tbuckley/cabot-search huggingface dataset:
Mature results of the LCCC1413 phase II trial of de-intensified chemoradiotherapy for HPV-associated oropharyngeal squamous cell carcinoma.
Authors: Bhishamjit S. Chera, Robert Amdur, Colette J. Shen, Gaorav P. Gupta, Xianming Tan, Mary Knowles, David N. Hayes, Jared Weiss, Juneko E. Grilley-Olson, Shetal Arvind Patel, Adam M. Zanation, Trevor Hackman, Jose Zevallos, Jeffrey Blumberg, Samip Patel, Mohit Kasibhatla, Nathan Christopher Sheets, Mark Christian Weissler, Wendell Gray Yarbrough, William M. Mendenhall
Journal: Journal of Clinical Oncology (2019)

6022 Background: To report the mature results from a prospective phase II clinical trial of highly de-intensified chemoradiotherapy (CRT) for patients with HPV-associated oropharyngeal squamous cell carcinoma (OPSCC). Methods: The major inclusion criteria were: 1) T0-T3, N0-N2, M0, 2) p16 positive, and 3) minimal/remote smoking history. Treatment was limited to 60 Gy intensity modulated radiotherapy with concurrent weekly intravenous cisplatin 30 mg/m 2 (second choice was cetuximab). Patients with T0-T2 N0-1 disease did not receive chemotherapy. All patients had a 10 to 12-week post-treatment PET/CT to determine need for planned neck dissection. The primary study endpoint was 2 year progression free survival (PFS). Secondary endpoint measures include 2 year local control (LC), regional control (RC), distant metastasis free survival (DMFS), cause specific survival (CSS) and overall survival (OS), and patient reported symptoms (PRO-CTCAE) and quality of life (EORTC QLQ-C30 &amp; H&amp;N35). Results: 114 patients were enrolled (median f/u of 28.8 months, range 2.6 to 51.4) with 84 having a minimum follow-up of 2 years. Smoking status was as follows: 47% never, 33% ≤ 10 pack years, and 19% &gt; 10 pack years. Post-treatment PET/CT complete response rate was 93% at the primary site and 80% in the neck. Eleven patients had planned neck dissection with 4 having pathological residual disease. Two year LC, RC, DMFS, PFS, CSS, and OS were the following: 96%, 99%, 91%, 88%, 97%, and 95%. Neither smoking status nor receipt of cetuximab correlated with recurrence. Four patients with recurrent disease had PIK3CA mutations. Thirty four percent of patients required a feeding tube (none permanent) for a median of 10.5 weeks. Mean pre- and 2-year post-treatment EORTC QOL scores were: Global 79/83 (lower worse), Swallowing 8/9 (higher worse), Dry Mouth 14/45 (higher worse), and Sticky Saliva 9/28 (higher worse). Mean pre- and 2 year post-treatment PRO-CTCAE (0 to 4 scale, higher worse) scores were: Swallowing 0.5/0.7 and Dry mouth 0.4/1.4. There were no ≥ Grade 3 late adverse events. Conclusions: Clinical outcomes with a highly de-intensified CRT regimen of 60 Gy IMRT with concurrent low-dose cisplatin are excellent in patients with HPV-associated OPSCC. Clinical trial information: NCT02281955.
Real-world efficacy of anti-PD-1 antibodies in advanced acral melanoma patients: A retrospective, multicenter study (JAMP study).
