bluuebunny/crossref_metadata_2025 huggingface dataset:
Correlates and determinants of nuclear epidermal growth factor receptor (EGFR) content in an oropharyngeal cancer tissue microarray
Authors: Psyrri A. , Weinberger P. , Yu Z. , Sasaki C. , Haffty B. , Kowalski D. , Burtness B.
Published: March 2020

6022

Background: We have previously reported nuclear localization of EGFR protein in oropharyngeal cancer tissue. Nuclear EGFR levels were inversely correlated with survival and response to radiotherapy. Here, we sought to identify determinants and correlates of nuclear EGFR content. Methods: We analyzed an oropharyngeal cancer tissue microarray for expression of key molecules of EGFR signaling cascade utilizing an automated image analysis technique (AQUA) scored on a scale of 0–255 which permits protein quantitation and subcellular localization. Patients with OSCC treated with radiotherapy (RT) or surgery and RT were eligible. Data were analyzed using Pearson correlations and multiple linear regression with robust standard errors. Results: Of the 95 tumors included in this study, 72 (75%) had sufficient tissue for analysis of nuclear EGFR. Nuclear EGFR levels were associated with membranous/cytoplasmic EGFR levels (rho=0.85, p<0.01), nuclear ERK2 (rho=0.34, p=0.01), tumor cyclin D1 (rho=−0.25, p=0.06) and the proliferation markers Ki-67 (rho=0.24,p=0.06) and PCNA (rho=0.38, p<0.01). Nuclear phosphorylated-Akt, PTEN, p53 levels did not correlate with nuclear EGFR level. In multivariable analysis, only PCNA retained its significant association (p=0.01). Conclusions: Our results are consistent with the preclinical model of translocation of membranous EGFR to the nucleus acting as a transcriptional factor and fostering cell proliferation. Nuclear EGFR may constitute a mechanism of resistance to current EGFR-targeted therapies.

No significant financial relationships to disclose.
Final results following exclusive chemotherapy for selected patients with squamous cell carcinoma of the laryngopharynx
Authors: Holsinger C. , Bassot V. , Brasnu D. , Laccourreye O.
Published: March 2020

6039

Purpose: To determine the long-term oncologic outcomes for patients with squamous cell carcinoma (SCC) of the laryngopharynx treated with exclusive chemotherapy after complete clinical response to induction chemotherapy. Materials and Methods: After platin-based induction chemotherapy, selected patients with a complete clinical and histologic response were treated exclusively with additional chemotherapy and observed closely. The rates of overall survival, disease control, and organ preservation were calculated. Results: Survival at 1- and 5-years was 94.5% and 60.2%, respectively. Main causes of death were metachronous second primaries (27) and intercurrent disease (23) than local recurrence (10), distant metastasis, (9) and nodal recurrence (4). The 1-, 3- and 5- year Kaplan-Meier local control estimates were 73.5%, 53.3%, and 50.3%, respectively. No variable was associated with local recurrence using a multivariate analysis. Salvage treatment resulted in an observed final 85.6% local control rate and varied from 96% in patients with glottic cancer to 71% in patients with tumor originating from other locations. Overall, this treatment approach was well-tolerated: 30 patients (20%) experienced grade 3 toxicity; two patients (1.4%) had grade 4 toxicity events. Overall, chemotherapy allowed for successful modulation of local therapy in 66% of patients (96/146). Conclusions: For selected patients, exclusive chemotherapy does not significantly impact survival and maintains function in a majority of patients. Most remarkable, platin-based chemotherapy permitted us to modulate and to diminish the extent of local therapy. Future work should be directed to identify markers of response and resistance to identify which patients are best suited for this approach.

No significant financial relationships to disclose.
Swallowing function after intensity modulated radiotherapy (IMRT) and chemotherapy for head and neck cancer
Authors: Caglar H. B. , Allen A. M. , Burke E. , Posner M. , Haddad R. , Norris C. , Annino D. , Wirth L. , Tishler R.
Published: March 2020

6046

Background: To evaluate the swallowing function of patients treated with intensity modulated radiation therapy (IMRT) + chemotherapy (CT) for HNSCC. Methods: Patients completing RT between 9/04 and 8/06 at the DFCI/BWH were evaluated with IRB approval. All patients had formal swallowing evaluation following the completion of therapy; patients with swallowing difficulty underwent video swallow and both stricture and aspiration were scored. Variables examined for correlation with swallowing pathology were: age, race, gender, smoking and alcohol history, primary site, LVI, PNI, RT intention (primary, postop) and use of induction CT. All variables were analyzed via two-sided t-test. Results: 96 patients were evaluated. Median follow-up 10 mos. 75% of the pts were given definitive RT and 25% received postop RT. 72% stage IV, 24% stage III. Primary sites: oropharynx-43, hypopharynx/larynx-17, oral cavity-13, nasopharynx-11, maxillary sinus-2 and unknown primary-10 pts. All pts received once daily IMRT. 9 pts received RT alone, 28 pts received sequential induction and concurrent (CT) and 59 pts received concurrent CT. 31 pts (32%) had some aspiration after therapy; 36 pts (37%) had evidence of a stricture following RT. All but 5 patients had percutaneous endoscopic gastrostomy placed prophylactically RT. Smoking history was the only significant factor found on univariate analysis to correlate with stricture (p=0.05) but not aspiration. Induction CT was not a significant factor in causing aspiration or stricture. 22 of the strictures (71%) resolved after dilation. RT doses to swallowing structures are under evaluation and will be presented. Conclusions: Aspiration and stricture are common side effects after radical treatment with IMRT and CT for HNSCC. Smoking has a significant negative impact on functional outcome.

