AbstractBackground.From 2014 to 2017, the Palliative Medicine Working Group developed and published best practice recommendations for the integration of palliative care in Comprehensive Cancer Centers (CCCs) in Germany. To evaluate the implementation level of these recommendations in the CCCs an online survey was performed. Based on the results of this study, strategic tandem partnerships between CCCs should be built in order to foster further local development.Materials and Methods.Directors of all CCCs were contacted by e‐mail between December 2017 and February 2018. At the time of the survey, 15 CCCs were funded by the German Cancer Aid. The level of implementation of the recommendations in individual CCCs was established using a transtheoretical model.Results.Between December 2017 and February 2018, all 15 contacted directors or their representatives of the CCCs took part in the survey. More than two thirds of the CCCs have a palliative service as well as a day clinic and palliative outpatient clinic. Regional networking and the provision of a palliative care unit were approved by all CCCs.Conclusion.The publication of best practice recommendations was a milestone for the integration of palliative care in the CCCs. The majority of the German CCCs already fulfill essential organizational and structural requirements. There is a particular need for optimization in the provision of a basic qualification for general palliative care and emergency admission personnel.Implications for Practice.In 2017, the Palliative Medicine Working Group in the network of the German Comprehensive Cancer Centers (CCCs) published the best practice recommendations it had developed for the integration of palliative medicine in CCCs in Germany. In order to evaluate the level of implementation of the recommendations, an online survey of the CCC directors was established. The majority of German CCCs fulfil elementary organizational and structural requirements. However, there is still room for improvement in the provision of a basic qualification for general palliative care and emergency admission personnel.
AbstractBackground.The end‐of‐life period is a crucial time in lung cancer care. To have a better understanding of the racial‐ethnic disparities in health care expenditures, access, and quality, we evaluated these disparities specifically in the end‐of‐life period for patients with lung cancer in the U.S.Materials and Methods.We used the Surveillance, Epidemiology, and End Results (SEER)‐Medicare database to analyze characteristics of lung cancer care among those diagnosed between the years 2000 and 2011. Linear and logistic regression models were constructed to measure racial‐ethnic disparities in end‐of‐life care cost and utilization among non‐Hispanic (NH) Asian, NH black, Hispanic, and NH white patients while controlling for other risk factors such as age, sex, and SEER geographic region.Results.Total costs and hospital utilization were, on average, greater among racial‐ethnic minorities compared with NH white patients in the last month of life. Among patients with NSCLC, the relative total costs were 1.27 (95% confidence interval [CI], 1.21–1.33) for NH black patients, 1.36 (95% CI, 1.25–1.49) for NH Asian patients, and 1.21 (95% CI, 1.07–1.38) for Hispanic patients. Additionally, the odds of being admitted to a hospital for NH black, NH Asian, and Hispanic patients were 1.22 (95% CI, 1.15–1.30), 1.47 (95% CI, 1.32–1.63), and 1.18 (95% CI, 1.01–1.38) times that of NH white patients, respectively. Similar results were found for patients with SCLC.Conclusion.Minority patients with lung cancer have significantly higher end‐of‐life medical expenditures than NH white patients, which may be explained by a greater intensity of care in the end‐of‐life period.Implications for Practice.This study investigated racial‐ethnic disparities in the cost and utilization of medical care among lung cancer patients during the end‐of‐life period. Compared with non‐Hispanic white patients, racial‐ethnic minority patients were more likely to receive intensive care in their final month of life and had statistically significantly higher end‐of‐life care costs. The findings of this study may lead to a better understanding of the racial‐ethnic disparities in end‐of‐life care, which can better inform future end‐of‐life interventions and help health care providers develop less intensive and more equitable care, such as culturally competent advanced care planning programs, for all patients.
