bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical outcomes of transoral robot-assisted supraglottic laryngectomy: An experience of a French cooperative evaluation group of transoral robotic surgery.
Authors: Ceruse Philippe , Lallemant Benjamin , Aubry Karine , Morinieres Sylvain , Vergez Sebastien , Benlyazid Adil , De Mones del pujol Erwan , Malard Olivier
Published: March 2020

6053

Background: Transoral, minimally invasive organ preservation surgeries are being increasingly used for laryngopharyngeal carcinomas to avoid the toxicities of combined chemotherapy and radiation therapy regimens. This study investigates the efficiency, safety, and functional outcomes of transoral robot assisted surgery (TORAS) for supraglottic laryngectomy. Methods: Experience of TORA supraglottic laryngectomy for patients with supraglottic carcinomas is presented in a multicentric study of a case series with planned data collection between 2009 and 2012. Results: Eighty-six of 262 patients underwent TORA supraglottic laryngectomy for supraglottic carcinomas. Thirty-three percent of patients were started an oral diet within 24 hours. For 77% of the other patients, the median use of a feeding tube was 8 days (0-10 months). Nine percent of them had a definitive percutaneous gastrostomy feeding. For 87% of patients no tracheotomy was performed, for 23% of the others patients, the median use of tracheotomy was 8 days, 3% of them had a definitive tracheotomy. Aspiration was observed in 22% of the patients in the postoperative course and was responsible for the death of one patient. Sixteen percent of the patients had a postoperative bleeding. Fifty percent of the patients received adjuvant radiation therapy based on pathology results. Conclusions: TORA supraglottic laryngectomy is a safe procedure with good functional outcomes and fast recovery but adverse events are possible. Consequently this technique needs a good selection of the patients to reduce the risk of postoperative complications.
Association of polymorphisms in genes related to cell cycle (ERP29, LEF1, MCC and PTCH1) and DNA transcription factors (IKBKAP and ZNF415) with base of tongue squamous cell carcinoma risk.
Authors: Lima Carmen Silvia Passos , Carvalho Benilton , Pellegrino Renata , Khater Leticia , Chone Carlos Takahiro , Lourenco Gustavo Jacob
Published: March 2020

6073

Background: Recently, we found 6.609 genetic single nucleotide polymorphisms (SNPs) with distinct frequencies between base of tongue squamous cell carcinoma (BTSCC) patients and controls. The study was performed using high-resolution DNA microarrays genotyping (Affymetrix). The SNPs identified never have been previously described with BTSCC risk. Some SNPs of interest were located in genes related to cell cycle (ERP29, LEF1, MCC and PTCH1) and DNA transcription (IKBKAP and ZNF415) and they were selected to validation process. Objective: Validate the SNPs ERP29 c.*293A>G (rs7114); LEF1 c.*1213A>G (rs2107028) and g.127267A>G (rs4245926); MCC c.*5077A>G (rs7033); PTCH1 g.27369025G>A (rs16909856) and g.27369324G>A (rs16909859); IKBKAP c.3214T>A (rs3204145) and ZNF415 c.*443A>G (rs3814) associated to BTSCC risk. Methods: Genomic DNA from 49 BTSCC patients and 49 controls was genotyping by TaqMan assays (Applied Biosystems). The differences between groups were analyzed by logistic regression model. Power analysis (PA) was used to verify the effect of sample size on the results obtained. Results: Eight SNPs identified by Affymetrix were validated by TaqMan assays. The frequencies of ERP29 c.*293AG+GG (30 vs 11%, P=0.03; PA=65%), LEF1 c.*1213AA+AG (95 vs 80%, P=0.02; PA=61%) and g.127267AA+AG (93 vs 78%, P=0.02; PA=56%), MCC c.*5077AA+AG (85 vs 64%, P=0.008; PA=67%), PTCH1 g.27369025GG+GA (90 vs 73%, P=0.005; PA=58%) and g.27369324GG+GA (90 vs 73%, P=0.008; PA=58%), IKBKAP c.3214TT+TA (90 vs 72%, P=0.01; PA=62%) and ZNF415 c.*443AA+AG (59 vs 41%, P=0.02; PA=43%) were more common in patients than in controls. Individuals with these genotypes were at 2.9(CI95%: 1.1-8.4), 3.9 (CI95%: 1.4-11.2), 4.0 (CI95%: 1.2-14.7), 3.5 (CI95%: 1.2-11.9), 5.0 (CI95%: 1.7-16.9), 4.5 (CI95%: 1.5-15.2), 4.1 (CI95%: 1.4-12.9), and 3.9 (CI95%: 1.2-13.7)-fold increased risks for BTSCC than others, respectively. Conclusions: Our data present for the first time evidence that inherited abnormalities in ERP29, MCC, LEF1, PTCH1, IKBKAP, and ZNF415 genes may be important determinants of BTSCC. Financial support: FAPESP and FINEP.
Multicenter, open-end, randomized controlled study using P53 gene recombinant adenovirus injection (rAd-p53) combined with chemotherapy for orofacial carcinoma (OFC): Phase IV clinical trial—Progress report and conclusion.
Authors: Yang Maolin , Li Longjiang
Published: March 2020

