A Phase II Study of Genexol‐PM and Cisplatin as Induction Chemotherapy in Locally Advanced Head and Neck Squamous Cell Carcinoma

2 months ago
AbstractLessons Learned. Induction chemotherapy with Genexol‐PM and cisplatin demonstrated modest tumor response in locally advanced head and neck squamous cell carcinoma.Considering favorable toxicity profiles and promising survival data, further studies on this regimen are warranted in patients with head and neck squamous cell carcinoma.Background.Genexol‐PM is a polymeric micellar formulation of paclitaxel without Cremophor EL. We investigated the efficacy and safety of Genexol‐PM plus cisplatin as induction chemotherapy (IC) in patients with locally advanced head and neck squamous cell carcinoma (LA‐HNSCC).Methods.Patients received Genexol‐PM (230 mg/m2) and cisplatin (60 mg/m2) every 3 weeks as IC. After three cycles of IC, definitive treatment of either concurrent chemoradiotherapy (CCRT) with weekly cisplatin (30 mg/m2) or surgery was performed. The primary endpoint was overall response rate (ORR) after IC.Results.Of 52 patients enrolled, 47 completed three cycles of IC, and the ORR was 55.8% (95% confidence interval, 42.3–69.3). Although there was one treatment‐related death, toxicity profiles to Genexol‐PM and cisplatin were generally favorable, and the most common grade 3 or 4 toxicities were neutropenia (15.4%), anorexia (7.7%), and general weakness (7.7%). Fifty‐one patients received definitive treatment (CCRT [n = 44] or radical surgery [n = 7]). The rate of complete response following CCRT was 81.8% (36/44). After a median follow‐up of 39 months, estimates of progression‐free survival (PFS) and overall survival (OS) at 3 years were 54.3% and 71.3%, respectively.Conclusion.IC with Genexol‐PM and cisplatin demonstrated modest tumor response with well‐tolerated toxicity profiles for patients with LA‐HNSCC.
Bhumsuk Keam, Keun-Wook Lee, Se-Hoon Lee, Jin-Soo Kim, Jin Ho Kim, Hong-Gyun Wu, Keun-Yong Eom, Suzy Kim, Soon-Hyun Ahn, Eun-Jae Chung, Seong Keun Kwon, Woo-Jin Jeong, Young Ho Jung, Ji-Won Kim, Dae Seog Heo

Comparison of the Clinicopathological Characteristics and Genetic Alterations Between Patients with Gastric Cancer with or Without Helicobacter pylori Infection

2 months ago
AbstractBackground.Helicobacter pylori (HP) can induce epithelial cells and intestinal metaplasia with genetic damage that makes them highly susceptible to the development of gastric cancer (GC).Materials and Methods.Between 2005 and 2010, 356 patients with gastric cancer who received curative surgery were enrolled. Analysis of HP, Epstein‐Barr virus (EBV) infection, PIK3CA amplification, and mutation analysis of 68 mutations in eight genes using a mass spectrometric single‐nucleotide polymorphism genotyping technology was conducted. The clinicopathological characteristics of patients with or without HP infection were compared.Results.Among the 356 patients, 185 (52.0%) had HP infection. For intestinal‐type GC, patients with HP infection were more likely to be younger and had fewer PI3K/AKT pathway genetic mutations than those without HP infection. For diffuse‐type GC, patients with HP infection were characterized by less male predominance, less lymphoid stroma, fewer microsatellite instability‐high tumors, and fewer PI3K/AKT pathway genetic mutations than those without HP infection. Patients with HP infection had less tumor recurrence and a better 5‐year overall survival (87.7% vs. 73.9%, p = .012) and disease‐free survival (64.1% vs. 51.3%, p = .013) than those without HP infection, especially for intestinal‐type GC. For EBV‐negative GC, patients with HP infection had fewer PI3K/AKT pathway mutations and a better 5‐year overall survival and disease‐free survival than those without HP infection. Multivariate analysis demonstrated that HP infection was an independent prognostic factor regarding overall survival and disease‐free survival.Conclusion.Patients with GC with HP infection were associated with fewer PI3K/AKT pathway genetic mutations and better survival than those without HP infection, especially for EBV‐negative and intestinal‐type GC.Implications for Practice.Patients with gastric cancer with Helicobacter pylori (HP) infection had fewer PI3K/AKT pathway genetic mutations, less tumor recurrence, and better survival than those without HP infection, especially for Epstein‐Barr virus (EBV)‐negative and intestinal‐type gastric cancer. HP infection is an independent prognostic factor regarding overall survival and disease‐free survival. Future in vivo and in vitro studies of the correlation among HP infection, PI3K/AKT pathway, and EBV infection in gastric cancer are required.
Wen-Liang Fang, Kuo-Hung Huang, Shih-Ching Chang, Chien-Hsing Lin, Ming-Huang Chen, Yee Chao, Su-Shun Lo, Anna Fen-Yau Li, Chew-Wun Wu, Yi-Ming Shyr

Minimally Invasive Cordotomy for Refractory Cancer Pain: A Randomized Controlled Trial

