bluuebunny/crossref_metadata_2025 huggingface dataset:
The role of PET for predicting nodal response in locally advanced (LA) head and neck squamous cell carcinoma (HNSCC) treated with chemoradiotherapy (CRT): Results of a prospective multicenter trial.
Authors: Schmitz Sandra , Van Maanen Aline , Rousseaux Laura , Andry Guy , Temam Stéphane , Dequanter Didier , Vergez Sebastien , Lallemant Benjamin , De Raucourt Dominique , Jegoux Franck , Hanin Francois-Xavier , Gregoire Vincent , Hamoir Marc
Published: September 2018

6013

Background: Controversy about neck management after CRT in patients with LA HNSCC persists due to low accuracy of CT/MR to asses the neck. As already demonstrated (Mehanna, NEJM 374, 2016), PET is an alternative to planned neck dissection (ND) thanks to its high negative predictive value (NPV). However, no conclusion could be drawn for patients (pts) with equivocal response (e.g. suspicion of residual disease on CT/MR but negative PET) because pathologic confirmation was lacking. Methods: Multicenter, prospective, nonrandomized trial including pts with LA HNSCC of oral cavity, oro- hypopharynx, larynx, staged N1, N2, N3, treated with CRT and evaluated 12 weeks after CRT by overall assessment (OA): clinical examination (CE), PET and CT/MR. ND was performed in incomplete regional response based on at least 1 positive evaluation method. Pathologic analyses (HE and KI67) were performed on ND samples. Primary objective was to determine the NPV and accuracy of PET as a single examination in the post CRT nodal assessment. Primary outcome was 2-year regional recurrence free survival rate (RRFSR). Results: 264/318 pts included completed full treatment and had post CRT OA. Median follow up was 40 months. No ND was proposed in 119 patients because of a negative OA; 145 patients had ND. The presence of viable cells was reported in 27 ND (18.6%). Sensitivity, specificity, PPV, NPV, accuracy of OA were 90.0%, 49.6%, 18.6%, 97.5%, 54.2% vs 69.7%, 75.3.%, 28.8%, 94.6%, 74.6% for PET alone. Kappa coefficient was of 0.838, indicating an almost perfect agreement. In pts with negative OA, RRFSR was 61.3% vs. 56.6% in pts with positive OA and ND (p=0.45). Using post CRT assessment with PET alone, RRFSR in pts with negative PET was 63.0% vs. 48.8% in pts with positive PET (p=0.04). Using PET assessment alone, 65/145 ND (44.8%) could have been avoided without compromising RRFSR. Conclusions: NPV using PET alone is 94.6%. Post CRT evaluation using only PET would have resulted in considerably fewer ND without jeopardizing neck control. PET alone is more accurate and more discriminant for predicting pts outcome. Clinical trial information: NCT00634777.
Dose escalation of radiotherapy (RT) for locally advanced head and neck carcinomas treated with concomitant chemotherapy (CT) and RT: Results of the GORTEC 2004-01 randomized trial.
Authors: Bourhis Jean , Auperin Anne , Alfonsi Marc , Sun xu Shan , Rives Michel , Pointreau Yoann , Lafond Cedrik , Boisselier Pierre , Graff Pierre , Thariat Juliette , Tao Yungan
Published: September 2018

6015

Background: Concomitant CT-RT is a well established standard of care (SoC) in locally advanced (LA) squamous cell carcinomas of the head and neck (SCCHN). While there is a well established dose effect relationship for RT alone in these cancers, it is not known whether this also applies to concomitant CT-RT. Methods: Patients were randomized between 75 Gy/7 weeks (Arm A) versus 70 Gy/35F in 7 weeks (Arm B). A sequential boost of 10 times 2.5 Gy after 50Gy/25F was given to the initial gross tumor volume (GTV) in Arm A. IMRT was used for arm A and 3D conformal RT for arm B. In both arms, patients (pts) received during RT 3 cycles of cisplatin at 100 mg/m2. Inclusion criteria were pts fit for receiving high dose cisplatin, non metastatic, non operated stage III-IV SCC of oral cavity, oro/hypopharynx. A 1:1 randomization was done by minimization on centers, N & T stages & GTV uni/bilateral. To detect a hazard ratio (HR) of 0.56 in locoregional (LR) control, inclusion of 310 pts was required to observe 109 LR progressions and achieve 85% power at 2-sided significance level of 0.05. Results: Between 2005 and 2015, 188 pts were randomized: 82% males, median age 58 years, 85% oropharynx. The accrual rate was slower than expected, due to the fact that IMRT became a SoC and was only allowed in arm A. As a consequence the trial was discontinued after inclusion of 188 patients. The majority of pts had stage IVa (73% vs 72%). All initial characteristics were well balanced between arms. The median follow-up was 4.7 years, not different between arms. Acute and late xerostomia were markedly improved in arm A (IMRT arm). The 1-year grade 0-1 salivary toxicity (RTOG) was 81% and 34% (p< 0.0001) in arm A and B respectively. At 3 years these rates were 92% vs 53% (p=0.0003). The increase of the dose to the GTV with IMRT did not transfer in a higher LR control probability with an adjusted HR of 0.88 [95%CI 0.51-1.52] (p=0.63). PFS, overall survival were not significantly different between the 2 arms. Conclusions: The dose escalation of RT to the GTV did not improve LR control in patients treated with concomitant CT-RT. This trial adds some new evidence level 1 in favor of IMRT in LA SCCHN. Clinical trial information: NCT00158678.
The impact of radiotherapy, in addition to chemotherapy, on overall survival in the initial management of patients with newly diagnosed metastatic head and neck squamous cell carcinoma.
Authors: Baliga Sujith , Kabarriti Rafi , Ohri Nitin , Guha Chandan , Kalnicki Shalom , Garg Madhur
Published: September 2018