6080

Background: The gene therapy product (Gendicine, rAd-p53) had pre-market studies done around 1998 indicated its efficacy in the treatment of squamous cell nasopharyngeal carcinoma in multi-modality treatment regimen. Gendicine has been used successfully in treating over 40 cancer types since then. With the advancement in optimization of combined treatment methods over the years, there was a need for a medium term efficacy study. This report summarizes our phase IV study. Methods: Patient selection, intervention and allocation were done according to GCP and supported by statistical analysis. Orofacial cancer (OFC) patients of advanced stages (III/IV) from multiple hospitals (n=30) in China were recruited for this open-end, randomized, controlled study (2009.7--2012.06). The 2 groups were rAd-p53+chemotherapy (GT+CT) (n=743) and CT alone (n=232). Patient exclusion rate were 20.81% (n=128) and 13.9% (n=28) respectively. Virus particles were delivered intra-tumorally at a dose of 109 (tumor cell/cm2 tumor area) x area x100 (virus multiplicity of infection, MOI), every 3d totally 10 times on d 1-28 inclusive. In synchrony with GT, 5-fluorouracil (5-FU, 250 mg/m2/d), on d 7-11 and d 25-29 along with carbocisplatin (KP, 400 mg/m2/d, i.v.), and with methotrexate (MTX, 50mg/m2 /d) on d 7, 14, 25, 32 were administered. The control group received 5-FU, KP and MTX. Results: For advanced OFC treated with GT+CT, the efficacy and QoL were significantly (p<=0.001) improved, the result was in accordance with our phase II/ III studies. Conclusions: This study proved rAd-p53 when used as an adjunct is safe and efficacious. The side-effect was mostly self-limiting low-grade to mild fever. The combined treatment modality had complete remission (CR) improved by 21.38%, relief ratio (RR) by 11.53% and clinical benefit ratio by 20.82% over GT-CT. Long-term follow-up will be continued.
Predictive biomarkers in a phase II trial of weekly carboplatin (CBDCA), paclitaxel (P), and cetuximab (C) induction and chemoradiation (CRT) in patients (pts) with resectable stage III/IVa,b head and neck squamous cell carcinoma (HNSCC): Eastern Cooperative Oncology Group E2303.
Authors: Psyrri Amanda , Lee Ju-Whei , Vasilakopoulou Maria , Pectasides Eirini , Burtness Barbara , Rimm David , Wanebo Harold J. , Forastiere Arlene A.
Published: March 2020

6081

Background: We studied the addition of C to a sequential regimen of weekly CBDCA and P followed by CBDCA-P-radiation in pts with locally advanced resectable HNSCC. Tissue-based biomarkers may aid in pt selection for such approaches. Methods: Sixty-three eligible pts withoperablestage III/IV HNSCC participated in E2303, an Eastern Cooperative Oncology Group (ECOG) phase II trial of induction chemotherapy with weekly C, P and CBDCA x 6 followed by CRT with concurrent weekly C, paclitaxel, carboplatin. A tissue microarray was constructed and b-catenin, E-cadherin, Epidermal Growth Factor Receptor Variant III (EGFRVIII), insulin-like growth factor-1 receptor (IGF1R), NF-kappa b, p53, PI3Kp85, PI3Kp110a, PTEN, ΝRAS, and pRb protein expression levels were assessed using automated quantitative protein analysis (AQUA). For each marker, time-to-event distributions (OS, PFS, and EFS) were estimated by Kaplan-Meier estimates and compared using log-rank tests. Multivariable Cox proportional hazards models were used to estimate hazard ratios and test for significance, with primary site (oropharynx vs. non-oropharynx), disease stage (III vs. IV), and other important markers adjusted in the model. All p-values are two-sided. A level of p < 0.05 is considered statistically significant. Results: Based on the continuous scale, pRb tended to association with EFS (p=0.05). On multivariable analysis, low pRb level was a significant predictor for improved EFS (p=0.048). Our pRb data analysis was based on 32 pts with marker data available. Conclusions: pRb level is a potential predictive biomarker for response to cetuximab. HPV E7 oncoprotein binds and degrades pRb; therefore, low pRb protein level might be a surrogate marker for HPV association.Large prospective studies will be required to determine the association between pRb, HPV status and response to cetuximab in HNSCC.
Combination lapatinib and capecitabine in advanced, incurable squamous cell carcinoma of the head and neck (SCCHN).
Authors: Weiss Jared , Hayes David N. , Algazy Kenneth M. , Desai Arati Suvas , Horn Brenda , Gulino Sara , Flowers Dale , Frazee Diane , Feldman Arthur M. , Staddon Arthur P. , Grilley-Olson Juneko E. , Cohen Roger B. , Langer Corey J.
Published: March 2020

6094

Background: In an era of increasing use of platinum-based induction chemotherapy and chemoradiotherapy, most metastatic/recurrent SCCHN patients (pts) have received multiple chemotherapeutic agents prior to being diagnosed with incurable disease, at which point PS is often poor, pts are often refractory to multiple agents, and standard therapies (Tx) are unacceptably toxic and inconvenient. Methods: We conducted a phase II study of 44 pts with metastatic/recurrent SCCHN with a primary endpoint of median OS. Pts received capecitabine 1,000 mg/m2 BID for 14/21 day cycles, with lapatinib at 1,250 mg daily for a total of four cycles. In the absence of disease progression or unacceptable toxicity, pts received maintenance Tx with lapatinib. Prior exposure to any chemotherapy other than capecitabine and lapatinib was allowed, as long as it was as part of therapy delivered with curative intent. Results: 36 of 44 planned patients are assessable at this time. 69% had prior resection, 75% prior radiation and 61% prior chemotherapy, of whom 18 (50%) had received prior platinum. Median age was 62, 11 pts (31%) had PS 0, 22 pts (61%) pts had PS1 and 3 pts (8%) had PS2. Median number of cycles given was 4; 14 pts have gone on to maintenance Tx. The most common grade 3-4 adverse events have included dehydration, diarrhea, and hand-foot syndrome, each occurring in 11% of pts. 2 patients did not have RECIST evaluable disease. Of the remaining 34 patients, 6 pts had PR and 1CR, for an ORR of 21% (24% in assessable pts). As of 1-31-13, 20 pts are alive, 2 are lost to followup, and 14 are deceased. Conclusions: The combination of capecitabine and lapatinib is tolerable and active in metastatic/recurrent head neck cancer, including pretreated patients. OS data, not yet mature, will be required to determine if this regimen is worthy of further testing. Clinical trial information: NCT01044433.
Superselective intra-arterial chemotherapy for oral cancer by subcutaneous implantation of an intra-arterial catheter and an infusion reservoir: A new chemotherapy method to improve the quality of life and curative effect.
Authors: Ohmae Masatoshi , Tohnai Iwai , Kato Itsuro , Nakazawa Mitsuhiro
Published: March 2020