2 months ago
AbstractBackground.Up to 30% of patients with cancer continue to suffer from pain despite aggressive supportive care. The present study aimed to determine whether cordotomy can improve cancer pain refractory to interdisciplinary palliative care.Materials and Methods.In this randomized controlled trial, we recruited patients with refractory unilateral somatic pain, defined as a pain intensity (PI) ≥4, after more than three palliative care evaluations. Patients were randomized to percutaneous computed tomography‐guided cordotomy or continued interdisciplinary palliative care. The primary outcome was 33% improvement in PI at 1 week after cordotomy or study enrollment as measured by the Edmonton Symptom Assessment Scale.Results.Sixteen patients were enrolled (nine female, median age 58 years). Six of seven patients (85.7%) randomized to cordotomy experienced >33% reduction in PI (median preprocedure PI = 7, range 6–10; 1 week after cordotomy median PI = 1, range 0–6; p = .022). Zero of nine patients randomized to palliative care achieved a 33% reduction in PI. Seven patients (77.8%) randomized to palliative care elected to undergo cordotomy after 1 week. All of these patients experienced >33% reduction in PI (median preprocedure PI = 8, range 4–10; 1 week after cordotomy median PI = 0, range 0–1; p = .022). No patients were withdrawn from the study because of adverse effects of the intervention.Conclusion.These data support the use of cordotomy for pain refractory to optimal palliative care. The findings of this study justify a large‐scale randomized controlled trial of percutaneous cordotomy.Implications for Practice.This prospective clinical trial was designed to determine the improvement in pain intensity in patients randomized to either undergo cordotomy or comprehensive palliative care for medically refractory cancer pain. This study shows that cordotomy is effective in reducing pain for medically refractory cancer pain, and these results can be used to design a large‐scale comparative randomized controlled trial that could provide the evidence needed to include cordotomy as a treatment modality in the guidelines for cancer pain management.
Ashwin Viswanathan, Aditya Vedantam, Kenneth R. Hess, Jewel Ochoa, Patrick M. Dougherty, Akhila S. Reddy, Dhanalakshmi Koyyalagunta, Suresh Reddy, Eduardo Bruera

Clinical Outcomes of Patients with Advanced Cancer and Pre‐Existing Autoimmune Diseases Treated with Anti‐Programmed Death‐1 Immunotherapy: A Real‐World Transverse Study

2 months ago
AbstractBackground.Patients with a history of autoimmune diseases (AIDs) have not usually been included in clinical trials with immune checkpoint inhibitors.Materials and Methods.Consecutive patients with advanced cancer, treated with anti‐programmed death‐1 (PD‐1) agents, were evaluated according to the presence of pre‐existing AIDs. The incidence of immune‐related adverse events (irAEs) and clinical outcomes were compared among subgroups.Results.A total of 751 patients were enrolled; median age was 69 years. Primary tumors were as follows: non‐small cell lung cancer, 492 (65.5%); melanoma, 159 (21.2%); kidney cancer, 94 (12.5%); and others, 6 (0.8%). Male/female ratio was 499/252. Eighty‐five patients (11.3%) had pre‐existing AIDs, further differentiated in clinically active (17.6%) and inactive (82.4%). Among patients with pre‐existing AIDs, incidence of irAEs of any grade was significantly higher when compared with patients without AIDs (65.9% vs. 39.9%). At multivariate analysis, both inactive (p = .0005) and active pre‐existing AIDs (p = .0162), female sex (p = .0004), and Eastern Cooperative Oncology Group Performance Status <2 (p = .0030) were significantly related to a higher incidence of irAEs of any grade. No significant differences were observed regarding grade 3/4 irAEs and objective response rate among subgroups. Pre‐existing AIDs were not significantly related with progression‐free survival and overall survival.Conclusion.This study quantifies the increased risk of developing irAEs in patients with pre‐existing AIDs who had to be treated with anti‐PD‐1 immunotherapy. Nevertheless, the incidence of grade 3/4 irAEs is not significantly higher when compared with control population. The finding of a greater incidence of irAEs among female patients ranks among the “hot topics” in gender‐related differences in immuno‐oncology.Implications for Practice.Patients with a history of autoimmune diseases (AIDs) have not usually been included in clinical trials with immune checkpoint inhibitors but are frequent in clinical practice. This study quantifies the increased risk of developing immune‐related adverse events (irAEs) in patients with pre‐existing AIDs who had to be treated with anti‐programmed death‐1 immunotherapy. Nevertheless, their toxicities are mild and the incidence of grade 3/4 irAEs is not significantly higher compared with those of controls. These results will help clinicians in everyday practice, improving their ability to offer a proper counselling to patients, in order to offer an immunotherapy treatment even to patients with pre‐existing autoimmune disease.
Alessio Cortellini, Sebastiano Buti, Daniele Santini, Fabiana Perrone, Raffaele Giusti, Marcello Tiseo, Melissa Bersanelli, Maria Michiara, Antonino Grassadonia, Davide Brocco, Nicola Tinari, Michele De Tursi, Federica Zoratto, Enzo Veltri, Riccardo…

Adding a Wider Range and “Hope for the Best, and Prepare for the Worst” Statement: Preferences of Patients with Cancer for Prognostic Communication

