Cranial Irradiation for Patients with Epidermal Growth Factor Receptor (EGFR) Mutant Lung Cancer Who Have Brain Metastases in the Era of a New Generation of EGFR Inhibitors

2 weeks 5 days ago
AbstractBackground.Immediate whole brain radiation (WBRT) has been the standard for patients with lung cancer with brain metastases. The study aims to evaluate the effect of immediate cranial irradiation in patients with epidermal growth factor receptor (EGFR) mutant lung cancer in the era of a new generation of EGFR inhibitors.Materials and Methods.Medical records of 198 patients with EGFR mutant non‐small cell lung cancer and brain metastases at initial metastatic diagnosis were reviewed. Patients were categorized into four groups: immediate WBRT, immediate cranial stereotactic radiosurgery (SRS), delayed radiation upon progression of cranial lesions (DRT), and never cranial irradiation (NRT). Overall survival (OS) and progression‐free survival related to EGFR inhibitors were analyzed.Results.The SRS group had the fewest brain metastases and fewest extracranial lesions, and the DRT and NRT groups had the smallest brain metastases. Median survival were 18.5, 55.7, 21.1, and 18.2 months for the WBRT, SRS, DRT, and NRT groups, respectively. Patients who had received EGFR T790M inhibitors survived longer (41.1 vs. 19.8 months). In multivariate analysis, the OS of patients in the SRS group was longer than that in the NRT group (adjusted hazard ratio [aHR]: 0.315). Patients who had fewer extracranial lesions and who had received EGFR T790M inhibitor treatments also survived longer (aHR: 0.442 and 0.357, respectively).Conclusion.Immediate stereotactic radiosurgery but not whole brain radiation was associated with longer survival. Because of patient heterogeneity and the introduction of EGFR T790M inhibitors, the timing and modality of cranial irradiation should be determined individually, and cranial irradiation may be omitted for selected patients.Implications for Practice.Immediate whole brain radiation has been the standard for patients with lung cancer with brain metastases. In this study, it was observed that, for patients with epidermal growth factor receptor (EGFR) mutant advanced lung cancer who had brain metastases, there was no difference in survival between patients who never received cranial irradiation and those who received whole brain radiation immediately. Patients who received immediate stereotactic radiosurgery or who had ever received EGFR T790M inhibitors survived longer. Patients who received immediate stereotactic radiosurgery have fewer brain metastases. These findings suggest that the timing and modality of cranial irradiation should be determined individually, and cranial irradiation may be omitted in selected patients.
Jih-Hsiang Lee, Hsuan-Yu Chen, Feng-Ming Hsu, Jin-Shing Chen, Wei-Yu Liao, Jin-Yuan Shih, Chong-Jen Yu, Kuan-Yu Chen, Tzu-Hsiu Tsai, James Chih-Hsin Yang

A First‐in‐Human Phase I Study of GC1118, a Novel Anti‐Epidermal Growth Factor Receptor Antibody, in Patients with Advanced Solid Tumors

3 weeks ago
AbstractLessons Learned. GC1118 is a novel fully human anti‐epidermal growth factor receptor (EGFR) antibody with unique binding epitopes and different ligand‐binding inhibitory activity compared with cetuximab or panitumumab.GC1118 showed promising antitumor activity, especially in patients with colorectal cancer resistant to prior EGFR antibody. Skin toxicities were more common and diarrhea was less frequent compared with other anti‐EGFR antibodies.Background.GC1118 is a novel monoclonal antibody targeting epidermal growth factor receptor (EGFR) with more potent ligand inhibition than cetuximab or panitumumab. We conducted a first‐in‐human, phase I study of GC118 in patients with refractory solid tumors.Methods.In the dose escalation part, GC1118 was administered on days 1, 8, 15, and 22, followed by a 2‐week rest, during which dose‐limiting toxicities (DLTs) were evaluated. In the expansion part, patients were enrolled into three cohorts (Cohort 1 [C1], patients with colorectal cancer [CRC] without prior anti‐EGFR treatment; Cohort 2 [C2], patients with CRC with tumors resistant to anti‐EGFR therapy; Cohort 3 [C3], EGFR‐overexpressing gastric cancer).Results.In the dose escalation part, 24 patients were treated at five dose levels: 0.3, 1.0, 3.0, 4.0, and 5.0 mg/kg. In the 5.0 mg/kg cohort, two patients experienced DLTs (skin toxicities). The maximum‐tolerated dose (MTD) was 4.0 mg/kg. Common adverse events were skin toxicities. In the expansion part, 39 patients were enrolled. In Cohort 1, stable disease (SD) was observed in 58%; in Cohort 2, partial response (PR) 17% and SD 8%; in Cohort 3, PR 8% and SD 17%.Conclusion.GC1118 showed promising antitumor activity and was well tolerated. Infrequent diarrhea compared with other anti‐EGFR antibodies might be advantageous for further development.
Do-Youn Oh, Keun-Wook Lee, Sae-Won Han, Jin Won Kim, Jung-Won Shin, Seong-Jin Jo, Jonghwa Won, Seokyung Hahn, Howard Lee, Woo Ho Kim, Yung-Jue Bang