6096

Background: We have developed a superselective intra-arterial chemotherapy (iaCT) approach for oral cancer, in which intra-arterial catheter is retrogradely inserted via the superficial temporal artery (STA) and/or occipital artery (OA). This approach increases chemotherapy efficiency but remarkably decreases activities of daily living (ADL) because the catheter penetrates the skin over the approaching artery (STA/OA). Methods: This study assessed our new outpatient iaCT approach involving implantation of an intra-arterial catheter connected to a subcutaneous infusion reservoir. We included 10 patients who had oral cancer treated using outpatient iaCT: tongue carcinoma, 7; cheek mucosal carcinoma, 1; upper gingival carcinoma, 1; palatal carcinoma, 1. In this approach, the STA or OA or both were percutaneously dissected out, a catheter was inserted, and the catheter tip was superselectively placed in the tumor-feeding artery. The extra-arterial catheter portion was implanted through a subcutaneous tunnel and was connected to a subcutaneous infusion reservoir implanted around the mastoid process. The patients were discharged after catheterization, and the chemotherapeutic agent was intra-arterially administered at the Outpatient Chemotherapy Center of Rinku General Medical Center once or twice a week. Intra-arterial infusion was repeated 6 times per course. Results: The response rate was 100%, i.e., 8 cases of CR and 2 of PR; patients with PR underwent surgery.Their ADLs were scarecely disturbed exept for ambulatory visits. Conclusions: In this approach, the catheter is completely implanted subcutaneously; therefore, usual catheter-related issues (e.g., infection, catheter fall out) rarely occur. Because this leads to very good ADLs, outpatient chemotherapy can be safely performed. Consequently, the quality of life (QOL) improves and medical expenses decrease.Our new outpatient iaCT approach improves QOL of and curative effects for oral cancer patients if the ambulatory convenience and the performance status are good.
Multicenter phase II trial of neoadjuvant carboplatin, weekly nab-paclitaxel, and trastuzumab in stage II-III HER2+ breast cancer: A BrUOG study.
Authors: Sinclair Natalie Faye , Sakr Bachir Joseph , Abu-Khalaf Maysa M. , Somlo George , Black Robert C , Chung Gina G. , Rizack Tina , Strenger Rochelle , Fenton Mary Anne , DiGiovanna Michael , Constantinou Maria , Lannin Donald R. , Legare Robert Duffy , Chagpar Anees B. , Sambandam Sundaresan T. , Bossuyt Veerle , Rosati Kayla , Harris Lyndsay , Sikov William M.
Published: March 2020

619

Background: Patients (pts) with human epidermal growth factor receptor-2 amplified (HER2+) breast cancers (BrCa) who achieve a pathologic complete response (pCR) with neoadjuvant chemotherapy (NAC) + trastuzumab (T) have an excellent prognosis (Cortazar, SABCS 2012). We tested a novel NAC + T regimen, designed to avoid potential cardiac and other toxicities associated with anthracyclines (A) and eliminate steroid premedication by replacing standard paclitaxel with nab-paclitaxel (nP). Methods: Clinical stage IIA-IIIC HER2+ BrCa pts received single agent either nP or T, with research biopsies and MRIs obtained before and after, then carboplatin (Cb) AUC 6 q3wks, nP 100 mg/m2and T 2 mg/kg weekly x 18 wks. If present, residual tumor was collected at surgery. Post-op pts complete a year of T; other adjuvant treatment is at MD discretion. Endpoints include clinical + pathologic response (pCR is defined as no invasive BrCa in breast + axillary nodes), residual cancer burden (RCB), treatment delivery and toxicities. Results: 53 pts (of 60 planned) are evaluable for response, median age 51 (34-72). Median delivered dose intensity for nP was 89 mg/m2/week; nP doses were omitted or reduced for neutropenia (ANC) (in 20% of pts) and neurotoxicity (Nt) (5%). Cb was reduced for thrombocytopenia (tcp) in 15%. Grade 3-4 toxicities: ANC 65%, tcp 22%, anemia 37%, Nt 7%. Serious adverse events: febrile neutropenia (5 pts), infections w/o neutropenia (4), vomiting, diarrhea or dehydration (7), thrombosis (2). LVEF fell by >10% in 3 pts with no clinical CHF. Response data are tabulated below: 28 pts (53%) achieved pCR or RCB class I; 15/21 who did not received A-based adjuvant chemotherapy. Of 38 clinically node-positive pts, 26 (68%) were node-negative at surgery. Conclusions: The Cb/nP/T regimen was well tolerated, with pCR rates comparable to those reported with A-containing regimens. Final treatment and response data will be presented; correlative studies will be reported separately. Clinical trial information: NCT00617942. [Table: see text]
Longer-term cardiac safety and outcomes of dose dense (dd) doxorubicin and cyclophosphamide (AC) followed by paclitaxel (T) and trastuzumab (H) with and without lapatinib (L) in patients (pts) with early breast cancer (BC).
Authors: Morris Patrick Glyn , Iyengar Neil M. , Patil Sujata , Chen Carol , Abbruzzi Alyson , Lehman Robert James , Steingart Richard , Oeffinger Kevin C. , Lin Nancy , Moy Beverly , Come Steven E. , Winer Eric P. , Norton Larry , Hudis Clifford , Dang Chau T.
Published: March 2020

