bluuebunny/crossref_metadata_2025 huggingface dataset:
TPF versus PF as induction therapy in unresectable head and neck cancer: A pharmacoeconomic analysis
Authors: Liberato N. L. , Licitra L. , Bogaerts J. , Danese G. , Marchetti M. , Quaglini S. , Rognoni C. , Rubrichi S. , Vermorken J. B.
Published: August 2020

6075

Background: Adding docetaxel to induction therapy with PF has been shown to improve overall survival of patients with head and neck cancer. On the basis of the raw data from the EORTC trial 24971/TAX 323 a pharmacoeconomic analysis has been performed. A National Healthcare System perspective and a 5-years temporal horizon have been adopted. Methods: A decision-analytic approach has been adopted, and a Markov model has been used to represent patient's weekly transitions among different health states, related to treatment (chemotherapy, radiotherapy, surgeries, palliative care) and disease status (complete/partial/no response, progression, recurrence). Constant or time-variant costs and quality of life adjustment factors have been assigned to each health state, together with transition probabilities to other states. A 3% discount factor has been used for costs sustained after the first year. The model allowed calculating expected life years (LYs), quality adjusted life years (QALYs) and costs. From these figures, incremental cost/effectiveness (ICER) and cost/utility (ICUR) ratios have been calculated. Robustness of results obtained with baseline values has been tested with probabilistic multivariate sensitivity analysis. Results: In the base case analysis, treatment with TPF yields an expectancy of 2.38 LYs and 1.53 QALYs at a cost of Euro (E) 23,018, which for PF were 1.93 LYs, 1.11 QALYs, and E 19,567, respectively. ICER and ICUR were E 7,669/LY and E 8,217/QALY, respectively. Sensitivity analyses were performed varying transition probabilities of 10%, costs of 30% and utility scores of 20% of their basal values. The analyses showed that 86% and 84% of the results lie below the threshold of E 50,000/LY and E 50,000/QALY, respectively. Conclusions: In our analysis TPF induction chemotherapy proved to be cost-effective with respect to PF, having an ICER and ICUR comparable to other widely accepted healthcare interventions.

[Table: see text]
Role of mixed lineage kinase 3 in response of head and neck squamous cancer cell lines to epidermal growth factor receptor (EGFR) inhibition
Authors: Conley B. A. , Leece C. M. , Chandana S. , Dowlashati S.
Published: August 2020

6076

Background: More efficacious treatments of head and neck squamous cancers (HNSCC) are urgently needed. HNSCC overexpress EGFR, yet the efficacy of EGFR inhibitors is marginal, with minimal effect on patient survival. Mixed lineage kinases (MLKs) are members of a large family of mitogen-activated protein kinase (MAPK) kinase kinases (MAPKKKs) that activate MAPK pathways, involving JNK, ERK 1/2 and p38 cell signaling pathways. (Gallo KA, Johnson GL, Nat Rev Mol Cell Biol. 2002;3:663–72) We explored the role of MLK3 in HNSCC as a possible therapeutic target. Methods: The requirement of MLK3 for cell proliferation and survival of HNSCC cell lines UM-SCC-38 and -47 (HPV+) (obtained from TE Carey, U Michigan) was investigated using RNA interference (siRNA) and MLK3 inhibitor K252a to inhibit the expression and activity of MLK3. Cells were also exposed to EGFR inhibitor Compound 56 at various concentrations. Proliferation was assessed with MTT after 72 h exposure. The effect of MLK3 inhibition on relevant cell signaling pathways was assessed by immunoblotting with activation-specific phosphoantibodies directed against MAPKs, the prosurvival kinase Akt and apoptotic proteins. Results: MLK3 is overexpressed in malignant HNSCC cell lines compared to normal tonsil lysate, and its expression can be inhibited by siRNA or K 252a. Inhibition of MLK3 expression is associated with downregulation of phospho-Akt and with decreased proliferation. Compound 56 inhibits proliferation at lower concentrations in HPV+ cell line UM-SCC-47 (10 microM) compared with UM-SCC-38 (25 microM), inhibits expression of pErk, and decreases expression of pAkt. Combining siRNA or K252a and compound 56 showed less pAkt expression and increased apoptosis (caspase 3 or PARP cleavage) compared with compound 56 alone. Conclusions: MLK3 may have a role in avoiding apoptosis in HNSCC cells. Its inhibition may enhance the effects of EGFR inhibition in HNSCC.

No significant financial relationships to disclose.
Effect of insulin-like growth factor 1 receptor inhibitor on sensitization of head and neck cancer cells to cetuximab and methotrexate
Authors: Hatakeyama H. , Parker J. , Wheeler D. , Harari P. , Levy S. , Chung C. H.
Published: August 2020

