite international evidence about fertility preservation (FP), several barriers still prevent the implementation of equitable FP practice. Currently, oncofertility competencies do not exist. The aim of this study was to develop an oncofertility competency framework that defines the key components of oncofertility care, develops a model for prioritizing service development, and defines the roles that health care professionals (HCPs) play.Materials and Method.A quantitative modified Delphi methodology was used to conduct two rounds of an electronic survey, querying and synthesizing opinions about statements regarding oncofertility care with HCPs and patient and family advocacy groups (PFAs) from 16 countries (12 high and 4 middle income). Statements included the roles of HCPs and priorities for service development care across ten domains (communication, oncofertility decision aids, age‐appropriate care, referral pathways, documentation, oncofertility training, reproductive survivorship care and fertility‐related psychosocial support, supportive care, and ethical frameworks) that represent 33 different elements of care.Results.The first questionnaire was completed by 457 participants (332 HCPs and 125 PFAs). One hundred and thirty‐eight participants completed the second questionnaire (122 HCPs and 16 PFAs). Consensus was agreed on 108 oncofertility competencies and the roles HCPs should play in oncofertility care. A three‐tier service development model is proposed, with gradual implementation of different components of care. A total of 92.8% of the 108 agreed competencies also had agreement between high and middle income participants.Conclusion.FP guidelines establish best practice but do not consider the skills and requirements to implement these guidelines. The competency framework gives HCPs and services a structure for the training of HCPs and implementation of care, as well as defining a model for prioritizing oncofertility service development.Implications for Practice.Despite international evidence about fertility preservation (FP), several barriers still prevent the implementation of equitable FP practice. The competency framework gives 108 competencies that will allow health care professionals (HCPs) and services a structure for the development of oncofertility care, as well as define the role HCPs play to provide care and support. The framework also proposes a three‐tier oncofertility service development model which prioritizes the development of components of oncofertility care into essential, enhanced, and expert services, giving clear recommendations for service development. The competency framework will enhance the implementation of FP guidelines, improving the equitable access to medical and psychological oncofertility care.
Prognostic Nomogram and Patterns of Use of FOLFIRI‐Aflibercept in Advanced Colorectal Cancer: A Real‐World Data Analysis
AbstractIntroduction.The VELOUR study evaluated the efficacy and safety of adding aflibercept to FOLFIRI (fluorouracil, leucovorin, irinotecan) in second‐line therapy for metastatic colorectal cancer (mCRC). However, a nomogram that can stratify patients according to prognosis is unavailable, and the frequency and effect of the pragmatic use of modified schedules in actual practice remains unknown.Method.The sample consists of 250 patients with mCRC treated with aflibercept and irinotecan‐based chemotherapy at nine Spanish academic centers between January 2013 and September 2015. The result of a Cox proportional hazards model regression for overall survival (OS), adjusted for covariates available in daily practice, was represented as a nomogram and web‐based calculator. Harrell's c‐index was used to assess discrimination.Results.The prognostic nomogram for OS includes six variables: Eastern Cooperative Oncology Group performance status, tumor location, number of metastatic sites, mutational status, better response to previous treatment(s), and carcinoembryonic antigen. The model is well calibrated and has acceptable discriminatory capacity (optimism‐corrected c‐index, 0.723; 95% confidence interval [CI], 0.666–0.778). Median OS was 6.1 months (95% CI, 5.1–8.8), 12.4 months (95% CI, 9.36–14.8), and 22.9 months (95% CI, 16.6–not reached) for high‐, intermediate‐, and low‐risk groups, respectively. Age, comorbidity, or use of modified FOLFIRI regimens did not affect prognosis in this series. Grade 3–4 adverse events were less common following modified schedules. The admission rate because of toxicity was higher in ≥65 years (9.7% vs. 19.6%; odds ratio, 2.26; p = .029).Conclusion.We have developed and internally validated a prognostic model for use in individuals with colorectal cancer initiating therapy with FOLFIRI‐aflibercept to predict both OS and the effect of pragmatic modifications of the classic regime on efficacy and safety. This can aid in decision making and in designing future trials.Implications for Practice.In this study, the authors developed and conducted the internal validation of a prognostic nomogram that makes it possible to stratify patients who are eligible for second‐line FOLFIRI‐aflibercept based on their probability of survival. This model was developed in a multicenter sample from nine Spanish hospitals. Furthermore, to increase the study's validity, the practical use of aflibercept in this setting was investigated, including doses or pragmatic modifications. The results suggest that the modified schedules often used in this daily clinical practice‐based patient population are associated with less severe toxicity without apparent detriment to survival endpoints. It is believed that these data complement the information provided by the VELOUR trial and are relevant for the oncologist in treating colon cancer in the second‐line setting.
