bluuebunny/crossref_metadata_2025 huggingface dataset:
Everolimus (RAD) as treatment in breast cancer patients with bone metastases only: Results of the phase II RADAR study.
Authors: Maass Nicolai , Harbeck Nadia , Mundhenke Christoph , Lerchenmuller Christian A. , Barinoff Jana , Lueck Hans-Joachim , Ettl Johannes , Aktas Bahriye , Kuemmel Sherko , Roesel Siegfried , Wagner Steffen , Müller Lothar , Bischoff Joachim , Luebbe Kristina , Schwedler Kathrin , Schmidt Marcus , Bauerschlag Dirk , Nekljudova Valentina , Loibl Sibylle , Von Minckwitz Gunter ,   German Breast Group
Published: March 2020

556

Background: RAD001 is an orally bioavailable rapamycin ester analogue, which acts by selectively inhibiting mTOR (mammalian target of rapamycin), a key player in downstream signaling of different pathways. In vitro, RAD stops formation and activity of osteoclasts. Treating progressive bone metastases in breast cancer (bc) with RAD seems reasonable. Methods: We evaluated RAD in a placebo-controlled, phase II, randomized discontinuation study in bc patients (pts) with bone metastases only. Pts were eligible if they had HER2-negative, hormone-receptor (HR)-positive or –negative bc, with a maximum of 2 previous lines of endocrine therapy (ET) and 1 previous line of chemotherapy (CT). All pts received zoledronate and pts with HR-positive bc could receive ET. All pts started with RAD during a run-in phase of 8 weeks. Pts with stable disease were randomized to RAD or placebo; pts with response continued with RAD and pts with progression went off study. Primary outcome was time to progression (TTP) in pts being stable on 8 weeks of RAD. It was assumed that placebo would obtain a median TTP of 8 weeks which would be increased to 16 weeks, thus requiring 76 randomized pts. It was expected that 70% of all pts would have stable disease after the run-in phase. Overall, 110 pts were needed. Due to slow recruitment and dysbalance between randomized and discontinued pts, recruitment stopped in 12/ 2010. Results: From 11/06 until 12/10, 89 pts were enrolled. Median age was 59.5 years. 93% had HR-positive disease. 15% had prior chemotherapy; 58% had prior ET for metastases. 1/3 received concomitant ET. Three pts did not start therapy, 41 discontinued during run-in phase, 32 due to progression. Six continued as responder. 39 pts with SD after run in phase were randomized to RAD or placebo. Twenty-seven stopped due to progression; 9 discontinued due to AE, 4 are still on treatment. 15 pts had 20 serious adverse events; 1 hyperglycemia and one alveolitis. The TTP in patients with RAD was 8.5 months vs. 2.9 months with placebo (HR: 0.559; 95% CI [0.284-1.10] p=0.092. Conclusions: Pts with bone metastases only had a longer TTP on RAD compared to pts on placebo. Overall 7/89 showed a sustained response on RAD + zoledronate ± ET.
Head and neck cancer in Fanconi anemia and dyskeratosis congenita.
Authors: Alter Blanche P , Giri Neelam , Savage Sharon H
Published: March 2020

5563

Background: Fanconi Anemia (FA) and dyskeratosis congenita (DC) are inherited bone marrow failure syndromes (IBMFS) with extraordinarily high risks of cancer, particularly head and neck squamous cell carcinoma (HNSCC). The standardized incidence ratios (SIR) for solid tumors are 40 in FA and 10 in DC, and for HNSCC 700 and 900 respectively. In the general population, cancers of the oropharynx may be associated with human papilloma virus (HPV) more than the oral cavity. The specific locations of HNSCC in FA and DC have not been reviewed, and thus the hypothetical role of HPV in these cancers is unknown. Methods: Literature cases were reviewed through PubMed searches using the terms “Fanconi anemia” and “dyskeratosis congenita”. All papers were reviewed, and details of the specific cancers recorded. FA literature included reports from 1927 through 2011, and DC literature from 1910 through 2011. Participants in the National Cancer Institute (NCI) IBMFS retrospective/prospective protocol (NCI 02-C-0052, opened in 2002) were also analyzed for cancer. The HPV vaccine was not available during most of the time frame of this study. Results: There were 411 cases of cancer among 2190 (19%) cases of FA described individually in the literature, and 21 cancer cases out of 116 (18%) FA patients in the NCI cohort. HNSCC were reported in 112 FA literature cases (5%), and 9 (8%) in the cohort. The oropharynx was the initial site for HNSCC in 31/112 literature cases (28%) and 3/9 NCI cases (33%). With regard to DC, 51/647 (8%) cases in the literature had cancer, as did 9 of 94 (10%) NCI participants. HNSCC were reported in 21/647 (3%) DC literature cases, and in 5/94 (5%) from the NCI cohort. Four of the 21 HNSCC (19%) in the literature were oropharyngeal, and 2/5 (40%) in the NCI cohort. The cumulative incidences of any HNSCC in the NCI FA and DC cohorts were 50% and 21% by 40 years of age (censored at death from other causes). Conclusions: Patients with FA and DC have extremely high risks of HNSCC at substantially younger ages than the general population. Approximately 30% of these cancers occur in the oropharynx. The HPV vaccine could be important in prevention of these cancers. Future studies of the HPV status of oral cavity and oropharynx HNSCC tumors from patients with FA and DC will be informative.
Should age affect our treatment decisions for head and neck cancer?
Authors: Carballido Estrella M. , Burton Jon N , Pelayo Miguel Ricardo , McCaffrey Judith C , Padhya Tapan , McCaffrey Thomas V , Trotti Andy , Rao Nikhil G , Reich Richard , Tanvetyanon Tawee , De Conti Ronald C. , Kish Julie Ann
Published: March 2020