6079

Background: Insulin-like growth factor 1 receptor (IGF1R) is highly expressed in head and neck squamous cell carcinoma (HNSCC) and IGF1R inhibitors have been shown to modulate sensitivity to selected chemotherapeutic agents and radiation. The combination effects of an IGF1R inhibitor, MK-0646, with cetuximab or cytotoxic agents that are commonly used in the treatment of recurrent and/or metastatic HNSCC were examined in cetuximab resistant and sensitive HNSCC cell lines. Methods: The cell lines, SCC1 and its cetuximab-resistant clone 1Cc8, were treated with MK-0646, cetuximab or methotrexate, and a combination of MK-0646 and each anti-cancer drug (MK-0646 was supplied by Merck & Co., Inc.). The effect of treatments on cell proliferation and anti-tumor activity was determined using MTS assay in vitro and in vivo using mouse xenografts generated from the cell lines. Overall changes in the gene and protein expressions with the treatments were determined by DNA microarrays and western blots. Results: The IGF1R inhibitor, MK-0646, showed high-sensitivity in vitro xenograft model in SCC1 as monotherapy and increased sensitivity to cetuximab in SCC1 and to methotrexate in 1Cc8 in combination. However, MK-0646 did not inhibit cell proliferation in vitro and in vivo in 1Cc8. The gene expression array and western blot analyses showed that MK-0646 decreased expression of AKT and dihydrofolate reductase (DHFR), a target of methotrexate. Increased expressions of AKT and DHFR have been shown to associate with cetuximab and methotrexate resistance as well as radiation resistance. Conclusions: The development of tolerance in response to the IGF1R inhibitor and cetuximab is common. Whereas IGF1R inhibitors may have little therapeutic impact in cetuximab resistant, the IGF1R inhibitor may modulate response to selected chemotherapeutic agents and to radiation. The IGF1R inhibitor appears to enhance cetuximab and methotrexate response, and modulates genes associated with radiation resistance thereby providing alternative regimens for recurrent and refractory HNSCC patients who have developed resistance to initial therapies.

No significant financial relationships to disclose.
Meta-analysis of the impact of human papillomavirus on cancer risk and overall survival in head and neck squamous cell carcinoma
Authors: Dayyani F. , Etzel C. , Liu M. , Ho C. , Lippman S. M. , Tsao A. S.
Published: August 2020

6080

Background: Human papillomavirus (HPV) is an important etiologic factor in HNSCC and its prevalence has been reported in several independent studies. We conducted a meta-analysis to determine the prevalence of HPV, its impact on risk of developing HNSCC and overall survival (OS). Methods: Pubmed search terms “HPV” and “HNSCC” were used to identify 40 clinical and translational studies between the years 1980–2008 that reported the prevalence of HPV in HNSCC. Statistical software STATA 10.0 was used in the meta-analyses to identify the association of HPV and HNSCC risk and OS. Pooled adjusted odds ratio (OR) or hazard ratio (HR) were obtained using a random-effects model. The amount of heterogeneity between studies was estimated with both the Chi-squared based Q test and the I2 statistic model. Potential sources of publication bias were detected using funnel plots. OS between the trials was compared in forest plot. Results: A total of 6,794 patients (pts) were included. The prevalence of HPV among HNSCC pts was 24.2%; and 86.8% of all HPV(+) tumors were HPV16. Thirteen studies (n = 1933 pts) determined HPV status by serology and the remainder detected HPV DNA in tumor tissue by PCR. Overall, HPV positivity conferred an increased risk for HNSCC (OR = 1.43; 95% CI 1.04–1.82). Risk for HNSCC among HPV16(+) pts was 4.47 times that of HPV16(-) pts. The OS was improved in HPV(+) pts compared to HPV(-) pts (HR = 0.40; 0.27–0.53). In HPV16(+) pts the HR for OS was 0.41 and the survival benefit was even more pronounced in the subgroup of HPV16(+) oropharyngeal cancers (HR = 0.38;0.17–0.58). Conclusions: This meta-analysis provides further evidence supporting the role of HPV as an important causative agent in HNSCC and supports HPV(+) HNSCC as a separate biologic entity which likely should be treated differently than HPV(-) HNSCC. Additional analysis on treatment outcomes to systemic and local therapy is ongoing.

No significant financial relationships to disclose.
Prognostic significance of metabolic adaptation for hypoxic environment in oral squamous cell carcinoma
Authors: Hong S. , Roh S. , Koh Y. , Won H. , Shim B. , Byun J. , Lee M. , Woo I. , Kang J. , Hong Y.
Published: August 2020

6082

Background: During tumor growth, tumor adapts the hypoxic environment and increases glycolysis. This metabolic switch is related to the aggressive malignant behavior. We investigated the connection between the biomarkers related to the glycolytic metabolism (HIF-1α, PDK-1, LDH-5) and clinicopathologic characteristics in oral cavity and oropharynx squamous cell carcinoma (SCC). Methods: Eligibility criteria was the patients diagnosed oral SCC, received curative radical resection and had available tissue samples. Immunohistochemical stain of the HIF-1α, PDK-1, and LDH-5 was done. Statistical analysis was performed to compare biomarkers between patients and time point. Results: Overall 74 patients were enrolled and stage grouping of the patients was as follows: stage I, 25 (33.8%) patients; stage II 17 (23.0%); stage III 8 (10.8%); stage IV 24 (32.4%). 25 patients were relapsed and 5-year disease-free survival (DFS) rate was 61.4%. High expression of HIF-1α was related to the advanced T stage (p = 0.029), more invasive tumor (p = 0.003) and tumor recurrence (p = 0.037). High expression of PDK-1 was related to the advanced N stage (p = 0.026) and high expression of LDH-5 was related to the lymphatics invasion (p = 0.028), advanced N stage (p = 0.020) and more invasive tumor (p = 0.015). The high expression of HIF-1α, PDK-1, and LDH-5 showed a significant correlation to each other. 16 (21.6%) patients were highly expressed all three markers. High expression of all three markers correlated with more invasive tumor (p = 0.004) and tumor recurrence (p = 0.017). In survival analysis, high expression of HIF-1α and LDH-5 associated with shorter DFS in log rank test (p = 0.002 and p = 0.016, respectively). High expression of all three markers was also associated with shorter DFS (p = 0.002). In multivariate Cox regression analysis, high expression of all three markers was strong independent prognostic factor for DFS (p = 0.021). Conclusions: The oral SCC which glycolytic metabolism was changed showed a more invasive and aggressive phenotype. Taken together, biomarkers related tumor metabolism may be independent prognostic markers for the DFS in the patients with oral SCC.