6035

Background: The role of radiation therapy (RT) in the upfront management of patients with metastatic head and neck squamous cell carcinoma (HNSCC) is not clearly defined. In this study, we used the National Cancer Database (NCDB) to assess the association between RT use and overall survival (OS) for patients with metastatic HNSCC who received chemotherapy. Methods: We analyzed the NCDB to identify patients with newly diagnosed metastatic HNSCC from 2004-2013 who were treated with upfront chemotherapy. Associations between the use of RT and OS were evaluated using the Kaplan Meier method, univariate and multivariate cox regression, propensity score matching, and sequential landmark analysis. Survival outcomes were also compared for patients receiving a biologically effective dose (BED) ≥72 Gy10 and < 72 Gy10. Results: We identified 3,516 patients diagnosed with metastatic HNSCC who were treated with chemotherapy, of which 2,288 (65%) were also treated with RT. The median follow up was 11.9 months. The addition of RT to chemotherapy was associated with prolonged survival (median 13.6 v 11.3 months, logrank p < 0.001). On multivariate analysis, the use of RT remained associated with prolonged survival (HR = 0.71, 95% CI 0.61-0.82, p < 0.001). After propensity score matching, the addition of RT was associated with improved median survival (13.5 v 11.2 months) and 5-year (17% v 7%) OS compared to chemotherapy alone (log rank, p < 0·001). Landmark analyses limited to patients who survived at least 3, 6, and 12 months after diagnosis continued to demonstrate improved OS with the addition of RT. Among patients treated with RT, the use of RT schedules with a BED exceeding 72 Gy10 was associated with prolonged survival (median 18.0 versus 11.7 months, logrank p < 0.001). Conclusions: For patients with metastatic HNSCC, the addition of RT to chemotherapy was associated with improved OS in this population based study. These results provide rationale for prospective randomized trials to validate these findings and to determine the optimal radiation therapy dose/fractionation and treatment schedule for these patients.
A pilot study of the pan-class I PI3K inhibitor buparlisib in combination with cetuximab in patients with recurrent/metastatic head and neck cancer.
Authors: Brisson Ryan J. , Dekker Allison , De Souza Jonas A. , Saloura Vassiliki , Vokes Everett E. , Seiwert Tanguy Y.
Published: September 2018

6039

Background: R/M HNC carries a poor prognosis with a median survival of 10-12 months. PI3K pathway aberrations are present in 30% of HNC. This pilot dose-escalation study assesses the safety and tolerability of the PI3K inhibitor buparlisib when given concurrently with cetuximab in R/M HNC, as well as assess efficacy in an expansion cohort. Methods: Patients (pts) with R/M HNC who were not amenable to curative intent therapy were enrolled. Pts were given oral buparlisib starting day -7 and daily thereafter. The dose of buparlisib was escalated in a 3+3 design (Level 1: 80mg daily, Level 2: 100 mg daily) followed by a dose expansion cohort. The maximum dose of buparlisib was 100 mg daily. Cetuximab (500mg/m2) was given intravenously every 14 days starting day 0. Pts continued on treatment until progression of disease. Prior cetuximab failure was allowed. Results: Of the 12 pts enrolled, 10 had at least 2 previous treatment regimens (11 with prior cetuximab). 5 pts were HPV+, 4 were HPV-, and 3 had unknown HPV status. 3 pts were treated at the 80 mg dose level while 9 were treated at the 100 mg dose level (3 + 6 patient expansion). Treatment was well tolerated with 2 pts experiencing grade 3 adverse events (AEs) (no grade 4 AEs). The most common AEs were fatigue (83.3%), maculopapular rash (50.0%), and anorexia (50.0%). 3 pts experienced grade 1 anxiety. There were no SAEs. Of the 10 pts who were evaluable for response one patient achieved a PR (10%), and 4 achieved stable disease (40%) per RECIST 1.1. Median overall survival was 280 days (HPV+: 370 days, HPV-:191 days). The study was closed early due to poor enrollment on the expansion cohort as patients opted for concurrently open immunotherapy trials. Conclusions: Based on this pilot study, buparlisib plus cetuximab proved to be well-tolerated and showed limited evidence of activity in a heavily pre-treated patient population. Further research is warranted to determine activity of buparlisib in a larger cohort of R/M HNC. Clinical trial information: NCT01816984.
Characterization of potential predictive biomarkers of response to nivolumab in CheckMate 141 in patients with squamous cell carcinoma of the head and neck (SCCHN).
Authors: Concha-Benavente Fernando , Gillison Maura L. , Blumenschein George R. , Harrington Kevin , Fayette Jérôme , Colevas A. Dimitrios , Licitra Lisa , Kasper Stefan , Even Caroline , Worden Francis P. , Saba Nabil F. , Haddad Robert I. , Tahara Makoto , Hasegawa Yasuhisa , Yen Chia-Jui , Lynch Mark John , Monga Manish , Geese William J. , Vokes Everett E. , Ferris Robert L.
Published: September 2018