5564

Background: Current opinion suggests elderly patients (pts) with head and neck cancer, those 65 or older, do not tolerate surgery, chemotherapy, or radiation as well as their younger counterparts. If this holds true, elderly pts may not be offered standard treatments to prevent assumed complications. Methods: A retrospective cohort study at our comprehensive cancer center was conducted of newly diagnosed pts with head and neck squamous cell carcinoma to explore differences in treatment-related complications between older and younger groups. We included data from the first 199 eligible pts (99 younger than 65 year old and 100 older than 65) evaluated between April 2009 and June 2010. Results: 79% of pts receiving treatment were male with a mean age of 54.9 and 71.6 years for the younger and older groups respectively. The older group had significantly more comorbidities (p < 0.001). The majority of older pts presented with oral cavity tumors (46%) while the oropharynx was the predominant site in the younger group (45%). 55% of younger and 49% of older pts presented with stage 4 disease across all sites. A total of 51 pts were p16 positive with no statistical differences between the groups. Surgery was the initial treatment for 57% of older pts (p < 0.008) while 46% of younger pts received concurrent chemotherapy and radiation as the primary treatment (p < 0.008). There was no statistically significant difference in surgical or radiation complications between the groups. Although most pts receiving chemotherapy experienced complications, older pts had slightly more (93% vs. 78%; p<0.031). The mean survival was 24.8 months with no statistical difference between groups. Significantly more pts in the older group, at last follow-up, were disease free (p < 0.012). Conclusions: The treatment of elderly pts with head and neck squamous cell carcinoma in our experience was congruent with that of younger pts. Elderly pts did not suffer more complications with surgery or radiation, however chemotherapy produced somewhat more complications in the elderly pts. Elderly pts did display less evidence of disease on follow-up. Age is always a consideration when treating individuals, but should not preclude the curative standard.
Correlation between PI3K/PTEN/AKT/mTOR pathway genetic variations and clinical outcome in patients with squamous cell carcinoma of the head and neck receiving cetuximab-docetaxel treatment.
Authors: Fusi Alberto , Pfisterer Katharina , Klinghammer Konrad Friedrich , Knoedler Maren , Nonnenmacher Anika , Keilholz Ulrich
Published: March 2020

5572

Background: The PI3K/PTEN/AKT/mTOR pathway is one of the most targeted in human cancers and alterations in the axis are frequent events in squamous cell carcinoma of the head and neck (HNSCC). Specific genetic variations in this pathway have been associated with variation in recurrence, survival and response in lung cancer and esophageal cancer. The aim of this study was to determine whether single nucleotide nucleotide polymorphisms (SNPs) in AKT1, AKT2, FRAP1, PI3KCA and PTEN identified in other cancers were associated with treatment response and clinical outcome in patients with HNSCC. Methods: Genomic DNA was extracted from FFPE tissue specimens of 45 patients with recurrent or initially metastatic HNSCC who received a combined treatment with docetaxel and cetuximab in a phase II study. Eleven single SNPs in the genes AKT1, AKT2, FRAP1 (mTOR), PIK3CA and PTEN were genotyped by means of Real Time PCR system or by direct sequencing and analysed for association with response to therapy and survival. Results: None of the SNPs was related to treatment response. Two SNPs (AKT2:rs8100018 and PTEN:rs12569998) were associated with variation in progression risk. The AKT2:rs8100018 homozygous variant resulted in increased risk, with a HR of 4.83 (95% CI, 1.11-21.03) and the PTEN:rs12569998 homozygous variant in an increased risk, with a HR of 2.36 (95% CI, 1.24-4.50). AKT2:rs8100018 and PTEN:rs12569998 genetic variation had an additive effect on risk of tumor progression. The AKT2:rs8100018 homozygous variant was significantly associated with overall survival (OS) with HR of 3.57 (95% CI, 1.06-12.00) while presence of one of the two variant alleles of AKT1:rs3803304 with a lower risk of death (HR: 0.51; 95% CI, 0.27-0.97). Conclusions: We found significant associations between common genetic variants in the PI3K/PTEN/AKT/mTOR pathway and outcome in patients with HNSCC. Despite the small sample size, patient cohort and treatment were homogeneous. As a consequence, evaluation of SNPs as a host factor may be considered in addition to tumor-specific mutations for personalized treatment development.
Gene expression as a predictor of radiotherapy or chemoradiotherapy response in head and neck squamous cell carcinoma patients: A molecular approach.
Authors: Lopez-Pousa Antonio , Leon Xavier , Quer Miquel , Quintana Ana , Vila Luis , Camacho Mercedes , Sullivan Ivana , Gallego Rubio Oscar , De Vega Josep M. , Farre Nuria , Barnadas Agust ,   Hospital Sant Pau
Published: March 2020