630

Background: The addition of H to chemotherapy has improved outcomes in HER2-positive early BC. This approach is associated with (w/) an increased risk (<4%) of congestive heart failure (CHF). At a median f/u of 36 months, the addition of anti-HER2 Rx to dose-dense (every 2 weeks) anthracycline-taxane therapy (Rx) was not associated with excess cardiotoxicity. Here we report the incidence of NYHA Class III/IV CHF in 2 phase II studies with longer follow-up. Methods: We conducted a retrospective review of pts w/ HER2 + early stage BC treated at MSKCC and DF/HCC on two trials: In trial A - pts received dd AC (60/600 mg/m2) x 4 → T (175mg/m2) x 4 (w/ pegfilgrastim) w/ H x 1 year. Trial B differed w/ use of weekly T (80mg/m2) x 12 and the addition of L (1000mg orally daily) x 1 year. In both trials, H was begun after completion of AC and concurrent with T. Left ventricular ejection fraction (LVEF) was prospectively assessed by multi-gated acquisition scan serially throughout Rx. Results: Trial A enrolled 70 pts and Trial B enrolled 95 pts w/ the median age of 46 years (range 27-73 years). Overall, the 5-year distant disease-free survival (DDFS) for trials A and B is 92% (95%Cl; 83-97%) and 89% (95%CI; 81-94%), respectively. The baseline median LVEF was 68% (range 52-81%). In total, 28 of 165 (17%) pts had pre-existing hypertension. Now at a median follow-up of 84 and 57 months respectively, only one (1.4%, 95%CI; 1.36-7.7%) and 4 (4.2%, 95%CI; 4.2-10.4%) pts developed CHF. Since our earlier report, 1 additional CHF event occurred (Trial B) at month 44. Conclusions: Longer follow-up of these 2 studies demonstrate that dd AC → TH with or without L is associated w/ a low risk of CHF. This is consistent w/ the long-term cardiac toxicity reported from the randomized phase III studies of H w/ conventionally scheduled anthracycline-based regimens (with or without taxanes). DDFS outcomes are also encouraging. Clinical trial information: NCT00482391.
Brain and tumor penetration of carbon-11–labeled lapatinib ([11C]Lap) in patients (pts) with HER2-overexpressing metastatic breast cancer (MBC).
Authors: Saleem Azeem , Searle Graham , Kenny Laura M. , Huiban Mickael , Waldman Adam , Downie Louise , Lau Mike , Murphy Philip S , Kozlowski Kasia , Lewis Yvonne , Woodley Laura , Hill Sam , Kamalakaran Aruloly , Hirschberg Sandra , Kaneko Tomomi , Aboagye Eric , Marini Luca , Coombes R. Charles
Published: March 2020

635

Background: About a third of HER2-overexpressing (HER2+) breast cancer pts will develop brain metastases in the course of their disease. Drug access to normal brain and brain metastases is therefore key to prevention and treatment of cerebral metastases. To provide direct evidence of Lap drug access and evaluate whether therapeutic doses of Lap act as a substrate for efflux transporters, thereby increasing Lap concentrations, we performed positron emission tomography (PET) studies with [11C]Lap. Methods: Pts with HER2+ MBC with an ECOG of <3 were grouped into 2 cohorts: with at least one 1-cm diameter brain metastasis or without brain metastases and underwent 90-minute dynamic cranial PET-CT scans after IV administration of a microdose (<1 mg) of [11C]Lap before and after 8 days of oral Lap (1500 mg once daily). Arterial blood samples were performed to assess [11C]Lap radioactivity contribution in blood and plasma, and the fraction of plasma [11C] radioactivity corresponding to metabolites. Tissue time-radioactivity curves (TACs) were generated and [11C]Lap exposure (AUC; area under TAC) derived for normal brain and brain metastases. Signal dissection of the total image activity was performed to remove the contribution of blood volume to the image and the actual tissue contribution due to [11C]Lap obtained. Results: 6 pts (3 with brain metastasis) were recruited. Arterial plasma analysis revealed that [11C]Lap contributed to >80% of activity in plasma at 60 minutes. Tissue data revealed [11C]Lap signal in normal brain was low with no appreciable uptake observed when corrected for blood volume contribution. [11C]Lap uptake was higher in brain metastases compared with normal brain and appreciable, even after correction for tissue blood volume contribution. Uptake was also observed in extra-cranial normal tissue. There was no difference in [11C]Lap uptake in normal brain and metastases between treatment-naïve and post-treatment scans. Conclusions: [11C]Lap uptake in brain metastases was higher than in normal brain. [11C]Lap drug access to brain metastases might therefore indicate possible efficacy against HER2+ brain metastases. Clinical trial information: NCT01290354.
Liposome-encapsulated doxorubicin plus cyclophosphamide followed by trastuzumab plus docetaxel as neoadjuvant therapy for HER2-positive breast cancer (BC): A multicenter single-arm phase II study.
Authors: Saracchini Silvana , Foltran Luisa , Sulfaro Sandro , Tuccia Fausto , Del Conte Alessandro , Bertola Manuela , Bassini Anna , Micheli Elvia , Manente Stefania , Gusso Giuseppina , Baresic Tania , Tumolo Salvatore
Published: March 2020