2 months ago
AbstractIntroduction.Although various phrases to communicate prognoses based on a certain concept have been proposed, no study has systematically investigated preferences of patients with cancer for actual phrases. We investigated whether phrases with a wider range and additional “hope for the best, and prepare for the worst” (hope/prepare) statement would be more preferable and explored variables associated with patients’ preferences.Materials and Methods.In a cross‐sectional survey, 412 outpatients with cancer self‐assessed their preferences for 13 phrases conveying prognostic information (e.g., phrases with or without median, typical range, and/or best/worst cases, and those with or without a hope/prepare statement) on a 6‐point scale (1 = not at all preferable; 6 = very preferable). We evaluated demographic data and the Coping Inventory for Stressful Situations and conducted multivariate regression analysis.Results.Regarding phrases with various ranges, the one including the median, typical range, and best/worst cases was more preferable (mean ± SD, 3.8 ± 1.3; 95% confidence interval [CI], 3.6–3.9) than the one with the median and typical range (3.4 ± 1.2; 3.3–3.6) or the one with only the median (3.2 ± 1.3; 3.1–3.3). Concerning the hope/prepare statement, the phrase including the median, typical range, uncertainty, and hope/prepare statement was more preferable (3.8 ± 1.4; 3.7–3.9) than the one without the statement (3.5 ± 1.2; 3.4–3.6). In multivariate analyses, task‐oriented coping was significantly correlated with preferences for phrases with explicit information.Conclusion.Overall, phrases with a wider range and the hope/prepare statement were preferable to those without them. When patients with cancer ask about prognoses, especially those with task‐oriented coping, clinicians may provide explicit information with a wider range and the hope/prepare statement.Implications for Practice.Discussing prognoses with patients with advanced cancer is among the most important conversations for clinicians. In this cross‐sectional survey to systematically investigate preferences of 412 patients with cancer for phrases conveying prognostic information, phrases with the median, typical range, and best/worst cases and those with the “hope for the best and prepare for the worst” (hope/prepare) statement were the most preferred. When patients with cancer ask about prognoses, clinicians may provide explicit information with a wider range and include the hope/prepare statement.
Masanori Mori, Maiko Fujimori, Hiroto Ishiki, Tomohiro Nishi, Jun Hamano, Hiroyuki Otani, Yu Uneno, Akira Oba, Tatsuya Morita, Yosuke Uchitomi

A Pairwise Meta‐Analysis of Induction Chemotherapy in Nasopharyngeal Carcinoma

2 months ago
AbstractBackground.Locoregionally advanced nasopharyngeal carcinoma has high risk of distant metastasis and mortality. Induction chemotherapy is commonly administrated in clinical practice, but the efficacy was quite controversial in and out of randomized controlled trials. We thus conducted this pairwise meta‐analysis.Materials and Methods.Trials that randomized patients to receive radiotherapy or concurrent chemoradiotherapy with or without induction chemotherapy were identified via searches of PubMed, MEDLINE, and ClinicalTrials.gov.Results.A total of ten trials (2,627 patients) were included. The pooled hazard ratios (HRs) based on fixed effect model were 0.68 (95% confidence interval [CI] 0.56–0.80, p < .001) for overall survival (OS) and 0.70 (95% CI 0.61–0.79, p < .001) for progression‐free survival (PFS), which strongly favored the addition of induction chemotherapy. The absolute 5‐year survival benefits were 8.47% in OS and 10.27% in PFS, respectively. In addition, based on the available data of eight trials, induction chemotherapy showed significant efficacy in reducing locoregional failure rate (risk ratio [RR] = 0.81, 95% CI 0.68–0.96, p = .017) and distant metastasis rate (RR = 0.69, 95% CI 0.58–0.82, p < .001).Conclusion.This pairwise meta‐analysis confirms the benefit in OS, PFS, and locoregional and distant controls associated with the addition of induction chemotherapy in nasopharyngeal carcinoma.Implications for Practice.According to the results of this meta‐analysis of ten trials, induction chemotherapy can prolong overall survival and progression‐free survival and improve locoregional and distant controls for nasopharyngeal carcinoma.
Pu-Yun OuYang, Xiao-Min Zhang, Xing-Sheng Qiu, Zhi-Qiao Liu, Lixia Lu, Yuan-Hong Gao, Fang-Yun Xie

Postsurgical Approaches in Low‐Grade Oligodendroglioma: Is Chemotherapy Alone Still an Option?

2 months 1 week ago
AbstractBackground.Patients with low‐grade gliomas (LGGs) with isocitrate dehydrogenase (IDH) mutation (mut) and 1p19q codeletion (codel) have a median overall survival of longer than 10 years. The aim of this study is to assess the role of postsurgical treatments.Subjects, Materials, and Methods.We evaluated patients with LGGs with IDH mut and 1p19q codel; IDH1/2 was performed by immunohistochemistry and quantitative polymerase chain reaction. In all wild‐type cases, we performed next‐generation sequencing. 1p19 codel analysis was performed by fluorescence in situ hybridization.Results.Among the 679 patients, 93 with LGGs with IDH mutation and 1p19q codel were included. Median follow‐up (FU) was 96.1 months. Eighty‐four patients (90.3%) were high risk according to Radiation Therapy Oncology Group criteria. After surgery, 50 patients (53.7%) received only FU, 17 (18.3%) chemotherapy (CT), and 26 (30.1%) radiotherapy (RT) with (RT + CT, 8 patients, 8.6%) or without (RT, 18 patients, 19.4%) chemotherapy. Median progression‐free survival (mPFS) was 46.3 months, 50.8 months, 103.6 months, and 120.2 months in patients with FU alone, with CT alone, with RT alone, or with RT + CT, respectively. Median PFS was significantly longer in patients who received postsurgical treatment (79.5 months, 95% confidence interval [CI]: 66.4–92.7) than patients who received FU (46.3 months, 95% CI: 36.0–56.5). Moreover, mPFS was longer in patients who received RT (alone or in combination with CT, n = 26, 113.8 months, 95% CI: 57.2–170.5) than those who did not (n = 67, 47.3 months, 95% CI: 36.4–58.2). In particular, temozolomide alone did not improve PFS with respect to FU.Conclusion.RT with or without chemotherapy, but not temozolomide alone, could extend PFS in IDH mut 1p19q codel LGGs.Implications for Practice.Low‐grade gliomas with high‐risk features, defined according to Radiation Therapy Oncology Group criteria, receive radiotherapy and/or chemotherapy as postsurgical treatments. Radiotherapy, however, has serious long‐term effects (cognitive impairment), which are to be taken into account in these young patients. Moreover, low‐grade gliomas with isocitrate dehydrogenase mutation and 1p19q codeletion (oligodendrogliomas) have an extremely long survival and a better prognosis. This study suggests that postsurgical treatments prolong the time before tumor progression in patients with good prognosis as well as those with oligodendroglioma. Moreover, temozolomide alone might not be effective in prolonging progression‐free survival.
Enrico Franceschi, Alicia Tosoni, Dario De Biase, Giuseppe Lamberti, Daniela Danieli, Stefano Pizzolitto, Elena Zunarelli, Michela Visani, Enrico Di Oto, Antonella Mura, Santino Minichillo, Chiara Scafati, Sofia Asioli, Alexandro Paccapelo, Stefania…