Authors: Yasuhiro Nakamura, Kenjiro Namikawa, Koji Yoshino, Shusuke Yoshikawa, Hiroshi Uchi, Katsunobu Goto, Yoshiyuki Nakamura, Satoshi Fukushima, Yukiko Kiniwa, Tatsuya Takenouchi, Hisashi Uhara, Toru Kawai, Naohito Hatta, Takeru Funakoshi, Yukiko Teramoto, Atsushi Otsuka, Haruki Doi, Dai Ogata, Shigeto Matsushita, Naoya Yamazaki
Journal: Journal of Clinical Oncology (2019)

9529 Background: Anti-PD-1 antibodies are used worldwide for patients (pts) with advanced melanoma. Clinical trials have demonstrated its efficacy and safety for nonacral cutaneous melanoma (NACM) in controlled settings. Since acral melanoma (AM) is epidemiologically and molecularly distinct from NACM, data on the real-world efficacy of anti-PD1 antibodies in advanced AM is still lacking. Thus, we aim to analyze the real-world efficacy and safety of anti-PD-1 antibodies in advanced AM. Methods: We retrospectively reviewed clinical records of advanced AM treated in any line with an anti-PD1 antibody at 21 Japanese institutions. Clinical response was assessed by (Response Evaluation Criteria in Solid Tumors) RECIST criteria. Survival was estimated using Kaplan-Meier analysis. Toxicity was assessed according to CTCAE 4.0. Results: A total of 193 pts (median age, 71 years) with advanced AM (subungual, 70; palm and sole, 123) were included in the study. Anti-PD-1 antibody was used as first-line therapy in 143 pts (74.1%). Nivolumab was used in 168 pts and pembrolizumab in 25 pts. Base-line lactate dehydrogenase (LDH) was within normal level in 102 pts (52.8%). The objective response rate (ORR) of all pts was 16.5% (complete response 3.1%, partial response 13.5%), and median overall survival (OS) was 18.1 months. Normal LDH level was significantly associated with better prognosis than abnormal level (median OS 24.9 vs 10.7 months; P &lt; 0.001). Although baseline demographics and characteristics were almost similar between subungual group and palm and sole group, ORR was significantly lower in the subungual group than in palm and sole group (6/70 pts [8.6%] vs 26/123 pts [21.1%]; P = 0.026); median OS was significantly poorer as well (12.8 vs 22.3 months; P = 0.031). Immune-related adverse events of grades 3 to 5 occurred in 27 pts (14.0%). One patient (0.5%) died of grade 5 myasthenia gravis. Conclusions: Real-world efficacy of anti-PD-1 antibodies in AM pts is limited. Notably, pts with subungual melanoma showed poorer response and survival, making them strong candidates for further research of efficacy of anti-CTLA-4 and anti-PD-1 combination therapy.
Phase II study of S-1 in patients (pts) with previously treated Invasive thymoma (IT) and thymic carcinoma (TC): North Japan Lung Cancer Study Group Trial 1203.
Authors: Kyoji Tsurumi, Shunichi Sugawara, Shoichi Kuyama, Taku Nakagawa, Daijiro Harada, Yoko Tsukita, Hisashi Tanaka, Kana Watanabe, Yoshiaki Mori, Toshiyuki Harada, Toshihiko Hino, Masanori Fujii, Akira Inoue
Journal: Journal of Clinical Oncology (2019)

8564 Background: Invasive thymoma and thymic carcinoma are rare epithelial neoplasms arise in the anterior mediastinum. Platinum-based chemotherapies are widely used for the first-line treatment for unresectable IT and TC. Although no standard treatment has been established for previously treated IT and TC, S-1 has demonstrated promising efficacy in some retrospective studies. Thus we conducted the first prospective multicenter phase II trial to evaluate the efficacy of S-1 for previously treated pts with advanced IT and TC. Methods: Eligible pts were aged 20 years or older with: advanced IT or TC not feasible to potentially curative treatments; disease progression after at least one regimen of platinum-based chemotherapy; Eastern Cooperative Oncology Group performance status 0-2; adequate organ function; written informed consent. Pts received S-1 orally, at a dose based on body surface area for 2 weeks in 3 weeks cycle until tumor progression or unacceptable toxicities. The primary endpoint was overall response rate (ORR) and secondary endpoints were progression-free survival (PFS), overall survival (OS), and toxicity profile. Assuming that ORR of 25% in eligible pts would indicate potential usefulness while ORR of 10% would be the lower limit of interest, with alpha = 0.05 and beta = 0.2 according to a Simon’s two-stage design, the estimated accrual was 40 pts. Results: Between June 2012 and August 2018, 40 pts were enrolled and all pts were eligible (IT, n = 20; TC, n = 20). Median age was 64.5 years (range, 40-82), 75% (30/40) were male. Median treatment cycle was 5.5 (range, 1-82). ORR was 17.5% (95% CI: 7.3-32.8; IT, 10%, TC, 25%), and disease control rate was 85% (IT, 95%, TC, 75%). With a median follow-up of 51.9 months, median PFS was 7.0 months (IT, 11.3 months; TC, 5.4 months), and median OS was 40.3 months (IT, 58.5 months; TC, 22.7 months). The major grade 3-4 toxicities were anorexia (10%) and pneumonitis (5%). No treatment-related death was observed. Conclusions: Although the primary endpoint was unmet, S-1 monotherapy showed the moderate effects and could be available option especially for previously treated advanced TC. Clinical trial information: 000008174.