Safety of Nivolumab plus Low‐Dose Ipilimumab in Previously Treated Microsatellite Instability‐High/Mismatch Repair‐Deficient Metastatic Colorectal Cancer
AbstractBackground.Early detection and management of treatment‐related adverse events (TRAEs) in patients receiving immune checkpoint inhibitors may improve outcomes. In CheckMate 142, nivolumab (3 mg/kg) plus low‐dose ipilimumab (1 mg/kg) provided durable clinical benefit (objective response rate [ORR] 55%, median duration of response not reached, 12‐month overall survival [OS] rate 85%) and manageable safety for previously treated microsatellite instability‐high and/or mismatch repair‐deficient (MSI‐H/dMMR) metastatic colorectal cancer (mCRC). In‐depth safety and additional efficacy outcomes from CheckMate 142 are presented.Materials and Methods.Safety assessments included frequency of TRAEs, select TRAEs (sTRAEs), and immune‐mediated adverse event incidences; time to onset (TTO); time to resolution (TTR); immune‐modulating medication (IMM) use; dose delay; and sTRAE occurrence after resuming therapy. Efficacy assessments included ORR and survival analyses in patients with sTRAEs with or without concomitant IMM treatment and patients without sTRAEs.Results.Among 119 patients, 25%, 23%, 19%, 5%, 5%, and 29% experienced an endocrine, gastrointestinal, hepatic, pulmonary, renal, or skin sTRAE, respectively; the majority (57%) were grade 1/2. sTRAEs occurred early (median TTO, 5.2–12.6 weeks). Nonendocrine sTRAEs resolved in most (>71%) patients (median TTR, 1.5–9.0 weeks). IMMs were used to manage sTRAEs in 22%–56% of patients (most resolved). Of patients with dose delay because of sTRAEs, 25 of 29 resumed treatment. Patients with or without sTRAEs had comparable ORR (57% vs. 52%) and 12‐month OS rates (93% vs. 75%). Similar results were observed in patients with or without sTRAEs regardless of IMM use (ORR 52% vs. 57%; OS rates 87% vs. 82%).Conclusion.The benefit‐risk profile of nivolumab plus low‐dose ipilimumab provides a promising treatment option for patients with previously treated MSI‐H/dMMR mCRC.Implications for Practice.Nivolumab (NIVO) plus low‐dose (1 mg/kg) ipilimumab (IPI) received U.S. Food and Drug Administration approval for patients with microsatellite instability‐high and/or mismatch repair‐deficient (MSI‐H/dMMR) metastatic colorectal cancer (mCRC) that progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan based on results from CheckMate 142. In this safety analysis, the majority of select treatment‐related adverse events (sTRAEs) occurred early, were managed using evidence‐based treatment algorithms, and resolved. Efficacy outcomes were comparable between patients with or without sTRAEs regardless of the use of concomitant immune‐modulating medications. The benefit‐risk profile of NIVO + low‐dose IPI provides a promising treatment option for MSI‐H/dMMR mCRC.