No significant financial relationships to disclose.
Why do women get mastectomy? Results from a population-based study
Authors: Morrow M. , Hamilton A. S. , Katz S. J.
Published: March 2020

605

Background: Persistently high rates of mastectomy (M) use for breast cancer have motivated lingering concerns about over-treatment. Yet, little information exists about the etiology of current rates of M. Methods: 2,030 women with non- metastatic breast cancer diagnosed from August 2005 to May 2006 and reported to the LA County SEER registry were identified and mailed a survey shortly after receipt of surgical treatment. Latina and African American women were over-sampled. Survey data were merged to SEER data. We report results on a 50% respondent sample (n=736) which will be updated based on a final respondent sample of 1400 patients (projected response rate, 72%). Results: M was ultimately performed in 279 women (37.9%): 47.3% (n=132) received initial M based on surgeon recommendation and most (80.8%) reported a clinical contraindication to breast conserving surgery (BCS); 69 patients (24.7%) chose M despite a surgeon recommendation for BCS or no recommendation favoring either procedure; and 28.0% (n=78) received M after initial attempts at BCS. This latter group included 16 of 22 patients who attempted BCS in spite of a surgeon recommendation for M. The failure rate of BCS in patients thought to be candidates for the procedure was 12.6%. One quarter of patients who received an initial recommendation for M sought a second opinion, and 80.6% reported concordance in recommendation for M between their first and second surgeons. Conclusions: Receipt of M in this large population sample was the result of clinical contraindications to BCS and, to a lesser extent, patient preference. The infrequent discordance in surgical opinions about the need for M and infrequent conversion to M in patients selected for BCS suggest that surgeons have accepted BCS and recognize standard contraindications to the procedure. Initiatives to improve surgical treatment decision-making should focus on patient perspectives about risk and benefits of surgical options and clinicopathologic features predictive of the success of re-excision after initial attempt at BCS.

[Table: see text]

No significant financial relationships to disclose.
Influence of the vascular endothelial growth factor-A (VEGF-A) 936C>T germinal polymorphism on tumoral VEGF-A expression in head and neck cancer patients (HNCP)
Authors: Etienne-Grimaldi M. , Formento J. L. , Francoual M. , Pagès G. , Onesto C. , Chamorey E. , Dassonville O. , Poissonnet G. , Milano G.
Published: March 2020

6050

Background: VEGF-A is a potent inducer of endothelial cell growth and tumor neo-vascularisation. We previously reported that tumoral VEGF-A expression is linked to overall survival in HNCP (Onesto et al. Br J Cancer 2006). The present purpose was to extend this study by analyzing VEGF-A gene polymorphisms since functional VEGF-A polymorphisms associated with serum VEGF-A and risk of cancer have been described. Methods: VEGF-A polymorphisms in position (relative to translation initiation) −2578C>A (promoter region), − 1498T>C (promoter region), −634G>C (5’UTR) and 936C>T (3’UTR) were analyzed (PCR-RFLP) in tumoral genomic DNA from 49 Caucasian HNCP (34 men, 15 women; 16 T1-T2, 33 T3-T4; 31% N0). Tumoral VEGF-A expression was measured with an ELISA kit. Results: Genotype distributions agreed with those predicted by the Hardy-Weinberg equilibrium. A linkage disequilibrium was observed between −2578C>A and −634G>C (p<0.001) as well as between −2578C>A and −1498T>C (p<0.001). Of note, tumoral VEGF-A expression was influenced by the 936C>T polymorphism, with a median at 540 pg/mg in CT+TT patients (N = 5) versus 940 pg/mg in CC patients (N = 44) (p = 0.064). VEGF-A expression was not related to any other polymorphisms. None of the analyzed polymorphisms was linked to node involvement or to tumor size. Unlike tumoral VEGF-A expression, the analyzed genotypes were not related to patient survival. Conclusions: In addition to the known influence of tumor hypoxia, the present data suggest that the 936C>T polymorphism can modulate tumoral VEGF expression, with the presence of the T allele associated with decreased VEGF-A expression. Determination of this germinal polymorphism may thus provide an easily accessible test that deserves further investigation as a potential factor to aid anti-angiogenic treatment selection.

No significant financial relationships to disclose.
Lack of effect of palifermin on the anti-tumor activity of cisplatin, cetuximab or panitumumab in the FaDu human head and neck carcinoma model
Authors: Borges L. , Brake R. , Radinsky R. , Starnes C.
Published: March 2020

6060

Background: The FaDu human pharyngeal carcinoma cell line expresses the receptors for both KGF and EGF. Palifermin is a recombinant form of human KGF. The objective of this study was to determine whether the combination of palifermin with cisplatin and the EGFR inhibitors cetuximab or panitumumab interferes with the anti-tumor activities of these agents in the FaDu head and neck xenograft model. Methods: FaDu tumor cells were implanted subcutaneously in CD1 nude mice. For the combination of palifermin with cetuximab and cisplatin, treatment began on day 9 and for the combination of palifermin with panitumumab and cisplatin, treatment began on day 10. The primary endpoint was the measure of tumor volume. Results: There was no statistically significant difference in tumor volume between the control arm and palifermin alone (p = 0.9993, 0.9831). Neither was there a statistically significant difference between the combination of palifermin, cisplatin and cetuximab compared to the combination of cisplatin and cetuximab (p = 0.7730). Similarly, there was no significant difference between the combination of palifermin, cisplatin and panitumumab compared to the combination of cisplatin and panitumumab (p = 0.9739). Conclusions: In drug combination settings, the addition of palifermin did not affect the therapeutic efficacy of cisplatin, cetuximab or panitumumab in any of the two- or three-way drug combinations. When used alone, palifermin did not promote the growth of the FaDu human xenograft despite the fact that these tumors express KGFR. The lack of interference of palifermin with the anti-tumor activity of cisplatin and the anti-EGFR target therapeutics suggests it is appropriate to move forward clinically investigating the use of palifermin in solid tumor settings in which these therapeutic modalities are used.