Recurrent Pneumonitis in Patients with Melanoma Treated with Immune Checkpoint Inhibitors

2 months 1 week ago
AbstractIntroduction.Immune checkpoint inhibitors (ICIs) have changed the oncologic landscape in the past few years. Alongside impressive antitumor responses, new novel immune‐related adverse events (irAEs) have emerged; pneumonitis is an irAE that can potentially be fatal and necessitates a proper management. No consensus exists regarding steroid treatment duration or drug rechallenge options. Our study describes the clinical and radiological course of melanoma patients diagnosed with immune‐related pneumonitis that has recurred because of rechallenge attempt or despite complete treatment discontinuation (unprovoked).Materials and Methods.The study population was composed of patients with metastatic melanoma who were treated with anti‐programmed cell death 1 (PD‐1) as monotherapy or in combination with anti‐cytotoxic T lymphocyte antigen‐4 and who were diagnosed with immune‐related pneumonitis. For recurrent cases after clinical and radiological resolution, we explored the differences from cases with no recurrence.Results.Nineteen out of 386 (4.8%) patients treated with ICI were diagnosed with pneumonitis. Median age was 66 years, and 53% were male. Compared with single‐agent nivolumab, patients treated with ipilimumab‐nivolumab combination presented with an earlier onset (27.5 vs. 10.3 weeks, respectively, p = .015) and had higher grades of severity. After complete resolution, rechallenge was attempted in seven patients; three of them had recurrent pneumonitis. Three other patients experienced recurrent pneumonitis despite complete discontinuation of the drug (unprovoked by rechallenge). The latter were characterized with an earlier onset of the first pneumonitis compared with those who did not experience recurrence (median, 12.4 vs. 26.4 weeks) and a shorter course of steroid treatment at first episode (median, 5.1 vs. 10 weeks). Recurrent cases were generally more severe than the first episode.Conclusion.Unprovoked recurrent pneumonitis is a new, poorly reported entity that requires further investigation. Our observations suggest that cases of pneumonitis that present early in the course of immunotherapy treatment may recur despite treatment discontinuation, thus necessitating closer monitoring and a longer course of steroid treatment.Implications for Practice.This article sheds light on a poorly described immune‐related adverse event: recurrent pneumonitis despite complete discontinuation of immunotherapy (unprovoked), in patients with advanced melanoma.
Nethanel Asher, Edith M. Marom, Guy Ben-Betzalel, Erez Nissim Baruch, Yael Steinberg-Silman, Jacob Schachter, Ronnie Shapira-Frommer, Gal Markel

Can Peripherally Inserted Central Catheters Be Safely Placed in Patients with Cancer Receiving Chemotherapy? A Retrospective Study of Almost 400,000 Catheter‐Days

2 months 1 week ago
AbstractBackground.Peripherally inserted central catheters (PICCs) are central venous catheters (CVCs) that are commonly used in onco‐hematologic settings for chemotherapy administration. As there is insufficient evidence to recommend a specific CVC for chemotherapy administration, we aimed to ascertain PICC‐related adverse events (AEs) and identify independent predictors of PICC removal in patients with cancer receiving chemotherapy.Materials and Methods.Information on adult patients with cancer with a PICC inserted for chemotherapy administration between September 2007 and December 2014 was extracted from six hospital databases. The primary outcome was PICC removal due to PICC‐related AEs (occlusion, infection, or symptomatic thrombosis). Independent predictors of PICC removal were identified using a multivariate Cox regression model.Results.Among the 2,477 included patients, 419 PICC‐related AEs (16.9%; 1.09 AEs per 1,000 PICC‐days) were reported. AEs increased when PICC was inserted at the brachial site (hazard ratio [HR], 1.37; 95% confidence interval [CI], 1.02–1.84) and with open systems (HR, 1.89; 95% CI, 1.24–2.88) and decreased in older men (HR, 0.63; 95% CI, 0.49–0.81).Conclusion.Use of PICC for chemotherapy administration was associated with a low all‐AEs rate. The basilic vein was the safer site, and valved systems had fewer AEs than open systems. More research is needed to explore the interaction between AEs, sex, and age.Implications for Practice.These findings provide clinicians with evidence that peripherally inserted central catheters (PICCs) are safe for chemotherapy administration. They also suggest that clinicians should limit the use of open systems when long chemotherapy regimens are scheduled. Moreover, alternatives to PICCs should be considered when administering chemotherapy to young men.
Sara Campagna, Silvia Gonella, Paola Berchialla, Giacomo Morano, Carla Rigo, Pietro Antonio Zerla, Raffaella Fuzzi, Gianvito Corona, Silvana Storto, Valerio Dimonte, Baudolino Mussa