An Eastern Hepatobiliary Surgery Hospital Microvascular Invasion Scoring System in Predicting Prognosis of Patients with Hepatocellular Carcinoma and Microvascular Invasion After R0 Liver Resection: A Large‐Scale, Multicenter Study
AbstractBackground.Microvascular invasion (MVI) is associated with poor postoperative survival outcomes in patients with hepatocellular carcinoma (HCC). An Eastern Hepatobiliary Surgery Hospital (EHBH) MVI scoring system was established to predict prognosis in patients with HCC with MVI after R0 liver resection (LR) and to supplement the most commonly used classification systems.Materials and Methods.Patients with HCC with MVI who underwent R0 LR as an initial therapy were included. The EHBH‐MVI score was developed from a retrospective cohort from 2003 to 2009 to form the training cohort. The variables associated with overall survival (OS) on univariate analysis were subsequently investigated using the log‐rank test, and the EHBH‐MVI score was developed using the Cox regression model. It was validated using an internal prospective cohort from 2011 to 2013 as well as three independent external validation cohorts.Results.There were 1,033 patients in the training cohort; 322 patients in the prospective internal validation cohort; and 493, 282, and 149 patients in the three external validation cohorts, respectively. The score was developed using the following factors: α‐fetoprotein level, tumor encapsulation, tumor diameter, hepatitis B e antigen positivity, hepatitis B virus DNA load, tumor number, and gastric fundal/esophageal varicosity. The score differentiated two groups of patients (≤4, >4 points) with distinct long‐term prognoses outcomes (median OS, 55.8 vs. 19.6 months; p < .001). The predictive accuracy of the score was greater than the other four commonly used staging systems for HCC.Conclusion.The EHBH‐MVI scoring system was more accurate in predicting prognosis in patients with HCC with MVI after R0 LR than the other four commonly used staging systems. The score can be used to supplement these systems.Implications for Practice.Microvascular invasion (MVI) is a major determinant of survival outcomes after curative liver resection for patients with hepatocellular carcinoma (HCC). Currently, there is no scoring system aiming to predict prognosis of patients with HCC and MVI after R0 liver resection (LR). Most of the widely used staging systems for HCC do not use MVI as an independent risk factor, and they cannot be used to predict the prognosis of patients with HCC and MVI after surgery. In this study, a new Eastern Hepatobiliary Surgery Hospital (EHBH) MVI scoring system was established to predict prognosis of patients with HCC and MVI after R0 LR. Based on the results of this study, postoperative adjuvant therapy may be recommended for patients with HCC and MVI with an EHBH‐MVI score >4. This score can be used to supplement the currently used HCC classifications to predict postoperative survival outcomes in patients with HCC and MVI.
Docetaxel, Oxaliplatin, and 5‐Fluorouracil (DOF) in Metastatic and Unresectable Gastric/Gastroesophageal Junction Adenocarcinoma: A Phase II Study with Long‐Term Follow‐Up
AbstractLessons Learned. Adding docetaxel to the modified FOLFOX7 backbone (DOF) is a feasible three‐drug combination therapy for advanced gastric cancer with high activity, providing evidence that leucovorin is not necessary in this setting.The DOF regimen represents an alternative to the FLOT (5‐FU 2,600 mg/m2 as 24‐hour infusion with leucovorin 200 mg/m2, oxaliplatin 85 mg/m2, and docetaxel 50 mg/m2) regimen that can be considered in select patients with advanced gastric cancer and is a potential choice in the curative setting.Background.The combination of docetaxel, cisplatin, and 5‐fluorouracil (5‐FU) demonstrates high response rates in advanced gastric cancer, albeit with increased toxicity. Given the efficacy of platinum‐taxane‐fluoropyrimidine regimens, this phase II study evaluated the efficacy and toxicity of docetaxel, oxaliplatin, and 5‐FU (DOF) for the treatment of metastatic or unresectable gastric or gastroesophageal junction (GEJ) adenocarcinoma.Methods.Patients with metastatic or unresectable gastric or GEJ adenocarcinoma with no prior therapy for metastatic disease received docetaxel 50 mg/m2 on day 1, oxaliplatin 85 mg/m2 on day 1, and 5‐FU 2,400 mg/m2 continuous intravenous infusion over 46 hours; cycles were repeated every 2 weeks. The primary endpoint was overall response rate (ORR).Results.Forty‐four patients were enrolled. Assessment of treatment response and toxicity was feasible in 41 and 43 patients, respectively. ORR was 73.2% (68.3% partial response; 4.9% complete response). Therapy was discontinued for progressive disease in 53%, toxicity in 26%, and death on treatment in 16%. Two patients underwent surgical resection. Thirty‐three patients (76.7%) received at least seven cycles (7–34). Grade 3–4 toxicities occurred in 31 patients (72.1%), including neutropenia (23.3%), neurologic (20.9%), and diarrhea (14.0%). Median overall survival was 10.3 months.Conclusion.DOF demonstrates a high response rate, expected safety profile, and prolonged survival and remains an option for select patients with unresectable or metastatic gastric or GEJ adenocarcinoma.