Knowledge and attitudes of permanent chemotherapy-induced alopecia among health care providers.
Authors: Jenna Rose Stoehr, Cory Kosche, Jennifer N. Choi
Journal: Journal of Clinical Oncology (2019)

142 Background: Reports of permanent chemotherapy-induced alopecia (PCIA) are increasing in the field of oncodermatology, but there is a dearth of information regarding how it is recognized and managed by health care providers (HCPs) across different medical specialties. Methods: An electronic survey was distributed to HCPs (resident physicians, attending physicians, and nurse practitioners) in the departments of dermatology, oncology, and general internal medicine (GIM) within one Midwestern hospital system. Results: Of the 62 participants (response rate: 13%), there were 19 from dermatology, 20 from oncology, and 23 from GIM. Responses were analyzed with descriptive statistics, and chi-square and ANOVA tests. There was a significant difference in the number of subjects that had heard of PCIA prior to starting the survey (Derm: 79%, Onc: 30%, GIM: 22%, p&lt;0.05). A larger percentage of dermatology and oncology HCPs knew the correct definition of the condition (alopecia persisting &gt;6 months) than GIM (42% and 45% vs. 17%) and significantly more had encountered patients with the condition (47% and 45% vs. 17%). More providers in dermatology and GIM knew how to diagnose PCIA compared to oncology (84% and 83% vs. 70%). Dermatology HCPs were the only participants who had attempted to treat patients with PCIA. Most providers across the three specialties believed that patients would accept PCIA treatment that was topical, oral, injectable, and required frequent administration or monitoring, but not treatment that was expensive or high risk. A majority of HCPs surveyed (94%) agreed that the diagnosis of PCIA is important. However, there was a significant difference in the confidence of HCPs in diagnosing and managing PCIA. A minority of dermatology providers (2/19) specified that they would refer to an alopecia or oncodermatology specialist, while the majority of oncology and GIM providers would refer to dermatology. Conclusions: The results of this survey identify knowledge gaps about PCIA amongst health care providers. Therefore, education and multidisciplinary engagement should be pursued in order to improve awareness, diagnosis, referral, and management of PCIA as part of survivorship care.
Health related quality of life analysis among testicular germ cell tumor survivors treated in a tertiary cancer hospital in India.