641

Background: Trastuzumab combined to sequential chemotherapy with taxanes and anthracyclines as primary treatment achieved high rates of pathologic complete response (pCR) in HER2 positive BC. Liposome-encapsulated doxorubicin (DLNP) shown equal efficacy but minor cardiotoxicity compared to doxorubicin. This phase II study aimed to evaluate the activity and safety of trastuzumab associated with chemotherapy for early or locally advanced HER2 positive BC. Methods: Primary objective of the study was pCR defined as the absence of residual invasive cancer both in the breast and regional nodes. Preoperative treatment included DLNP (60 mg/mq iv) plus cyclophosphamide (600 mg/mq iv) every 3 weeks for 4 cycles followed by docetaxel (35 mg/mq iv) plus trastuzumab (4 mg/mq loading dose iv, then 2 mg/mq iv) weekly for 16 weeks. Patients (pts) were scheduled to receive adjuvant trastuzumab (8 mg/mq loading dose, then 6 mg/mq iv) every 3 weeks for 12 cycles and radiation and hormonal therapy according to guidelines. Results: From December 2005 to September 2011, 43 pts were treated at 3 centers in Italy. 39 out of 43 pts were evaluable for the purpose of the study. Median age was 53 years (range: 31-78). The majority of pts had cT2 (63%), grade 3 (93%), N+ (77%) ER positive (56%) and MIB-1 ≥20% (77%). pCR was reported in 19 (49%) of 39 pts. The histological regression score (Von Minckwitz G, J Clin Oncol 2012) is shown in the Table. A significant correlation between MIB-1 ≥20% at baseline and pCR was observed (p=0.018). Pts with pCR had a time to response (29.4 weeks, 95% CI 28-31) lower than pts without pCR (32.9 weeks, 95% CI 27-39). No cardiac toxicity or discontinuation of trastuzumab was reported. After a median follow-up of 30 months only 2 pts relapsed, both with pCR. Conclusions: This study confirms the high activity of trastuzumab combined with chemotherapy based on anthracyclines and taxanes as primary treatment for HER2 positive BC. DLNP is an active and safe option to minimize cardiotoxicity. [Table: see text]
Association between high-cost imaging and hospice use at the end of life of cancer patients.
Authors: Dinan Michaela A , Setoguchi Soko , Curtis Lesley H , Cheung Winson Y.
Published: March 2020

6504

Background: Use of high cost imaging modalities can inform prognosis and potentially de-escalate unnecessary care at the end of life of cancer patients, but it may also be associated with increased health care expenditures. This analysis investigated the association of hospital-level use of advanced imaging studies with aggressiveness of care near death, as measured by hospice enrollment. Methods: Using SEER-Medicare, patients who died from common solid tumors between 2002 and 2007 were identified and hospital-level utilization of CT, MRI and PET scans were categorized into quartiles. Patients were assigned to the hospital at which they spent the majority of their inpatient days during the last 6 months of life. Multivariate-adjusted logistic regression models based on tumor type were constructed to correlate imaging use with late as well as all hospice admissions, defined as enrollment within 3 days and 18 months of death, respectively. Results: A total of 7,876 breast, 31,933 lung, 12,877 colorectal and 9,137 prostate cancer patients were included. High cost imaging varied across tumor types with rates being highest for lung cancer (mean of 2.29 CT, 0.58 MRI and 0.21 PET scans per patient) and lowest for prostate cancer (mean of 1.25 CT, 0.41 MRI, and 0.01 PET scans per patient) in the 6 months before death. Overall hospice use was least frequent in colorectal cancer (50% of patients) while late hospice admission was most common in lung cancer (11% of patients). Hospitals within the top quartile of imaging use generally had decreased odds of hospice utilization and higher likelihood of late hospice enrollment across most cancer types (Table). Conclusions: In this large cohort, receipt of care near end of life in hospitals with the highest rates of advanced imaging use was associated with lower use of and later enrollment to hospice. High cost imaging is not correlated with de-escalation of aggressive care. [Table: see text]
Determining value of high cost cancer therapies and discussing cost of cancer care: The patient perspective.
Authors: Rajguru Saurabh , Carmichael Lakeesha , Cetnar Jeremy Paul
Published: March 2020

6512

Background: A trend in cancer treatment is the growing number of high-priced therapies which offer marginal clinical benefits. This has led ASCO to issue guidelines stressing the importance of discussing treatment costs with patients. There are many identified barriers which limit communication of cost including oncologists’ fears that patients may view this discussion as inappropriate. We attempted to assess cancer patients’ views on discussion of treatment costs with their oncologists, as well as, their views on high-cost drugs (HCDs), including the belief that there is a cohort of patients who would forgo high-priced treatment even if there was no out-of-pocket expense. Methods: We surveyed patients with advanced prostate cancer. The survey consisted of demographic information and an 11-item questionnaire. We also gave them a hypothetical scenario in which they were asked how much they would be willing-to-pay (WTP) for a $100K drug that would improve survival on average by four months with minimal side-effects (modeled after Provenge). The survey was administered to patients in clinic prior to their visit. Results: Of the patients approached, 169 responded (88% response rate). Seventeen percent stated they would not want treatment with HCDs even if they had no out-of-pocket expenses (more likely to be older (>70) and have an annual household income of >$60K). Another 21% stated they would accept treatment only if they had no out-of-pocket expenses. The median WTP for the hypothetical drug was $20K. Most patients (79%) agree that a discussion of costs with their physician is appropriate and 69% would want to have this discussion. Most patients (82%) agree that prognosis is important when making treatment decisions however 66% of patients did not know their cancer stage. Only 37% agree that the oncologist or the patient should consider the country’s healthcare costs when making treatment decisions. Conclusions: Prostate cancer patients clearly want to have discussions regarding costs-of-care with their oncologists. There is a group who would forgo treatment with high-cost drugs that yield only modest survival benefits. Their motivation is unknown, but is hypothesized to reflect a value-based judgment.
Adoption of robot-assisted surgery and its impact on treatment patterns for newly diagnosed localized prostate cancer.
Authors: Shih Ya-Chen T. , Hu Jim C. , Shen Chan , Eggener Scott E.
Published: March 2020