Uterine and Cervical Adenosarcoma: A Retrospective Study of Overall Oncologic Outcomes and Fertility Preservation in Early‐Stage Disease
AbstractBackground.The management of adenosarcoma is based on the limited available data. This study aimed to explore the characteristics and oncologic outcomes of patients with uterine and cervical adenosarcoma.Materials and Methods.A total of 21 and 32 cases of cervical and uterine adenosarcoma, respectively, were retrospectively reviewed in Peking Union Medical College Hospital between April 2006 and March 2019.Results.The median follow‐up time was 37.5 months (range, 1–153 months). The disease progression rate (DPR) was significantly higher in patients with uterine adenosarcoma compared with those with cervical adenosarcoma (28.1% vs. 4.8%). The curve of progression‐free survival significantly differed. For those with cervical adenosarcoma, the presence of a tumor stalk was a protective factor, whereas heterologous elements (HE) presented a risk factor for disease progression. For those with uterine adenosarcoma, the presence of a tumor stalk was an independent protective factor, whereas lymphovascular space invasion (LVSI) was an independent risk factor for disease progression. Moreover, HE was an independent risk factor for mortality. Fertility‐sparing surgery (FSS) was performed in four and five patients with cervical and uterine adenosarcoma, respectively. Regarding FSS, combined with cases in previous studies, the DPR of patients with uterine adenosarcoma was relatively higher compared with those with cervical adenosarcoma.Conclusion.We found that cervical adenosarcoma had a better prognosis than uterine adenosarcoma. The presence of a tumor stalk was a protective factor, whereas HE and LVSI were risk factors for prognosis. For those with uterine adenosarcoma, if FSS was administered, robust evaluation would be necessary. The small sample size limits the ability to make any strong conclusions about FSS.Implications for Practice.Uterine cervical adenosarcoma had a better prognosis than uterine adenosarcoma. For patients with cervical adenosarcoma, the presence of a tumor stalk was a protective factor and the presence of heterologous elements (HE) was a risk factor for disease progression. For those with uterine adenosarcoma, the presence of a tumor stalk was a protective factor and lymphovascular space invasion was a risk factor for disease progression. Moreover, HE was a risk factor for mortality. Regarding fertility‐sparing surgery (FSS), the disease progression rate was higher in patients with uterine adenosarcoma compared with those with cervical adenosarcoma. For patients with uterine adenosarcoma, if FSS was administered, hysteroscopy and robust imaging evaluation would be necessary.