No significant financial relationships to disclose.
Clinicopathologic predictors of distant metastasis in head and neck cancer
Authors: Holsinger F. C. , Dong W. , Bekele N. , Weber R. S. , Kies M. S. , Glisson B. S.
Published: August 2020

6086

Background: Despite advances in achieving improved locoregional control for patients with head and neck cancer (HNC), overall survival has not improved in the last 30 years. Several studies have implicated distant metastasis as a potential cause, hindering progress in the treatment of HNC. However, little is known about which patients fail systemically. We therefore sought to identify clinico-pathological factors that are associated with distant metastasis as the only cite of failure. Methods: We retrospectively studied 389 patients with head neck squamous cell carcinomas with distant metastases as the primary site of failure excluding all patients with locoregional recurrence and those receiving chemotherapy at primary presentation. The median follow up period was 5.3 years. An estimate of the risk of DM and DM free survival by prognostic factors was calculated using multivariate analysis and Cox proportional modeling. Results: Overall, 11% (43/389) of the patients developed DM. With univariate analysis, site of the tumor arising within the laryngopharynx, T stage (T3–4), N stage>2, and metastasis to level IV were significantly associated with DM. However, using Cox proportional hazards regression modeling, two clinicopathologic variables, N classification >N2b and diminishing degree of histologic differenention, were found to be most significantly associated with the development of systemic, distant metastasis. For patients staged as N2b or N2c, there was a relative risk (RR) of 6.13 (95% CI: 2.61 - 14.38; p < 0.0001) for developing DM. For patients staged as N3, the RR was 8.23 (95% CI: 2.39 - 28.38; p < 0.001). For patients with poorly differently HNSCC, RR was 11.01 (95% CI: 1.42 - 85.15; p = 0.022) Conclusions: Recognizing patients at primary presentation with tumors with the highest risk for the development of DM might le us to selectively treat them aggressively with systemic therapy to eradicate the tumor, thus improving overall survival rates.

No significant financial relationships to disclose.
Optimal timing of radioactive tracer for sentinel node biopsy in breast cancer patients
Authors: Reuter N. P. , Bower M. R. , Scoggins C. R. , Martin R. C. , McMasters K. M. , Chagpar A. B.
Published: August 2020

611

Background: While sentinel node biopsy (SNB) is well established as a minimally invasive means of staging the axilla in breast cancer patients, the optimal timing of injection of technetium 99m sulfur colloid (Tm) for SNB remains unclear. Methods: In a prospective multicenter study of 4131 patients who had a SNB for breast cancer followed by axillary node dissection, 3305 patients had a SNB using Tm with the elapsed time from injection to SNB being recorded. These 3305 patients formed the cohort of interest for this study. The dose of Tm remaining at the time of SNB was calculated with the formula mCiremaining=mCiinjected*0.5^(elapsed hours/6). Patients with injection of Tm ≤12h and >12h were compared using SPSS. Results: The mean age of the 3305 patients in this study was 60 years, with a mean tumor size of 1.8 cm. A sentinel node (SN) was identified in 95% of patients. SN identification (ID) was not affected by mCi injected (p=0.88), mCi remaining at time of SNB (p=0.13), or type of Tm (filtered vs. unfiltered, p=0.37). There was a statistically non-significant trend of more SN's removed in the ≤12h group (3.2 vs. 2.5, p=0.06). False negative rate was not affected by mCi injected (p=0.39), mCi remaining at time of SNB (p=0.24), or type of Tm (filtered vs. unfiltered, p=1.00). The overall false negative (FN) rate was 8.0%. Of the 3305 patients in this study, 3221 were injected ≤12h prior to SNB and 84 were injected >12h prior to SNB. For the patients injected ≤12h compared to >12h, there was no difference in SN ID rate, FN rate, counts of the hottest node, or background counts despite more mCi injected and less mCi remaining at SNB in the >12h cohort (see Table). Conclusions: Injecting Tm >12h prior to SNB has an acceptable SN identification rate, and the FN rate was not significantly different than injecting Tm ≤12h prior to SNB.

[Table: see text]

No significant financial relationships to disclose.
Effective treatment of triple-negative breast cancer with targeted cytotoxic somatostatin analogue AN-162 (AEZS-124)
Authors: Seitz S. , Schally A. V. , Gluck S. , Rick F. , Szalontay L. , Hohla F. , Papadia A. , Köster F. , Ortmann O. , Buchholz S.
Published: August 2020