No significant financial relationships to disclose.
Low-dose gemcitabine and radiation alternated to cisplatin/5fu in stage IV squamous cell carcinoma of the head and neck (HN- SCC): A phase II trial
Authors: Benasso M. , Vigo V. , Bacigalupo A. , Ponzanelli A. , Marcenaro M.
Published: March 2020

6062

Background: At the National Institute for Cancer Research of Genoa, Italy, we conducted two consecutive phase II single-institution trials testing the addition of gemcitabine into an alternating chemo-radiation (CT/RT) regimen that is considered standard of care in our Institute for patients (pts) with loco-regional advanced HN-SCC (NEJM, 327:1115,1992). In the former trial (ALT-G trial; 47 pts) high dose gemcitabine was administered with cisplatin and RT (Annals of Oncology, 15:646,2004). Methods: In the present trial (ALT-g trial) 3 courses of cisplatin, 20 mg/m2/day and 5-fluorouracil, 200 mg/m2/day, days 1–5 (weeks 1, 4, 7) alternated to 3 courses of standard RT (weeks 2–3, 5–6, 8–9) up to 60 Gy and gemcitabine, 40 mg/m2 on monday of each week of RT, were administered to 47 pts with stage IV (42 pts) or relapsed after surgery (5 pts), unresectable SCC of the oral cavity (11 pts), oropharynx (11 pts) hypopharynx-larynx (24 pts). None had previously received CT or RT. Results: Seven pts (15%) did not complete the planned treatment. Four of them died due to pulmonary embolism (2 pts), fulminant pneumonia (1 pt) or uncertain causes (1 pt). Main grade 3–4 other than local toxicities were: neutropenia (11%), neutropenia with fever (6%), thrombocytopenia (30%), anemia (17% grade 3). 27 pts reached a CR (57%). 7 PRs were rendered disease-free by surgery mainly on the neck (final CR rate: 72%). At a median follow-up of 37 months, 3-yr results and acute local toxicity are compared with those from ALT-G trial and from our data-base of pts treated with alternating cisplatin/5-FU and RT without gemcitabine (ALT): Conclusions: In conclusion, the addition of low-dose gemcitabine into a consolidated cisplatin/5FU and RT alternating program may improve the outcomes with an acceptable increase in acute severe mucositis.

No significant financial relationships to disclose.

[Table: see text]
Phase II study of capecitabine (X) as palliative treatment for patients (p) with squamous head and neck cancer (HNC) with locoregional and/or metastatic relapse after previous platinum-based treatment (PBT): An interim analysis
Authors: Martínez-Trufero J. , Isla D. , Adansa J. C. , Hitt R. , Cruz J. J.
Published: March 2020

6074

Background: PBT is the standard therapy for HNC and is widely used as first line treatment. Nevertheless the incidence of relapse remains still high. Therefore, new non-platinum drugs need to be asses as second line treatment options. Taking into account the results obtained with X in HNC, we proposed this study to evaluate activity and tolerability of X when used as palliative monotherapy for relapsed HNC p previously treated with PBT. Methods: Patients aged 18–75 years, ECOG PS 0–2, with advanced squamous HNC with locoregional and/or metastatic relapse previously treated with PBT and adequate bone marrow, renal and hepatic functions were included. X (1,250 mg/m2 BID) during 14 days was administered every 21 days, for at least 2 cycles. Objective response rate (ORR) was assessed according RECIST criteria and toxicity following NCI-CTC v2 criteria. Results: Sixteen patients with median age 57 years old, all of them male, ECOG 0/1 (33.3% / 66.7%) and with squamous HNC, were analyzed. Twelve p had local disease, 4 p adenopathies and 6 p lung metastases. Median time since HNC diagnosis was 30.4 months and since disease extension diagnosis, 1.8 months. All p received a total of 58 cycles of X (median 3, range 1–6) and the median relative dose intensity was 92%. Four p were not evaluable for response (1 is still on treatment; 3 died, 2 due to unknown reasons and 1 due to an infection). ORR was 16.7%.The median follow-up time was 3.3 months, median TTP was 4.2 months and median OS was 4.7 months. Hematological toxicity G3/4 was reported in 2 p. The only grade 4 non-hematological toxicity was dysphagia in 1 p; grade III toxicities were: asthenia (2 p), anorexia (1 p), dehydratation (1 p), diarrhea (1 p), mucositis (1 p), weight loss (1 p) and palmar-plantar erythrodysesthesia (1 p). The most common grade II toxicity was asthenia (2 p). Conclusions: Capecitabine seems to be an active, feasible and well tolerated palliative treatment for advanced HNC patients that have previously received platinum-based schedules.