Long‐Term Survival Outcomes After Liver Resection for Binodular Hepatocellular Carcinoma: A Multicenter Cohort Study
AbstractBackground.The long‐term prognosis after liver resection for multinodular (≥3 nodules) hepatocellular carcinoma (HCC) is generally considered to be unfavorable. However, the role of liver resection for binodular HCC is less investigated.Subjects, Materials, and Methods.From a multicenter database, consecutive patients who underwent curative‐intent liver resection for binodular HCC and without macrovascular invasion between 2003 and 2015 were retrospectively reviewed. Patients’ clinical variables as well as perioperative and long‐term survival outcomes were analyzed. Univariable and multivariable analyses were performed to identify the risk factors associated with overall survival (OS) and recurrence‐free survival (RFS) after curative resection.Results.Of 263 enrolled patients, the perioperative 30‐day mortality and morbidity rates were 1.5% and 28.5%. The 1‐, 3‐, and 5‐year OS and RFS rates were 81.5%, 52.4%, and 39.1% and 57.1%, 35.8%, and 26.6%, respectively. Multivariable Cox‐regression analyses identified preoperative alpha‐fetoprotein level >400 μg/L, tumor size with a sum of two nodules >8 cm, tumor size ratio of large/small nodule >1.5 (asymmetrical proportion), unilateral hemiliver distribution of two nodules, distance of ≤3 cm between two nodules, and microvascular invasion in any nodule as independent risk factors associated with decreased OS and RFS.Conclusion.Liver resection was safe and feasible in patients with binodular HCC, with acceptable perioperative and long‐term outcomes. Sum of two tumor sizes, size ratio and distribution, and distance between two nodules were independent risk factors associated with long‐term survival outcomes after surgery. These results may guide clinicians to make individualized surgical decisions and estimate long‐term prognosis for these patients.Implications for Practice.Liver resection was safe and feasible in patients with binodular hepatocellular carcinoma, with acceptable perioperative and long‐term outcomes. The sum of two tumor sizes, the size ratio and distribution of the two nodules, and the distance between two nodules were independent risk factors associated with long‐term overall survival and recurrence‐free survival after liver resection. The results of this study may guide clinicians to make individualized surgical decisions, estimate long‐term prognosis, and plan recurrence surveillance and adjuvant therapy for these patients.
AbstractThe primary objective of this article is to assist oncologists and advanced practice prescribers to safely and effectively minimize risk when providing opioids for cancer pain relief. The majority of people with cancer are unlikely to misuse or divert opioid medications, yet the prescriber is often unaware of those who are at risk for these behaviors. To provide skillful pain management to each patient in the oncology setting, while limiting harm to the community, all prescribers must consider the potential for risk of misuse, addiction, or diversion. To minimize this risk to the greatest degree possible, it is imperative to include a thorough risk assessment when conducting a comprehensive pain evaluation. This information is then used to triage pain relief interventions based upon the degree of risk, including whether or not to incorporate opioids into the plan of care. Risk mitigation strategies, incorporating universal precautions, are implemented to assess, monitor, and reduce the potential for opioid misuse. Universal precautions include strategies such as the use of urine toxicology, state prescription drug monitoring programs, and agreements. Ongoing monitoring is conducted with the goal being to identify aberrant behaviors early so that they can be addressed and managed appropriately. Referral to addiction specialists may be warranted when substance use disorder precludes safe use of opioids.Implications for Practice.Throughout the trajectory of cancer care, opioid use is often indicated, and, in fact, it may be unethical to limit or prohibit the use of opioids when pain is severe. Oncologists face the significant challenge of providing cancer pain control that is safe and effective, while limiting individual risk for abuse or overdose and keeping the community free of diverted substances. Most oncology providers report inadequate training in chronic pain principles and in managing addiction. Risk assessment and mitigation measures can be incorporated within oncology care to enhance effective pain management while reducing the potential for harm.
A Multicenter Comparison of Complementary and Alternative Medicine (CAM) Discussions in Oncology Care: The Role of Time, Patient‐Centeredness, and Practice Context
AbstractBackground.Little is known about how complementary and alternative medicine (CAM) is discussed in cancer care across varied settings in the U.S.Methods.In two practices affiliated with one academic medical center in southern California (SoCal), and one in the upper Midwest (UM), we audio‐recorded patient‐clinician interactions in medical oncology outpatient practices. We counted the frequency and duration of CAM‐related conversations. We coded recordings using the Roter Interaction Analysis System. We used chi‐square tests for bivariate analysis of categorical variables and generalized linear models for continuous variables to examine associations between dialogue characteristics, practice setting, and population characteristics with the occurrence of CAM discussion in each setting followed by multivariate models adjusting for clinician clustering.Results.Sixty‐one clinicians and 529 patients participated. Sixty‐two of 529 (12%) interactions included CAM discussions, with significantly more observed in the SoCal university practice than in the other settings. Visits that included CAM were on average 6 minutes longer, with CAM content lasting an average of 78 seconds. In bivariate tests of association, conversations containing CAM included more psychosocial statements from both clinicians and patients, higher patient‐centeredness, more positive patient and clinician affect, and greater patient engagement. In a multivariable model including significant bivariate terms, conversations containing CAM were independently associated with higher patient‐centeredness, slightly longer visits, and being at the SoCal university site.Conclusion.The frequency of CAM‐related discussion in oncology varied substantially across sites. Visits that included CAM discussion were longer and more patient centered.Implications for Practice.The Institute of Medicine and the American Society of Clinical Oncology have called for more open discussions of complementary and alternative medicine (CAM). But little is known about the role population characteristics and care contexts may play in the frequency and nature of those discussions. The present data characterizing actual conversations in practice complements a much larger literature based on patient and clinician self‐report about CAM disclosure and use. It was found that CAM discussions in academic oncology visits varied significantly by practice context, that the majority were initiated by the patient, and that they may occur more when visit time exists for lifestyle, self‐care, and psychosocial concerns.