619

Background: Triple negative breast cancers (TNBC) represent a distinct subtype of breast cancer being negative to ER, PR and HER2 and are associated with poor prognosis. Limited systemic treatment options exist for TNBC. TNBC cells express somatostatin receptors (SSTR). Therefore, to investigate preclinical characteristics of TNBC we used a novel targeted cytotoxic somatostatin analogue AN-162 containing doxorubicin (DOX) which binds to the subtypes 2, 3 and 5 of SSTR. Methods: The expression of SSTR in HCC 1806 human TNBC cell line was detected by RT-PCR. Cytotoxic effect of AN-162 in vitro was visualized by ethidium bromide staining fluorescence microscopy. Internalization of AN-162 into HCC 1806 cells was tested by 125Iodide-labeled AN-162 uptake assays and the presence of DOX in the nucleus was measured by fluorescence assays after separating the nucleus from the cytoplasm. For in vivo experiments, HCC 1806 TNBC cells were xenografted subcutaneously into nude mice which were then randomized into four groups receiving AN-162, DOX, an unconjugated mixture of DOX and somatostatin analogue RC-160 at the same equimolar dose of 2.5 μmol/kg (1.45 mg/kg Dox equivalent) i.v. (q7d 4x) and vehicle solution control. Results: HCC 1806 TNBC cell line was positive for the expression of all five SSTR receptor subtypes. Ethidum bromide staining of cells treated with 2.5 μM of AN-162 for 30 min demonstrated cell death after 24h by fluorescence microscopy. Uptake assays with AN-162 showed specific internalization of AN-162 into the cells mediated through the sstrs. After treatment of the cells with 2.5 μM AN-162 for 10 or 30 min, DOX could be detected in the nucleus by fluorescence assays. In vivo, AN-162 significantly (p<0.05) inhibited tumor growth of HCC 1806 xenografts compared to Control, DOX and the unconjugated mixture of DOX+RC-160 from day 14 and the inhibition remained significant until the end of the study on day 35. Conclusions: Our results indicate that treatment with targeted cytotoxic somatostatin analogue AN-162 produces a greater inhibition of tumor growth than DOX alone in somatostatin receptor positive TNBC. Our findings support the concept of targeted chemotherapy based on cytotoxic peptide analogues for the treatment of breast cancer and other cancers.

No significant financial relationships to disclose.
Effect of modest delays in primary surgical treatment on progression of tumor size in breast cancer patients
Authors: Wagner J. L. , Warneke C. , Bedrosian I. , Mittendorf E. , Babiera G. , Kuerer H. , Hunt K. , Yang W. , Sahin A. , Meric-Bernstam F.
Published: August 2020

622

Background: Evaluation of medical co-morbidities, coordination of reconstructive surgery and referral to tertiary care centers can delay surgical treatment in breast cancer. These delays raise concerns for tumor progression in the interim. We evaluated the time from initial imaging at a cancer center to surgical treatment and the change in tumor size. Methods: We identified 823 patients who underwent surgery as their first therapeutic modality for invasive breast cancer diagnosed from December 2003 to September 2005. Baseline tumor size was determined by mammogram (MMG) and ultrasound (US) reports, and tumor size at surgery was determined by pathology reports. Results: The median time from imaging at our facility to surgery was 0.69 months (range 0.03 to 4.34). Multivariate modeling indicated that older patient age, undergoing total mastectomy, and undergoing reconstruction predicted a longer time from initial imaging to surgery. Comparing radiographic to pathologic size, a moderate correlation was demonstrated for both MMG (Spearman r = 0.58; p < 0.0001) and US (Spearman r = 0.66, p < 0.0001). Pathologic size was the same as MMG size in 14%, smaller in 49%, and larger in 37% of patients. Differences in tumor size estimates were not significantly associated with time lapse between MMG and surgery, but in a multivariate model, MMG tumor size, tumor histology, and tumor grade were significant predictors (p < 0.0001 for all) of differences in mammographic and pathologic size. The pathologic tumor size was the same as US in 10%, smaller in 38%, and larger in 52% of patients. Time lapse to surgery was not significantly associated with differences in US and pathologic tumor size. In a multivariate model, US tumor size (p < 0.0001), tumor histology (p = 0.0006) and tumor grade (p = 0.005) were significant predictors of differences in US and pathologic tumor size estimates. Conclusions: There is no evidence that time lapse from initial imaging to surgical intervention leads to significant changes in tumor size thus allowing patients to complete preoperative workup and planning without significant clinical disease progression.

No significant financial relationships to disclose.
The utility of a real-time RT-PCR assay for the detection of metastases greater than 0.2 mm in sentinel lymph nodes of breast cancer patients confirmed by detailed histological analysis
Authors: Kurosumi M. , Kobayashi Y. , Takei H.
Published: August 2020

628

Background: Analysis using real time RT-PCR for the detection of metastases in lymph nodes (LN) increases sampling but is associated with a risk of too much sensitivity as compared to histological analysis. Determining the appropriate cutoff value is important in introducing this system to routine clinical practice. Our study confirms the reliability of the cutoff values of a real-time RT-PCR assay (GeneSearch, Veridex LLC) to detect metastases larger than 0.2 mm by detailed 0.2 mm frozen section histological diagnosis. Methods: 129 sentinel and non-sentinel lymph nodes were obtained by sentinel LN biopsy from 79 breast cancer patients. All LNs were cut in half. One half of each LN was used for routine intra-operative diagnosis. The other LN half had sections cut every 0.2 mm for histological analysis. All frozen sections were H&E stained and examined by on-site pathologists. These sections were then re-stained immunohistochemically using a pancytokeratin antibody (AE1/AE3) for detecting submicrometastses. All remaining tissue between the histology sections was assayed by the real-time RT-PCR assay using the genetic markers mammaglobin (MG) and cytokeratin-19 (CK-19) (note: tissue processing method was investigational and off-label). Cutoff values were pre-set in a large US study (n = 304). Results: Compared to the histological diagnosis using 0.2 mm interval frozen sections, the real-time RT-PCR results were as follows; sensitivity of 100.0% (34/34), specificity of 93.7% (89/95), and overall accuracy of 95.3% (123/129). Submicrometastases were recognized by IHC in 3 of 95 samples (2 solitary and 1 multiple sites) diagnosed as negative by H&E-stain sections, and 3 samples were negative for RT-PCR. Conclusions: Results of 0.2 mm interval histological analysis suggest a near perfect sensitivity of the real time RT-PCR assay, allowing reliable detection of LN metastases larger than 0.2 mm. In addition, at least three samples with submicrometastases detected by immunohistochemistry for pancytokeratin were above the preset cutoff values of this real time RT-PCR assay.