No significant financial relationships to disclose.
Clinical predictors of larynx preservation (LP) after multiagent concurrent chemoradiotherapy (MCCRT)
Authors: Rodriguez C. P. , Adelstein D. J. , Rybicki L. , Saxton J. P. , Lorenz R. R. , Wood B. G. , Strome M. , Esclamado R. M. , Lavertu P. , Carroll M.
Published: March 2020

6075

Background: Identification of patients (pts) with larynx and hypopharynx (HP) squamous cell cancer (SCC) most likely to benefit from a LP strategy remains problematic. We retrospectively reviewed the Cleveland Clinic experience using MCCRT to identify potential clinical predictors for success. Methods: Definitive CCRT was considered appropriate for pts with locoregionally confined larynx or HP SCC except for those with cartilage invasion or laryngeal destruction. Cisplatin (20 mg/m2/day) and 5-FU (1,000 mg/m2/day) were given as continuous intravenous infusions on days 1–4 during the first and fourth weeks of either once or twice daily radiation. Laryngectomy was only performed for locally persistent or recurrent disease. Results: Between 1989 and 2006, 115 pts were treated; 87 (76%) were male, and 102 (89%) were white. The median age was 59 (range 31–77) years. The primary site was the HP in 46 pts (40%) , supraglottis in 50 (43%) and glottis in 19 (17%). Tumor was T1 in 4 (3%), T2 in 31 (27%), T3 in 42 (37%), T4 in 37 (32%), and TX in 1 (1%). Disease was stage II in 8 (7%), III in 34 (30%), and IV in 73 (63%). With a median follow up of 62 (range 5–195) months, the 5-year Kaplan-Meier projected local control rate without surgery is 82%. Residual primary site disease was found in only 5 pts after MCCRT. Primary site recurrence developed in 14 more pts. Surgical salvage was successful in 13 of these 19 pts (68%). The 5-year projected local control rate (including surgical salvage) is 94%. Late complications after successful LP included permanent tracheotomy in 3, and feeding tube dependence in 7 pts. For all 115 pts, the 5-year projected freedom from recurrence is 64%, overall survival 58% and laryngectomy-free survival 52%. Local control without surgery was more likely in pts with T1–2 compared to T3–4 tumors (97% vs. 75%, P=0.01), but was not predicted by age, race, tumor differentiation, primary site, nodal status, stage, radiation schedule (daily vs. twice daily), baseline hemoglobin, or continued smoking. Conclusions: This MCCRT regimen can be expected to result in successful LP in all clinical subsets of appropriately selected pts with larynx and HP SCC. Although local failure was more likely in pts with T3 or T4 tumors, it was infrequent, and subsequent surgical salvage was highly effective.

No significant financial relationships to disclose.
Efficacy of breast MRI in elderly women
Authors: Yu J. , Morris E. , Park A. , Cody H. , Gemignani M. L.
Published: March 2020

608

Background: Breast MRI is useful in evaluating extent of disease and screening of high risk patients, especially younger patients with dense breasts. The utility of MRI in the elderly population is currently unknown. The purpose of this study was to review the use of breast MRI and MRI findings in elderly women. Methods: Retrospective review identified women over the age of 70 who underwent breast MRI at our institution between 11/2000 and 12/2005. Clinicopathologic features, MRI results and mammograms (MMG) were reviewed. Results: 228 patients were identified. The mean age was 73.5 years (range 70–91). Forty-three patients (19%) had no history of breast cancer, 99 (43%) had a history of breast cancer, and 86 (38%) had a current diagnosis of breast cancer at the time of MRI. Ninety-two patients (40%) underwent MRI for screening, 49 (21%) as further workup for an abnormal MMG or physical finding, and 78 (34%) for extent of disease assessment. MRI found 49 additional sites of abnormality and 15 additional cancers (14% false positive). Five cancers were detected in women with no current diagnosis of cancer. In patients with a diagnosis of cancer at the time of MRI, 10 additional cancers were found: 7 in the contralateral breast and 3 additional ipsilateral sites. Conclusions: MRI detected an additional 15 mammographically occult breast cancers in this population of women over the age of 70. MRI was efficacious in screening as well as evaluating extent of disease, with a relatively low false-positive rate of 14%. Breast MRI is a useful tool in the evaluation of elderly patients; further study in the use of MRI for screening in this population is needed.

[Table: see text]

No significant financial relationships to disclose.
Quantification of a panel of prognostic markers gives a novel method for predicting radiosensitivity in head and neck squamous cell carcinoma cell lines
Authors: Roberg K. B. , Farnebo L. , Norberg-Spaak L.
Published: March 2020