5590

Background: There are not validated markers of radioresistance in patients with a head and neck squamous cell carcinoma (HNSCC). The objective of our study was to explore the relationship between response to radiotherapy and the expression at transcriptional level of a panel of genes related with the HNSCC carcinogenic process. Methods: The study group was 76 consecutive HNSCC patients treated with radiotherapy (n=51) or chemoradiotherapy (n=25) with curative intention, and a minimum follow-up of three years. Thirty-seven patients were T1-T2 tumors and 16 had an advanced tumor (T3-T4). Biopsy specimens were performed from the primary tumor before treatment and conveniently stored until processing. Expression of genes related with cell cycle (cyclin D1), apoptosis (Bcl-XL), angiogenesis (VEGF), inflammation (IL-8), and tissue invasiveness (MMP-2 and MMP-9) were examined using a RT-PCR method. The continuous value of the mRNA expression level was evaluated with a classification and regression tree (CRT) method, considering the local control of the disease achieved with radiotherapy as the dependent variable. Results: During the follow-up 26 patients (33.8%) had a local failure. The CRT method found a significant relationship between VEGF and MMP-9 expression and local control of the disease. According the expression level of VEGF and MMP-9 the patients were classified in three groups: the A group (n=19) defined by a low expression of VEGF, the B group (n=19) defined by a high expression of VEGF and a low expression of MMP-9 and the C group (n=38) defined by a high expression of both VEGF and MMP-9. The 5-year local recurrence free survival was: A group 94.7% (CI 95%: 84.7-100%), B group 83.3% (CI 95%: 66.1-100%), and C group 37.6% (CI 95%: 21.0-54.2%). There were significant differences in the local control of the disease according to the VEGF and MMP-9 expression values (test log rank, P<0.0001). Conclusions: Expression of VEGF and MMP-9 genes may be a radiosensitivity marker for patients with HNSCC treated with radical intention. We didn’t find prognostic significance for other genes explored.
Impact of exogenous female hormone use (EHU) on breast cancer (BC) recurrence as assessed by the 21-gene assay (Oncotype DX).
Authors: Ledesma Wendy M. , Onitilo Adedayo A. , Zhang Chong , Kim KyungMann , Andreason Molly , Charlson John A. , Ridolfi Kimberly , Engel Jessica Marie , Wisinski Kari Braun , Millholland Robert , Dean James T , Tevaarwerk Amye
Published: March 2020

563

Background: Observational studies suggest that EHU, such as oral contraceptive (OCPs) or postmenopausal hormone replacement therapy (HRT), increases the risk of developing BC. However, the prognosis of women taking EHU compared to nonusers remains controversial. The Oncotype Dx 21-gene assay RS predicts the distant recurrence risk for early stage, HR+ BC. We assessed RS in patients (pts) on EHU at diagnosis (users) vs nonusers. Methods: Retrospective chart review was conducted on BC pts with a RS, diagnosed 2005–2010. Stage, grade, estrogen (ER), progesterone (PR) and HER2 receptor status were abstracted. Manual review of medications, as well as electronic data pull within ≤5yrs of diagnosis, defined users as pts on EHU within 1 yr of diagnosis for ≥1 yr. Nonusers had been on EHU > 5 yrs before diagnosis or never. Comparisons between EHU users and nonusers were made using two-sample tests; chi-square or Fisher’s exact test for discrete data such as stage and ER status and t-test or Wilcoxon rank sum test for continuous data such as RS. All tests were at a two-sided significance level of 0.05. Results: 495 pts had RS. EHU was documentable for 475, 77 were using exogenous hormone at diagnosis. Type of hormone use included systemic HRT (48%), OCPs (36%), other (4%), and unknown (12%). For users vs nonusers, mean RS was 17 vs 19, (p=0.007, t-test). See table for other predictors. Conclusions: Prior study shows21-gene assay predict distant recurrence risk for HR+BC. In our study, an association existed between EHU and lower RS, suggesting that BC developing on EHU may have less risk of recurrence. Prospective evaluation is warranted. [Table: see text]
Prognostic factor Ki67 for breast cancer patients in each subgroup.
Authors: Niikura Naoki , Masuda Shinobu , Terada Mizuho , Terao Mayako , Kumaki Nobue , Oshitanai Risa , Morioka Toru , Tuda Banri , Okamura Takuho , Saito Yuki , Suzuki Yasuhiro , Tokuda Yutaka
Published: March 2020

565

Background: Immunohistochemical (IHC) Ki67 has described it as a prognostic and predictive marker for breast cancer. The St. Gallen Consensus Meeting determined that Ki67 labeling index is chiefly important for distinguishing between “Luminal A” and “Luminal B (HER2 negative)” subtypes and is a predictive marker for chemotherapeutic efficacy. However, the high and low cutoff points remain controversial. Our objective is to compare survival in patients with low, intermediate, and high Ki67 levels in each subgroup. Methods: We retrospectively identified all the patients in the Tokai University breast cancer database for whom IHC Ki67 data were available between January 1, 2000, and December 31, 2010. Ki67 was defined as low if <10% Ki67 was detected, as Intermediate if 10–20% Ki67 was detected, and as high if >20% Ki67 was detected. To assess Ki67 levels and survival outcomes, survival curves were calculated using the Kaplan–Meier method and compared using the log-rank test. Results: We identified 1331 primary breast cancer patients without metastasis, of whom 686 received neoadjuvant or adjuvant chemotherapy. Patients with high Ki67 had poorer relapse-free survival (RFS) than patients with intermediate (p = 0.009) and low Ki67 (p < 0.001). Patients with intermediate Ki67 had poorer RFS than patients with low Ki67 (p < 0.001). In ER-positive cases (n = 1059), patients with high and intermediate Ki67 had poorer RFS than patients with low Ki67 (p < 0.001 and p = 0.002, respectively). In HER2-positive and ER-negative cases (n = 103), patients with high Ki67 had poorer RFS than patients with low Ki67 (p = 0.002). In triple-negative cases (n = 164), patients with high Ki67 tended to have poorer RFS than patients with low Ki67 (p = 0.064). Conclusions: Our data demonstrated that low, intermediate, and high Ki67 levels may be used to differentiate prognosis in ER-positive cancer patients as well as HER2-positive and triple-negative cancer patients.
Prospective study of the impact of using the 21-gene recurrence score assay on clinical decision making in women with estrogen receptor-positive, HER2-negative, early-stage breast cancer in France.
Authors: Gligorov Joseph , Pivot Xavier B. , Naman Herve L. , Jacot William , Spaeth Dominique , Misset Jean-Louis , Largillier Remy , Sautiere Jean-Loup , de Roquancourt Anne , Pomel Christophe , Rouanet Philippe , Rouzier Roman , Penault-Llorca Frederique Madeleine ,   Francilian Breast Intergroup
Published: March 2020