[Table: see text]
Does it matter where you go for breast cancer surgery?
Authors: Hofer T. P. , Hawley S. T. , Katz S. J.
Published: August 2020

6504

Background: Variation in receipt of local therapy for breast cancer has motivated research addressing whether treatment differences are attributable to surgeons. We assessed the amount of variation in receipt of mastectomy and breast reconstruction attributable to surgeons and evaluated patient and surgeon factors associated with treatment variability. Methods: Women with non-metastatic breast cancer aged 20–79 diagnosed from June 2005-February 2007 in Detroit and Los Angeles were surveyed after surgical treatment (response rate 72%, N = 2,260). Attending surgeons were surveyed (response rate 76.1%, N = 318). Patient and surgeon data were merged to SEER data (1764 patients and 295 surgeons). Two dependent variables were receipt of mastectomy and reconstruction. Patient variables were age, ethnicity, marital status, tumor size, behavior, and grade. Surgeon factors included age, gender, years in practice, percent of total practice devoted to breast cancer, hospital setting, and 3 scales measuring patient management processes. We used separate random effects models for each dependent variable to determine the amount of treatment variation attributable to surgeons and the amount of within-surgeon variability explained by patient and surgeon factors. Results: The number of patients per surgeon ranged from 1 to 35 (mean 5.5). One-third of women received mastectomy, 30% of whom received reconstruction. The amount of variation in mastectomy attributable to individual surgeons was moderate (8%, median odds ratio 1.7). Patient factors explained half this variation, while surgeon factors explained very little (<1%). The amount of variation in reconstruction attributable to individual surgeons was large (18%, median odds ratio 2.3), with patient level factors explaining one third of this variation. One surgeon level factor (propensity to refer to a plastic surgeon prior to surgery) explained an additional third of the variance. Conclusions: These results suggest that individual surgeons and their attributes contribute only modestly to the variation in primary surgery for breast cancer. By contrast, individual surgeons play a much larger role in explaining the wide variation in receipt of breast reconstruction- primarily through preoperative referral to plastic surgeons.

No significant financial relationships to disclose.
The impact of socioeconomic status (SES) on stage of cancer at time of diagnosis: A population-based study in Ontario, Canada
Authors: Booth C. M. , Li G. , Mackillop W. J.
Published: August 2020

6505

Background: Lower SES is known to be associated with worsened cancer survival. Here we evaluate the impact of SES on stage of cancer at diagnosis in Ontario which has universal health insurance. Methods: All incident cases of breast, colon, rectal, non-small cell lung, cervical and larynx cancer diagnosed in Ontario 2003–2005 were identified using the Ontario Cancer Registry. Stage information is only captured routinely for patients seen at Ontario's 8 Regional Cancer Centers (RCCs). This represents approximately 68% of the population and forms the basis for all analyses. Using a best stage grouping approach, cases were assigned stage based on pathologic TNM if available and clinical TNM otherwise. The population of Ontario was divided into quintiles based on community median household income reported in the 2001 Canadian census. Using postal code at time of diagnosis cases were assigned to quintiles (Q); Q1 represents the communities where the poorest 20% of the Ontario population resided. Comparisons between Q1 and Q2–5 were made using the chi-square test. A Cox model was used to evaluate overall survival, SES, stage, and age. Results: Stage at diagnosis was available for 19,239/23,254 (83%) of cases seen at RCCs. Among cases with breast cancer, those in Q1 were less likely to have stage I disease (43 vs 47%, p = 0.004) and more likely to have stage IV disease (5 vs 4%, 0.008) than Q2–5. With lung cancer, cases in Q1 were more likely to have stage I disease compared to Q2–5 (16 vs 13%, p = 0.015). Distribution of stage I and stage IV disease did not differ by SES across other individual diseases. However, for all 6 cancers combined, cases in Q1 were less likely than Q2–5 to have stage I disease (27 vs 30%, p = 0.001) and more likely to have stage IV disease (21 vs 18%, p < 0.0001). We found significant gradients in 3-year overall survival across Q1-Q5 for breast (5% absolute difference in survival, p < 0.001), colon (4%, p = 0.049), and cervical (18%, p = 0.031) cancers. Adjustment for stage and age only slightly diminished these survival gradients. Conclusions: Despite universal health care, SES remains associated with survival among patients with cancer in Ontario. These data suggest that the difference in outcome is only partially explained by differences in stage at diagnosis.