AbstractIntroduction.Nivolumab alone and in combination with ipilimumab is approved for the treatment of patients with metastatic renal cell carcinoma (RCC) who received prior vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR‐TKI) and those who are treatment naive, respectively. However, the clinical activity of nivolumab in non‐clear cell RCC (nccRCC) is unknown, as these patients were excluded from the trials.Materials and Methods.We reviewed the records of patients who received nivolumab for nccRCC and ccRCC with >20% rhabdoid with the primary endpoint to assess the objective response rate (ORR). We assessed radiographic response using RECIST, v1.1. Secondary endpoints were progression‐free survival (PFS) and overall survival (OS). We also reviewed the literature to identify studies reporting on the clinical activity of immune checkpoint inhibitors in nccRCC, and performed a meta‐analysis of proportions for ORR and disease control rate (DCR).Results.Twelve patients (30%) had papillary histology, 11 (27.5%) had unclassified, 8 (20%) had ccRCC with rhabdoid component, 5 (12.5%) had chromophobe, 3 (7.5%) had translocation, and 1 (2.5%) had mucinous tubular and spindle cell carcinoma. Overall, seven patients (21.6%, 95% confidence interval [CI], 8.7%–37.9%) had an objective response, including three patients (8.8%, 95% confidence interval [CI], 1.9%–23.7%) who achieved a complete remission. At a median follow‐up of 24.5 monoths (95% CI, 17.7–32.6), median PFS was 4.9 monoths (95% CI, 3.53–10.27) and median OS was 21.7 monoths (95% CI, 7.83 mo to not reached). There were no treatment‐related deaths. We also identified two retrospective studies reporting best ORR in patients with nccRCC receiving PD‐1/PD‐L1 checkpoint blockade. The ORR and DCR for the total cohort were, respectively, 18.6% (95% CI, 11.9%–26.4%) and 53.4% (95% CI, 44.2%–62.5%).Conclusion.Nivolumab demonstrated activity in unclassified nccRCC and ccRCC with >20% rhabdoid; further randomized clinical trials are warranted.Implications for Practice.This article reports on the clinical activity and safety of immune checkpoint inhibitors in non‐clear cell kidney cancer. The retrospective data with the meta‐analysis provides a summary that will help guide the treatment of this rare and heterogeneous group of kidney cancers.
AbstractImmune checkpoint inhibitor treatment has been approved by the U.S. Food and Drug Administration for the treatment of a wide range of cancer types, including hepatocellular carcinoma. Workup and management of immune‐mediated hepatitis, pancreatitis, or cholangitis that develops during immune checkpoint inhibitor treatment can be challenging. Immune‐mediated hepatitis can be particularly challenging if patients have underlying viral hepatitis or autoimmune hepatitis. Patients with positive hepatitis B virus DNA should be referred to a hepatologist for antiviral therapy prior to immune checkpoint inhibitor treatment. With untreated hepatitis C virus (HCV) and elevated liver enzymes, a liver biopsy should be obtained to differentiate between HCV infection and immune‐mediated hepatitis due to anti‐programmed cell death protein 1 (PD‐1) therapy. If autoimmune serologies are negative, then this supports a case of immune‐mediated hepatitis secondary to anti‐PD‐1 therapy, rather than autoimmune hepatitis. In this case, an empiric steroid therapy is reasonable; however, if the patient does not respond to steroid therapy in 3–5 days, then liver biopsy should be pursued. The incidence of immune checkpoint‐induced pancreatitis is low, but when it does occur, diagnosis is not straightforward. Although routine monitoring of pancreatic enzymes is not generally recommended, when pancreatitis is suspected, serum levels of amylase and lipase should be checked. Once confirmed, a steroid or other immunosuppressant (if steroids are contraindicated) should be administered along with close monitoring, and a slow tapering dosage once the pancreatitis is under control. Patients should then be monitored for recurrent pancreatitis. Finally, immune therapy‐related cholangitis involves elevated bilirubin and alkaline phosphatase and, once diagnosed, is managed in the same way as immune‐mediated hepatitis.Key Points.Immune‐mediated hepatitis, pancreatitis, and cholangitis are found in patients receiving or who have previously received immune checkpoint inhibitors.To work up immune‐mediated hepatitis, viral, and autoimmune serologies, liver imaging will help to differentiate immune‐mediated hepatitis from hepatitis of other etiology.Hepatology consult may be considered in patients with a history of chronic liver disease who developed hepatitis during immune checkpoint inhibitor treatment.Liver biopsy should be considered to clarify the diagnosis for case in which the hepatitis is refractory to steroid or immunosuppressant treatment.Immune‐mediated pancreatitis is treated with steroid or other immunosuppressant with a slow tapering and should be monitored for recurrence.Implications for Practice.All patient receiving or who have previously received immune checkpoint inhibitors should be monitored closely for immune‐mediated hepatitis, pancreatitis, and cholangitis. Workup and management of immune‐mediated hepatitis, pancreatitis, and cholangitis should follow the package insert of immune checkpoint inhibitors. Hepatology consultation should be considered in patients with a history of chronic liver disease.