A Systematic Review and Network Meta‐Analysis of Regorafenib and TAS‐102 in Refractory Metastatic Colorectal Cancer

3 weeks ago
AbstractBackground.Regorafenib at different dosing strategies and TAS‐102 are treatment options for refractory metastatic colorectal cancer (mCRC). We aimed to evaluate the comparative effectiveness evidence supporting these different strategies.Materials and Methods.We searched different databases for randomized controlled trials evaluating TAS‐102 or regorafenib in patients with refractory mCRC who failed prior oxaliplatin, irinotecan, and fluoropyrimidine. Outcomes of interest included overall survival (OS) and progression‐free survival (PFS). The overall effect was pooled using the DerSimonian random effects model. We conducted network meta‐analysis based on White's multivariate meta‐regression to pool evidence from direct and indirect comparisons.Results.Six trials at low risk of bias (2,445 patients) were included. Direct comparisons showed that Rego 160 and TAS‐102 as monotherapy were superior to best‐supportive care (BSC) in terms of PFS (Rego 160: hazard ratio [HR], 0.4; 95% confidence ratio [CI], 0.26–0.63; TAS‐102: HR, 0.46 CI, 0.40–0.52) and OS (Rego 160: HR, 0.67; CI, 0.48–0.93; TAS‐102: HR, 0.67; CI, 0.57–0.80). Network analysis showed no statistically difference in PFS or OS between Rego 160 and TAS‐102. Rego 80+ was superior to BSC in terms of OS (HR, 0.44; CI, 0.23–0.84) and PFS (HR, 0.37; CI, 0.21–0.66). Rego 80+ was associated with statistically nonsignificant improvement in OS and PFS compared with TAS‐102 and Rego 160.Conclusion.Regorafenib 160 and TAS‐102 appear to have similar efficacy. Rego 80+ is shown to be superior to BSC. A trend for improved OS was observed with Rego 80+ versus Rego 160 or TAS 102.Implications for Practice.Regorafenib at a dose of 160 mg and TAS‐102 appear to have similar efficacy in patients with refractory metastatic colorectal cancer. Regorafenib with a dose escalation strategy is superior to best‐supportive care. Given its tolerability and the observed trend in survival benefit compared with regorafenib 160, dose escalation strategy of regorafenib (80+) may be the preferred option in this setting.
Mohamad Bassam Sonbol, Raed Benkhadra, Zhen Wang, Belal Firwana, Daniel J. Walden, Kabir Mody, Joleen M. Hubbard, M. Hassan Murad, Daniel H. Ahn, Tanios Bekaii-Saab

Long‐Term Survivors in Metastatic Pancreatic Ductal Adenocarcinoma: A Retrospective and Matched Pair Analysis