6082

Background: The present study was undertaken to evaluate the possibility of using the expression of a panel of proteins involved in apoptosis and/or growth control as predictive markers for radiotherapy response. Methods: Nine head and neck squamous cell carcinoma (HNSCC) cell lines were selected to represent different parts of the spectrum of in vitro radiosensitivity. These cell lines have an intrinsic radiosensitivity (IR) between 1.4 and 2.6 measured with a 96 well plate clonogenic assay. Results: Fourteen proteins e.g. Bcl-2, Bcl-XL, Bax, Bad, Bak, Puma, survivin, COX-2, Hsp70, MDM2, p53, EGFR, cyklin D1 and SMAD4 were investigated in above mentioned cell lines and in normal oral keratinocytes (NOK). Each protein was quantified using Western blot analyse and the relative densiometric value from each blot was adjusted for actin and standardized to NOK. The correlation between each protein and IR was analyzed but none significant correlation was found. When combine different proteins, EGFR, Survivin, Bcl-2, Bak, Hsp70 and Smad4 together show the highest significant correlation to the IR. As Western blot is a semi quantitative method we decided that a division into groups depending on the level of protein expression would give a more realistic description of the prognostic value of the detected changes The protein expression was classified into four groups (0–4 point; no, small, middle or large changes compared to NOK) and each p53 mutation got one point. We named this grouping Number of Negative Points (NNP). The NNP for all 15 factors together show a significant correlations to IR, R=0.826 and P= 0.006. A multivariate statistical calculation was carried out to select the combination of factors that had the strongest correlation to IR and the best combination was EGFR, survivin and p53 mutations, R=0.935 and P<0.001. Conclusions: Our results show that it is only possible to predict the IR of tumor cells if combinations of prognostic factors can be analysed. Taken together, we here present a novel method that gives the possibility to combine different prognostic factors and which also enhances the chance to predict the radiosensitivity of HNSCC cells.

No significant financial relationships to disclose.
Effect of oral pilocarpine on xerostomia and quality of life in patients receiving curative radiotherapy for head and neck cancers
Authors: Goyal S. , Sharma D. N. , Julka P. K. , Rath G. K.
Published: March 2020

6088

Background: Xerostomia is the most debilitating condition following irradiation (RT) in patients with head and neck cancers. The present study intended to evaluate the effect of salivary stimulants such as pilocarpine given concurrent with RT on xerostomia and quality of life in these patients. Methods: In a prospective study conducted between July 2004 and May 2006, 60 patients receiving curative (radical or postoperative) RT for squamous cell head and neck carcinoma were randomized into two groups; group A (n=30) received concurrent pilocarpine 5 mg thrice daily for 12 weeks starting on day 1 of RT while group B (n=30) did not receive pilocarpine. Xerostomia was assessed using RTOG/EORTC criteria, and Quality of life (QOL) using EORTC QLQ-C30 version 3.0 and QLQ-H&N35 questionnaires in phases I-V: preradiation, week 4 of RT, and at 1, 3 and 6 months following completion of RT. Results: Oral dryness was the commonest toxicity, its incidence in phase II being 80% in group A and 89% in group B. By phase V, 13% patients in group A and none in group B had recovered to their pretreatment status. When compared with group B, group A had a significantly lower incidence of oral dryness in phases III (p=0.001), IV (p=0.014) and V (p=0.009) and lesser speech difficulty in phase V (p=0.021). QOL evaluation showed a decline in functional scores and rise in symptom scores during radiation with subsequent improvement to pretreatment levels in phase V. Group A had a significantly higher physical functioning score than group B in phases III (p=0.037) and IV (p=0.027), a better emotional functioning score in phases III (p=0.046) and IV (p=0.008), and a higher global health score, especially in phases II (p=0.012) and III (p=0.001). QLQ-C30 symptom scores were comparable between the 2 groups while H&N35 symptom scores were higher in group B with higher painkiller use in phase II (p=0.043) and IV (p=0.011), and higher dryness (p=0.025), sticky saliva (p=0.021) and constipation (p=0.011) in phase IV. Conclusions: Concurrent pilocarpine during head and neck RT helps maintain salivary function, reduces xerostomia and improves the quality of life in these patients, both during and after RT, especially in terms of parameters related directly to xerostomia.

No significant financial relationships to disclose.
Cost-effectiveness analysis of the EORTC 24971 (TAX 323) trial comparing docetaxel plus cisplatin and 5-fluorouracil versus standard treatment (cisplatin and 5-fluorouracil) as induction chemotherapy followed by radiation therapy in locally advanced unresectable squamous cell carcinoma of the head and neck (SCCHN)
Authors: Jansen J. , Vermorken J. B. , Boote D. , Joulain F. , Parthan A.
Published: March 2020

6090

Background: The phase III EORTC 24971 clinical trial (TAX 323) showed that induction chemotherapy followed by radiation therapy increases time to progression and improves outcomes in unresectable SCCHN patients. [Remenar et al. ASCO 2006; Abs 5516] Induction chemotherapy with cisplatin/5-FU (PF) is a standard regimen for patients with locally advanced SCCHN. The economic impact of adding docetaxel to cisplatin/5-FU (TPF) in this setting was assessed using a Markov state-transition model. Methods: The Markov model includes four health states (based on WHO criteria for measuring objective response): stable, response, progression, and death. Efficacy data from the TAX 323 clinical trial were used to derive transition probabilities between the health states. Adverse event rates were also derived from TAX 323. Data for resource utilization and costs for the UK were derived from the literature and from an advisory board of clinicians. In order to calculate quality adjusted life years (QALYs), utilities were derived by mapping the global score on the Health Related Quality of Life Questionnaire Core-30 (QLQ-C30) to the EQ-5D. Results: Patients survived longer in the TPF arm versus PF (2.5 vs. 2.0 years). Total costs for TPF and PF were £31,203 and £26,944, respectively. The incremental discounted cost per QALY gained for TPF versus PF was £9,859/QALY, which is below the £20,000 cost-effectiveness threshold suggested by NICE as a guide to the acceptability of a technology. Conclusion: Docetaxel, when given as induction chemotherapy in combination with cisplatin/5-FU, is cost-effective compared with PF in locally advanced unresectable SCCHN patients. Treating SCCHN patients with TPF followed by radiation represents good value for money based on the results of the analysis.