6050

Background: Nivolumab, an anti-programmed death-1 (PD-1) monoclonal antibody, demonstrated longer median overall survival (7.5 vs 5.1 months) and improved response (13.3% vs 5.8%) versus investigator choice chemotherapy (ICC) in patients with recurrent SCCHN after platinum failure in CheckMate 141 (NCT02105636), a randomized, open-label Phase 3 trial. We screened peripheral blood lymphocytes (PBL) to identify biomarkers which may predict response to nivolumab. Methods: Paired baseline (day 1) and on treatment (day 43) PBL samples (n = 36; 24 nivolumab; 12 ICC) were analyzed using multicolor flow cytometry and a non-competing anti-PD-1 antibody. Results were correlated with clinical outcome: responders (complete/partial response) and non-responders (stable or progressive disease). Results: Levels of CD8+ T cells at baseline and on treatment were higher in nivolumab responders compared to non-responders (23% vs 13%; P< 0.05). Interestingly, PD-1+ CD8+ and PD-1+ CTLA-4+ CD8+ effector T cells (likely exhausted T cells) decreased about 2-fold following nivolumab in both responders and non-responders ( P< 0.05), whereas, the decrease in CTLA-4+ CD8+ effector T cells following nivolumab was significant in responders only (8% vs 5%; P< 0.05). Levels of PD-1+ TIM-3+ CD8+ effector cells decreased following nivolumab in non-responders only (11% vs 7%; P< 0.05), a similar non-significant reduction was observed in responders. Levels of PD-1+ Tregs were lower in responders than non-responders at baseline (19% vs 33%; P< 0.01), and following nivolumab (12% vs 20%; P< 0.001). As in T-effector cell populations, PD-1+ Tregs decreased about 1.6-fold after nivolumab in both responders and non-responders ( P< 0.01). Interestingly, baseline Ki67+ Treg levels were lower in non-responders (28% vs 17%; P< 0.05). Conclusions: Response to nivolumab may be associated with higher levels of CD8+ T cells and CTLA-4+ CD8+ effector T cells, and lower PD-1+ CD8+ effector T cells and PD-1+ Tregs at baseline. Targeting both PD-1 and CTLA-4 axes is warranted in SCCHN to overcome suppressive signals in CD8+ effector T cells and in Treg cells expressing both checkpoint receptors. Clinical trial information: NCT02105636.
A phase II randomized, multicentric clinical trail comparing recombinant human endostatin plus intensity-modulated radiotherapy versus concurrent chemoradiotherapy in locally advanced low-risk nasopharyngeal carcinoma.
Authors: Kang Min , Lin Shaomin , Zhu Haisheng , Liao Sihui , Huang Haixin , Yu Bin , Wang Hongqian , Liu Meilian , Zhu Jinxian , Huang Guang , Qin Yutao , Wei Zhuxin , Du Qinghua , Hu Kai , Zhang Tingting , Zhou Pingting , Liao Xueyin , Wang Rensheng
Published: September 2018

6063

Background: A prospective, randomized, and multicentric phase II study was performed to evaluate the short-term efficacy and safety of Endostar plus intensity-modulated radiotherapy (IMRT) versus concurrent chemoradiotherapy(CCRT) in locally advanced low-risk nasopharyngeal carcinoma(NPC). Methods: From September 2014 to August 2016, 120 patients with low-risk NPC at stages III-IVa from 9 centers were randomly divided into experimental group (Endostar plus radiotherapy (ERT); n = 60) and control group (CCRT; n = 60). ERT patients were given Endostar (7.5 mg/m2/day) by continuous intravenous infusion (CIV) from 5 days before radiotherapy for consecutive 10 days for 2 cycles with an interval of 14 days. Then, ERT patients received 2 cycles of 10 days of maintenance treatment with Endostar after radiotherapy. The CCRT patients were given cisplatin (100 mg/m2) on days 1, 22, and 43 for 3 cycles. Immediate and 3-month efficacy and adverse effects were evaluated between the two groups. ClinicalTrials registration number was NCT02237924. Results: All patients were eligible for toxicity and response analysis. Regarding immediate efficacy, the complete response(CR) rates were 45.0% for ERT arm and 33.3% for CCRT arm in nasopharynx (P = 0.190), and 43.3% for ERT arm and 36.7% for CCRT arm in regional nodes (P = 0.456). Three months after RT, the CR rates were 71.2% for ERT arm and 60.0% for CCRT arm in nasopharynx (P = 0.151), and 74.6% for ERT arm and 63.3% for CCRT arm in regional nodes (P = 0.172). The rate and severity of leukopenia, hemoglobin reduction and thrombocytopenia in ERT arm were significantly lower than CCRT arm (P < 0.01). The occurrence rates of Xerostomia, oral mucositis, nausea / vomiting, constipation and weight loss in ERT arm were significantly lower than those in CCRT arm (P < 0.01). Conclusions: The present study demonstrates that ERT has similar short-term efficacy on locally advanced low-risk NPC compared with CCRT, but the acute adverse effects of ERT are fewer, and the compliance and tolerability of patients are better. Clinical trial information: NCT02237924.
LIHNCS: Lugol’s Iodine in Head and Neck Cancer Surgery—A multi-centre, randomised, controlled trial assessing the effectiveness of Lugol’s Iodine to assist excision of moderate dysplasia, severe dysplasia and carcinoma in-situ at mucosal resection margin of oral and oropharyngeal squamous cell carcinoma.
Authors: McCaul James Anthony , McMahon Jeremy McMahon , Quantrill Jacqueline , Gilbert Kayleigh , Mehanna Hisham Mohamed , Shaw Richard , McConkey Christopher C , Gouldesbrough David , Robinson Max , Dunn Janet
Published: September 2018