Sidedness Matters: Surrogate Biomarkers Prognosticate Colorectal Cancer upon Anatomic Location

2 months 1 week ago
AbstractBackground.Anatomic location of primary tumors across the colon correlate with survival in the metastatic setting, whereas left‐sided tumors may exhibit superior survival compared with right‐sided tumors. The Oncotype Recurrence Score (RS) assay is a clinically validated predictor of recurrence risk in patients with stage II colorectal cancer (CRC). Previous studies had indicated that without adjuvant chemotherapy, CDX2‐negative stage II CRC tumors are associated with a lower rate of disease‐free survival than CDX2‐positive stage II CRC tumors. We aimed to evaluate whether these two validated prognostic biomarkers may correlate with primary tumor location, and whether tumor location may reflect differential prognosis in stage II CRC.Materials and Methods.We retrospectively analyzed patients with T3 mismatch repair‐proficient (MMR‐P) stage II CRC for whom RS assay was performed. Pathological report was reviewed for exact primary tumor location and CDX2 immunostaining. RS and CDX2 expression were correlated with primary tumor location.Results.The analysis included 1,147 patients with MMR‐P stage II CRC (median age 69 years [range 29–93]). Tumor distribution across the colon was as follows: 46% (n = 551) were right‐sided and 54% (n = 596) were left‐sided. RS was higher in right‐sided tumors (p = .01). The RS results gradually decreased across the colon (cecum, highest score; sigmoid, lowest score; p = .04). Right‐sided tumors exhibited more CDX2‐negative tumors (p = .07).Conclusion.Our study indicates that right‐sided colorectal tumors may display worse prognosis compared with left‐sided tumors in MMR‐P stage II CRC. Primary tumor location may serve as a prognostic factor that should be taken into account for recurrence risk assessment and consideration of adjuvant treatment.Implications for Practice.Sidedness matters, even in stage II colorectal cancer (CRC). Using two previously established prognostic tools, the Oncotype DX assay and CDX2 expression, this study found that right‐sided tumors may display worse prognosis compared with left‐sided tumors in mismatch repair‐proficient stage II CRC. Therefore, primary tumor location should be taken into account for recurrence risk assessment and consideration of adjuvant treatment.
Irit Ben-Aharon, Tal Goshen-Lago, Michal Sternschuss, Sara Morgenstern, Ravit Geva, Alexander Beny, Ygael Dror, Mariana Steiner, Ayala Hubert, Efraim Idelevich, Katerina Shulman, Moshe Mishaeli, Sophia Man, Nicky Liebermann, Lior Soussan-Gutman, Baruch…

A Case of Donor‐Transmitted Non‐Small Cell Lung Cancer After Liver Transplantation: An Unwelcome Guest

2 months 1 week ago
AbstractCancer transmission with organ donation has been previously reported with a variety of malignancies and organ transplants. The risk of transmission through organ transplantation from donors with a history of previously treated malignancies has been addressed by guidelines from transplant societies. Herein, we report a case of a patient who developed lung cancer confined to the liver after liver transplantation with no known history of malignancy in the donor. The suspicion of donor origin arose after positron emission tomography‐computerized tomography scan showed metastatic lung cancer only involving the transplanted liver without a primary focus. Genetic analysis of the malignant cells confirmed donor origin of the cancer.
Mohamad B. Sonbol, Kevin C. Halling, David D. Douglas, Helen J. Ross

High IDO1 Expression Is Associated with Poor Outcome in Patients with Anal Cancer Treated with Definitive Chemoradiotherapy

2 months 1 week ago
AbstractBackground.This study characterizes the tumor‐immune microenvironment in pretreatment, localized anal squamous cell carcinoma (ASCC), including two markers that have not previously been studied in ASCC: indoleamine 2,3 dioxygenase 1 (IDO1) and human leukocyte antigen (HLA) class I.Materials and Methods.Retrospective review identified 63 patients with ASCC receiving definitive chemoradiation between 2005 and 2016 with pretreatment tissue available. Immunohistochemistry was used to quantify cluster of differentiation 8 (CD8), programmed cell death protein 1, programmed death‐ligand 1, HLA class I, and IDO1. Cox proportional hazards models evaluated associations between outcomes and immune markers, controlling for clinical characteristics.Results.With a median follow‐up of 35 months, 3‐year overall survival was 78%. The only marker found to have a robust association with outcome was tumor IDO1. In general, the percentage of tumor cells expressing IDO1 was low (median 1%, interquartile range 0%–20%); however, patients with >50% of tumor cells expressing IDO1 had significantly worse overall survival (hazard ratio [HR] 4.7, p = .007) as well as higher local recurrence (HR 8.6, p = .0005) and distant metastasis (HR 12.7, p = .0002). Tumors with >50% IDO1 were also more likely to have the lowest quartile of CD8 infiltrate (<40 per high‐power field, p = .024).Conclusion.ASCC has a diverse immune milieu. Although patients generally do well with standard therapy, IDO1 may serve as a prognostic indicator of poor outcome and could help identify a patient population that might benefit from IDO‐targeted therapies.Implications for Practice.After definitive chemoradiation, patients with locally advanced anal cancer may experience significant treatment morbidity and high risk of recurrence. The goal of the current study is to identify novel prognostic factors in the tumor‐immune microenvironment that predict for poor outcomes after definitive chemoradiation. This study characterizes the tumor‐immune microenvironment in pre‐treatment, localized anal squamous cell carcinoma (ASCC), including two markers which have not previously been studied in ASCC: indoleamine 2,3 dioxygenase 1 (IDO1) and HLA class I. With a median follow‐up of 3 years, this study demonstrated that high IDO1 expression is correlated with significantly worse 3‐year overall survival (88% vs. 25%). Whereas recent studies of IDO1 inhibitors have shown mixed results, this study suggests that patients with anal cancer with high IDO1 expression have dismal prognosis and may represent a patient population primed for response to targeted IDO1 inhibition.
Devarati Mitra, Nora K. Horick, Diane G. Brackett, Kent W. Mouw, Jason L. Hornick, Soldano Ferrone, Theodore S. Hong, Harvey Mamon, Jeffrey W. Clark, Aparna R. Parikh, Jill N. Allen, David P. Ryan, David T. Ting, Vikram Deshpande, Jennifer Y. Wo