AbstractOpioids are required by a majority of patients with advanced cancer. Oncologists and palliative care clinicians are faced with the challenge of safely prescribing opioids in the current environment of an opioid crisis. Many patients with cancer use opioids unsafely, store them in unsecure locations, and do not dispose of unused opioids, leading to increased availability of these opioids for others to misuse. More than 50% of people who misuse opioids obtain the drugs from a friend or relative with or without their consent. Patient and provider education has been shown to improve safe opioid use, promote secure storage, and also increase disposal of unused opioids safely in drug take‐back programs that are now widely available. This article highlights the importance of patient education and cautious opioid prescribing in patients with cancer.Implications for Practice.The current opioid crisis makes it challenging to effectively manage cancer pain. Providers play a prominent role in minimizing opioid misuse. Cautious prescribing with limits enforced on the quantity of opioids prescribed, close follow‐up, and consistent and frequent provision of opioid education are a must. Evidence points to the impact of patient education in promoting safety around opioid use. Most people who misuse prescription opioids obtain them from family or friends. Storing opioids in the open or not disposing of unused opioids increases the availability of these opioids for misuse by others. The importance of not sharing, always locking up, and disposing of unused and expired opioids must be highlighted as part of the opioid education that must be delivered every time that opioids are prescribed. Information about local drug take‐back programs may also help increase disposal of unused opioids.
Anti‐PD‐1 Immunotherapy‐Induced Flare of a Known Underlying Relapsing Vasculitis Mimicking Recurrent Cancer
AbstractSafe use of immune checkpoint blockade in patients with cancer and autoimmune disorders requires a better understanding of the pathophysiology of immunologic activation. We describe the immune correlates of reactivation of granulomatosis with polyangiitis (GPA)—an antineutrophil cytoplasmic antibody (ANCA)‐associated vasculitis—in a patient with metastatic urothelial carcinoma treated with pembrolizumab. After PD‐1 blockade, an inflammatory pulmonary nodule demonstrated a granulomatous, CD4+ T‐cell infiltrate, correlating with increased CD4+ and CD8+ naïve memory cells in the peripheral blood without changes in other immune checkpoint receptors. Placed within the context of the existing literature on GPA and disease control, our findings suggest a key role for PD‐1 in GPA self‐tolerance and that selective strategies for immunotherapy may be needed in patients with certain autoimmune disorders. We further summarize the current literature regarding reactivation of autoimmune disorders in patients undergoing immune checkpoint blockade, as well as potential immunosuppressive strategies to minimize the risks of further vasculitic reactivation upon rechallenge with anti‐PD‐1 blockade.Key Points. Nonspecific imaging findings in patients with cancer and rheumatological disorders may require biopsy to distinguish underlying pathology.Patients with rheumatologic disorders have increased risk of reactivation with PD‐(L)1 immune checkpoint blockade, requiring assessment of disease status before starting treatment.Further study is needed to evaluate the efficacy of treatment regimens in preventing and controlling disease reactivation.