AbstractLessons Learned.HyperAcute Renal immunotherapy was well tolerated and demonstrated antitumor activity in patients requiring salvage‐line treatment for metastatic renal cell carcinoma (mRCC).HyperAcute Renal immunotherapy was safely administered with concomitant salvage‐line treatments for mRCC, and it may be a candidate for inclusion in novel combinations for salvage treatment of mRCC because of its unique mechanism of action.Background.HyperAcute Renal (HAR) immunotherapy exploits a naturally occurring barrier to xenotransplantation and zoonotic infections in humans to immunize patients against metastatic renal cell carcinoma (mRCC) cells. HAR consists of two allogeneic renal cancer cell lines genetically modified to express α(1,3)Gal, to which humans have an inherent pre‐existing immunity.Methods.Patients with refractory mRCC were eligible for this phase I dose‐escalation trial. Concomitant treatment was permitted after the initial 2 months of HAR monotherapy. HAR was injected intradermally weekly for 4 weeks then biweekly for 20 weeks, totaling 14 immunizations. The primary endpoint was safety and determination of a maximum tolerated dose (MTD).Results.Among 18 patients enrolled, two grade 3 adverse events (AEs) were attributed to HAR, lymphopenia and injection site reaction, and no grade 4/5 AEs occurred. The recommended phase II dose (RP2D) was 300 million cells. One patient had a partial response and eight patients had stable disease, for a disease control rate of 50% (9/18). Median overall survival with low‐dose HAR was 14.2 months and was 25.3 months with high‐dose HAR.Conclusion.In pretreated mRCC, HAR immunotherapy was well tolerated and demonstrated antitumor activity. HAR immunotherapy may be a candidate for inclusion in novel combinations for salvage treatment of mRCC.
AbstractAs the use of immune checkpoint inhibitors for several different malignancies becomes more mainstream, their side‐effect profile raises new challenges. In 2011, the Food and Drug Administration approved the first checkpoint inhibitor for the treatment of advanced melanoma, and since then, checkpoint inhibitors have demonstrated efficacy in many other tumor types. Given the frequent use of immune checkpoint inhibitors in a wide range of cancers today, the diagnosis and management of their immune‐mediated toxicities need special attention. One of the most common is immune‐mediated colitis. Workup and management of immune‐mediated colitis can be challenging and is the purpose of this review.Key Points.Rate of immune mediated colitis differ from different kind of immune checkpoint inhibitor treatment.To work up immune‐mediated colitis, tests to rule out infectious etiologies of diarrhea, colonoscopy and abdominal image will help to differentiate immune mediated colitis from colitis from other etiology.Patients with mild colitis can be managed with supportive therapies alone, but more severe cases may require immunomodulators such as steroid. Refractory cases may require tumor necrosis factor (TNF) inhibitors, such as infliximab in addition to steroid treatment.Implications for Practice.Immune‐mediated colitis in patients who are receiving or have received immune checkpoint inhibitor requires early recognition, prompt and aggressive medical treatment to avoid severe colitis, which can be life‐threatening or lead to a colectomy.
AbstractTesticular cancer is one of the few tumor types that have not yet benefited from targeted therapy. Still no new active agents for treating this cancer have been identified over the past 15 years. Once patients are refractory to cisplatin‐based chemotherapy, they will be expected to die from testicular cancer. This report describes a 21‐year‐old man who was refractory to chemotherapy and immunotherapy. Whole exome sequencing and low‐depth whole genome sequencing confirmed the KRAS gene amplification, which may lead to the tumor cells’ progression and proliferation. After discussion at the molecular tumor board, the patient was offered paclitaxel, carboplatin, and sorafenib (CPS) based on a phase III clinical trial of melanoma with KRAS gene copy gains. After treatment with CPS, the patient achieved excellent curative effects. Because of a nearly 50% frequency of KRAS amplification in chemotherapy‐refractory testicular germ cells, CPS regimen may provide a new therapy, but it still warrants further validation in clinical studies.Key Points.Chemotherapy‐refractory testicular cancer has a very poor prognosis resulting in a lack of effective targeted therapies.
KRAS gene amplification occurs in nearly 20% of testicular cancer and 50% of chemotherapy‐refractory testicular cancer.