3 weeks ago
AbstractBackground.Metastatic pancreatic ductal adenocarcinoma (mPDAC) is an aggressive malignancy with a median overall survival (OS) of between 8 and 11 months. However, a significant number of patients experience a longer survival, more than 18 months. The aim of this study was to describe the “long‐term survivor” population and to evaluate clinical and pathological factors that might affect survival.Materials and Methods.All patients with mPDAC diagnosed in the Centre Leon Bérard (Lyon, France) between January 2010 and June 2015 and who survived more than 18 months were identified. They were compared with a control cohort matched on age, sex, performance status, stage at diagnosis, primary tumor localization, treatment, and liver metastasis. Their clinical features, treatment modalities, and outcomes were analyzed.Results.A total of 94 patients were included, 47 in each cohort. Both cohorts had identical characteristics as follows: women (51%), performance status ≤1 (95.7%), median age at diagnosis (60 years), and metastasis at diagnosis (83%). Median OS was 26.87 months (95% confidence interval [CI] 23–31.08) in the long‐term survivor group (LS group) and 9.79 months (95% CI 5.75–11.86) in the control group (C group). Potential factors of long‐term survival were explored with a logistic model (LS group vs. C group). Three factors were identified as significant prognostic factors in the univariate analysis: lymphopenia (odds ratio [OR] ref: yes = 0.26), neutrophil‐to‐lymphocyte ratio (NLR; OR ref >5 = 0.31), and peritoneal carcinomatosis (OR ref: yes = 0.40). NLR was the only remaining factor in our backward selection procedure.Conclusion.A significant subset of patients with mPDAC can achieve long‐term survival (≥18 months) in 2018. We identified low NLR as a significant prognostic factor associated with long‐term survival in mPDAC.Implications for Practice.Metastatic pancreatic ductal adenocarcinoma (mPDAC) is one of the most lethal types of cancer. A subset of patients with mPDAC can achieve long‐term survival (≥18 months) with a modern chemotherapy regimen, such as FOLFIRINOX or gemcitabine/nab‐paclitaxel. We identified low neutrophil‐to‐lymphocyte ratio (NLR) as a significant prognostic factor associated with long‐term survival in mPDAC. Prognostic factors such as NLR might allow accurate selection of patients with mPDAC in order to consider individual therapeutic approaches. NLR should be used as a stratification factor in clinical trials.
Pauline Rochefort, Audrey Lardy-Cleaud, Matthieu Sarabi, Francoise Desseigne, Anne Cattey-Javouhey, Christelle de la Fouchardiere

Risk of Osteoporosis and Fractures in Patients with Thyroid Cancer: A Case‐Control Study in U.S. Veterans

3 weeks ago
AbstractBackground.Data on osteoporosis and fractures in patients with thyroid cancer, especially men, are conflicting. Our objective was to determine osteoporosis and fracture risk in U.S. veterans with thyroid cancer.Materials and Methods.This is a case‐control study using the Veterans Health Administration Corporate Data Warehouse (2004–2013). Patients with thyroid cancer (n = 10,370) and controls (n = 10,370) were matched by age, sex, weight, and steroid use. Generalized linear mixed‐effects regression model was used to compare the two groups in terms of osteoporosis and fracture risk. Next, subgroup analysis of the patients with thyroid cancer using longitudinal thyroid‐stimulating hormone (TSH) was performed to determine its effect on risk of osteoporosis and fractures. Other covariates included patient age, sex, median household income, comorbidities, and steroid and androgen use.Results.Compared with controls, osteoporosis, but not fractures, was more frequent in patients with thyroid cancer (7.3% vs. 5.3%; odds ratio [OR], 1.33; 95% confidence interval [CI], 1.18–1.49) when controlling for median household income, Charlson/Deyo comorbidity score, and androgen use. Subgroup analysis of patients with thyroid cancer demonstrated that lower TSH (OR, 0.93; 95% CI, 0.90–0.97), female sex (OR, 4.24; 95% CI, 3.53–5.10), older age (e.g., ≥85 years: OR, 17.18; 95% CI, 11.12–26.54 compared with <50 years), and androgen use (OR, 1.63; 95% CI, 1.18–2.23) were associated with osteoporosis. Serum TSH was not associated with fractures (OR, 1.01; 95% CI, 0.96–1.07).Conclusion.Osteoporosis, but not fractures, was more common in U.S. veterans with thyroid cancer than controls. Multiple factors may be contributory, with low TSH playing a small role.Implications for Practice.Data on osteoporosis and fragility fractures in patients with thyroid cancer, especially in men, are limited and conflicting. Because of excellent survival rates, the number of thyroid cancer survivors is growing and more individuals may experience long‐term effects from the cancer itself and its treatments, such as osteoporosis and fractures. The present study offers unique insight on the risk for osteoporosis and fractures in a largely male thyroid cancer cohort. Physicians who participate in the long‐term care of patients with thyroid cancer should take into consideration a variety of factors in addition to TSH level when considering risk for osteoporosis.
Maria Papaleontiou, Mousumi Baner&#x0237;ee, David Reyes-Gastelum, Sarah T. Hawley, Megan R. Haymart