6513

Background: With the rapid increase of robotic surgical systems in hospitals, it is important to understand the impact on treatment patterns for localized prostate cancer. The objective of this study is to determine whether the presence of robotic surgical systems independently influenced rates of surgery, radiation, and active surveillance for localized prostate cancer. Methods: We conducted an observational study using National Cancer Database (NCDB) state-level data, 2002-2010. Our study cohort includes patients newly diagnosed with clinical stage I-III prostate cancer from 48 states and Washington D.C. in the United States. The number of robotic systems installed in each state over time was obtained from publicly available information on-line. We characterized the state-level treatment pattern as the proportion of patients having surgery, radiation and active surveillance as their first course of treatment. Results: Between 2002 and 2010, the average number of robotic surgical systems per state increased from 2 to 26.3, while the unadjusted rate of surgery increased from 37.5% to 52.4%, radiation therapy decreased from 43.3% to 30.2%, and active surveillance increased from 7.0% to 9.3%. For every 10 additional robotic systems installed in a state, there would be a 2.5% increased rate of surgery (p<0.01), accompanied by a 1.3% (p=0.04) and 1.0% (p<0.01) decrease in the rate of radiation and active surveillance, respectively. Subgroup analyses suggest that the robotic adoption crowding out effect on radiation and active surveillance was driven primarily by men with stage I-II prostate cancer. If the adoption trajectory for robotic systems continues, the increased cost of treating localized prostate cancer in 2012 will be close to $27 million. Conclusions: During a period of rapid acquisition of robotic surgical systems, we found the number of robotic systems available at the state-level is significantly and directly associated with a higher rate of surgery for localized prostate cancer, and lower rates of radiation therapy and active surveillance.
The cost per patient of deviations from evidence-based standards of oncology care.
Authors: Forastiere Arlene A. , Flood William A. , Yedwab Erik , Kozlovsky Vlad , Whyler Elaine , Alley Evan W. , Frick Kevin D.
Published: March 2020

6515

Background: Practice variation contributes to the high cost of healthcare and wasteful spending; by contrast, adherence to evidence-based (EB) clinical guidelines is advocated to improve quality and potentially lower cost. We sought to estimate the average cost per patient associated with unjustified deviations from EB national standards for use of chemotherapy, supportive drugs, and radiotherapy. Methods: The ITA Partners/eviti, Inc. database of oncology treatment plans (TPs) reviewed for payers for adherence to national guideline recommendations (e.g. ASCO, ASTRO, NCI, NCCN Compendium, FDA) was used to calculate the variance in cost between submitted TPs with unwarranted deviations from EB standards and EB care. For prospective reviews, the final EB treatment given was known and for retrospective reviews, the variance was estimated based on the EB alternative with the lowest cost. AWP pricing was used to calculate chemotherapy and supportive drug costs, and Medicare pricing for radiotherapy. First order savings were calculated. An annual trend of 8% was applied from the mid-data period to 2013 (Milliman Client Report 2010). Results: From March 2009 to March 2012, a total of 2775 consecutive patients had TPs submitted and of these, 730 patients had unjustified, non-EB TPs. All cancer types, stage and treatment intent (curative, non-curative) were included. The cost of EB treatment was less than the submitted TP for 622 (85%) patients, more for 9 (1%), and zero (could not be taken due to payer plan definitions) for 99 (14%). Descriptive statistics for the cost per patient of non-EB TPs trended to 2013 showed: mean $25,579, median $13,882, standard deviation $40,958. Conclusions: In this unselected population comprising all cancers, 26% had TPs that did not conform to EB standards or could not be medically justified. Our conservative estimate of the average per patient overspend (first order) on inappropriate treatment validates the potential for quality care to lower cost and deliver huge value to patients, physicians, and payers. [Table: see text]
Sensitivity of Medicare claims to identify recurrence.
Authors: Warren Joan L , Mariotto Angela , Melbert Danielle , Schrag Deborah , Doria-Rose Paul , Penson David F. , Yabroff K. Robin
Published: March 2020

6522

Background: Cancer registries do not collect recurrence data. As a result, researchers have used health claims to impute recurrence for cancer patients by identifying cancer therapy or metastatic disease after initial treatment. The validity of this approach has not been established. We used the linked SEER- Medicare data to assess the sensitivity of Medicare claims for cancer recurrence. Methods: Although the SEER-Medicare data do not explicitly capture recurrence, we applied criteria to identify patients likely to have had a recurrence, defined as patients diagnosed with Stage II/III colorectal (CRC) and female breast cancers from 1994-2003 who received initial cancer surgery, had at least a 90-day break in treatment following initial treatment, who then died from cancer in 1994-2008. For these patients, we reviewed all claims from the end of the treatment break to death for indicators of recurrence. Indicators included additional therapy (cancer surgery, chemotherapy, RT), diagnosis codes for metastasis, and end-of-life care. We used multivariate logistic regression analysis to evaluate patient factors associated with receipt of additional cancer therapy. Results: The first indicator of recurrence for CRC patients (n=6,910) and breast patients (n=3,826) was additional therapy (38.8% and 35.2%), metastasis diagnosis codes (36.0% and 45.7 %), or end-of-life care (16.7% and 12.8 %). Eight percent of patients had no indicator of recurrence before death; 40% of patients had no additional cancer therapy before death. Patients age 70 and older were less likely to have additional therapy (p<0.05), in adjusted analyses. Conclusions: Identifying recurrence through additional cancer therapy will miss about 40 percent of patients with recurrences; particularly older patients. Over 20% of patients with recurrence were first identified by hospice admission, late in the course of their illness, or had no indicator of recurrence in the claims. We conclude that Medicare data have limited potential to identify cancer recurrence. These findings may not apply to younger cancer patients, who are more likely to undergo additional cancer treatment for recurrence.
Impact of care at NCI-designated comprehensive cancer centers (NCICCC) on outcome in adolescents and young adults (AYA) with central nervous system tumors (CNSt).
Authors: Wolfson Julie Anna , Sun Can-Lan , Kang Tongjun , Bhatia Smita
Published: March 2020