KRAS amplification may activate the MAPK signaling pathway, and inhibition of MAPK by sorafenib combined with paclitaxel and carboplatin could be a viable option based on a phase III clinical trial of melanoma.To the authors’ knowledge, this is the first report of response to sorafenib‐based combination targeted therapy in a patient with chemotherapy‐refractory testicular cancer.Clinical genomic profiling can confirm copy number variation of testicular cancer and provide insights on therapeutic options.
AbstractBackground.Oncology research increasingly involves biospecimen collection and data sharing. Ethical challenges emerge when researchers seek to use archived biospecimens for purposes that were not well defined in the original informed consent document (ICD). We sought to inform ongoing policy debates by assessing patient views on these issues.Materials and Methods.We administered a cross‐sectional self‐administered survey to patients with cancer at an academic medical center. Survey questions addressed attitudes toward cancer research, willingness to donate biospecimens, expectations regarding use of biospecimens, and preferences regarding specific ethical dilemmas.Results.Among 240 participants (response rate 69%), virtually all (94%) indicated willingness to donate tissue for research. Most participants (86%) expected that donated tissue would be used for any research deemed scientifically important, and virtually all (94%) expected that the privacy of their health information would be protected. Broad use of stored biospecimens and data sharing with other researchers increased willingness to donate tissue. For three scenarios in which specific consent for proposed biobank research was unclear within the ICD, a majority of patient's favored allowing the research to proceed: 76% to study a different cancer, 88% to study both inherited (germline) and tumor specific (somatic) mutations, and 70% to permit data sharing. A substantial minority believed that research using stored biospecimens should only proceed with specific consent.Conclusion.When debates arise over appropriate use of archived biospecimens, the interests of the research participants in seeing productive use of their blood or tissue should be considered, in addition to addressing concerns about potential risks and lack of specific consent.Implications for Practice.This survey evaluated views of patients with cancer regarding the permissible use of stored biospecimens from cancer trials when modern scientific methods are not well described in the original informed consent document. The vast majority of patients support translational research and expect that any biospecimens they donate will be used to advance knowledge. When researchers, policy makers, and those charged with research oversight debate use of stored biospecimens, it is important to recognize that research participants have an interest in productive use of their blood, tissue, or data, in addition to considerations of risks and the adequacy of documented consent.
AbstractBackground.The efficacy of epidermal growth factor (EGF) receptor (EGFR) inhibitors in patients with non‐small cell lung cancer (NSCLC), pancreatic cancer (PC), or colorectal cancer (CRC) has been demonstrated. However, dermatological reactions to these inhibitors can cause significant physical and psychosocial discomfort. The objective of the present study was to evaluate the efficacy of EGF ointment for EGFR inhibitor‐related skin adverse events (ERSEs).Materials and Methods.This placebo‐controlled, double‐blind, multicenter, pilot phase III trial enrolled patients with NSCLC, PC, or CRC treated with EGFR inhibitors. Patients with grade ≥2 ERSEs were included. Patients were randomized to three treatment arms: arm 1, placebo; arm 2, 1 ppm of EGF ointment; and arm 3, 20 ppm of EGF ointment. Patients applied ointment to their skin lesions twice daily.Results.Efficacy evaluation was available for 80 patients (9 for PC, 28 for NSCLC, and 43 for CRC). Responses were 44.4% in arm 1, 61.5% in arm 2, and 77.8% in arm 3. There was a linear correlation between EGF concentrations and responses (p = .012). Quality of life (QoL) was assessed for 74 patients. Maximum changes in composite scores by Skindex‐16 after treatment were significantly different among arms (mean ± SD: −5.2 ± 8.6 for arm 1, −11.7 ± 14.2 for arm 2, and − 18.6 ± 17.7 for arm 3; p = .008). EGF arms showed significant improvement in emotions (p = .005) and functioning (p = .044) scores over the placebo arm.Conclusion.EGF ointment is effective for managing ERSEs. It can also improve patients’ QoL compared with placebo. Clinical trial identification number. NCT02284139Implications for Practice.Patients with non‐small cell lung cancer, pancreatic cancer, or colorectal cancer who are treated with epidermal growth factor (EGF) receptor (EGFR) inhibitors may experience dermatologic reactions to their treatment. This study investigated the benefit of an EGF ointment in the treatment of these adverse events and observed the ointment to be effective in managing EGFR inhibitor‐related skin adverse events.