No significant financial relationships to disclose.
The access to oncology drugs in France, Germany, Italy, Spain, and the United Kingdom: A comparison based on data from 1998 to 2007
Authors: Wilking N. E. , Jönsson B.
Published: August 2020

6525

Background: Drugs constitute a key element in the treatment of solid tumors and in haematology. We have analysed the access and uptake of oncology drugs in 27 countries over a 10 year period (1998–2007) based on sales data provided by IMS Health ( www.comparatorreports.se ). Methods: In this special analysis we study a set of “mature” cancer drugs ( irinotecan, aromatase inhibitors (AIs), oxaliplatin, docetaxel, rituximab, gemcitabine, trastuzumab and imatinib) available in 2002 or before and a set of “new” cancer drugs (bortezomib, cetuximab, bevacizumab, pemetrexed, erlotinib, sorafinib, sunitinib and dasatinib) available in 2003 or later. The “mature” drugs have been selected based on the fact that they have been available for a long period of time (at least 5 years) and that there is accumulated evidence based on clinical trials, epidemiological studies and clinical experience that they have had a major and clinically relevant impact on the outcome in different areas of oncology. Results: We see very different patterns of use in countries studied. The total use of cancer drugs (€/capita) in 2007 is highest in France and lowest in the UK, with the other countries at a relatively similar level in between. The pattern of use of “new drugs” follows that of “mature drugs”, but the very low use of new drugs in UK is noticeable. The differences seen between groups are also reflected in the use of individual drugs, although for example AIs and trastuzumab in the “mature” group have a more uniform use across the countries. The expected survival for cancer patients have been, in general, lower in the UK compared to other western European countries, but further studies are needed to establish the impact of treatment patterns on population outcome. Conclusions: The similarity in use of both “mature” and “new” oncology drugs indicate that differences in access, found for example between France and UK, is related to health care system factors rather that evidence on outcome of use of the drugs.

[Table: see text]

[Table: see text]
Breast cancer patients' quality of care: Does racial concordance matter or is it just a matter of trust?
Authors: Joseph K. P. , Franco R. , Fei K. , Bickell N.
Published: August 2020

6537

Background: As insurers consider paying for performance and quality measures grow in importance, factors that affect patients' perceived quality of cancer care matter. Concordance by race in physician-patient relationships has been associated with patient satisfaction and use of health care, however how that is mediated is unclear. Methods: 210 of 300 eligible women stage I or II breast cancer at 1 of 8 participating NYC hospitals responded to our survey (70% response rate): 20% were African-American (AA), 40% were white, and 30% were Hispanic and 9% were other races. Trust is based on a validated scale and calibrated to a 100 point scale (Cronbach α = 0.76). Bivariate analyses and logistic models were used to identify factors associated with patient ratings of quality of care. Results: Only 55% of women rated the quality of their cancer care as excellent. AA women breast cancer patients were less likely to rate their care as excellent (p=0.004). Compared to women who didn't rate their care as excellent, those who rated it excellent had greater trust in their physician (p < 0.0001) and indicated that were treated well by their physicians' office staff (p = 0.01). Of note, AA patients had lower levels of trust (p = 0.004). Women who were of the same race as their physician did not perceive better quality of care as compared to those who were not racially concordant (p = 0.18); nor did they have higher trust in their physician (p = 0.59). Multivariate models evaluating the role of patient race, education, income, knowing which physician to talk to, how well the staff treated the patient, and racial concordance with physician, found that trust in physician was significantly associated with patient perception of excellent quality care (aRR = 1.38; 95%CI: 1.03–1.65) and being AA was associated with worse perceived quality (aRR = 0.47; 95%CI: 0.21–0.88) (model c = 0.79; p < 0.0001). Conclusions: Racial concordance between physicians and patients does not directly affect patients' perceived quality of care. However, women's trust in their physician and their perceived treatment by office staff are associated with excellent cancer care quality ratings. Efforts should be made to increase effective intercultural communication particularly among AA women in order to improve ratings of cancer care quality.

No significant financial relationships to disclose.
Randomized clinical trial eligibility rates for chemotherapy (CT) and antiangiogenic therapy (AAT) in a population-based cohort of newly diagnosed non-small cell lung cancer (NSCLC) patients
Authors: Fehrenbacher L. , Ackerson L. , Somkin C.
Published: August 2020

6538

Background: NSCLC leads the US in cancer deaths, but randomized clinical trials (RCT) of CT with/without antiangiogenic therapy (AAT) are relatively slow to accrue. Treatment guidelines for NSCLC are based on RCTs that enroll patients with a mean age of 62–64 without serious comorbidities. SEER mean age of NSCLC diagnosis in the US is 70. Methods: 326 consecutively diagnosed (from January 1, 2006) NSCLC patients from a large prepaid health care delivery system (Kaiser Permanente Northern California-KPNC), were retrospectively evaluated by manual chart and electronic medical record review for eligibility criteria (EC) to enter treatment defining RCTs, i.e. E4599, S0023. The KPNC members are representative of the regional population. Ineligibility, the main endpoint, was determined on imaging and laboratory tests and history in the medical record. This may overestimate eligibility. Results: Age at diagnosis:<60years-18%, <65–28%, <70–50%, >75–34%, >80–18%; mean (SD)age- 69.3 (10.6). Male:Female 51:49%. Adeno-49%; Squamous-22%; LargeCell-2.5%; NSC NOS-27%. Current/former smokers-90%. Staging: IA-14%; IB-13%; IIA+B-4%; IIIA-17%; IIIB+IV-52%. Surgical resection-26%. When standard RCT eligibility criteria were applied to the entire cohort, 34% (CI 29%-39%) were eligible. Only 23% (CI 19%-28%) were both eligible and <75yo. stage IIIB+IV patients were 29% (CI 24%-36%) eligible at all ages, 20% (15%-26%) were both eligible and <75yo. When AAT EC were added, 21% (17%-26%) were eligible for all ages, 14% (CI 10%-18%) eligible and <75yo., and 9%(CI 6%-13%) eligible and <70yo. Conclusions: Treatment guidelines for NSCLC are based on RCTs enrolling the healthiest quartile of the youngest half of patients. The majority of NSCLC patients are excluded by trial eligibility criteria or subjective age criteria from entering CT and/or AAT RCTs. Toxicities in these older and more comorbid NSCLC patients likely alter the risk:benefit ratio. RCTs specific for the 70+yo and comorbid NSCLC patients are needed to help define the best therapy for this understudied majority of lung cancer patients.