Characteristics of BRAF V600E Mutant, Deficient Mismatch Repair/Proficient Mismatch Repair, Metastatic Colorectal Cancer: A Multicenter Series of 287 Patients

3 weeks 4 days ago
AbstractBackground.BRAFV600E mutations occurring in about 10% of metastatic colorectal cancers (mCRCs) are usually associated with a poor outcome. However, their prognostic factors are unknown.Materials and Methods.We built a multicenter clinico‐biological database gathering data from patients with BRAFV600E‐mutant mCRC treated in one of the 16 French centers from 2006 to 2017. The primary endpoint was to identify prognostic factors using a Cox model.Results.We included 287 patients (median age, 67 years [28–95]; female, 57%). Their median overall survival was 20.8 months (95% confidence interval [CI], 17.97–27.04), and median progression‐free survival in the first‐line setting was 4.34 months (95% CI, 3.81–5.03). Chemotherapy regimen and biological agents (antiangiogenic or anti‐epidermal growth factor receptor) were not associated with overall and progression‐free survival. Stage IV disease (synchronous metastases) and absence of curative‐intent surgery were statistically associated with poor overall survival. Among the 194 patients with mismatch repair (MMR) status available, overall survival was significantly longer in patients with deficient MMR tumors compared with those with proficient MMR tumors (adjusted hazard ratio = 0.56; p = .009).Conclusion.Despite that BRAFV600E‐mutant mCRCs are associated with poor overall and progression‐free‐survival, patients with deficient MMR tumors and/or resectable disease experienced a longer survival. These results highlight the importance of MMR testing and resectability discussion in patients with BRAFV600E mCRC in day‐to‐day practice.Implications for Practice.Mismatch repair (MMR) testing and resectability discussion in patients with BRAFV600E metastatic colorectal cancer (mCRC) should be performed in day‐to‐day practice to steer treatment decision making in patients with BRAFV600E‐mutant mCRC.
Christelle de la Fouchardiere, Romain Cohen, David Malka, Rosine Guimbaud, Heloise Bourien, Astrid Lievre, Wulfran Cacheux, Pascal Artru, Eric Francois, Marine Gilabert, Emmanuelle Samalin-Scalzi, Aziz Zaanan, Vincent Hautefeuille, Benoit Rousseau,…

Dancing with Deterrents: Understanding the Role of Abuse‐Deterrent Opioid Formulations and Naloxone in Managing Cancer Pain

3 weeks 4 days ago
AbstractPrescription opioids are commonly prescribed for the relief of many kinds of pain syndromes, including cancer pain. In order to combat the growing rates of abuse and misuse of prescription opioids, the Centers for Disease Control and Prevention, along with the U.S. Food and Drug Administration and multiple pharmaceutical companies, have implemented many risk mitigation strategies. Abuse‐deterrent drug delivery technology and more consistent prescribing of the opioid antagonist, naloxone, are two of the mechanisms of reducing harm in patients on chronic opioid therapy. Abuse‐deterrent technology is implemented into different commercially available opioid products with the intent of discouraging manipulation of the opioid or making the use of the manipulated opioid less appealing. Use of the opioid antagonist, naloxone, for reversal of intentional or unintentional opioid overdose is a safe and effective means to reduce potential risk in patients who are on opioids for pain management. These mechanisms have multiple advantages and limitations that influence their practical use specifically in patients with cancer pain. Patients with cancer pain have unique therapeutic needs and goals, and their balance of treatment risks and benefits differs from that of other kinds of chronic pain disorders. This article provides an overview of the advantages and limitations of these specific harm‐reduction strategies and provides guidance on how to practically utilize them when caring for patients with cancer pain.Implications for Practice.Treating cancer pain has important and unique considerations compared with other chronic, noncancer pain disorders. The use of risk mitigation strategies for opioid prescribing as promoted by the Centers for Disease Control and Prevention does not translate seamlessly to patients with cancer. It is crucial to be wary of the advantages and pitfalls of all risk mitigation strategies related to opioid use in patients with cancer pain. Careful examination of patient‐specific risks and benefits should always be considered when implementing pharmacologic treatment and harm‐reduction strategies for the management of cancer pain.
Megan T. Mitchell