568^

Background: The 21-gene Oncotype DX Recurrence Score (RS) is a validated assay to help inform the appropriate treatment of estrogen receptor-positive (ER+), early stage breast cancer in the adjuvant setting. Treatment traditions regarding choice of adjuvant treatment vary significantly in different countries. This prospective multicenter study is the first to assess the impact of using the Oncotype DX assay in the French clinical setting. Methods: A total of 100 consecutive patients with ER+, HER2-negative, node negative or pN1 (mi) breast cancer were enrolled. Overall treatment recommendation change, change from chemoendocrine to endocrine alone and change from endocrine alone to chemoendocrine treatment were recorded. Medical oncologists completed questionnaires regarding their confidence in their recommendation before and after knowing the patient’s RS. A preliminary analysis was conducted on the first 92 evaluable patients with data available at the time of abstract submission. Final data will be presented at the meeting. Results: Prior to Oncotype DX 49% of patients were recommended chemoendocrine treatment and 51% endocrine treatment alone. After having the RS, 26% were recommended chemoendocrine treatment and 74% endocrine treatment alone. The overall reduction in chemotherapy recommendation from 49% to 26% was significant (p<0.001). Of patients originally recommended chemoendocrine treatment, 58% were changed to endocrine treatment alone after having the RS. Of patients originally recommended endocrine treatment, 11% were changed to chemoendocrine treatment after receiving the RS. There was a significant improvement in physician confidence in treatment recommendations (p=0.002) when using Oncotype DX. Conclusions: These are the first prospective data regarding the impact of using Oncotype DX in France. Using Oncotype DX was associated with a significant change in treatment decisions and an overall reduction in chemotherapy use. The data are consistent with those presented from Germany, Spain, the UK and the US.
Breast cancer in Sub-Saharan Africa: 1,000 patients with primary breast cancer in Addis Ababa followed for up to 5 years.
Authors: Kantelhardt Eva Johanna , Zerche Peter , Trocchi Pietro , Mathios Assefa , Reeler Anne , Tufa Gemechu , Yonas Bekuretsion , Stang Andreas , Thomssen Christoph , Bogale Solomon Desalegne
Published: March 2020

580

Background: There is little information on breast cancer (BC) patients (pts) receiving standardized treatment in Sub-Saharan Africa. This study evaluates pts presenting 2005-10 at the University Radiotherapy Center in Addis Ababa, the only institution in the country offering standardized radiotherapy, systemic therapy and free endocrine treatment (ET) during that time. Methods: All pts with histologically verified BC were included. Ethical approval was obtained. Axios/AstraZenaca provided free ET. Therefore, the majority of pts underwent regular follow-up (FUP). We analyzed survival at 18 months by means of Kaplan-Meier survival analysis. We assumed right-censoring to be unrelated to the risk of metastasis. In a worst case sensitivity analysis, we considered all censored pts developing metastasis. Results: Pts with primary diagnosis between July 1st, 2005 and December 31st, 2010 were included (n=1303). The majority of pts were female (95.2%), most (52.3%) postmenopausal. Mean age was 44.1yrs (20-88yrs). Stages 1-4 presented in 3/19/53/25% respectively (36% unknown). Grade 2 tumors were seen in 434 out of 574 pts (58%). Estrogen receptor was pos. in 251 out of 381 pts (66%). Most M0-pts (n=942) underwent surgery (84%), received chemotherapy (59%), and received ET (63%). Median FUP was 18.4 months, 186 events (metastases) occurred. Metastasis-free survival (MFS) was 86%. Worst case analysis on censored observations revealed that MFS declined down to 52%. Pts with early stage 1/2 showed a better MFS than pts with stage 3 disease (93 to 77%). Surgery (no surgery 78% vs surgery 87%) and ET (79% vs 89%) improved MFS. The 5-year MFS for stage 1/2 was 78% and stage 3 was 38%. Conclusions: To our knowledge this is the first presentation of clinical features in 1300 pts with BC in Sub-Saharan Africa. Most pts in Addis Ababa (AA) are <45yrs and present at stage 3/4. Differences to 5-year MFS from Europe stage 1/2 around 90% (AA 78%) and stage 3 around 70% (AA 38%) are smaller in pts treated with surgery and ET. This data is consistent with overall survival in a treated pt cohort from Uganda stage 1/2: 74% and stage 3/4: 39% (n=285) (Gakwaya Brit J Cancer 2008). Policies should focus on earlier presentation and access to care.
Comorbidity, chemotherapy toxicity, and outcomes among older women receiving adjuvant chemotherapy for breast cancer (BC).
Authors: Klepin Heidi D. , Pitcher Brandy , Ballman Karla V. , Kimmick Gretchen Genevieve , Kornblith Alice B. , Cohen Harvey Jay , Hurria Arti , Winer Eric P. , Hudis Clifford , Muss Hyman Bernard
Published: March 2020