No significant financial relationships to disclose.
The journey from cancer patient to cancer survivor: A 5-year longitudinal study
Authors: Snyder C. F. , Earle C. C. , Herbert R. J. , Neville B. A. , Frick K. D.
Published: March 2020

6501

Background: The appropriate care for cancer survivors after active treatment ends is unclear. This study explores the mix of physician specialties survivors see and how this mix affects their receipt of preventive care. Methods: We conducted a retrospective, longitudinal cohort study of stage 1–3 colorectal cancer survivors age 65+ diagnosed in 1997. The cohort was followed for a 5-year survivorship period, starting 365 days after diagnosis. Using the SEER-Medicare database, we examined physician visits and preventive care services for each year during the five year survivorship period. We investigated how receipt of preventive services relates to the mix of physician specialties seen: primary care provider (PCP) only, oncologist only, both PCP and oncologist, neither PCP nor oncologist. Results: 1,541 patients met the eligibility criteria (mean age 76, 43% male, 85% White). Over the five years of survivorship, the mean numbers of PCP visits increased (4.2, 4.1, 4.5, 4.6, 4.7) while the mean number of oncology visits decreased (1.3, 1.0, 0.8, 0.7, 0.5). In year 1 of survivorship, 37% of patients saw both a PCP and oncologist, 44% only a PCP, and 8% only an oncologist. By year 5, the respective numbers were 21%, 62%, and 4%. The rates of cholesterol screening (33%), mammography (43%), and cervical cancer screening (19%) were highest during the first year of survivorship. Compared to patients who saw only a PCP, only an oncologist, or neither, patients who had visits to both a PCP and oncologist were more likely to get flu shots, cholesterol screening, mammograms, cervical cancer screening, and bone densitometry (all p<.0001). Conclusions: The mix of providers seen and preventive care received evolves during the first 5 years of survivorship. As shared care between PCPs and oncologists shifts to care by PCPs only, the rate of preventive care drops, particularly for cancer screenings. These results support the need for a survivorship care plan that explicitly outlines the roles of PCPs and oncologists and ensures proper preventive care.

No significant financial relationships to disclose.

[Table: see text]
Reliability of data collection for the National Comprehensive Cancer Network (NCCN) non-Hodgkin lymphoma (NHL) multi-center outcomes database: A methodological approach
Authors: Kho M. E. , Lepisto E. M. , Niland J. C. , terVeer A. , LaCasce A. S. , Friedberg J. W. , Weeks J. C.
Published: March 2020

6525

Background: Clinical trials and outcomes studies often rely on non-physicians to abstract complex data from medical records. We assessed the reliability of chart abstraction among personnel groups in a multi-center outcomes study of indolent/aggressive NHL treated in NCCN centers. Methods: We developed 20 standardized charts of patients with newly-diagnosed NHL. Raters included 6 Clinical Research Associates from participating sites (CRAs), 3 project staff who conduct CRA training, and 3 medical oncologists. Raters each received a set of standardized charts, detailed instructions and training on a sample chart and abstracted all charts independently. We assessed reliability on 5 variables: MD-reported and rater-determined disease stage; International Prognostic Index (IPI- low-low intermediate, intermediate-high, high); Charlson comorbidity index score; and presence of any item from the Charlson index. We used intraclass correlation coefficients (ICCs) to calculate reliability. We considered coefficients from 0–0.20 ‘slight’, 0.21–0.40 ‘fair’, 0.41–0.60 ‘moderate’, 0.61–0.80 ‘substantial’ and >0.80 ‘almost perfect’(1). Results: Overall reliability was “almost perfect/substantial” for MD-reported stage, rater-determined stage, and IPI, but only “moderate” for the 2 Charlson-based comorbidity measures (Table). Reliability varied by rater group; no rater group was consistently more reliable than others. Conclusions: Trained CRAs abstracted key clinical variables with a very high degree of reliability, and performed at a level similar to study trainers and oncologists. Elements of the Charlson index were less reliable than other data types, possibly due to inherent ambiguity in the index itself. Use of trained CRA staff is reasonable to collect stage and IPI scores in a multi-center outcomes study, however abstracted Charlson scores should be interpreted with caution. (1)Biometrics. 1977. 33:159–74.

No significant financial relationships to disclose.

[Table: see text]
Preferences for adjuvant chemotherapy (ACT) in early breast cancer: The benefits needed to make extended treatment with docetaxel, doxorubicin, and CMF worthwhile
Authors: Duric V. , Francis P. , Simard-Lebrun J. , Chan A. , Chirgwin J. , Harvey V. , Sullivan A. , Simes R. , Coates A. S. , Stockler M.
Published: March 2020