Safety and Success of Repeat Lung Needle Biopsies in Patients with Epidermal Growth Factor Receptor‐Mutant Lung Cancer

3 weeks 4 days ago
AbstractBackground.Postprogression repeat biopsies are critical in caring for patients with lung cancer with epidermal growth factor receptor (EGFR) mutations. However, hesitation about invasive procedures persists. We assessed safety and tissue adequacy for molecular profiling among repeat postprogression percutaneous transthoracic needle aspirations and biopsies (rebiopsies).Materials and Methods.All lung biopsies performed at our hospital from 2009 to 2017 were reviewed. Complications were classified by Society of Interventional Radiology criteria. Complication rates between rebiopsies in EGFR‐mutants and all other lung biopsies (controls) were compared using Fisher's exact test. Success of molecular profiling was recorded.Results.During the study period, nine thoracic radiologists performed 107 rebiopsies in 75 EGFR‐mutant patients and 2,635 lung biopsies in 2,347 patients for other indications. All biopsies were performed with computed tomography guidance, coaxial technique, and rapid on‐site pathologic evaluation (ROSE). The default procedure was to take 22‐gauge fine‐needle aspirates (FNA) followed by 20‐gauge tissue cores. Minor complications occurred in 9 (8.4%) rebiopsies and 503 (19.1%; p = .004) controls, including pneumothoraces not requiring chest tube placement (4 [3.7%] vs. 426 [16.2%] in rebiopsies and controls, respectively; p < .001). The only major complication was pneumothorax requiring chest tube placement, occurring in zero rebiopsies and 38 (1.4%; p = .4) controls. Molecular profiling was requested in 96 (90%) rebiopsies and successful in 92/96 (96%).Conclusion.At our center, repeat lung biopsies for postprogression molecular profiling of EGFR‐mutant lung cancers result in fewer complications than typical lung biopsies. Coaxial technique, FNA, ROSE, and multiple 20‐gauge tissue cores result in excellent specimen adequacy.Implications for Practice.Repeat percutaneous transthoracic needle aspirations and biopsies for postprogression molecular profiling of epidermal growth factor receptor (EGFR)‐mutant lung cancer are safe in everday clinical practice. Coaxial technique, fine‐needle aspirates, rapid on‐site pathologic evaluation, and multiple 20‐gauge tissue cores result in excellent specimen adequacy. Although liquid biopsies are increasingly used, their sensitivity for analysis of resistant EGFR‐mutant lung cancers remains limited. Tissue biopsies remain important in this context, especially because osimertinib is now in the frontline setting and T790M is no longer the major finding of interest on molecular profiling.
Florian J. Fintelmann, Fabian M. Troschel, Martin W. Kuklinski, Shaunagh McDermott, Milena Petranovic, Subba R. Digumarthy, Amita Sharma, Amelie S. Troschel, Melissa C. Price, Lida P. Hariri, Matthew D. Gilman, Joanne O. Shepard, Lecia V. Sequist, Zofia…

Navigating Challenging Conversations About Nonmedical Opioid Use in the Context of Oncology

3 weeks 4 days ago
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.
Zachary Sager, Julie Childers

Phase II, Multicenter, Randomized Trial of Docetaxel plus Prednisone with or Without Cediranib in Men with Chemotherapy‐Naive Metastatic Castrate‐Resistant Prostate Cancer