Authors: Abhishek Raj, Lalit Kumar, Atul Sharma, Raja Pramanik, Atul Batra, Amlesh Seth, Mukurdipi Ray, KP Haresh, Seema Kaushal, Ranjit Sahoo
Journal: Journal of Clinical Oncology (2019)

e16057 Background: Testicular Germ Cell Tumor (TGCT) is a highly curable malignancy treated with surgery, radiotherapy and chemotherapy. The available literature has conflicting results on quality of life (QoL) of survivors determined using various tools. There is no Indian data on QoL among TGCT patients. Methods: The study was a prospective case-control study. EORTC QLQ-C30 questionnaire were administered to survivors (last treatment completed at least 2 years back) and healthy age matched controls attending the uro-malignancy clinic of AIIMS between 1 st January 2017 to 31 st December 2018. The functional, symptom and global QoL scales were scored as per EORTC manual and were compared with each other using student t-test and Mann-Whitney test. The data was analysed with stata v.13.0. Results: The mean scores of all domains of functional scales and global QoL of 114 TGCT survivors were significantly worse than 100 controls except role functioning and cognitive functioning (Table). The symptom scores of cases were significantly worse for each domain except insomnia and constipation (Table). There was no difference in QoL parameters between Seminoma or Non-Seminoma or different stages of GCT. Conclusions: The QoL among TGCT survivors was significantly inferior indicating the long term physical, emotional, social, sexual and financial effects of disease and its treatment on survivors. More robust tools and studies are needed to better define QoL among survivors. ± SD of Functional, symptom and Global QoL Scales) [Table: see text]
A phase II study of capecitabine (Cape) or 5-fluorouracil (5-FU) with pegylated interferon alpha-2b (Peg-IFNA-2b) in unresectable/metastatic cutaneous squamous cell carcinoma (CSCC).
Authors: Jameel Muzaffar, Nikhil I. Khushalani, Jeffery Scott Russell, Janaki Parameswaran, Kedar Kirtane, Janis De La Iglesia, Robbert Slebos, Christine H. Chung
Journal: Journal of Clinical Oncology (2019)

e21020 Background: Patients (pts) with unresectable/metastatic CSCC have a poor prognosis, and until recently had limited treatment options. Based on encouraging efficacy in case report series, we conducted a phase 2 trial to evaluate the efficacy of CAP or 5-FU in combination with Peg-IFNA-2b in advanced CSCC. Methods: Eligible pts with measurable unresectable/metastatic CSCC were treated with CAP (1000mg/m2 PO twice daily days 1-14) or 5-FU (800 mg/m2 IV days 1-4), and Peg-IFNA-2b (subcutaneously at 3ug/kg weekly) in a 21-day cycle for up to 9 cycles, intolerable toxicity or progression. The primary objective was to assess overall response rate (ORR) while secondary objectives were safety and survival. Exploratory correlative tissue immune markers were studied using multiplex immunohistochemistry (mIHC) on pre- and post-treatment optional tumor biopsies. Results: Poor accrual led to early study closure after enrolling 8 pts. All pts were male, median age was 73.5 yrs. The ORR was 25% (1 CR, 1 PR); 4 pts had SD, 1 with PD and 1 withdrew consent prior to first restaging. The pt with CR had previously progressed on anti-PD1 therapy; tissue mIHC from this pt showed an increase in CD8+ cells prior to starting trial therapy. Due to the low sample size the 6 and 12-month survival estimates for OS and PFS are the same, 87.5% and 50% for 6 and 12 months respectively. Grade ≥ 3 or higher toxicities included decreased WBC (n = 3), fatigue, failure to thrive, anemia (all n = 2), and neutropenia, dehydration, hand-foot syndrome (all n = 1). Dose reductions were frequently encountered. Conclusions: Combination CAP/5-FU plus Peg-IFNA-2b has activity in advanced CSCC but with considerable toxicity at studied doses. The small sample size precludes meaningful conclusions on efficacy, though the CR observed post-PD1 progression might warrant further investigation of this combination as a therapeutic strategy given the recent approval of cemiplimab in CSCC. Clinical trial information: NCT02218164.
Chronobiological features of melatonin receptors (MT1) expression in breast cancer cells.