6528

Background: Small benefits are judged sufficient to make ACT worthwhile by women who have had either 6 cycles of CMF or 4 cycles of AC. We sought to determine the benefits needed to make longer and more intensive regimens worthwhile. Methods: 293 women who completed ACT 3 to 39 months earlier were presented 4 hypothetical scenarios based on known survival times (5 and 15 years) and rates (65% and 85% at 5 years) without ACT using validated, standardised interviews. 179 were in a randomized trial (BIG 02–98) testing addition of docetaxel (T) to a standard regimen including doxorubicin (A) and classical CMF; 114 were treated outside of the trial at the same centres. Women also rated their recollections of health-related quality of life during ACT. Results: The median age was 55 (range 25 to 78), 36% had a college or university degree, and 62% had dependants. The regimens (and their duration) in the trial were: 4 cycles of A or AC then 3 cycles of CMF (24w) in 31% of the women; 4 cycles of AT followed by 4 cycles of CMF (24w) in 29%; and 3 cycles of A then 3 cycles of T then 3 cycles of CMF (30w) in 40%. The regimens outside of the trial were: 4 cycles of AC (12w) in 52%; 6 cycles of CMF (24w) in 20%; and 4 cycles of AC then 3 cycles of CMF (24w) in 23%. A 2% gain in 5-year survival rates or a 6-month gain in survival duration was judged sufficient to make ACT worthwhile by 62–67% of women. Gains of more than 5% in 5-year survival rates or more than 2 years in survival duration were judged necessary to make ACT worthwhile by 10–20% of women. Women's preferences were strongly associated with the aversiveness of their treatment. Women who had more problems with physical well-being, coping with treatment, and nausea or vomiting judged larger benefits necessary to make their ACT worthwhile (p<.0001). Preferences were unaffected by chemotherapy regimen, duration, context in a trial, age, time between treatment and interview, and social circumstances (p>.2). Conclusions: As in previous studies, small benefits were judged sufficient to make ACT worthwhile, even if it lasted 6–7 months, and included docetaxel, doxorubicin and CMF.

No significant financial relationships to disclose.
Estimating the real cost of adjuvant (adj) trastuzumab (T) in patients (pts) with HER-2+ (H+) early stage breast cancer (ESBC): Potential impact of reduced use of expensive oncology drugs (EOD) in metastatic breast cancer (MBC)
Authors: O'Cearbhaill R. , Wilson E. , deFrein A. , Qadir Z. , McDonnell D. , Crown J.
Published: March 2020

6534

Background: Pts with H+ early stage BC have an approximately 35% risk of developing MBC (BCIRG001). T has been reported to reduce this risk by 33–50%, but costs approximately €;30k per pt, a burden some health systems deem unsustainable. This risk reduction might however result in decreased utilization of EOD in MBC, lowering the societal cost of adjT. We attempted to estimate the cost per relapse prevented (Crp), and the real cost of adjT, allowing for potential savings in prevented cases of MBC. Methods: We conducted a retrospective analysis of the mean cost per pt of AdjT (1 year) and of EOD in MBC in St. Vincent's University Hospital. We devised an equation to calculate the Crp for adj T. Crp=[A-M(NRA/104)]/[NRA/104] where A = cost per pt for adjT, M = EOD cost per pt with MBC, N = % of pts relapsing after standard adj treatment, RA = % reduction in the risk of relapse after adjT (over standard adj). Results: H+ pts with MBC received T (average 34 cycles €;2,400 each) with a combination of the following drugs: docetaxel (x8 €;1,500), gemcitabine (x5 €;1,215), capecitabine (x8 €;400), vinorelbine ( x19 €;187). Only 2 pts received bevacizumab (Bev) (x15 €;3,000). In our unit the mean EOD cost per pt with MBC was €;108k. The cost per relapse prevented for a 33% and a 50% reduction in relapse rate would be €;152k and €;63k, respectively. Furthermore, assuming a 50% reduction in the rate of relapse (from 35 to 17.5%) the real cost of adjT per pt treated is not €;30k, but approximates €;11k (€;30k×100-{17.5x €;108k}). Conclusions: The reduced utilization of EOD in MBC likely has a very beneficial impact on the societal cost of adjT. Confirmation of the efficacy of shorter adjT (e.g. FinnHer) would produce further benefit. The increasing use of novel EOD in MBC e.g. Bev would make adjT even more cost-effective.

No significant financial relationships to disclose.
Measuring quality with the Quality Oncology Practice Initiative (QOPI) at a university comprehensive cancer center
Authors: Blayney D. W. , Miela G. , Markstrom D. , Hanauer D. , McNiff K. , Neuss M.
Published: March 2020

6535

Background: QOPI is a tool which measures adherence to both guidelines and to process for use in quality improvement. QOPI was designed and pilot tested predominately in physician office practices [Neuss et al, JCO 23:6233]. We tested QOPI at UMCCC, a large, hospital-based, academic cancer center, where medical documents are stored in a free-text electronic record, in a paper-based hospital record, and in clinic charts. In 2006, 136 physicians and 58 mid-level practitioners provided 66,699 clinic visits and oversaw 37,500 infusion visits. Methods: The tumor registry selected consecutive cases of breast (BrCa), lung, and colorectal cancer (CRC), and lymphoma (L), diagnosed between minus 6 and minus 30 months from day 0 of each QOPI round. Forty charts with each tumor type and 40 deceased patient records were identified for each round. A clinical pharmacist accessed the pharmacy database to obtain drug data, and the tumor registrar abstracted the three other chart formats, using an electronic text search tool [Hanauer et al Proc ASCO 2006 abs 6080] for the electronic record. De-identified data were submitted to a secure, ASCO-hosted server, for analysis. Results: In the Spring 2006 round, 163 charts yielding 1641 measures required 148 hours of abstractor effort, for an average of 54 minutes (mins) per chart and 5.4 mins per measure. In the Fall, 2006 round, 236 charts yielding 2334 measures required 256.5 hours of effort for 65 mins per chart and 6.6 mins per measure. For comparison, a survey of QOPI practices for the Fall round yielded 29 mins per chart. UMCCC treatment (Rx) and process measures are shown in the table . Conclusions: Abstracting for QOPI measures, using abstractors not involved in patient care, is labor intensive but feasible at a large cancer center. QOPI has allowed UMCCC to assess concordance with guidelines and other quality measures, provides comparison data to other practices, and identifies processes for improvement. The evolution of QOPI will include data transfer from electronic records.