6065

Background: Oral cavity and oropharynx cancer are increasing worldwide but survival has not significantly improved over the last thirty years. Presence of dysplasia or carcinoma in-situ at surgical margins following resection of squamous carcinoma (SCC) of the head and neck is associated with increased local recurrence and reduced survival. While carcinoma can usually be distinguished from normal mucosa, dysplasia is less readily distinguished at operation. We describe outcomes of LIHNCS, a RCT assessing effectiveness of Lugol’s iodine staining for visualization and excision of margin dysplasia at primary surgery. Methods: Patients planned for curative surgical resection of oral cavity/ oropharynx SCC were recruited. Participants were randomised 1:1 into either a standard surgical treatment arm or surgical treatment including Lugol’s iodine staining according to defined SOP. Randomisation was stratified by centre and surgeon using computer-generated random permuted blocks. Data monitors, pathologists and external reviewers were blinded to treatment allocations. Chief investigator, surgeons and other health care professionals were blinded to results. Primary endpoint is presence of carcinoma or dysplasia at mucosal margins. Results: Sixty-five surgeons in 24 centres recruited and LIHNCS was powered for 300 cases. Following successful recruitment, extension was granted for progression to 409, including 300 T1 and T2 cases. Patient acceptance was 89%. Median follow up is 36.5 months and 118 patients have died to date. Significantly fewer patients in the Lugols arm required further mucosal resection after primary surgery (p = 0.005). In as treated analysis dysplasia is reduced at resection margins for T1 and T2 tumours (p = 0.04). Conclusions: Lugol's iodine visualisation of dysplasia at curative surgical resection of oral and oropharynx SCC is associated with reduced requitement for further mucosal resection and appears to result in reduced dysplasia at mucosal resection margins. Clinical trial information: ISRCTN03712770.
Treatment outcomes of 257 patients with locally advanced nasopharyngeal carcinoma treated with nimotuzumab plus intensity-modulated radiotherapy with or without chemotherapy: A single institution experience.
Authors: Zheng Wang Fang , Jiang Chuner
Published: September 2018

6079

Background: To report the long-term outcome and toxicitie of locally advanced nasopharyngeal carcinoma (NPC) treated with nimotuzumab plus intensity- modulated radiotherapy (IMRT) with or without chemotherapy. Methods: From October 2009 to March 2014, 257 newly histology-proven, non-metastatic NPC patients were retrospectively enrolled. They are aged 10-76 years. The distribution of disease was stage III in 150 (58.4%), stage IV A in 88 (34.2%), and stage IV B in 19 (7.4%). All the patients received the treatment of nimotuzumab plus IMRT, and 239 cases were used for cisplatin-based chemotherapy. Acute and late radiation-related toxicities were graded according to the Acute and Late Radiation Morbidity Scoring Criteria of Radiation Therapy Oncology Group. The accumulated survival was calculated according to the Kaplan-Meier method. Log-rank test was used to compare the survival difference. Multivariate analysis was performed using Cox’s proportional hazard model. Results: All patients had completed the combined treatment. With a median follow-up of 48 months (range, 13–94 months), the estimated 3-year and 5-year overall survival rates were 92.6% and 86.2%, respectively. Univariate analysis showed that age, T stage, clinical stage and neoadjvant chemotherapy were related with OS. Multivariate analysis indicated that age and clinical stage were independent prognosticators. The median cycle for nimotuzumab addition was 12 weeks. The incidence of grade 3–4 acute mucositis and leukocytopenia were 10.9% and 9.3%, respectively, with no cases of skin rash and infusion reaction. Xerostomia was the most common late complication, and the degree of dry mouth in most survivors was mild-to-moderate at the last follow-up time. Conclusions: Nimotuzumab plus IMRT with or without chemotherapy showed promising outcomes in terms of loco-regional control and survival, without increasing the incidence of radiation-related toxicities for patients.
Phase Ib study of cetuximab + BYL719 + IMRT in stage III-IVB head and neck squamous cell carcinoma (HNSCC).
Authors: Dunn Lara , Riaz Nadeem , Baxi Shrujal S. , McBride Sean Matthew , Sherman Eric Jeffrey , Michel Loren , Haque Sofia , Katabi Nora , Wong Richard J. , Xiao Han , Lee Nancy Y. , Fury Matthew G. , Ho Alan Loh , Pfister David G.
Published: September 2018

6081

Background: Activation of the PI3K/mTOR signaling pathway is common in HNSCC. PI3K inhibitors have been shown to enhance radiosensitivity. BYL719 is an α-specific PI3K inhibitor that is synergistic and efficacious when combined with cetuximab, an FDA-approved radiosensitizing agent in HNSCC. This study evaluates the addition of BYL719 to cetuximab and radiation in the treatment of locally advanced HNSCC. Methods: This is a single-institution, phase I study. Patients with Stage III-IVB HNSCC received cetuximab 400 mg/m2 IV loading dose prior to intensity modulated radiation therapy (IMRT), followed by 250 mg/m2 weekly infusions during IMRT. BYL719 was given orally during IMRT in 3 dose levels (DLs): 1) 200 mg, 2) 250 mg, and 3) 300 mg per day in a standard 3 + 3 dose escalation design. Results: 11 patients are evaluable; median age-60 years (36-73); Stage III-1, IVA-9, IVB-1; oropharynx primary-9, unknown primary-2; HPV-positive -10. 8 patients completed treatment. 3 patients were treated on DL 1 and 2 without a dose limiting toxicity (DLT). Both patients on DL 3 experienced a DLT of grade 3 mucositis. Related adverse events (AEs) of any grade experienced by all 8 patients include: mucositis, weight loss, and hyperglycemia. Related grade 3 and 4 AEs in at least 2 patients include: mucositis (4), dysphagia (4), and decreased lymphocyte count (2). An additional 3 patients have been enrolled onto DL 2 and are undergoing treatment. All other patients had a complete response (CR) on post-treatment PET (from 6/2015 - 9/2016) and remain free of disease. Of 6 patients with mutational analysis, 1 had an activating PIK3CA mutation associated with a rapid response on serial intra-treatment MRIs. Conclusions: BYL719 administered at DLs 200 mg or 250 mg oral daily with cetuximab and IMRT resulted in expected AEs of radiation-based treatment with cetuximab and tolerable class-related AEs of PI3K inhibitors. BYL719 300 mg oral daily exceeds the maximum tolerated dose; the phase II recommended dose is pending completion of expansion of DL 2. All patients who completed treatment had a CR. Further evaluation of the addition of BYL719 to the platinum-sparing regimen of cetuximab + IMRT in the treatment of locally advanced HNSCC is warranted. Clinical trial information: NCT02282371.
Post-discharge transitions of care for hospitalized patients with advanced cancer.
Authors: Lage Daniel E , Nipp Ryan David , D'Arpino Sara , Moran Samantha M.C. , Hochberg Ephraim P. , Traeger Lara , Jackson Vicki A. , Cashavelly Barbara J. , Martinson Holly S , Ryan David P. , Greer Joseph A. , Temel Jennifer S. , El-Jawahri Areej
Published: September 2018