Authors: Alexandre Tavartkiladze, Ani Gvajaia, Pati Revazishvili
Journal: Journal of Clinical Oncology (2019)

e12581 Background: According to WHO data, Breast Cancer is the most prevalent malignancy in women. The biological role of Melatonin in the etiology and pathogenesis of the tumour disease has already been approved by a number of research studies. The purpose of our investigation was the assessment of features of Melatonin receptor circadian expression in circulating tumour cells of breast cancer (CTCs). Methods: We observed 34 patients (aged 36-68) with breast cancer (various immunophenotypes). CTCs were separated from patients’ venous blood every third day, in 02:00-04:00 pm and in 02:00-04:00 am intervals. The cells were taken from each patient 4 times. On CTCs, MT1 – receptor expression was assessed using immunocytochemical method. Results: Results of the study revealed that Melatonin receptor expression in breast cancer patients is characterised by the noticable circadian rhythmics. MT1–receptor expression peak by CTCs was detected at 02:00-04:00 am i.e. at night. The less aggressive tumor the higher is the extent of the receptor expression (density). Respectively, in hormone dependent and Her2/neu (negative) tumors the highest expression of the MT1–receptor occurs in hormone dependent and Her2/neu(positive) tumors–medium expression and in triple negative breast Cancer (TNBC) cells–the lowest expression, while in some TNBC–circulating tumor cells MT1 receptor expression has not been detected at all. Conclusions: Hence, based on our the results, we can conclude that Melatonin as the expression of main biochemical marker receptors of bio-rhythms in breast cancer cells, has highly expressed chronobiological nature and directly correlates with histological types of tumor, that provides conditions for the development of new chronotherapeutic strategies in breast cancer treatment.
Gene expression profiles of peripheral blood mononuclear cells from patients with advanced non-small cell lung cancer treated with anti-PD-1 monoclonal antibodies.
Authors: Jie Wu, Yee Him Cheung, Weihua Huang, Changhong Yin, John T Fallon, Nevenka Dimitrova, Michael Paul Fanucchi
Journal: Journal of Clinical Oncology (2019)

e14107 Background: Anti-PD-1 monoclonal antibodies have improved the outcome for patients with advanced non-small cell lung cancer (NSCLC). The goal of this study is to characterize the longitudinal gene expression profiles of peripheral blood mononuclear cells (PBMCs) in patients with advanced NSCLC treated with anti-PD-1 monoclonal antibodies and to evaluate the potential of this technology to predict response to therapy. Methods: PBMCs were collected using density centrifugation from patients with stage III/IV NSCLC before the first (T0) and second (T1) treatments, and, for responding patients, before the third (T2), fourth (T3), fifth (T4) and sixth (T5) treatments. Total RNA was extracted, and libraries were prepared using TruSeq Stranded mRNA LT Sample Prep Kit and sequenced by Illumina NextSeq. The paired-end reads were mapped to human reference hg38 using STAR and gene expressions were calculated using RSEM. Longitudinal differential gene expression with pathway analysis and principal component analysis (PCA) was performed across all time points. Genes with Bonferroni-adjusted p values &lt; 0.05 were selected for pathway enrichment analysis with DAVID. Results: Nine of 15 patients have been enrolled. Six patients had a PR by RECIST 1.1, 2 patients have had stable/PD, 1 patient too early. Differential gene expression (DE) is available for the 8 patients with response assessment. There was differential expression of certain genes between T0 and T1 in the following pathways in responders but not in stable/PD: T cell receptor complex (p = 3.1E-6), regulation of immune response (p = 2.5E-5), T cell costimulation (p = 3.9E-3) were upregulated. CD24 is downregulated, while C4B is upregulated. Using PCA analysis we detected strong signal from the beta-hemoglobin HBB transcript. We observed HBG1 and HBM consistently upregulated at T1 (adjusted p = 7.9E-19 and p = 2.3E-10 respectively) through to T4 (adjusted p = 8.8E-27 and p = 3.8E-18 respectively). Conclusions: Anti-PD-1 monoclonal antibodies induce DE of genes in PBMCs from patients with advanced NSCLC. This technology may provide a predictive test for response to anti-PD-1 monoclonal antibodies.
Overall survival trends for cervical cancer in the modern era: A U.S.A. population based analysis.