Feasibility Assessment of Using the Complete Patient‐Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO‐CTCAE) Item Library

2 months 2 weeks ago
AbstractThe patient‐reported outcomes version of the Common Terminology Criteria for Adverse Events (PRO‐CTCAE) complements capture of symptomatic adverse events (AEs) by clinicians. Previous trials have typically used a limited subset of relevant symptomatic AEs to reduce patient burden. We aimed to determine the feasibility of administering all 80 AEs included in the PRO‐CTCAE library by approaching consecutive patients enrolled in a large academic phase I program at three points in time. Here, we report a preplanned analysis after enrolling the first 20 patients. All items were answered on 51 of 56 potential visits (adherence 91%). Three (5%) additional PRO‐CTCAE assessments were partially completed, and two (4%) were missed because of conflicting appointments. No patient withdrew consent or chose not to complete the assessments once enrolled on study. Future trials of experimental drugs that incorporate the PRO‐CTCAE should consider using this unselected approach to identify adverse events more completely.
Daniel Shepshelovich, Kate McDonald, Anna Spreafico, Albiruni R.A. Razak, Philippe L. Bedard, Lillian L. Siu, Lori Minasian, Aaron R. Hansen

Efficacy of Split Schedule Versus Conventional Schedule Neoadjuvant Cisplatin‐Based Chemotherapy for Muscle‐Invasive Bladder Cancer

2 months 2 weeks ago
AbstractNeoadjuvant cisplatin‐based chemotherapy (NAC; 70 mg/m2) is standard of care for muscle‐invasive bladder carcinoma (MIBC). Many patients (pts) cannot receive cisplatin because of renal impairment, and administration of cisplatin 35 mg/m2 on day 1 + 8 or 1 + 2 (i.e., split schedule) is a commonly used alternative. In this retrospective analysis, we compared complete (pT0) and partial (
Chelsea K. Osterman, Dilip S. Babu, Daniel M. Geynisman, Bianca Lewis, Robert A. Somer, Arjun V. Balar, Matthew R. Zibelman, Elizabeth A. Guancial, Gianna Antinori, Shun Yu, Vivek Narayan, Thomas J. Guzzo, Elizabeth R. Plimack, David J. Vaughn, Chunkit…

Evaluating the Strength of the Association Between Industry Payments and Prescribing Practices in Oncology

2 months 2 weeks ago
AbstractBackground.Financial relationships between physicians and the pharmaceutical industry are common, but factors that may determine whether such relationships result in physician practice changes are unknown.Materials and Methods.We evaluated physician use of orally administered cancer drugs for four cancers: prostate (abiraterone, enzalutamide), renal cell (axitinib, everolimus, pazopanib, sorafenib, sunitinib), lung (afatinib, erlotinib), and chronic myeloid leukemia (CML; dasatinib, imatinib, nilotinib). Separate physician cohorts were defined for each cancer type by prescribing history. The primary exposure was the number of calendar years during 2013–2015 in which a physician received payments from the manufacturer of one of the studied drugs; the outcome was relative prescribing of that drug in 2015, compared with the other drugs for that cancer. We evaluated whether practice setting at a National Cancer Institute (NCI)‐designated Comprehensive Cancer Center, receipt of payments for purposes other than education or research (compensation payments), maximum annual dollar value received, and institutional conflict‐of‐interest policies were associated with the strength of the payment‐prescribing association. We used modified Poisson regression to control confounding by other physician characteristics.Results.Physicians who received payments for a drug in all 3 years had increased prescribing of that drug (compared with 0 years), for renal cell (relative risk [RR] 1.81, 95% confidence interval [CI] 1.58–2.07), CML (RR 1.22, 95% CI 1.08–1.39), and lung (RR 1.69, 95% CI 1.58–1.82), but not prostate (RR 0.97, 95% CI 0.93–1.02). Physicians who received compensation payments or >$100 annually had increased prescribing compared with those who did not, but NCI setting and institutional conflict‐of‐interest policies were not consistently associated with the direction of prescribing change.Conclusion.The association between industry payments and cancer drug prescribing was greatest among physicians who received payments consistently (within each calendar year). Receipt of payments for compensation purposes, such as for consulting or travel, and higher dollar value of payments were also associated with increased prescribing.Implications for Practice.Financial payments from pharmaceutical companies are common among oncologists. It is known from prior work that oncologists tend to prescribe more of the drugs made by companies that have given them money. By combining records of industry gifts with prescribing records, this study identifies the consistency of payments over time, the dollar value of payments, and payments for compensation as factors that may strengthen the association between receiving payments and increased prescribing of that company's drug.
Aaron P. Mitchell, Aaron N. Winn, Jennifer L. Lund, Stacie B. Dusetzina

Neoadjuvant Management of Early Breast Cancer: A Clinical and Investigational Position Statement