[Table: see text] [Table: see text]
Paradoxical benefit of increased distance of residence from cancer treatment hospitals (CTH) in the United Kingdom (UK)
Authors: Crawford S. M. , Sauerzapf V. , Jones A. P. , Haynes R. , Zhao H. , Forman D.
Published: March 2020

6536

Background: UK residents have, through the National Health Service, access via primary care referral to diagnostic and treatment services free of charge. However there is evidence of uneven uptake by cancer patients. Methods: We have undertaken a cancer registry based study relating socioeconomic characteristics of the patient's place of residence and travel to CTH to uptake and outcome. We report here these relationships according to whether patients underwent any surgery, radiotherapy or chemotherapy. Results: The Table shows the number of patients by site and the percentage receiving any of the specified treatments. Against each deprivation quartile defined by the index of multiple deprivation (DQ1 is least deprived) is given the odds ratio (95% confidence interval) by logistic regression analysis of receiving treatment as it increases with each minute of travel time between home and hospital after allowing for age, sex, and whether or not the CTH was a specialised cancer centre plus site in bowel and lung cancer type. The tendency for odds ratios to be greater with increasing deprivation is significant (Kendall concordance = 0.6417, p=0.022). Conclusions: We observed an increase in treatment activity with increasing travel time to the CTH when a ‘distance decay’ effect was expected. We hypothesise that this relates to the difficulties of providing primary care in the deprived urban areas in which most CTH are situated. Higher odds ratios for more deprived people suggest that the distance advantage compensates for the effect of deprivation.

No significant financial relationships to disclose.

[Table: see text]
Quality and consistency of phase III clinical trial abstracts presented at an Annual Meeting of the American Society of Clinical Oncology compared with their subsequent full-text publications
Authors: Tam V. C. , Hotte S. J.
Published: March 2020

6537

Background: Practice guidelines and evidence summaries in oncology are developed by experts to assist providers in making appropriate decisions regarding management. These documents result from a systematic review of literature from medical journals and meeting proceedings. Because there is often less rigorous peer reviewing of abstracts published in these proceedings compared to journal publications, the quality of evidence provided by these abstracts is uncertain. Methods: We identified abstracts describing phase III clinical trials of chemotherapy, chemoradiotherapy, immune therapy and hormone therapy presented at the 36th ASCO Annual Meeting in May 2000. We searched Medline and Pubmed for all corresponding publications. Data was extracted from the abstracts and publications meeting our inclusion criteria. Results: A total of 192 abstracts were identified. Seventy-four abstracts met our inclusion criteria. Six years after the 2000 ASCO Annual Meeting, 74% of these abstracts had corresponding publications. 39% of the abstracts explicitly indicated that they were reporting interim results. The primary endpoint was stated in 34% of the abstracts and 100% of the published papers. The primary outcome result differed by greater than five percent between the abstract and publication in 25% of the abstracts. The statistical significance of the primary outcome changed in 7% of the abstracts with publications. The final conclusion was consistent between the abstract and publication for 92% of the abstracts with reported conclusions. Conclusions: ASCO annual meeting abstracts of phase III trials appear to consistently reflect final published results and can likely be used in practice guidelines. However, occasional discrepancies underline the need for caution in completely adopting these results prior to full publication.

No significant financial relationships to disclose.
Trends in the quality of abstracts of articles describing randomized controlled cancer trials (RCTs) from 1975–2004
Authors: Cescon D. W. , Booth C. M. , Wang L. , Tannock I. F. , Krzyzanowska M. K.
Published: March 2020

6541

Background: Busy oncologists may rely on abstracts to obtain most of their information from published reports. Here we evaluate the quality of abstracts in articles reporting RCTs, and whether quality of reporting has changed over time. Methods: Reports of RCTs evaluating systemic therapy for breast, colorectal and non-small cell lung cancer published 1975–2004 in 6 major journals were identified. The quality of abstracts was evaluated using a scale which awards 1 point for full and 1/2 point for partial reporting of each of 6 items: study rationale, statement of primary endpoint, description of intervention, treatment effect size, P-values or confidence intervals (CI), and toxicity. The scale was a modification of one previously developed to assess quality of reporting of conference abstracts. Trends in the reporting of individual items and composite scores were evaluated over three 10-year periods (1975–84, 1985–94, 1995–2004) using descriptive statistics. Results: Of 326 eligible articles, 319 had an abstract. Unstructured abstracts were common before 1994 ( Table ). The minimum and maximum quality scores assigned were 0.5 and 6/6. Median quality scores improved significantly with time (from 2.5 to 4.5/6, P < .001), as did inclusion of each of the individual items (P < .001). In the most recent 10-year period, three variables were adequately reported in less than half of abstracts (primary endpoint 38.0%, rationale 38.6%, toxicity 40.4%). Since the publication of the revised CONSORT statement in 2001, reporting of these items has improved (58.2%, 47.8%, 44.8% for 2002–2004). Conclusions: Quality of abstracts for published RCTs has improved over time, but deficiencies still exist. Items requiring improved reporting include identification of the primary endpoint, description of rationale, and a summary of toxicity.

No significant financial relationships to disclose.

[Table: see text]