6504

Background: Patients with advanced cancer experience frequent hospitalizations and burdensome transitions of care post-discharge. We examined predictors of discharge location for patients with advanced cancer. Methods: We prospectively enrolled patients with advanced cancer with unplanned hospitalizations from 9/14 to 3/16. Upon admission, we used the Edmonton Symptom Assessment Scale and Patient Health Questionnaire-4 to assess physical and psychological symptoms, respectively. We used logistic regression models to identify predictors of discharge to location other than home, including post-acute care (PAC) [skilled nursing facility or long term acute care hospital] or hospice [any setting]. We used Cox regression models adjusted for clinical variables to assess the relationship between discharge location and survival. Results: Out of 932 patients, 726 (77.9%) were discharged home, 118 (12.7%) to PAC and 88 (9.4%) to hospice. Compared with patients discharged home, those discharged to PAC or hospice had higher symptom burden, including dyspnea, constipation, low appetite, drowsiness, fatigue, depression, and anxiety (all p < 0.05). Patients discharged to PAC or hospice vs. home were more likely to be older (OR 1.03, p < 0.0001), live alone (OR 1.95, 95% CI: 1.25-3.02, p < 0.003), have impaired mobility (OR 5.08, 95% CI: 3.46-7.45, p < 0.0001), longer length of stay (OR 1.15, 95% CI: 1.11-1.20, p < 0.0001), higher ESAS physical symptoms (OR 1.02, 95% CI: 1.003-1.032, p < 0.017), and higher PHQ-2 depression symptoms (OR 1.13, 95% CI: 1.01-1.25, p < 0.027). Patients discharged to hospice vs. PAC were more likely to receive palliative care consultation (OR 4.44, 95% CI: 2.12 to 9.29, p < 0.0001) and have shorter length of stay (OR 0.84, 95% CI: 0.77 to 0.91, p < 0.0001). Compared with patients discharged home, those discharged to PAC had lower survival (HR 1.53, 95% CI 1.22-1.93, p < 0.0001). Conclusions: Patients with advanced cancer discharged to PAC or hospice have substantial physical and psychological symptom burden and poor physical function. Patients discharged to PAC also have inferior survival compared with those discharged home. They may benefit from targeted interventions to improve their quality of life and care.
Utilization of consultative molecular tumor board in community setting.
Authors: Farhangfar Carol J. , Morgan Oshuna , Concepcion Charlene , Hwang Jimmy J. , Mileham Kathryn Finch , Carrizosa Daniel R. , Dellinger Beth , Farhangfar Farhang , Kim Edward S.
Published: September 2018

6508

Background: Physicians in the community have a broad range of experience using genomics data to inform treatment decisions. They typically have a heavier patient load than found in academic centers and treat a variety of tumor types. Genomic data has been reportedly used less than anticipated, even when results were actionable. Monthly didactic molecular tumor boards have been implemented in a number of cancer centers to try to fill gaps in knowledge. Methods: A weekly virtual consultative molecular tumor board (MTB) was implemented (Mar 2016) at an academic hybrid, multi-site community-based cancer institute to provide rapid molecularly-driven treatment guidance to physicians, augment genomics education, provide supporting documents for off-label use and clinical trials. A baseline survey was performed prior to first MTB. MTB assessments were summarized and provided to treating physician. Data was abstracted from the electronic medical records and clinical trials management system. Descriptive statistics were utilized to summarize utilization of MTB and treatment recommendations. Results: Genomics testing with a large panel (~600 genes) was requested for 809 patients (Jun 2015-Feb 2017). The MTB received 81 requests for review from 32 physicians from 14 locations. Most commonly reviewed disease sites were lung, ovary, pancreatic, colon, breast and head and neck cancers; 37% of reviews requested were for rare tumors. Median time to review request was 15 days from receipt of results. MTB recommendations were followed in 70% of cases, 16% continued current/other therapy, 11% declined rapidly (hospice/died), and 3% of patients decided against recommendations. Forty-four (44) percent were screened for recommended clinical trials; 26% went on study. Conclusions: Implementation of a weekly virtual consultative MTB facilitates molecularly-driven treatment decisions in community setting, especially in rare tumor types and enhances clinical trial accruals.
Comparison of comorbidity measures to predict postoperative lung cancer survival in the National Cancer Database (AFT-03).
Authors: Wong Melisa L. , McMurry Timothy L. , Stukenborg George J. , Francescatti Amanda B. , Amato-Martz Carla , Schumacher Jessica R. , Greenberg Caprice Christian , Chang George J. , Winchester David P , McKellar Daniel P. , Walter Louise Christie , Kozower Benjamin D.
Published: September 2018