3 weeks 4 days ago
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.
Elisabeth Heath, Lance Heilbrun, Heather Mannuel, Glenn Liu, Primo Lara, J. Paul Monk, Thomas Flaig, Amado Zurita, Philip Mack, Ulka Vaishampayan, Philip Stella, Daryn Smith, Susan Bolton, Arif Hussain, Anas Al-Janadi, Daniel Silbiger, Muhammad Usman, S…

The Development of an International Oncofertility Competency Framework: A Model to Increase Oncofertility Implementation

3 weeks 5 days ago
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.
Antoinette Anazodo, Paula Laws, Shanna Logan, Carla Saunders, Jo Travaglia, Brigitte Gerstl, Natalie Bradford, Richard Cohn, Mary Birdsall, Ronald Barr, Nao Suzuki, Seido Takae, Ricardo Marinho, Shuo Xiao, Qiong-Hua Chen, Nalini Maha&#x0237;an, Madhuri…

Prognostic Nomogram and Patterns of Use of FOLFIRI‐Aflibercept in Advanced Colorectal Cancer: A Real‐World Data Analysis

3 weeks 5 days ago
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.
Ana Fernandez Montes, Carlos Lopez Lopez, Guillem Argiles Martinez, David Paez Lopez, Ana Maria Lopez Munoz, Beatriz Garcia Paredes, David Gutierrez Abad, Carmen Castanon Lopez, Paula Jimenez Fonseca, Javier Gallego Plazas, Maria Carmen Lopez Doldan, Eva…

Safety of Nivolumab plus Low‐Dose Ipilimumab in Previously Treated Microsatellite Instability‐High/Mismatch Repair‐Deficient Metastatic Colorectal Cancer

3 weeks 5 days ago
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.
Michael A. Morse, Michael J. Overman, Leighanne Hartman, Taline Khoukaz, Edith Brutcher, Heinz-Josef Lenz, A&#x0237;lan Atasoy, Tong Shangguan, Huanyu Zhao, Bassel El-Rayes

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

4 weeks ago
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.
Xiu-Ping Zhang, Kang Wang, Xu-Biao Wei, Le-Qun Li, Hui-Chuan Sun, Tian-Fu Wen, Zong-Tao Chai, Zhen-Hua Chen, Jie Shi, Wei-Xing Guo, Dong Xie, Wen-Ming Cong, Meng-Chao Wu, Wan Yee Lau, Shu-Qun Cheng

Docetaxel, Oxaliplatin, and 5‐Fluorouracil (DOF) in Metastatic and Unresectable Gastric/Gastroesophageal Junction Adenocarcinoma: A Phase II Study with Long‐Term Follow‐Up

4 weeks ago
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.
Ari Joseph Rosenberg, Alfred Rademaker, Howard S. Hochster, Theresa Ryan, Thomas Hensing, Veena Shankaran, Lisa Baddi, Devalingam Mahalingam, Mary F. Mulcahy, Al B. Benson III

Uterine and Cervical Adenosarcoma: A Retrospective Study of Overall Oncologic Outcomes and Fertility Preservation in Early‐Stage Disease

1 month ago
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.
Zhen Yuan, Dongyan Cao, Mei Yu, Keng Shen, Yonglan He

Long‐Term Survival Outcomes After Liver Resection for Binodular Hepatocellular Carcinoma: A Multicenter Cohort Study

1 month ago
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.
Ming-Da Wang, Chao Li, Jun Li, Wan-Guang Zhang, Wei-Qin Jiang, Jiong-Jie Yu, Hao Xing, Han Wu, Jun Han, Zhen-Li Li, Xin-Fei Xu, Ting-Hao Chen, Ya-Hao Zhou, Wei-Min Gu, Hong Wang, Yong-Yi Zeng, Yao-Ming Zhang, Timothy M. Pawlik, Wan Yee Lau, Meng-Chao Wu,…

Risk Assessment and Monitoring of Patients with Cancer Receiving Opioid Therapy

1 month ago
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.
Judith A. Paice
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1 hour 59 minutes ago
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