A Practical Guide for the Follow‐Up of Patients with Advanced Basal Cell Carcinoma During Treatment with Hedgehog Pathway Inhibitors
AbstractThe Hedgehog pathway inhibitors (HPIs), vismodegib and sonidegib, are increasingly employed in the treatment of patients with advanced basal cell carcinoma (BCC). The aim of this review is to create a synthesis of available information in the literature regarding the follow‐up of patients with advanced BCC treated with HPIs and to provide the treating physician with a structured practical guide to standardize clinical practice. Several challenges during treatment are addressed: to optimally evaluate tumor responses, to differentiate between resistance (HPI rechallenge not possible) and recurrence (HPI rechallenge may be possible) in case of BCC regrowth, to readily assess for toxicity and tolerability issues, to provide patients with practical ways and behaviors to effectively cope with adverse events, and to improve patient adherence and quality of life.Implications for Practice.This is a practical guide for clinical practice regarding the monitoring and follow‐up of patients with advanced basal cell carcinoma (BCC) during treatment with the Hedgehog pathway inhibitors (HPIs) vismodegib and sonidegib. This review aims to bridge the gap in knowledge of assessing tumor response for BCC with both an externally visible component and an infiltrating component measurable with imaging. Furthermore, it addresses the follow‐up for adverse events as a challenging multistep process involving practices aiming to readily assess new‐onset symptoms of HPI toxicity, perform total‐body skin examination, and improve patient adherence and quality of life.
AbstractAdvanced adrenocortical carcinoma (ACC) is an aggressive disease with poor prognosis, and the current therapeutic options, such as mitotane or platinum‐based chemotherapy regimens, often offer limited efficacy. Here, we present the first report, to the author's knowledge, of metastatic ACC with positive octreoscan scintigraphy that was successfully treated with octreotide long‐acting release (LAR). A patient with metastatic ACC who showed poor tolerance to mitotane received octreotide LAR because of positive octreoscan scintigraphy. She obtained major partial response to the somatostatin analog. Interestingly, the expression of somatostatin receptor 2 from the previous local recurrence lesion was negative. The next‐generation sequencing‐based circulating tumor DNA analysis in the patient was performed and failed to identify any alterations. These findings suggest that octreotide LAR may be a good option for the treatment of metastatic ACC in selected patients.
Phase II Study of Bendamustine and Ofatumumab in Elderly Patients with Newly Diagnosed Diffuse Large B‐Cell Lymphoma Who Are Poor Candidates for R‐CHOP Chemotherapy
AbstractLessons Learned. The combination of ofatumumab and bendamustine in elderly patients with diffuse large B‐cell lymphoma demonstrated modest efficacy compared with standard of care.The poor response may have been due to patient age and the high rate of treatment discontinuation.Background.This phase II trial evaluated the efficacy of bendamustine and ofatumumab in elderly patients with newly diagnosed diffuse large B‐cell lymphoma (DLBCL) who were not candidates for rituximab cyclophosphamide, doxorubicin, vincristine, and prednisone (R‐CHOP).Methods.Patients received IV 90 mg/m2 bendamustine on days 1 and 2 of cycles 1 through 6 and IV 1,000 mg ofatumumab on days 1 and 8 of cycle 1 and on day 1 of cycles 2 through 6. Both drugs were administered at the U.S. Food and Drug Administration‐approved dose for combination therapy. All patients received premedications before each infusion of ofatumumab and hematopoietic growth factors. Treatment was administered in 21‐day cycles, with restaging after cycle 3 and cycle 6. The primary endpoint was complete response rate (CRR).Results.Twelve of 21 enrolled patients completed treatment; median age was 83 years. The most common reasons for treatment discontinuation were disease progression (three patients), intercurrent illness (two patients), and death (one patient due to drug‐related sepsis and bowel necrosis and one patient due to unknown cause). Thrombocytopenia (14%), neutropenia (10%), diarrhea (10%), vomiting (10%), and dehydration (10%) were the most common grade ≥3 treatment‐related adverse events. The overall response rate was 90.5% and the CRR was 33.3%. Median progression‐free survival (PFS) and overall survival (OS) were 8.6 and 12.0 months, respectively.Conclusion.The combination of ofatumumab and bendamustine is feasible in elderly patients with DLBCL.