6519

Background: Comprehensive assessment of comorbidity in cancer registries is critical for comparative effectiveness research. The National Cancer Database (NCDB) measures comorbidity with a diagnosis code-based Charlson Comorbidity Index (CCI) abstracted from discharge abstracts or billing face sheets. However, the prognostic performance of this code-based CCI has not been compared with a medical chart-based CCI or individual comorbid conditions in a nationally representative sample of patients with lung cancer. Methods: Through a special study of the NCDB, cancer registrars performed chart abstraction for 18 perioperative comorbid conditions for 9,640 randomly selected patients with stage I-III non-small cell lung cancer resected in 2006-07 at 1,150 Commission on Cancer-accredited facilities. We compared the prognostic performance of the NCDB code-based categorical CCI (0, 1, 2+), special study chart-based continuous CCI, and individual comorbid conditions in 3 separate Cox proportional hazards models for 5-year postoperative overall survival. All models adjusted for demographic and clinical characteristics. Results: Median age was 67 (IQR 60-74). The most common comorbidities were COPD (40%) and CAD (21%). Five-year postoperative overall survival was 55.5%. Agreement between the code- and chart-based CCIs was 51.9% with the code-based CCI underestimating comorbidity for 36.2% patients. The model including individual comorbid conditions had the best prognostic performance (R2 0.196, C index 0.654). COPD, CAD, CHF, dementia, diabetes, moderate/severe renal and liver disease, peripheral vascular disease, psychiatric disorder, and substance abuse were independently associated with decreased survival. The chart-based CCI model (R2 0.189, C index 0.650) predicted postoperative survival better than the code-based CCI model (R2 0.181, C index 0.645). Conclusions: The NCDB code-based CCI underestimates comorbidity in patients with surgically resected lung cancer. The chart-based CCI and data on individual comorbid conditions improved prognostic performance and would be valuable additions to the NCDB to strengthen comparative effectiveness research.
Changes in insurance coverage associated with health care reform for cancer survivors aged 19-64 years.
Authors: Davidoff Amy J. , Guy Gery P , Hu Xin , Gonzales Felisa A , Han Xuesong , Zheng Zhiyuan , Ekwueme Donatus U. , Jemal Ahmedin
Published: September 2018

6527

Background: Beginning in 2014, Medicaid eligibility was expanded in over half of states, enrollment was simplified, and insurance marketplaces were created in all states with premium subsidies for selected individuals, as a result of implementation of the Affordable Care Act (ACA). We examine changes in insurance coverage for cancer survivors overall, and for targeted subgroups affected by specific ACA elements. Methods: We pooled data for cancer survivors aged 19-64 years from the 2012-2015 National Health Interview Survey. Using information on family structure, income, and employment, and linked state-specific Medicaid eligibility policies, we assigned survivors to 3 targeted groups: 1) Medicaid eligible pre-ACA; 2) Medicaid expansion eligible; 3) eligible for premium tax credits for Marketplace plans; and 3 groups not targeted for benefit: a) eligibility gap (income < 100% federal poverty level (FPL) in states not expanding Medicaid); b) with alternative “affordable” coverage; and c) high income ( > 400% FPL). Linear probability regressions examined pre(2012-13)/post(2014-15) coverage changes by eligibility category, adjusting for demographic characteristics. Results: Among 4,115 (wtd N = 6.90M) cancer survivors, insurance pre-ACA was 69% private, 15.2% public, and 12.2% uninsured. Post-ACA, overall public coverage increased by 3.2 percentage points (pct pt) (p = .036), whereas the percent uninsured decreased by 4.5 pct pt (p < .001). Relative to the high income category, the adjusted percent uninsured decreased by 8.4 pct pt (95% CI:1.2-15.5) among pre-ACA Medicaid eligible, by 16.7 pct pt (95% CI:8.9-24.4) among the newly Medicaid eligible, and by 11.3 pct pt (95% CI:1.0-23.4; p = .069) among premium subsidy eligible. No coverage gains were observed for the other 2 categories. Approximately 531,000 cancer survivors remained uninsured after ACA implementation, with over half eligible for either Medicaid (12%) or subsidized Marketplace plans (44%). Conclusions: In the first 2 years post-ACA, cancer survivors experienced substantial increases in insurance coverage, with changes limited to targeted subgroups. Over half of remaining uninsured were eligible for coverage.
Validation of natural language processing (NLP) for automated ascertainment of EGFR and ALK tests in SEER cases of non-small cell lung cancer (NSCLC).
Authors: Goulart Bernardo H. L. , Silgard Emily , Baik Christina S. , Bansal Aasthaa , Greenwood-Hickman Mikael Anne , Hanson Annika , Ramsey Scott David , Schwartz Stephen
Published: September 2018

6528

Background: The Surveillance, Epidemiology, and End Results (SEER) registries lack information on the Epidermal Growth Factor Receptor (EGFR) mutation and Anaplastic Lymphoma Kinase (ALK) gene rearrangement test results. With the goal of enabling population-based outcomes research in molecularly selected NSCLC subgroups, we conducted a validation study of NLP for ascertainment of EGFR and ALK testing from electronic pathology reports (e-paths) of patients included in the Seattle-Puget Sound (SPS) and Kentucky Cancer (KCR) SEER registries. Methods: We obtained 4,278 and 1,041 e-paths pertaining to 1,634 and 565 patients with stage IV non-squamous NSCLC diagnosed from 1/1/2011 to 12/31/2013 and included in the SPS and KCR registries, respectively. Two oncologists independently reviewed all reports to generate a gold-standard dataset. We used 855 of the SPS reports to train hybrid rule-based and machine learning algorithms for detection of test status (reported vs. not reported), and test result if reported (positive vs negative) for EGFR mutational analysis and ALK testing by FISH, IHC, or gene sequencing. In the remaining 3,423 SPS reports, we conducted a 5-fold cross-validation analysis to estimate the internal NLP sensitivity, specificity, positive predictive value, and negative predictive value for test status and results, respectively. We used a hierarchical rules system to assess the NLP accuracy at the patient level. For external validation, we repeated all analyses in the KCR dataset. Results: In the SPS internal validation report sample, the validity metrics ranged from 97% to 99% for EGFR and ALK test status, and from 95% to 100% for EGFR and ALK test results, respectively. In the KCR external validation report sample, the metrics ranged from 74% to 96% for EGFR and ALK test status, and 2% to 100% for test results, respectively. At the patient level, the NLP accuracy for EGFR and ALK was 95% and 96% (SPS cohort), and 70% and 72% (KCR cohort) respectively. Conclusions: NLP is a valid method for determining EGFR and ALK test status and results for patients included in SEER registries with access to e-path, but the algorithms likely need to be registry-specific.
Financial conflicts of interest at three prominent oncology clinical pathway vendors.
Authors: Daly Robert Michael , Bach Peter , Page Ray D.
Published: September 2018