6537

Background: AYA (15-39y) have not seen survival improvement as in younger or older ages with similar cancer diagnoses, leaving an AYA Gap. Pediatric protocol use is associated with superior survival among 15-21y-olds, but impact of site of care for complex diseases with poor prognosis (such as CNSt) that require multidisciplinary, evidence-based care available at NCICCC, are unstudied. Methods: We constructed a cohort of 746 AYA with newly diagnosed CNSt, reported to the LA cancer registry from 1998-2008; 133 (18%) were treated at the 3 NCICCC in LA county. We examined clinical (WHO grade, diagnosis (dx) year, site of care) and demographic (age at dx, gender, SES, insurance, race/ethnicity) variables univariately; we included only those with p<0.1 in the final multivariable model (retaining WHO and NCICCC). Analysis was stratified by time from dx (≤2y, n=746; >2y, n=493) to examine impact of care at NCICCC among AYA with aggressive disease (resulting in death within 2y from dx) vs. those who survived 2y from dx – representing disease likely amenable to new strategies for control. Results: 5y overall survival (OS) was 59% and did not differ by site of care (p=0.2). Multivariable analysis restricted to the first 2y revealed an increased risk of death among those with high WHO grade (HR 4.7, p<.0001); public/no insurance (HR 1.7, p=0.0006); and African American/Asian (HR 2.1, p=0.0006) or Hispanic (HR 1.4, p=0.08) origin; site of care did not impact mortality. Among 2-y survivors, high WHO grade (HR 1.7, p=0.002) continued to be associated with increased risk of death. However, receipt of care at non-NCICCC site (HR 1.6, p=0.056) was also associated with increased risk of death. Examination of access to care at NCICCC revealed that after adjusting for WHO grade and gender, older age (22-39y (OR 0.3, p<0.0001), low SES (OR 0.6, p=0.04), and non-white ethnicity (OR 0.5, p=0.004), decreased likelihood of care at NCICCC. Conclusions: Population-based data reveal better OS in 2-y AYA survivors of CNSt receiving care at NCICCC. Older AYAs from low SES and non-white backgrounds are less likely to use NCICCC. AYA barriers to accessing NCICCC care are currently being explored.
The cost implications of prostate cancer screening in the Medicare population.
Authors: Ma Xiaomei , Wang Rong , Long Jessica B. , Ross Joseph S. , Soulos Pamela R. , Yu James B. , Makarov Danil V. , Gold Heather Taffet , Gross Cary Philip
Published: March 2020

6549

Background: Recent debate about prostate specific antigen (PSA)-based testing for prostate cancer screening among older men has rarely considered the cost associated with screening. Methods: We assembled a population-based cohort of male Medicare beneficiaries aged 66-99 years who had never been diagnosed with prostate cancer at the end of 2005 (n = 84,699) and followed them for two years to assess the cost of PSA screening and downstream procedures (biopsy, pathology, and hospitalization due to biopsy complications) at both the national and the hospital referral region (HRR) level. The relation of screening cost to stage of prostate cancer at diagnosis at the HRR level was analyzed using multivariate Poisson models. We also evaluated the initial treatment cost of Medicare fee for service beneficiaries diagnosed with prostate cancer during 2006-2007 (n = 31,653). Results: Approximately 42.8% of the 84,699 men received PSA screening tests during the two-year study period, with 2.4% undergoing biopsy. The annual expenditures by the national fee for service Medicare program were $454 million for screening and $1.79 billion for initial treatment (in 2009 US dollars). The mean annual screening cost at the regional (HRR) level ranged from $16 to $65 per beneficiary. Downstream biopsy-related procedures (biopsy, pathology, and hospitalization due to biopsy complications) accounted for 73% of the overall screening costs and varied significantly across regions. Compared with men residing in HRRs that were in the lowest quartile for screening expenditures, men living in the highest HRR quartile were significantly more likely to be diagnosed with prostate cancer of any stage [incidence rate ratio (IRR) = 1.23, 95% confidence interval (CI): 1.07-1.42] and localized cancer (IRR = 1.31, 95% CI: 1.13-1.53). Conclusions: Medicare prostate cancer screening-related expenditures are substantial, vary considerably across regions, and are positively associated with rates of cancer diagnosis.
Longitudinal trends in costs for palliative radiation for metastatic prostate cancer.
Authors: Robinson Timothy J , Dinan Michaela A , Li Yanhong , Lee Robert , Reed Shelby D.
Published: March 2020