Authors: Andrew Jonathan Huang, Karen Elisabeth Huang
Journal: Journal of Clinical Oncology (2019)

e17024 Background: In the past two decades, several advancements have been made in the treatment of cervical cancer such as concurrent chemotherapy, robotic surgery, intensity modulated radiotherapy, 3D brachytherapy planning, and MRI visualization, yet most published survival data is based on historical treatment paradigms. We sought to report domestic treatment outcomes in the modern era to determine if current treatment paradigms resulted in higher overall survival rates. Methods: We queried the Surveillance, Epidemiology, and End Results (SEER) database for patients with cancers of the cervix uteri diagnosed between 2004-2010, had 5-year survival data recorded, and a specific AJCC 6 th edition stage assigned. We excluded patients diagnosed after 2010 as the dataset only included survival information until the end of 2015. We used the FIGO 2006 report on cervical cancer as our historical comparator. Chi-square tests were used to determine statistical significance. Results: 32,028 patients in the database met the criteria specified above. The 5-year survivals by stage are compared in the table below. Survival was statistically inferior in SEER patients with stage IIa disease but superior in SEER patients with stage IIIb, IVa, and IVb disease. When comparing SEER patients diagnosed in the earlier (2004-2007) versus the later half of the study period (2008-2010), there were no clinically relevant differences in 5-year survival except in stage IVA patients (19.8% vs 26.6%, p &lt; 0.0001). Conclusions: The 5-year overall survival rates in women with cervical cancer here in the USA in the modern era were similar to those published in the 2006 FIGO report. Inferior outcomes were seen in stage IIa patients but superior outcomes were seen in stage IIIb+ patients. [Table: see text]
Cabazitaxel with abiraterone versus abiraterone alone randomized trial for extensive disease following docetaxel: the CHAARTED 2 Trial: A trial of the ECOG-ACRIN Cancer Research Group (EA8153).
Authors: Christos Kyriakopoulos, Yu-Hui Chen, Fenghai Duan, Robert Jeraj, Jun Luo, Emmanuel S. Antonarakis, Glenn Liu, Michael Anthony Carducci
Journal: Journal of Clinical Oncology (2019)

TPS5094 Background: The E3805 CHAARTED trial showed a significant survival benefit from early treatment with docetaxel in patients (pts) with high-volume metastatic hormone-sensitive prostate cancer (HSPC). However, eventually all these patient will develop castration-resistant disease (CRPC) and it is currently unknown what is the optimal treatment in that setting. We hypothesize that treatment with a second round of chemohormonal therapy –this time in the CRPC setting- will improve outcomes. Methods: This is a prospective randomized phase II open label trial led by ECOG-ACRIN. Pts (N = 210) with metastatic CRPC who have previously received docetaxel for HSPC will be randomized to 2 treatment arms (1:1): abiraterone/prednisone plus cabazitaxel for up to 6 cycles versus abiraterone/prednisone alone. Stratification factors include ECOG performance status, time from initiation of ADT to development of CRPC and visceral versus bone only metastases. The primary objective is to evaluate the efficacy of abiraterone/prednisone plus cabazitaxel versus abiraterone/prednisone alone. The primary endpoint of the trial is progression-free survival (PFS), defined clinically or radiographically. Secondary endpoints include PSA response, radiographic response, time to PSA progression, overall survival and safety. Exploratory objectives include response assessment based on AR-V7 status as well as by NaF PET/CT imaging. Key inclusion criteria include: metastatic CRPC, prior treatment with at least 3 cycles of docetaxel for metastatic HSPC, no prior treatment for CRPC (radium-223 or sipuleucel-T excluded), ECOG performance status of 0-2 and peripheral neuropathy of less than 2. The study was activated on 02/08/2018. As of 01/21/2019, 28/210 pts have been enrolled. Support: CA180820, CA180794, CA180799, CA180802; and Genzyme Corporation, a subsidiary of Sanofi S.A. Clinical trial information: NCT03419234.