6015

Background: Comorbidity increases with age. We evaluated how comorbidity was associated with toxicity and clinical outcomes among older women with BC who received adjuvant chemotherapy. Methods: Cancer and Leukemia Group B (CALGB 49907) enrolled 633 women ≥65 years with early stage BC and randomized them to standard adjuvant chemotherapy (AC or CMF) or capecitabine (N Eng J Med 360:2055, 2009). 329 women on the Quality of Life companion study completed a pre-treatment health survey (Older American Resources and Services Questionnaire, physical health subscale). The survey evaluates 14 conditions and the degree to which each interferes with daily activities (rated from 1 “not at all” to 3 “a great deal”). Comorbidity was analyzed as follows: 1) total number 2) comorbidity burden score (summed conditions multiplied by interference rating); and 3) individual diseases. Primary outcomes were: 1) grade 3-5 toxicity (incident and cumulative); 2) time to relapse (TTR), and 3) overall survival (OS). Contingency table methods were used to evaluate the association between comorbidity and toxicity. Cox proportional hazards models were used to evaluate TTR and survival outcomes. Results: Among 329 women [median age 71 years (range 65-89), 86% white, 98% ECOG performance score 0-1, 75% stage 1-2] the median number of comorbidities was 2 (0-10), median comorbidity burden score was 3 (0-25), and most common conditions were arthritis (58%) and hypertension (54%). Few patients had diabetes (17%), heart disease (16%), and pulmonary disease (9%). No comorbidity measure was associated with toxicity or TTR. With a median follow-up of 5.4 years, increasing comorbidity was associated with shorter OS. For each additional comorbid condition the hazard of death increased by 18% (HR 1.18 [95% CI; 1.06-1.33]) after adjusting for age, tumor size, treatment, node status and receptor status. Comorbidity burden score was similarly associated with OS (HR 1.08 [95% CI; 1.03-1.14]), while no specific condition was independently associated. Conclusions: Among older women with good functional status, comorbidity was not associated with toxicity or BC relapse. However, comorbidity burden was associated with shorter OS.
A critical evaluation of oncology clinical practice guidelines.
Authors: Reames Bradley Norman , Krell Robert Wallace , Ponto Sarah Nicks , Wong Sandra L.
Published: March 2020

6020

Background: Clinical Practice Guidelines (CPGs) play an essential role in cancer care today, but there are significant concerns regarding their content and reliability. In 2011, the Institute of Medicine (IOM) report “Clinical Practice Guidelines We Can Trust” created standards for developing trustworthy CPGs. Using these standards as a benchmark, we sought to evaluate recent oncology guidelines. Methods: CPGs and consensus statements addressing the screening, evaluation or management of the four leading causes of cancer-related mortality in the US (non-small cell lung, breast, prostate and colorectal cancers) published between January 2005 and December 2010 were identified using MEDLINE. A standardized scoring system based on the eight standards set forth by the IOM was devised, and the methodology, content and disclosure policies of CPGs were critically evaluated by four independent reviewers. All CPGs were given two scores; points were awarded out of a possible 8 major criteria and 20 sub-criteria. Results: We identified 168 CPGs for inclusion in the study; 45% were from US groups. None of the CPGs fully met all the IOM standards. On average, CPGs only met 2.8 of 8 standards set forth by the IOM (mean 2.8 points out of 8, SD 1.7; 8.3 out of 20, SD 4.3). Less than half of CPGs were based on a systematic review. Only half of CPG panels addressed conflicts of interest. Overall, the CPGs were most consistent with IOM standards for transparency regarding the development process, articulation of recommendations, and use of external review. Most did not comply with standards for inclusion of patient and public involvement in the development or review process, nor did they specify their process for updating. CPGs from the US had higher overall scores than CPGs from international groups. CPGs addressing non-small cell lung cancer had higher overall scores (mean 3.9) than those for other cancers. Conclusions: The vast majority of oncology CPGs fails to meet the IOM standards for trustworthy guidelines. Notably, most CPGs are not based on systematic reviews, lack full disclosure, and do not include all relevant stakeholders in the guideline process. This highlights the need for improved CPG development processes.
Trade-offs associated with axillary lymph node dissection: Implications of the eligibility versus enrollment in ACOSOG Z0011.
Authors: Krishnan Monica Shalini , Recht Abram , Bellon Jennifer Ruth , Punglia Rinaa S.
Published: March 2020

6022

Background: Results from ACOSOG Z0011 suggest axillary lymph node dissection (ALND) may not be necessary for patients following positive sentinel lymph node biopsy (SLNB). Concerns have been raised regarding generalizability of this trial, given the low-risk patient population. It is uncertain whether a subgroup who would have been eligible for ACOSOG Z0011 but were not adequately represented in the study may still benefit from ALND. Methods: We constructed a decision analysis using a Monte Carlo model to simulate axillary recurrence risk, lymphedema, and quality of life of women aged 45, 55 and 75 y/o with Stage II cancers following breast conserving surgery (BCS) with positive SLNB who were then treated with ALND and whole-breast radiation (BRT) or BRT alone. Women were divided into two risk groups based on the Memorial Sloan-Kettering Cancer Center non-sentinel lymph node (NSLN) nomogram: those with risk of residual nodal involvement of 30-60% (high risk); and those with risk less than 30% (low risk, similar to the Z0011 patients). Probabilities and utilities for health states were derived from prior studies. Results: BRT alone resulted in improved quality-adjusted life expectancy (QALE) in the low-risk group, while ALND with BRT resulted in improved QALE in the high-risk group. Overall survival (OS) was similar at 5 years with both treatment strategies in both groups but was superior with ALND at 20 years in the high risk group (Table). Differences in outcomes decreased with increasing age. In the low-risk group, sensitivity analysis showed BRT alone is preferred unless the axillary recurrence risk with BRT is greater than 1.6% or the lymphedema risk with ALND is less than 10%. In the high-risk group, ALND with BRT is the preferred strategy unless the axillary recurrence risk with BRT is less than 2.3%. Conclusions: Patients who would have been eligible for ACOSOG Z0011 but are at higher risk of having residual nodal disease following BCS and positive SLNB may benefit from ALND plus BRT rather than BRT alone. [Table: see text]
Patterns of diagnostic imaging and cumulative radiation exposure among long-term young adult cancer survivors.
Authors: Daly Corinne , Urbach David , Stukel Therese A. , Deitel Wayne , Nathan Paul C. , Paszat Lawrence Frank , Baxter Nancy N.
Published: March 2020