2 months 3 weeks ago
AbstractBackground.Neoadjuvant treatment is increasingly one of the preferred therapeutic options for early breast cancer and may have some unique outcomes, such as identifying predictive and prognostic factors of response or increasing the knowledge of individual tumor biology.Design.A panel of experts from different specialties reviewed published clinical studies on the neoadjuvant management of breast cancer. Recommendations were made that emphasized the clinical multidisciplinary management and the investigational leverage in early breast cancer.Results.Neoadjuvant therapy has equivalent efficacy to adjuvant therapy, and it has some additional benefits that include increasing breast conservation, assessing tumor response, establishing prognosis based on the pathological response, and providing a “second opportunity” for nonresponding patients. Achieving pathological complete remission because of neoadjuvant therapy has been correlated with long‐term clinical benefit, particularly in HER2‐positive and triple‐negative breast cancer. In addition, the neoadjuvant setting is a powerful model for the development of new drugs and the identification of prognostic markers. Finally, neoadjuvant therapy has proven to be cost‐effective by reducing nondrug costs, avoiding radical surgery, and reducing hospital stays when compared with other treatment approaches.Conclusion.Neoadjuvant therapy has clinical benefits in early breast cancer and provides in vivo information of individual breast cancer biology while allowing the investigation of new treatment approaches. Access to neoadjuvant therapy should be an option available to all patients with breast cancer through multidisciplinary tumor management.Implications for Practice.Neoadjuvant treatment should be strongly considered as a therapeutic option for localized breast cancer and is a powerful tool for understanding breast cancer biology and investigating new treatment approaches.
Ramon Colomer, Cristina Saura, Pedro Sanchez-Rovira, Tomas Pascual, Isabel T. Rubio, Octavio Burgues, Lourdes Marcos, Cesar A. Rodriguez, Miguel Martin, Ana Lluch

A Pilot Study of Vinorelbine Safety and Pharmacokinetics in Patients with Varying Degrees of Liver Dysfunction

2 months 3 weeks ago
AbstractBackground.Vinorelbine has demonstrated anticancer activity and is primarily metabolized in the liver. This single‐institution, phase I pilot study describes the safety and pharmacokinetics of vinorelbine in patients with varying degrees of hepatic impairment.Materials and Methods.Patients with treatment‐refractory solid tumors were enrolled into treatment arms based on vinorelbine dose (weekly infusions of 7.5–30 mg/m2) and liver function (normal liver function, mild, moderate, or severe liver dysfunction). Vinorelbine pharmacokinetics were evaluated to describe its relationship with liver function. Indocyanine green (ICG) clearance was assessed for correlation with pharmacokinetics.Results.Forty‐seven patients were enrolled, and a total of 108 grade 3–4 treatment‐related adverse events (AEs) occurred. Of these, grade 3–4 myelosuppression was the most common (34.3%). Thirty‐three (30.6%), 22 (20.4%), and 9 (8.3%) grade 3–4 AEs were observed in the vinorelbine 20 mg/m2/severe, 15 mg/m2/moderate, and 7.5 mg/m2/severe liver dysfunction groups, respectively, with the majority being nonhematologic toxicities. ICG clearance decreased as liver function worsened. Vinorelbine pharmacokinetics were not correlated with ICG elimination or the degree of liver dysfunction.Conclusion.For patients with severe liver dysfunction (bilirubin >3.0 mg/dL), vinorelbine doses ≥7.5 mg/m2 are poorly tolerated. The high incidence of grade 3–4 AEs with 15 mg/m2 vinorelbine in moderate liver dysfunction (bilirubin 1.5–3.0 mg/dL) raises concerns for its safety in this population. Vinorelbine pharmacokinetics are not affected by liver dysfunction; however, levels of the active metabolite 4‐O‐deacetylvinorelbine were not measured and may be higher in patients with liver dysfunction if its elimination is impacted by liver impairment to a greater degree than the parent drug.Implications for Practice.Vinorelbine remains widely prescribed in advanced malignancies and is under development in immunotherapy combinations. Given vinorelbine is primarily hepatically metabolized, understanding its safety and pharmacokinetics in liver dysfunction remains paramount. In this phase I pilot study, weekly vinorelbine at doses ≥7.5 mg/m2 is poorly tolerated in those with severe liver dysfunction. Furthermore, a high incidence of grade 3–4 toxicities was observed with vinorelbine at 15 mg/m2 in those with moderate liver dysfunction. Vinorelbine pharmacokinetics do not appear affected by degree of liver dysfunction. Further evaluation of levels of the free drug and active metabolites in relationship to liver function are warranted.
Jun Gong, May Cho, Rohan Gupta, Timothy W. Synold, Paul Frankel, Christopher Ruel, Marwan Fakih, Vincent Chung, Dean Lim, Joseph Chao

A Cost‐Effectiveness Analysis of Nivolumab and Ipilimumab Versus Sunitinib in First‐Line Intermediate‐ to Poor‐Risk Advanced Renal Cell Carcinoma