Conformity to Clinical Practice Guidelines at Initial Management in Adult Soft Tissue and Visceral Tumors since the Implementation of the NetSarc Network in Eastern France
AbstractBackground.Soft tissue sarcomas are rare and heterogenous tumors that are hard to diagnose. The aim of this study was to evaluate local practices and conformity to clinical practice guidelines (CPGs) for their initial diagnostic management.Materials and Methods.Patients were carriers of a soft tissue or visceral tumor, presented at a sarcoma tumor board (STB) between 2010 and 2016. Conformity to CPGs was evaluated using ten criteria designed for this purpose. Associations between different factors and conformity to composite criteria, reflecting the three main diagnostic steps (imaging, biopsy and histological report) were analyzed.Results.A total of 643 patients were included. A preoperative tumor imaging assessment and a biopsy were performed according to CPGs in 80.8% and 36.8% of the cases, respectively. When done, the first surgical resection was R0 in 30.3% of cases, R1 in 28.6%, and R2 in 10.9%. The rest of the operated patients with sarcoma had a second surgical excision (11.4%), an intraoperative fragmentation (4.3%), or margins were unknown (14.4%). Six of the ten quality criteria presented a conformity rate higher than 70%. Two criteria with a conformity rate lower than 20% were the most controversial: presentation at a STB before biopsy and freezing of a tumor fragment. A multivariate analysis revealed that the common predictor of nonconformity to composite criteria was the initial management in a nonexpert center.Conclusion.Initial diagnostic management requires improvement, especially outside of specialized centers.Implications for Practice.This article supports the essential need to refer patients with soft tissue tumors to specialized centers to improve the management of sarcomas beginning at the diagnostic phase. Indeed, the reported data were very similar to those already described at the national level of the NetSarc network and indicate the necessity to keep raising awareness about this simple issue: early referral to reference centers will save lives.
AbstractBackground.Delta‐like protein 3 (DLL3) is a Notch ligand that has an important role in the tumorigenesis of small cell lung cancer (SCLC). Recently, rovalpituzumab tesirine (Rova‐T), a DLL3‐targeted antibody‐drug conjugate, has been developed for treating SCLC. DLL3 is a transcriptional target of the achaete‐scute homolog‐1 (ASCL1) transcription factor, which is involved in pulmonary neuroendocrine cell development. However, the relationship between DLL3 and/or ASCL1 expression and the clinical features of SCLC remains unknown, especially for early‐stage resected SCLC. This study aimed to investigate the expression of DLL3 and ASCL1 in resected SCLC samples using immunohistochemical analysis.Materials and Methods.We collected 95 surgically resected SCLC samples, which were formalin fixed and paraffin embedded. Immunohistochemistry staining was performed to investigate the correlation between the expression of either DLL3 or ASCL1 and clinicopathological features of study patients.Results.Seventy‐seven (83%) of 93 immunohistochemically evaluable samples were positive for DLL3 (expression in ≥1% of tumor cells), and DLL3‐high expression (≥75%) was observed in 44 samples (47%). Sixty‐one (64%) of 95 samples were positive for ASCL1 (expression in ≥5% of tumor cells). A positive correlation was observed between DLL3 and ASCL1 expression. DLL3 and ASCL1 expression were not associated with survival in SCLC patients. DLL3 was more prevalent in patients with advanced clinical disease.Conclusion.DLL3 and ASCL1 were highly expressed in patients with surgically resected SCLC. DLL3 and ASCL1 may be targets for the treatment of SCLC.Implications for Practice.This article examines the relationship between delta‐like protein 3 (DLL3) and achaete‐scute homolog‐1 (ASCL1) protein expression with the clinical features of 95 surgically resected small cell lung cancer (SCLC). DLL3 is attracting attention because rovalpituzumab tesirine (Rova‐T), a DLL3‐targeted antibody‐drug conjugate, was developed recently. DLL3 and ASCL1 were highly expressed in patients with surgically resected SCLC. DLL3 and ASCL1 may be targets for the treatment of early‐stage SCLC, including with Rova‐T.
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