6027

Background: Young adults surviving a diagnosis of malignancy have a considerable life expectancy, however, little is known about radiation exposure from diagnostic imaging in these patients. This study aims to describe patterns of imaging and radiation exposure in young adult cancer survivors (YAS) and cancer-free controls in Ontario, Canada. Methods: We conducted a population-based retrospective study. Young adults aged 20-44 diagnosed with an invasive malignancy between 1992 and 1999 who lived at least 5 years without recurrent disease were identified in the Ontario Cancer Registry. YAS were matched 1:5 to randomly selected cancer-free controls on calendar year of birth, sex, and geographic location. Radiological procedures were identified through Ontario Health Insurance Plan administrative data. The rate at which individuals underwent diagnostic procedures after surviving 5-years was compared between survivors and controls using Poisson regression. Cumulative radiation exposure due to computed tomography (CT) and standard x-ray were calculated. Results: 20,911 YAS and 104,524 controls had a median of 13.5 years observation time after cancer diagnosis/referent date. The rate of CT scanning after 5 year survival was higher in YAS (rate ratio= 3.59, 95% CI: 3.46 – 3.73) and varied according to malignancy type (Table). Over the course of diagnosis, treatment and surveillance to 10 years, the average YAS was exposed to 33.8 mSv of radiation, 4.4 times the radiation exposure an individual in the general population received. 47% of YAS cumulative dose was attributed to exposure 5 years or more after diagnosis. Conclusions: YAS undergo imaging and are exposed to diagnostic irradiation at a significantly higher rate than controls even after 5 years of recurrence free survival. Alternative imaging techniques not associated with exposure to radiation should be considered for these patients. [Table: see text]
How do elderly cancer survivors fare? A comparison of characteristics, health status, health behaviors, and spending between Medicare beneficiaries with and without a cancer history.
Authors: Ke Xuehua , Zuckerman Ilene H. , Pandya Naimish B. , Shaffer Thomas , Snyder Claire Frances , Stuart Bruce C. , Davidoff Amy J.
Published: March 2020

6028

Background: Prior research on cancer (Ca) survivors has been limited to small cohorts or claims data with limited measures. In this study we used population-based survey data to characterize multiple dimensions of the survivor experience including socioceonomic status, health status and behaviors, and healthcare spending, comparing survivors to beneficiaries w/o a Ca history. Methods: Data were pooled from the 1997-2007 Medicare Current Beneficiary Survey (MCBS) including linked claims (3 yrs prior to MCBS enrollment to concurrent). Ca survivors were identified from ICD-9-CM codes on claims or self report of a prior Ca dx, survived 2+ yrs from observed Ca dx, and had no active treatment, hospice enrollment or death in the selected survivorship yr. Beneficiary characteristics and healthcare use were based on self report augmented by claims-based measures. Bivariate and multivariate analyses were used to compare survivors’ characteristics and spending to controls. Results: The study included 3,921 survivors and 7,056 subjects w/o Ca. Among survivors, breast (21%), prostate (21%), and colorectal (16%) were most common Ca sites. Compared to controls without (w/o) Ca, survivors had higher income and assets, were more likely to have supplemental medical and prescription drug coverage (74% vs. 70%), had more comorbid conditions as measured by Charlson Comorbidity Index score >=2 (18% vs. 15%), and a smoking history (60% vs. 53%); survivors were less likely to avoid visiting doctors (22% vs. 30%), and more satisfied with the quality of medical care received (96% vs. 92%). Survivors had higher annual healthcare spending (mean $12,095 vs. $8,928) and outpatient drug spending ($2,205 vs. $1,898). All differences in healthcare use and spending remained significant after adjusting for socioeconomic status, health conditions, and behaviors. Conclusions: Elderly Ca survivorshad more supplemental insurance coverage, stronger preferences for medical care, used more preventive services, and had higher spending compared to beneficiaries w/o Ca. These patterns may reflect the effects of survivorship on need for healthcare and care seeking behaviors.
Longitudinal changes in health care utilization by adult survivors of childhood cancer in the Childhood Cancer Survivor Study (CCSS).
Authors: Casillas Jacqueline N. , Liu Qi , Hudson Melissa M. , Greenberg Mark , Yeazel Mark W. , Ness Kirsten K. , Robison Leslie L. , Armstrong Gregory T. , Leisenring Wendy M. , Yasui Yutaka , Oeffinger Kevin C. , Nathan Paul C.
Published: March 2020