No significant financial relationships to disclose.
Interpreting out-of-pocket expenditures for cancer patients: The importance of considering baseline household income information
Authors: Oatis W. S. , Nonzee N. , Markossian T. , Shankaran V. , McKoy J. , Evens A. , Gordon L. , Winter J. , Calhoun E. , Bennett C. L.
Published: August 2020

6541

Background: Few studies have examined cancer-related out-of-pocket costs (expenses resulting from cancer morbidity and treatment that are not covered by insurance) as a function of baseline household income. We report income-adjusted out-of-pocket cost ratios for 50 patients with lymphoma and 156 patients with breast cancer. Methods: Patients with lymphoma or breast cancer provided 3-month retrospective documentation of cancer-related out-of-pocket costs. Costs were adjusted for income by dividing monthly costs by monthly household income. Direct medical costs include costs related to medications, doctor visits, and hospital stays. Direct non-medical costs are cancer-related peripheral costs, such as transportation and meals. Indirect costs are costs due to lost income. Results: Of our study patients, 83% were Caucasian, 65% were married, 53% were employed, and 65% had at least a bachelor's degree. All patients were undergoing active treatment and had insurance. Mean monthly out-of-pocket costs for patients with lymphoma were slightly greater than for those with breast cancer ($1,888 vs $1,455, respectively). Among patients with an annual income of $30,000 or less, the total monthly out-of-pocket costs were more than 3 times the monthly household income for patients with lymphoma and equal to the monthly household income for patients with breast cancer. The total mean income-adjusted cost ratio was 1.75 for patients with aggressive non-Hodgkin lymphoma versus 0.42 and 0.61 for those with indolent non-Hodgkin lymphoma or Hodgkin disease, respectively. Conclusions: Cancer-related out-of-pocket expenses disproportionately affect lower-income individuals with lymphoma or breast cancer and are primarily driven by the financial burden of co-payments for medical care. Future studies should evaluate out-of-pocket costs in relation to household income to determine more accurately the economic burden of cancer.

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No significant financial relationships to disclose.
The validity of cause of death coding within the Surveillance, Epidemiology, and End Results (SEER) Registry
Authors: Hu C. , Xing Y. , Cormier J. N. , Chang G. J.
Published: August 2020

6544

Background: Disease-specific survival (DSS) analysis within large cancer registries is more informative than other methods of survival analysis but requires accurate information regarding the cause of death (COD). The purpose of this study was to evaluate the validity of the COD code for patients diagnosed with colon cancer and the extent to which it varies with regard to age, sex, and race within SEER. Methods: Patients with colon adenocarcinoma were identified from SEER (ver. 2008) from 1988 to 1998 to have at least 7 years of follow-up. Relative survival (RS) was calculated matching for age, sex, and the year of diagnosis using U.S. life-tables. Colon cancer cause of death was then assigned using SEER COD recode for colon and rectal death (21040–50). The number of observed and expected deaths by year was calculated to estimate deaths attributable to colon cancer. The ratio of this number to the recorded cause of death was defined as the validity of the COD code in SEER. Results: 86,641 patients were identified. Relative survival declined during the first 7 years of observation but then leveled indicating a minimum number of deaths subsequently attributable to colon cancer. At year 7 the observed number of deaths for the SEER cohort was 49,104; the expected number of deaths using life tables was 17,173. The difference (31,931) is theoretically attributable to colon cancer. Within the SEER cohort, 30,227 deaths were coded colorectal cancer deaths, an estimated validity of 94.6%. Stratified results demonstrated validity was sensitive to race but not age or gender (table). Conclusions: Cause of death coding for colon cancer in SEER is highly valid, suggesting that the use of DSS for colon cancer is appropriate.

[Table: see text]

No significant financial relationships to disclose.
Impact of patient age on quality of care in the treatment of colorectal cancer: Results from the Florida Initiative for Quality Cancer Care (FIQCC)
Authors: Siegel E. , Shibata D. , Malaga M. , Fulp W. , Lee J. , Jacobsen P.
Published: August 2020