AbstractBackground.Nuclear protein of the testis (NUT) carcinoma is a rare and aggressive malignancy associated with rearrangements of the nuclear protein of the testis (NUT) gene on chromosome 15q14. Because of its rarity, this tumor is often underdiagnosed and underreported, and there is limited literature regarding its biology and optimal management.Methods and Results.We report our experience of five patients with pediatric NUT carcinoma, all of whom presented with midline head and neck mass. In spite of aggressive multimodality treatment, only one patient survives.Conclusion.NUT carcinoma has a dismal prognosis in spite of aggressive multimodality management (surgery and adjuvant chemotherapy and/or radiation). Novel strategies are required to improve outcomes of patients with this tumor.
AbstractBackground.With the accelerated development of next‐generation sequencing (NGS), identified variants, and targeted therapies, clinicians who confront the complicated and multifarious genetic information may not effectively incorporate NGS‐based circulating tumor DNA (ctDNA) analysis into routine patient care. Consequently, standardized ctDNA testing reports are of vital importance. In an effort to guarantee high‐quality reporting performance, we conducted an investigation of the current detection and reporting practices for NGS‐based ctDNA analysis.Materials and Methods.A set of simulated ctDNA samples with known variants at known allelic frequencies and a corresponding case scenario were distributed to 66 genetic testing laboratories for ctDNA analysis. Written reports were collected to evaluate the detection accuracy, reporting integrity, and information sufficiency using 21 predefined criteria.Results.Current reporting practices for NGS‐based ctDNA analysis were found to be far from satisfactory, especially regarding testing interpretation and methodological details. Only 42.4% of laboratories reported the results in complete concordance with the expected results. Moreover, 74.2% of reports only listed aberrations with direct and well‐known treatment consequences for the tumor type in question. Genetic aberrations for which experimental agents and/or drug access programs are available may thus be overlooked. Furthermore, methodological details for the interpretation of results were missing from the majority of reports (87.9%).Conclusion.This proof‐of‐principle study suggests that the capacity for accurate identification of variants, rational interpretation of genotypes, comprehensive recommendation of potential medications, and detailed description of methodologies need to be further improved before ctDNA analysis can be formally implemented in the clinic.Implications for Practice.Accurate, comprehensive, and standardized clinical sequencing reports can help to translate complex genetic information into patient‐centered clinical decisions, thereby shepherding precision oncology into daily practice. However, standards, guidelines, and quality requirements for clinical reports of next‐generation sequencing (NGS)‐based circulating tumor DNA (ctDNA) analysis are currently absent. By using a set of simulated clinical ctDNA samples and a corresponding case scenario, current practices were evaluated to identify deficiencies in clinical sequencing reports of ctDNA analysis. The recommendations provided here may serve as a roadmap for the improved implementation of NGS‐based ctDNA analysis in the clinic.
AbstractBackground.Advanced‐stage Hodgkin lymphoma (HL) is a curable malignancy, although outcomes remain poor in certain patients. It remains unclear if recent advances have improved their population‐level survival over time.Materials and Methods.Using the Surveillance, Epidemiology, and End Results database, we identified patients aged ≥18 years with stage III or IV classical HL as the first primary malignancy, diagnosed between 2000 and 2014 and treated with chemotherapy. Patients were stratified by date of diagnosis into three groups (2000–2004, 2005–2009, 2010–2014) to assess the trends in overall survival (OS).Results.A total of 9,042 patients with a median age of 41 years were included. The use of frontline radiation therapy decreased in each period (21.3% [2000–2004] vs. 15.5% [2005–2009] vs. 10.7% [2010–2014]; p < .001). Three‐year OS was significantly higher for patients diagnosed between 2010 and 2014 (81.8%) and 2005 and 2009 (80.6%) compared with 2000 and 2004 (78.5%; p = .0008 and .02, respectively). Whereas outcomes were poorest in the age >60 cohort, similar improvements were also seen in 3‐year OS over the three time periods within this patient population. On multivariate analysis, diagnosis in the earlier period and minority race were associated with higher mortality. Females and married patients had significantly lower mortality risk.Conclusion.Survival of patients with advanced‐stage HL has continued to improve over time, suggesting the impact of evolving treatment approaches. Three‐year OS in the contemporary period remains inadequate at 81.8%, highlighting the need for continued research to improve their outcomes.Implications for Practice.This article evaluates contemporary outcomes for advanced‐stage Hodgkin lymphoma (HL) in the U.S. using the Surveillance, Epidemiology, and End Results database. Although overall survival (OS) has improved in each 5‐year period since 2000, the 3‐year OS from 2010 to 2014 remains inadequate at 81.8% and is limited by patient demographics. New therapies are indicated to improve clinical outcomes in advanced‐stage HL.