6030

Background: The incidence of late effects increases as childhood cancer survivors age. Survivors require lifelong care focused on the risks arising from prior cancer therapy (survivor-focused care). Methods: We assessed longitudinal changes in health care utilization in adult survivors of childhood cancer participating in the CCSS. Utilization at baseline and most recent follow-up was classified into one of three mutually exclusive hierarchical categories: no health care, general medical care, or survivor-focused care. Relative risk (RR) and 95% confidence intervals (CI) were calculated for predictors of reduction in care over time from survivor-focused to general or no care. Multivariable models, adjusted for key treatment exposures, were created to assess the risk factors for reductions in level of care over time. Results: Among 8591 eligible survivors, mean age at last follow-up was 35.1 years (SD=7.8) with a mean of 11.6 years (SD=2.2) since baseline. Of 3993 (46%) survivors who reported survivor-focused care at baseline, 2383 (59.7%) reported a lower level of care at follow-up. Among 4598 (54%) not receiving survivor-focused care at baseline, 915 (20%) reported survivor-focused care at follow-up. Baseline predictors of a decreased level of care were no health insurance (RR=1.5, 95% CI 1.2-1.9), male sex (RR=1.4, 95% CI 1.2-1.6), being 10-19 years from diagnosis compared with 20+ years (RR=1.4, 95% CI 1.1-1.7). In contrast, factors associated with a maintenance in survivor-focused care were Canadian residency compared to U.S. residency with insurance (RR=0.7, 95% CI 0.6-0.9), unemployment (RR=0.8, 95% CI 0.7-0.9), physical limitations (RR=0.7, 95% CI 0.6-0.9), cancer-related pain (RR=0.7, 95% CI 0.5-0.8), poor emotional health (RR=0.7, 95% CI 0.5-0.9), having mild-moderate (RR=0.5, 95% CI 0.4-0.6) or severe-disabling chronic health condition (RR=0.6, 95% CI 0.5-0.7). Conclusions: Less than a third of adult survivors of childhood cancer report survivor-focused care. Rates decrease over time. Targeted interventions to maximize survivor-focused care in at-risk survivors should be tested so preventive and risk-reducing opportunities are not lost.
Life expectancy (LE) and the receipt of conservative versus active treatment in men with prostate cancer (CaP): A population-based study.
Authors: Royce Trevor Joseph , Todd Jonathan , Stokes William A. , Allen Ian M. , Chen Ronald C.
Published: March 2020

6032

Background: Prostate-specific antigen (PSA) screening increases the diagnosis of low-risk and potentially clinically insignificant CaP, which raises concern for possible overtreatment. The National Comprehensive Cancer Network (NCCN) guidelines recommend surveillance (conservative management) for patients with less than 10 years LE diagnosed with low-risk cancer. In contrast, NCCN recommends active treatment for high-risk CaP, the most aggressive form of this disease, irrespective of LE. We examine patterns of care in CaP patients in the Surveillance, Epidemiology and End Results (SEER) registry by LE. Methods: 152,578 men with non-metastatic CaP diagnosed from 2004-8 were included. Gleason, PSA, and clinical stage were used for risk-categorization per D’Amico criteria. The sample was dichotomized into men 76 years and younger (who have an average LE of 10 years or more based on the US Social Security Administration actuarial period life tables) vs. 77 years and older (less than 10 years average LE). Logistic regression models examined factors associated with each treatment modality. Results: 56% of patients age 77 and older with low-risk CaP received conservative management, and 44% active treatment (Table). However, conservative management was just as common in older patients with high-risk cancer (62%); 21% of younger patients with high-risk CaP also received conservative management. Multivariable analysis showed decreased use of conservative management over time in older patients (OR 0.78 for 2008 vs. 2004, 95%CI 0.71-.86, p<.001). African American race, being unmarried, and older age were also significantly associated with conservative management. Conclusions: There may be overtreatment of low-risk CaP patients age 77 and older, which is worsening in recent years. Correspondingly, there appears to be undertreatment of elderly patients with high-risk CaP, the most aggressive form of this disease. [Table: see text]
Racial differences in delay of treatment for localized prostate cancer (CaP): A population-based study.
Authors: Stokes William Allen , Hendrix Laura H , Royce Trevor Joseph , Allen Ian M. , Wang Andrew , Chen Ronald C.
Published: March 2020

6037

Background: African-Americans (AA) are diagnosed with more advanced CaP than Caucasians (CA) and are more likely to die from CaP. Treatment delay is a potentially modifiable obstacle to care and clinically may be more important in AA patients because of more aggressive cancer at diagnosis. We examined time from diagnosis to curative treatment (surgery or radiation) in AA and CA patients in the Surveillance, Epidemiologic and End Results (SEER)-Medicare linked database. Methods: 21,454 CA and 2,506 AA patients who were diagnosed with non-metastatic CaP from 2004-08 and received treatment within 12 months of diagnosis were included. Linear regression was used to examine factors associated with number of days from diagnosis to treatment initiation, and logistic regression to assess odds of treatment within 6 months of diagnosis. Results: AA patients were more likely to have high-risk CaP than CA patients (39 vs. 35%), and less likely to have low-risk CaP (27 vs. 31%) (p<.001). Time to treatment was significantly prolonged for AA patients in all risk groups of CaP, and the difference was most prominent for high-risk patients (median 105 days for AA vs. 96 days for CA, p=.002). Racial differences in time to treatment persisted in multivariable analysis (Table). Sensitivity analyses examining the proportion of AA and CA patients initiating treatment within 6 months of diagnosis revealed similar results. Conclusions: AA patients, especially those with high-risk CaP, experience longer treatment delays than CA patients. This is the first large-scale study to examine treatment delays in AA and CA patients with CaP. The differences found may contribute to our understanding of racial disparities in CaP treatment outcomes. [Table: see text]
Utilization of accelerated partial breast irradiation for ductal carcinoma in situ, 2002-2007: Report from the National Cancer Data Base.
Authors: Czechura Tomasz , Yao Katharine , Huo Dezheng , Shaikh Arif , Winchester David Porter , Winchester David J.
Published: March 2020