6548

Background: The quality of colorectal cancer (CRC) treatment has been suggested to vary by age, with older patients receiving poorer quality care. As part of a state-wide quality improvement effort, the FIQCC developed and implemented methods to assess the quality of care of several cancers among practices across the state of Florida. The current report focuses on the variability of adherence to CRC quality indicators for treatment and surveillance by patient age. Methods: Medical chart reviews were conducted of all patients first seen by a medical oncologist for CRC in 2006 at one of the 10 FIQCC sites (2 academic/8 community). Abstractors were trained and periodically monitored. Abstraction focused on assessing adherence to quality indicators consistent with evidence-, consensus-, and regulatory-based guidelines. Variability in adherence across age quartiles was evaluated using a Fisher's exact test. Of the 475 patients whose charts were reviewed, 53% were male, 80% were diagnosed with colon cancer and the median age was 65 years (range 27 to 92 years). Results: Adherence was consistently (p values>.05) high across all age quartiles for presence of chemotherapy flow sheets (85%-93%), assessment of body-surface area (98%-100%) and performance of complete colon evaluation within 12 months of surgery (87%-89%). Moderate-to-low adherence was consistent by age for performance of CEA test before (74%-84%) or in the 6 months after (75%-82%) surgery/chemotherapy, and documentation of planned chemotherapy dose (51%-59%). Adherence decreased with increasing age for documentation of discussion/referral for chemotherapy in non-metastatic CRC cases (100%, 99%, 93%, and 89%; p = 0.001), but was consistently adhered to for all ages among metastatic cases (100%). The documentation of consent for patients treated with chemotherapy also varied by age-quartile (63%. 57%, 79%, and 73%; p = 0.02). Conclusions: Overall quality of CRC treatment was not consistent across the broad spectrum of patient age. Our data suggest age related disparity in the recommendation for adjuvant chemotherapy. Efforts should be made to understand the reasons for these differences and to improve and standardize the quality of CRC care for patients across all age groups.

No significant financial relationships to disclose.
Adherence to National Quality Forum (NQF) colorectal cancer indicators among members of the Florida Initiative for Quality Cancer Care (FIQCC) consortium
Authors: Shibata D. , Siegel E. , Malafa M. , Lee J. , Fulp W. , Jacobsen P.
Published: August 2020

6563

Background: FIQCC is a consortium of 10 institutions participating in a comprehensive practice-based system of quality self-assessment across a number of cancer types. The NQF has endorsed several performance measures to assess the quality of care for colorectal cancer (CRC) patients. We have sought to identify adherence to NQF CRC indicators among members of FIQCC. Methods: Comprehensive chart reviews were conducted for all patients with CRC first seen in 2006 by a medical oncologist at one of the 10 FIQCC sites (2 academic/8 community). NQF quality measures included: 1) consideration or administration of chemotherapy to patients with stage III colon cancer (CC); 2) completeness of pathology reporting for CRC; 3) >12 regional lymph nodes (LN) examined for resected CC. Statistical comparisons were performed using chi-squared analysis. Results: The population consisted of 475 patients (250 men and 225 women) with a median age of 65 years (range 27–92). Chemotherapy was considered/administered in 96.5% (136/141) of stage III CC patients. With respect to CRC pathologic reporting, there was strong compliance (>90%) for reporting the number of LN examined and involved by tumor, proximal/distal margin status, depth of invasion, and histologic grade. However, only 225 of 295 (76.2%) reports documented lymphovascular invasion status. Radial margin status was included for 45% (27/60) of surgical rectal cancer specimens. Only 73.9% (173/234) of CC cases had >12 LN examined. Of the NQF measures, significant differences across practice sites were noted for the reporting of histologic grade (p = 0.0002), proximal/distal margin status (p = 0.049), and lymphovascular invasion (p < 0.0001). Conclusions: Although there was uniformly strong adherence to the application of adjuvant therapy for stage III CC across FIQCC sites, the adequacy of lymphadenectomy and LN examination for resected CC was lower and varied considerably across sites. There remains room for improvement of pathologic CRC reporting across the whole consortium as well as at individual sites. The FIQCC initiative allows for the identification of targets for global quality improvement as well as of specific measures for individual institutions.

No significant financial relationships to disclose.
What price for a year of life? A survey of U.S. and Canadian oncologists
Authors: Berry S. R. , Neumann P. J. , Bell C. , Nadler E. , Evans W. C. , Palmer J. , Strevel E. , Ubel P. A.
Published: August 2020

6565

Background: New cancer drugs are increasingly expensive and raise difficult questions about the magnitude of therapeutic benefit needed to justify their incremental cost. In this context, it is unclear whether oncologists endorse standard thresholds of $50,000 to $100,000 per year of life. Methods: We surveyed 1,379 U.S. and 356 Canadian (Cdn) oncologists and asked how much longer a patient would need to survive metastatic cancer to justify the expense of a new treatment. To determine the stability of attitudes towards cost-effectiveness (CE) we randomized oncologists to receive two different versions of the scenario in which the price of the new treatment was varied (higher versus lower drug cost). In the U.S. survey, oncologists were also randomized to receive surveys in which we varied the provision of contextual information about the CE of several familiar interventions. Both U.S. and Cdn oncologists were asked to indicate what they “thought was ‘good value for money’ expressed as cost per life-year gained (LYG).” Results: Response rate was 57% in the U.S. and 48% in Canada. CE ratios implied by oncologists’ responses differed significantly between the groups randomized to the higher versus lower price of the hypothetical treatment (p < 0.001 U.S., p < 0.0001 Canada), but were independent of randomization to varying contextual information (p > 0.1). The median willingness to pay for a quality-adjusted year of life ranged from $150,000 (for oncologists considering the lower priced drug) to $250,000 (for those considering the more expensive drug) in both countries. Among those who considered the more expensive drug, 25% of respondents implicitly endorsed a CE ratio greater than $600,000 (U.S.) and $500,000 (Canada). In contrast, when asked directly to indicate CE ratios that were good value for the money outside of the clinical scenario, 70% (U.S.) and 64% (Canada) of respondents indicated values of less than $100,000 per LYG. Conclusions: Oncologists responding to our survey provided inconsistent views on how much benefit expensive new drugs should provide to be worthwhile. This suggests that means of eliciting input from physicians that reflect more stable attitudes need to be developed to appropriately inform decision-makers.

No significant financial relationships to disclose.