AbstractLessons Learned.Studies targeting the androgen receptor (AR) signaling pathway in aromatase inhibitor (AI)‐resistant breast cancer are limited.Bicalutamide, one of the commonly used AR inhibitors in prostate cancer, in combination with AI, did not show synergistic activity in patients with estrogen receptor‐positive and AI‐resistant disease in this phase II, single‐arm study.The clinical benefit rate and objective response rate at 6 months were 16.7% and 0%, respectively, and the study was terminated after the first stage.Background.Endocrine resistance is a major problem in clinical practice. Studies have shown that androgen receptor (AR) signaling activation may be one of the mechanisms, and targeting AR showed some promising results in AR‐positive triple‐negative breast cancer. The aim of this study was to assess the efficacy and safety of bicalutamide plus another aromatase inhibitor in patients with nonsteroidal aromatase inhibitor (AI) or steroidal AI resistance and estrogen receptor (ER)‐positive and AR‐positive advanced breast cancer.Methods.A Simon's two‐stage, phase II, single‐arm study was conducted. We assumed the clinical benefit rate (CBR) of 40% would be significant in clinical practice. In this case, if ≥4 patients of the 19 patients in the first stage benefited from treatment, the CBR would achieve the assumed endpoint. If fewer than four patients benefited from treatment in the first stage, the trial would be terminated. All patients received bicalutamide 50 mg per day orally plus another aromatase inhibitor. The primary outcome was CBR; secondary outcomes included objective response rate (ORR), progression‐free survival (PFS), and tolerability.Results.A total of 19 patients enrolled in the first stage, and 18 patients met all criteria for analysis. The trial terminated according to protocol after the first stage. After a median follow‐up of 14 months, the CBR at 6 months was 16.7% (3/18); no patients with partial or complete response were observed. The median PFS was 2.7 months. Bicalutamide in combination with AI was well tolerated.Conclusion.Bicalutamide in combination with another AI did not show synergistic activity in patients with ER‐positive breast cancer and AI resistance. Results suggest that no more large‐sample clinical trials should be conducted in this population for overcoming endocrine resistance.
AbstractBackground.The prognostic value of 1q21 gain in newly diagnosed multiple myeloma (NDMM) remains controversial. Our aim was to investigate the prognostic value of 1q21 gain in a Chinese population.Materials and Methods.We retrospectively identified 565 patients with NDMM from multiple centers in China.Results.We detected 1q21 gain in 222 (39.3%) patients, among whom 144 had three copies of 1q21, 57 had four copies of 1q21, and 21 had at least five copies of 1q21. Copy number variation did not show any effect on the disease outcome. Multivariate analysis indicated that 1q21 gain was an independent factor for poor prognosis, but we found that 1q21 gain was strongly associated with other high‐risk factors, such as del(17p), t(4;14), t(14;16), lactate dehydrogenase (LDH) level >300 U/L and International Scoring System (ISS) stage II–III (p < .001). Further analysis revealed that in the absence of other high‐risk factors, isolated 1q21 gain resulted in similar progression‐free survival (PFS; 52.0 vs. 52.8 months, p = .810) and overall survival (OS; not reached vs. not reached, p = .833); additionally, when present with other high‐risk cytogenetic abnormalities or increased LDH levels, 1q21 gain lost its prognostic power. However, the presence of 1q21 gain increased the adverse impact of ISS stage. Furthermore, 1q21 gain predicted poor PFS and OS in patients who received bortezomib‐based regimens. Moreover, autologous stem cell transplantation reversed the poor prognosis in patients with 1q21 gain.Conclusion.Our results show that heterogeneity exists among patients with 1q21 gain and suggest that we should assess the impact of 1q21 gain on prognosis according to different treatment regimens and accompanying high‐risk factors.Implications for Practice.1q21 gain is one of the most common chromosomal aberrations in multiple myeloma (MM); however, the prognostic value of 1q21 gain remains controversial. This study investigated the prognostic value of 1q21 gain in a Chinese population with newly diagnosed MM. The results showed that heterogeneity exists among patients with 1q21 gain and suggested that the impact of 1q21 gain on prognosis should be assessed according to different treatment regimens and accompanying high‐risk factors. These results could help stratify risk in patients with MM and guide treatment decisions.