6554

Background: Prostate cancer is a leading contributor to cancer health care costs, with end of life care composing a substantial portion of overall costs. In recent years, palliative treatment of metastases has been characterized by the use of more complex radiation planning and delivery systems. However, little is known about how costs of palliative radiation treatment in patients with metastatic prostate cancer have changed over this period. Methods: Retrospective analysis of SEER-Medicare data of men aged 66 and older who died from metastatic prostate cancer between 2000 and 2007. Inclusion criteria included all fee-for-service beneficiaries treated with radiation therapy for bony metastases in the last year of life. Direct costs were obtained by summing Medicare carrier and outpatient facility payments for all radiation treatment claims following an initial radiation treatment claim for bony metastases and adjusted to 2008 dollars using Consumer Price Indexes for medical care. Results: A total of 1,705 men met study inclusion criteria. Median age at diagnosis was 74, median time from diagnosis to death was 47 months, and 37% of men had distant metastatic disease at the time of diagnosis. Total Medicare payments for radiation therapy for bony metastases increased from an average of $2,763 to $3,989 for men who died from prostate cancer in 2000 vs. 2007. Outpatient facility claims for radiation therapy increased relative to carrier claims, composing 48% ($1,316) and 57% ($2,276) of all radiation treatment Medicare payments in 2000 vs. 2007 (All P < 0.001). Conclusions: Between 2000 and 2007, average Medicare payments for palliative radiation therapy for bony prostate cancer metastases increased by roughly a third. The majority of increased costs were observed within outpatient facility claims, suggesting a shift in the administration of palliative radiation therapy from free-standing clinics to hospital-based outpatient facilities. Changes in end of life palliative radiation therapy for men with prostate cancer may impact future increases in Medicare health care expenditures.
Risk for dose-limiting chemotherapy-induced peripheral neuropathy in black women with breast cancer.
Authors: Speck Rebecca M , Farrar John T , Sammel Mary D , Mao Jun J , Stineman Margaret G , Hennessy Sean , DeMichele Angela
Published: March 2020

6560

Background: Chemotherapy induced peripheral neuropathy (CIPN) is a potentially dose-limiting toxicity. Recent data from early stage breast cancer clinical trials has suggested that black women are at increased risk for CIPN. We examined whether black race was a risk factor for dose-limiting CIPN events in a general academic practice. Methods: This retrospective cohort study included 260 women, (27.3% black) that received neoadjuvant or adjuvant paclitaxel for non-metastatic breast cancer. The primary outcome was a dose-limiting (DL) event (dose delay, dose reduction, or treatment discontinuation) attributed to CIPN (DL-CIPN). Cox proportional hazards models were used to analyze patient level and treatment level factors related to DL-CIPN. Survival time was represented by cumulative dose in milligrams of paclitaxel received. The final model included independent risk factors (p<0.05) of DL-CIPN and confounders that when adjusted for altered the crude estimate by 10% or more. Results: There were 39 DL-CIPN events; 5 were excluded from analyses for being a subsequent event. For the 34 DL-CIPN events, the median cumulative dose received at time of DL-CIPN event was 925 mg (range=256-1520 mg), which differed significantly (p<0.001) from the 188 women who had no dose-limiting event of any cause (median=1272, range=928-2136 mg). Black race was the only statistically significant independent risk factor for DL-CIPN. Compared to whites, black women had a greater than two-fold increased risk of DL-CIPN (HR=2.29, 95%CI=1.17-4.50). After adjusting for oncologist, menopausal status, obesity (BMI≥30), and regimen (80mg/m2 weekly for 12 cycles vs. 175mg/m2 bi-weekly for 4 cycles) the risk of DL-CIPN for blacks compared to whites was HR=3.35 (95%CI=1.54-7.28). Conclusions: Our findings contribute to the growing body of evidence that black race is associated with CIPN symptom onset and severity. Efforts to elucidate mechanisms, increase clinicians’ awareness of the greater susceptibility of black women to CIPN, and the development of symptom management strategies, effective in ensuring adequate adherence to chemotherapy, are crucial.
Uptake and disparities of neoadjuvant therapy for stage III non-small cell lung cancer.
Authors: Becker Daniel Jacob , Levy Benjamin Philip , Grossbard Michael L.
Published: March 2020

6571

Background: The optimal use and sequence of radiation therapy (RT), chemotherapy, and surgery for patients with stage III non-small cell lung cancer (NSCLC) is unknown. We conducted a cross-sectional study using the Surveillance Epidemiology and End Results (SEER) population-based cancer registry to examine the relationship between year of diagnosis and receipt of neoadjuvant RT for patients with stage III NSCLC diagnosed in the United States from 2000 to 2008, with additional focus on the role of race and treatment location. Methods: Thirteen SEER registries were used for data analysis. Patients diagnosed with stage III NSCLC treated with both surgery and RT between the years 2000 and 2008 were included. We used multiple logistic regression to describe the relationship between type of therapy for lung cancer and year of diagnosis. Covariates identified for analysis included age, grade, sex, race, ethnicity, and SEER registry. Results: The total sample size was 393,711 of which 5,949 patients met our inclusion criteria. The cohort had a mean age of 64, was predominantly white (85.8%) and had predominantly high grade tumors (50.9%). Use of neoadjuvant RT for stage III NSCLC was lowest in 2000 and higher in every year from 2002 to 2008 (OR 1.325 in 2002, p= 0.035; 1.921 in 2007, p<0.0001). Substantial heterogeneity among registries existed, with more neoadjuvant RT use in Seattle and San Francisco-Oakland (OR 1.83, 1.698 p<0.0001 and 0.0002 respectively) and less use in Metropolitan Detroit, New Jersey and Louisiana (OR 0.754, 0.570, 0.493, p=0.25, <0.0001, and <0.0001 respectively). Black race was significantly associated with lack of neoadjuvant therapy without controlling for registry, but the association weakened after controlling for registry (OR 0.81, p=0.072). Conclusions: The use of neoadjuvant RT for stage III NSCLC substantially increased from 2000 to 2008. Location of treatment was strongly associated with receipt of neoadjuvant therapy and outweighed the association of race and therapy. The effort to equitably distribute care should focus additional study on the important role of regional and local medical culture in determination of medical care.