6529

Background: The American Society of Clinical Oncology (ASCO) reports that in 2015 62% of oncology practices are adhering to a clinical pathway and 31% are adhering to more than one pathway. ASCO and the American Medical Association have raised concerns about the conflicts of interest of those that design these pathways. Methods: Using the public Centers for Medicare and Medicaid Services Open Payments database, we abstracted the 2015 financial conflicts of interest for the 2016 voting members of the Value Pathways (a combined effort of US Oncology and NCCN), the medical oncology committee chairs for Via Oncology, and the medical advisory board for eviti. We focused on national pathway vendors and on non-research general payments, such as gifts, consulting, and speaker fees. Results: Nearly all involved in pathway development received non-research general payments in 2015, including 92% of US oncology, 84% of NCCN, 84% of Via Oncology, and 69% eviti. The average general payments ranged from $3.5K for US Oncology Value Pathways voting members to $15.3K for NCCN Value Pathways voting members. Eight percent of US Oncology voting members, 19% of the eviti medical advisory board, 28% of Via Oncology chairs, and 42% of NCCN voting members received $10,000 or more in general payments in 2015. Conclusions: Given the prominent role clinical pathways have on oncologists’ prescribing behavior and the often subjective nature of determining on-pathway treatment, pathway vendors should take care to make accessible their conflict of interest policies and elucidate how they manage relationships of concern.Steps would include potentially limiting the number of committee members receiving payments and limiting the amount of general payments to each physician.
Thirty-day readmissions in metastatic cancer patients: Room for improvement?
Authors: Solomon Rachel , Egorova Natalia , Franco Rebeca , Bickell Nina A.
Published: September 2018

6541

Background: To date, cancer has been excused from most readmission reduction efforts. Yet reported readmission rates for cancer patients discharged from medical services are as high as 27%. Some readmissions for patients with metastatic disease may be avoidable. We assessed the prevalence of potentially preventable readmissions and associated factors in adult patients with metastatic cancer. Methods: We measured 30 day readmissions for dehydration, cancer-related pain, and failure to thrive in patients with primary diagnosis metastatic cancer on index admission to a New York State hospital between December 1, 2012 and December 31, 2014. We used competing risk models to assess the effects of demographics, comorbidities, hospital type, payor, and discharge disposition. Results: During the study period, 11,275 patients had 19,307 index hospitalizations with primary diagnosis, metastatic cancer. The 30 day readmission rate was 24.5% of which 8.9% (424) were potentially preventable. Black (HR 1.26, 1.17-1.35) and Hispanic patients (HR 1.19, 1.09-1.31) had higher rates of readmission than whites. Being older (HR per 10 years of age 0.94, 0.90-0.97), female (HR 0.95, 0.91-0.99), having private insurance (HR 0.87, 0.87-0.81) and discharge to hospice (HR 0.62, 0.42-0.91) decreased risk of readmission. Discharge home with services (HR 1.21, 1.14-1.27) or to a skilled nursing facility (SNF) (HR 1.11, 1.01-1.23) conferred higher risk than going home unaided. Index hospitalization at public hospitals increased risk (HR 1.1, 1.02-1.18); teaching hospitals were protective (HR 0.84, 0.774-0.92). Patients with potentially preventable readmissions were younger (HR per 10 years of age 0.85, 0.78-0.93). Compared to those who went home unaided, patients discharged with services were more likely (HR 1.31, 1.05-1.64) and those discharged to SNF were less likely to have avoidable returns (HR 0.55, 0.37-0.81). Payor, gender, race, comorbidities, and index hospital type did not contribute. Conclusions: While the overall rate of potentially preventable admissions among metastatic cancer patients is low, higher readmission rates among those discharged home with help suggests that services supplied are not sufficient to address their health needs.
National coverage analyses for NCI clinical trials: A pilot project to reduce participation barriers.
Authors: Denicoff Andrea , Mishkin Grace , Good Marjorie J. , Patrichuk Lucille , Ragard Lawrence , Hurtado Kathleen R , Willenberg Kelly , Szczepanek Connie M. , Dawson Casey , Alexander-Young Morgen , Strandberg Debra L , Kardell Julie , McCartney Sara , Sullivan Mary Beth , Kelly Michael , Montello Michael , McCaskill-Stevens Worta J. , Abrams Jeffrey S. , Mooney Margaret M. ,   NCI Coverage Analysis Working Group
Published: September 2018