AbstractBackground.Limited data exist on transfusion burden and transfusion‐related iron overload in adult survivors of solid malignancies.Methods.Hospital‐specific cancer registry data of patients with solid tumor receiving systemic anticancer treatment between January 2008 and September 2009 at the Oncology Department of the Leiden University Medical Center (The Netherlands) were retrieved and cross‐referenced with red blood cell (RBC) transfusion records. Individual lifetime transfusion burden was captured in April 2015. Multitransfused long‐term survivors with serum ferritin >500 μg/L were subsequently screened for hepatic and cardiac iron overload using 1.5 Tesla magnetic resonance imaging.Results.The study population consisted of 775 adult patients with solid cancer (45.2% male; median age, 58 years; >75% chemotherapy‐treated), 423 (54.6%) of whom were transfused with a median of 6.0 RBC units (range 1–67). Transfusion triggers were symptomatic anemia or hemoglobin <8.1–8.9 g/dL prior to each myelosuppressive chemotherapy cycle. We identified 123 (15.9%) patients across all tumor types with a lifetime transfusion burden of ≥10 RBC units. In the absence of a hemovigilance program, none of these multitransfused patients was screened for iron overload despite a median survival of 4.6 years. In 2015 at disclosure of transfusion burden, 26 multitransfused patients were alive. Six (23.1%) had hepatic iron overload: 3.9–11.2 mg Fe/g dry weight. No cardiac iron depositions were found.Conclusion.Patients with solid malignancies are at risk for multitransfusion and iron overload even when adhering to restrictive RBC transfusion policies. With improved long‐term cancer survivorship, increased awareness of iatrogenic side effects of supportive therapy and development of evidence‐based guidelines are essential.Implications for Practice.In the presence of a restrictive transfusion policy, ∼30% of transfused adult patients with solid cancer are multitransfused and ∼50% become long‐term survivors, underscoring the need for evidence‐based guidelines for the detection and management of transfusion‐related iron overload in this group of patients. In each institution, a hemovigilance program should be implemented that captures the lifetime cumulative transfusion burden in all patients with cancer, irrespective of tumor type. This instrument will allow timely assessment and treatment of iron overload in cancer survivors, thus preventing organ dysfunction and decreased quality of life.
AbstractBackground.Patients with advanced lung neuroendocrine neoplasms (NENs) have few treatment options. Capecitabine and temozolomide have recently showed significant activity in patients with pancreatic neuroendocrine tumors (NETs), but data in lung NETs are limited.Methods.We retrospectively reviewed the records of patients treated at a large referral center to identify patients seen between January 2008 and September 2018 with metastatic lung NENs who received treatment with capecitabine and temozolomide (CAPTEM). Patients with small cell lung cancer were excluded. The primary endpoint was overall response rate per RECIST 1.1. Secondary endpoints included progression‐free survival, overall survival, and toxicity.Results.Twenty patients were identified who received treatment with capecitabine and temozolomide. Fourteen (70%) had typical lung NETs, five had (25%) atypical carcinoids, and one (5%) had disease defined as a large‐cell neuroendocrine carcinoma. Nineteen patients were evaluable for response. Six (30%) patients exhibited a best response of partial response per RECIST 1.1 criteria, 11 (55%) stable disease, and 2 (10%) progressive disease; objective response rate was 30%, and disease control rate was 85%. Eleven patients eventually progressed, only six of whom exhibited progression per RECIST 1.1 criteria. Median progression‐free survival was 13 months (95% confidence interval [CI], 4.4–21.6 months). Median overall survival was 68 months (95% CI, 35.3–100.7 months). Toxicity profile was mild with mainly grade 1, expected toxicities. Six patients required dose reduction because of toxicity.Conclusion.The CAPTEM regimen is associated with a high response rate and a relatively tolerable toxicity profile in lung NENs. This regimen warrants further exploration in a prospective clinical trial.Implications for Practice.Patients with advanced lung neuroendocrine neoplasms have very few systemic treatment options. The capecitabine and temozolomide regimen has previously shown significant activity in patients with pancreatic neuroendocrine tumors (NETs) but has not been explored in metastatic lung NETs. This study showed that this regimen is associated with a high response rate (30%) and a relatively tolerable toxicity profile in this population.