6040

Background: The use of accelerated partial breast irradiation using brachytherapy (APBI-b) for patients with invasive cancer is increasing but data for ductal carcinoma in situ (DCIS) cases are limited. The American Society of Radiation Oncology (ASTRO) guidelines suggest that APBI-b should be used only on a "cautionary" or "on trial" basis for women with DCIS. The purpose of this study was to examine utilization trends and correlates of APBI-b use for patients with DCIS. Methods: A total of 70,043 postlumpectomy patients from the National Cancer Database diagnosed with DCIS between 2002 and 2007 were studied. Chi-square tests and logistic regression models were used to determine trends and factors related to APBI-b use. Results: The use of APBI-b increased from 0.7% in 2002 to 10.0% in 2007 (p<0.001). Independent predictors APBI-b use were age, race, insurance status, comorbidity index, facility type, and facility location. Older patients were more likely to use APBI-b; relative to patients 30-39 years old, the OR for patients 80-89 years old was 5.9 (95% CI: 3.7-9.6). APBI-b use was higher in whites (4.9%), compared to blacks (4.4%), Hispanics (2.8%), and Asian pacific islanders (1.5%; p<0.001). Compared to noninsured, Medicare (OR=2.1, 95% CI: 1.3-3.3) and managed care patients (OR=2.0, 95% CI: 1.3-3.2) were more likely to undergo APBI-b. 2.3% of community cancer programs, 5.7% of comprehensive community programs and 4.1% of academic/research programs utilized APBI-b for treating DCIS (p<0.001). The use of APBI-b varied significantly by facility location; the West and South regions of the country were more likely to use APBI-b (OR=14, 95% CI: 10.1-19.6) than the Northeast region. 91% of the APBI-b patients fit the ASTRO "cautionary" guideline and 9% of patients fit the ASTRO "on trial" guidelines. In 2002, 4% of ABPI-b patients fit the "on trial" guidelines which increased to 8.6% in 2007 (p<0.001). Conclusions: The use of APBI-b for DCIS increased from 2002-2007. APBI-b use varies by socioeconomic and facility factors with age being the most significant factor. Future studies are needed to determine the indications for APBI-b in patients with DCIS.
Prospective evaluation of perceived barriers to medication adherence by patients on oral antineoplastics.
Authors: Muluneh Benyam , Alexander Maurice , Deal Allison Mary , Deal Meredith , Markey Janell , Neal Jennifer , Bernard Stephen A. , Valgus John , Dressler Lynn G.
Published: March 2020

6042

Background: Appropriate use of oral antineoplastics (OA), especially those with a food-effect, is a challenge for patients and clinicians. Patient adherence is essential to optimize outcomes, minimize toxicity, minimize bias in clinical trials, and reduce health care costs. As the use of OA grows, due to the narrow therapeutic margin, it is critical to understand the barriers to patient adherence. The purpose of this study was to analyze cancer patients’ use of OAs and identify opportunities to improve patient adherence. Methods: We developed and tested a 30-question survey to address frequency and reasons for reducing/skipping doses; sources of information for OA use; perceived importance of food-drug effects, and ease of understanding directions on vial label. Surveys, consisting of Likert scale and multiple choice questions, were distributed to adult cancer patients on OAs at the UNC Cancer Hospital clinics. Results: Seventy-seven patients taking OAs with CML, RCC, breast cancer, and GI tumors completed the survey with a response rate of 97%. This was a well-educated population with 71% having completed some college; 54% female and 58% older than 50 years. Forty-three percent of patients taking drugs with a significant food-drug effect (sorafenib, pazopanib, lapatinib, imatinib, nilotinib, and capecitabine) did not think about the last time they ate before taking their OA and 23% did not know that their OA had a food-drug effect. In addition, 21% of patients indicated they intentionally skipped/cut back on their OAs and 38% of those did not inform their physician. Although 97% reported no difficulty reading instructions on drug vial, nearly 20% had some difficulty understanding the directions. Conclusions: There are three main barriers associated with appropriate use of OAs: confusion or misunderstanding about the timing of drug with food; reducing/stopping drug without informing MD; and difficulty understanding directions on the drug vial label. A multipronged integrated approach involving the pharmacist, physician and nurse is needed to optimize communication of directions for optimal OA use.
Osteoporosis screening among prostate cancer survivors treated with androgen deprivation therapy.
Authors: Morgans Alicia Katherine , Smith Matthew Raymond , O'Malley A. James , Keating Nancy Lynn
Published: March 2020

6045

Background: Androgen deprivation therapy (ADT), the standard systemic treatment for prostate cancer, has adverse effects including bone loss and fractures. Current national guidelines suggest that men receiving ADT undergo dual energy x-ray absorptiometry (DXA) before and during ADT to better characterize fracture risk. We assessed receipt of DXA testing in a population-based cohort of men treated continuously with ADT for at least 1 year and identified factors associated with testing. Methods: Using Surveillance, Epidemiology, and End Results-Medicare data, we identified men aged >65 with local or regional prostate cancer diagnosed during 2001-2007 and followed through 2009 who received at least 1 year of continuous ADT. We identified receipt of DXA testing in the 18-month period beginning 6 months before the first dose of ADT. We used logistic regression to identify factors associated with DXA testing, including patient and tumor characteristics and the physicians with whom they had outpatient visits. Results: Among 28,960 men treated with ADT for ≥1 year, 6.5% had at least one DXA scan from 6 months before the first dose of ADT through 1 year after. DXA testing increased over time, with men initiating ADT in 2007-2009 more likely to be tested than those treated in 2001-2002 (10.0% vs. 3.4%, OR 2.29, 95% CI 1.83-2.85). Men aged ≥85 were less likely than men aged 66-69 to undergo testing (OR 0.76, 95% CI 0.65-0.89). Black men were less likely than white men to undergo testing (OR 0.92, 95% CI 0.61-0.86), as were men living in areas with lower educational attainment (P<.001). Compared with men seeing a urologist but no medical oncologist or primary care provider (PCP), men seeing a medical oncologist and a urologist (OR 2.11, 95% CI 1.39-3.21) and those seeing a medical oncologist, urologist and PCP (OR 2.59, 95% CI 2.01-3.34) had higher odds of testing. Conclusions: Few men receiving ADT for prostate cancer undergo DXA testing, with particularly low rates of testing among older men, black men, and those living in areas with low educational attainment. Visits with a medical oncologist were associated with increased odds of testing. Interventions are needed to increase bone density testing among men receiving long-term ADT.