6542

Background: Since the implementation of the ACA, many insurers have followed Medicare’s lead in covering routine care costs associated with clinical trials (CTs). However, questions remain on how to distinguish routine care from non-billable research costs, and this has important financial implications for both sites and patients. As a result, many sites individually conduct coverage analyses (CAs) prior to opening CTs to determine billable routine costs. This is a significant duplication of effort for NCI network CTs that are open at hundreds of sites. A 2015 ASCO-NCI initiative identified the centralized creation of CAs for national CTs as a potential solution to reduce site burden, increase CT transparency and billing compliance, and ultimately reduce barriers to CT participation. We provide initial findings from the resulting NCI pilot program. Methods: NCI set up a Coverage Analysis Working Group (CAWG) made up of representatives from NCI’s Cancer Trials Support Unit (CTSU), network groups, NCI, and billing compliance consultants. CAWG created a CA template and development process for NCI network trials. CAWG will survey site users in April 2017 to evaluate the first year of the pilot project. Results: CAs for 7 CTs were first posted to the CTSU website on 4/20/16. As of January 2017, CAs have been posted for 22 CTs: 17 NCTN and 5 NCORP. This represents 14.6% of the 150 large, later-phase network trials available on the CTSU. These CAs had been posted for a mean of 219 days (median 238) as of 1/31/17. In this time, CAs were downloaded an average of 319 times (median 301), for a total of 7,007 downloads. An additional 26 CAs have been posted for MATCH (n = 20) and LUNG-MAP (n = 6) sub-studies and downloaded 7,035 times. Survey results evaluating this CA pilot will be presented in June 2017. Conclusions: Providing centralized CAs to NCI’s national network trials is feasible and well received with sites reporting that this pilot is reducing the time and effort of opening CTs and improving CT funding transparency. Collaboration is needed with CMS and third party payers to enhance clarity around CT coverage policy and billing compliance, along with continued feedback to make further improvements to reduce trial barriers.
Assessing performance status and clinical outcomes with wearable activity monitors.
Authors: Gresham Gillian K. , Neeman Elad , Hendifar Andrew Eugene , Li Quanlin , Tuli Richard , Rimel Bj , Walsh Christine S. , Spiegel Brennan , Figlin Robert A. , Piantadosi Steven , Shinde Arvind Manohar
Published: September 2018

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Background: Performance status (PS) is assessed to inform treatment decisions and predict outcomes in cancer. PS is often evaluated using ECOG or KPS scales, limited by their subjective and static nature. Wearable activity monitors provide oncologists with the opportunity to obtain continuous objective data on patients’ daily activity including steps, stairs climbed, and sleep. We evaluated the association between wearable activity monitor data, PS, and clinical outcomes. Methods: Patients with advanced cancer were enrolled in a prospective, observational study conducted at Cedars-Sinai Medical Center. Patients wore a Fitbit Charge HR for 3 consecutive clinic visits. ECOG/KPS were rated by treating physicians and serious adverse events (AE, clinically relevant grade 3+ by CTCAE v4), hospitalizations, and 6-month survival were collected. Correlations between PS and activity metrics were calculated. Multivariable regression models were fit to predict AEs and hospitalizations with activity data. The association between activity metrics and time to death was evaluated using survival analysis. Results: 35 patients (median age 62 years, 53% male) were evaluated. Most had gastrointestinal cancers (82%). Patients had ECOG PS of 0 (20%), 1 (40%), 2 (23%), and 3(17%). There were 10 (29%) pts with serious AEs, 14 (40%) hospitalizations, and 11 (31%) deaths. Average daily steps were significantly correlated with ECOG PS and KPS (r=0.73 and 0.70, respectively). Relationships between activity metrics, AEs, hospitalizations, and overall survival (OS) are displayed in the table below. Conclusions: We found a significant association between wearable activity monitor data and the risk of AEs, hospitalization and death. There is a strong correlation between step counts and KPS/ECOG PS. The potential of wearable activity data to predict outcomes and supplement PS assessment should be explored in future studies. Clinical trial information: NCT02659358. [Table: see text]
Does coaching goals of care discussion skills make a difference?
Authors: Bickell Nina A. , Adelson Kerin B. , Gonsky Jason Parker , Pintova Sofya , Levy Benjamin Philip , Lin Jenny J. , Franco Rebeca , Egorova Natalia , Smith Cardinale B.
Published: September 2018

6586

Background: Advanced cancer patients often have a poor understanding of their cancer prognosis. Goals of Care (GoC) discussions provide information about the cancer, its treatment & prognosis and elicit patient values. Little is known about the best ways to enhance patient understanding, clarify values and move GoC discussions earlier in the disease process. We report the effect of coaching oncologists on GoC discussions. Methods: We recruited oncologists & their advanced cancer patients with < 2 year prognosis to a RCT testing a coaching model communication skills training. Patients were surveyed after their post-imaging visit. We define GoC discussions as patient report that their doctor talked about their cancer prognosis and clarified things most important to them given their disease. Outcome variables assess the impact of GoC on patients’ knowledge on what to expect and clarity of values. Results: We enrolled 22/25 (88%) oncologists and 70% of eligible patients of whom 96 (55%) completed a survey. On average, doctors were 44 yrs old (32-66) and in practice 14.5 yrs (5-40). Patients’ mean age was 62 yrs (20-95), 40% females, 58% white, 24% Latino & 22 % black. Overall, 2/3 of patients reported their treatment’s goal was to cure their cancer; 14% reported cure to be unlikely. Patients felt more knowledgeable (79% vs 21%; p = 0.02) when their doctors discussed treatments, side effects & quality of life. When patients were asked about things important to them, they report being a bit clearer about their values (65% vs 35%; p = 0.16). Compared to controls, intervention patients felt more knowledgeable (78% v 63%; p = 0.17) but did not feel clearer about their values (60% v 54%; p = 0.59). Multivariate modeling found that poor health literacy (OR = 0.2; 95%CI: 0.07-0.82), having a GoC discussion (OR = 10.2; 1.7-63.1) and being in the intervention group (OR = 8.8; 1.4-55.2) significantly affected knowledge (model c = 0.88; p < 0.01). However, discussing what’s important to patients did not help patients feel clearer about their values (OR = 2.7; 0.6-12.2; model c = 0.82; p < 0.05). Conclusions: Using a coaching model to teach oncologists communication skills may improve patients’ understanding of what to expect with their cancer but does not impact their clarity of values. Clinical trial information: NCT02374255.