2 months 3 weeks ago
AbstractBackground.The treatment paradigm of advanced renal cell carcinoma (RCC) has changed rapidly in recent years. In first‐line treatment of intermediate‐ to poor‐risk patients, the CheckMate 214 study demonstrated a significant survival advantage for nivolumab and ipilimumab versus sunitinib. The high cost of combined immune‐modulating agents warrants an understanding of the combination's value by considering both efficacy and cost. The objective of this study was to estimate the cost‐effectiveness of nivolumab and ipilimumab compared with sunitinib for first‐line treatment of intermediate‐ to poor‐risk advanced RCC from the U.S. payer perspective.Materials and Methods.A Markov model was developed to compare the costs and effectiveness of nivolumab and ipilimumab with those of sunitinib in the first‐line treatment of intermediate‐ to poor‐risk advanced RCC. Health outcomes were measured in life‐years and quality‐adjusted life‐years (QALYs). Drug costs were based on Medicare reimbursement rates in 2017. We extrapolated survival beyond the trial closure using Weibull distribution. Model robustness was addressed in univariable and probabilistic sensitivity analyses.Results.The total mean cost per‐patient of nivolumab and ipilimumab versus sunitinib was $292,308 and $169,287, respectfully. Nivolumab and ipilimumab generated a gain of 0.978 QALYs over sunitinib. The incremental cost‐effectiveness ratio (ICER) for nivolumab and ipilimumab was $125,739/QALY versus sunitinib.Conclusion.Our analysis established that the base case ICER in the model for nivolumab and ipilimumab versus sunitinib is below what some would consider the upper limit of the theoretical willingness‐to‐pay threshold in the U.S. ($150,000/QALY) and is thus estimated to be cost‐effective.Implications for Practice.This article assessed the cost‐effectiveness of nivolumab and ipilimumab versus sunitinib for treatment of patients with intermediate‐ to poor‐risk metastatic kidney cancer, from the U.S. payer perspective. It would cost $125,739 to gain 1 quality‐adjusted life‐year with nivolumab and ipilimumab versus sunitinib in these patients.
Daniel Reinhorn, Michal Sarfaty, Moshe Leshno, Assaf Moore, Victoria Neiman, Eli Rosenbaum, Daniel A. Goldstein

Changes in the Use of Comprehensive Geriatric Assessment in Clinical Trials for Older Patients with Cancer over Time

2 months 3 weeks ago
AbstractBackground.The objective of this study was to describe the implementation of comprehensive geriatric assessment (CGA) in clinical trials dedicated to older patients before and after the creation of the International Society of Geriatric Oncology in the early 2000s.Subjects, Materials, and Methods.All phase I, II, and III trials dedicated to the treatment of cancer among older patients published between 2001 and 2004 and between 2011 and 2014 were reviewed. We considered that a CGA was performed when the authors indicated an intention to do so in the Methods section of the article. We collected each geriatric domain assessed using a validated tool even in the absence of a clear CGA, including nutritional, functional, cognitive, and psychological status, comorbidity, comedication, overmedication, social status and support, and geriatric syndromes.Results.A total of 260 clinical trials dedicated to older patients were identified over the two time periods: 27 phase I, 193 phase II, and 40 phase III trials. CGA was used in 9% and 8% of phase II and III trials, respectively; it was never used in phase I trials. Performance status was reported in 67%, 79%, and 75% of phase I, II, and III trials, respectively. Functional assessment was reported in 4%, 11%, and 13% of phase I, II, and III trials, respectively. Between the two time periods, use of CGA increased from 1% to 11% (p = .0051) and assessment of functional status increased from 3% to 14% (p = .0094).Conclusion.The use of CGA in trials dedicated to older patients increased significantly but remained insufficient.Implications for Practice.This article identifies the areas in which research efforts should be focused in order to offer physicians well‐addressed clinical trials with results that can be extrapolated to daily practice.
Olivia Le Saux, Claire Falandry, Hui K. Gan, Benoit You, Gilles Freyer, Julien Peron

M1b Disease in the 8th Edition of TNM Staging of Lung Cancer: Pattern of Single Extrathoracic Metastasis and Clinical Outcome

2 months 3 weeks ago
AbstractBackground.The 8th edition of TNM staging of non‐small cell lung cancer (NSCLC) has revised M classification and defined M1b disease with single extrathoracic metastasis, which is distinguished from M1c with multiple extrathoracic metastases. We investigated the prevalence, characteristics, and overall survival (OS) of M1b disease in patients with stage IV NSCLC.Methods.The study reviewed the medical records and imaging studies of 567 patients with stage IV NSCLC to determine M stage using the 8th edition of TNM staging. Clinical characteristics and OS were compared according to M stages.Results.Among 567 patients, 57 patients (10%) had M1b disease, whereas 119 patients (21%) had M1a disease and 391 patients (69%) had M1c disease. Squamous histology was more common in M1b (16%) than in M1a (6%) and M1c (6%; p = .03). The median OS of patients with M1b disease was 14.8 months, compared with 22.6 months for patients with M1a and 13.4 months for those with M1c disease (p < .0001). Significant OS differences of M1b compared with single‐organ M1c and multiorgan M1c groups were noted (single‐organ M1c vs. M1b: hazard ratio [HR], 1.49; p = .02; multiorgan M1c vs. M1b: HR, 1.57; p = .01) in multivariable analyses adjusting for smoking and systemic therapy types. Among patients with M1b disease, the brain was the most common site of single metastasis (28/57; 49%), followed by bone (16/57; 28%). Single brain metastasis was more frequently treated with local treatment (p < .0001).Conclusion.M1b disease was noted in 10% of patients with stage IV NSCLC. Squamous histology was more common in M1b group than others. The brain was the most common site of single metastasis and was often treated locally.Implications for Practice.The newly defined group of M stage consists of a unique subset among patients with stage IV non‐small cell lung cancer that can be studied further to optimize treatment approaches.
Hyesun Park, Suzanne E. Dahlberg, Christine A. Lydon, Tetsuro Araki, Hiroto Hatabu, Michael S. Rabin, Bruce E. Johnson, Mizuki Nishino
1 hour 51 minutes ago
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