AbstractIn the light of recent advances in the immunotherapy field for breast cancer (BC) treatment, especially in the triple‐negative subtype, the identification of reliable biomarkers capable of improving patient selection is paramount, because only a portion of patients seem to derive benefit from this appealing treatment strategy. In this context, the role of programmed cell death ligand 1 (PD‐L1) as a potential prognostic and/or predictive biomarker has been intensively explored, with controversial results. The aim of the present review is to collect available evidence on the biological relevance and clinical utility of PD‐L1 expression in BC, with particular emphasis on technical aspects, prognostic implications, and predictive value of this promising biomarker.Implications for Practice.In the light of the promising results coming from trials of immune checkpoint inhibitors for breast cancer treatment, the potential predictive and/or prognostic role of programmed cell death ligand 1 (PD‐L1) in breast cancer has gained increasing interest. This review provides clinicians with an overview of the available clinical evidence regarding PD‐L1 as a biomarker in breast cancer, focusing on both data with a possible direct impact on clinic and methodological pitfalls that need to be addressed in order to optimize PD‐L1 implementation as a clinically useful tool for breast cancer management.
AbstractImmune checkpoint blockade (ICB) is an approved therapy for advanced metastatic mismatch repair (MMR)‐deficient cancer regardless of tissue of origin. Although therapy is effective initially, recurrence rates are significant, and long‐term outcomes remain poor for most patients. It is not currently recommended to give sequential ICB for advanced MMR‐deficient colorectal cancer (CRC) or for patients with metastatic cancer from Lynch syndrome. The need for subsequent therapy options in advanced MMR‐deficient cancer beyond the first ICB regimen arises in clinical practice, and there are often no effective standard chemotherapies or other targeted therapies. We report the case of a Lynch syndrome patient with metastatic CRC and urothelial cancer who was treated sequentially with pembrolizumab (targeting PD1), atezolizumab (targeting PD‐L1), brief rechallenge with pembrolizumab, and finally the combination of ipilimumab (targeting CTLA‐4) and nivolumab (targeting PD1). Over a 28‐month period the patient experienced prolonged disease control with each different regimen the first time it was given, including metabolic response by positron emission tomography and computed tomography scanning and tumor marker reductions. The case suggests that some patients with advanced MMR‐deficient CRC may experience meaningful clinical benefit from multiple sequential ICB regimens, a strategy that can be further tested in clinical trials.Key Points.The case exemplifies clinical benefit from sequential immune checkpoint blockade in a patient with Lynch syndrome with advanced metastatic colorectal cancer and urothelial cancer.Metabolic response, with decreased fluorodeoxyglucose avidity on positron emission tomography and computed tomography, and reductions in tumor markers, such as carcinoembryonic antigen, were helpful in this case to monitor disease status over a 28‐month period of therapy.The concept of sequential immune checkpoint blockade in patients with advanced mismatch repair‐deficient cancer merits further study to determine which patients are most likely to benefit.
AbstractTumor‐treating fields (TTFields) are a noninvasive antimitotic cancer treatment consisting of low‐intensity alternating electric fields delivered to the tumor or tumor bed via externally applied transducer arrays. In multiple in vitro and in vivo cancer cell lines, TTFields therapy inhibits cell proliferation, disrupts cell division, interferes with cell migration and invasion, and reduces DNA repair. Human trials in patients with primary glioblastoma showed an improvement in overall survival, and trials in patients with unresectable malignant pleural mesothelioma showed favorable outcomes compared with historical control. This led to U.S. Food and Drug Administration approval in both clinical situations, paving the way for development of trials investigating TTFields in other malignancies. Although these trials are ongoing, the existing evidence suggests that TTFields have activity outside of neuro‐oncology, and further study into the mechanism of action and clinical activity is required. In addition, because TTFields are a previously unrecognized antimitotic therapy with a unique mode of delivery, the oncological community must address obstacles to widespread patient and provider acceptance. TTFields will likely join surgery, systemic therapy, and radiation therapy as a component of multimodality management of patients with solid malignancies.Implications for Practice.Tumor‐treating fields (TTFields) exhibit a broad range of antitumor activities. Clinically, they improve overall survival for patients with newly diagnosed glioblastoma. The emergence of TTFields has changed the treatment regimen for glioblastoma. Clinicians need to understand the practical issues surrounding its use in the multidisciplinary management of patients with glioblastoma. With ongoing clinical trials, TTFields likely will become another treatment modality for solid malignancies.
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