bluuebunny/crossref_metadata_2025 huggingface dataset:
Conditional survival probability for head and neck squamous cell cancer: Results from the SEER 11 Dataset
Authors: Fuller C. D. , Wang S. J. , Goldwein J. W. , Thomas C. R. , Weber R. S. , Hoffman H. T. , Rosenthal D. I.
Published: March 2020

5519

Background: Survival for most cancers is typically reported as a 5-yr percentage from the time of diagnosis. Surviving patients e.g., desire to know if their likelihood for survival has improved, given that they have lived X-years since diagnosis. Conditional survival (CS) is a calculated probability of survival that demonstrates the changing likelihood of demise during a span of intervals after diagnosis. The specific aim of this study is to assess the CS for patients with head and neck squamous cell carcinoma (HNSCC). Methods: The study population included HNSCC patients from the Surveillance, Epidemiology, and End Results (SEER 11) Program. Cumulative survival rates were calculated using JMP v6 (SAS, Cary, NC) with the product-limit method, and derived on the basis of the subsequent annual survival data. Results were also sub-stratified by site of disease. Results: 90,526 patients with histologically confirmed HNSCC diagnosed from 1973 to 2001 were included. The cumulative HNSCC crude cohort 5-year CS at diagnosis is 33%, and 38% at one-year after diagnosis. 5-year CS is 43% at 2 years post-diagnosis, where it plateaus for the next 8 one-year intervals. Sub-site analysis reveals similar CS trends for all HNSCC sites except the nasopharynx. Nasopharynx cancer CS, in contrast, progressively increases over all intervals. Conclusions: HNSCCC 5-year mortality risk stabilizes within 2–3 years after diagnosis, and with the exception of nasopharyngeal cancers, does not substantially improve thereafter. The SEER data represent the largest pooled dataset for HNSCC, but do not necessarily address all relevant issues contributing to risk for death. These data, however, do provide useful estimates for HNSCC patients with known survival after diagnosis, and may have utility in the design of clinical trials which incorporate survival modeling.

[Table: see text]

No significant financial relationships to disclose.
Swallowing function for patients treated on E2399: A phase II trial of function preservation with induction paclitaxel/carboplatin followed by radiation plus weekly paclitaxel
Authors: Murphy B. A. , Smith K. , Cmelak A. , Forastiere A.
Published: March 2020

5524

ECOG 2399 is a phase II organ preservation study using induction chemotherapy followed by concomitant chemoradiation in unresectable patients with squamous cancer of the larynx or oropharynx. A correlative study was undertaken to assess acute and long-term swallowing. Methods: Swallow evaluations were done at baseline, 3, 12 and 24 months posttreatment. Self-report measures consisted of the PSS-HN and FACT-HN. Objective measures include the Modified Barium Swallow (MBS) scored using a physiologic measure, the Dysphagia Outcome Severity Scale (D) and a functional measure, the Functional Communication Measure (F). Both D and F are graded on a 7-point scale (7 = normal through 1 = absent swallow/unable to take p.o). Results: The number of evaluable D and F assessments at each time point: baseline 97/99, 3 months 72/73, 12 months 40/41, 24 months 24/26. The scores presented in the table are expressed in percentages. Conclusions: The majority of patients presented with objective abnormalities on MBS, but swallow function remained largely intact. At 3 months, swallowing was markedly impaired (severe 18 and 24%, moderate 20 and 21%). By 12 months, swallowing had improved for most patients; however, a significant percentage of patients had persistent mild deficits (5–6). Severe swallowing abnormalities were found in less than 10% of patients at 12 and 24 months. Sponsored, in part, by Bristol-Myers-Squibb.

[Table: see text]

[Table: see text]
A Phase II study of axitinib (AG-013736), a potent inhibitor of VEGFRs, in patients with advanced thyroid cancer
Authors: Kim S. , Rosen L. S. , Cohen E. E. , Cohen R. B. , Forastiere A. , Silva A. M. , Liau K. F. , Archer R. L. , Bycott P. , Vokes E. E.
Published: March 2020

5529

Background: Elevated levels of VEGF have been found in thyroid tumor tissue compared to normal thyroid. Axitinib (AG-013736) is a novel small molecule inhibitor of the receptor tyrosine kinases with picomolar potency against VEGFR 1, 2 & 3 and nanomolar potency against PDGFR-beta and KIT. A phase I study in solid tumors identified 5 mg BID as the therapeutic dose. A phase II study in renal cell cancer demonstrated significant efficacy with a response rate (RR) of 46% (Rini et al, ASCO 2005). This study examined the safety and efficacy of AG-013736 (AG) therapy for advanced thyroid cancer. Methods: 32 patients (pts) refractory to or not suitable candidates for Iodine (131I) treatment were treated with AG 5 mg p.o. BID. Eligibility included measurable disease and ECOG performance status (PS) of 0 or 1. A Simon 2 stage minimax design was used (alpha = 0.1; beta = 0.1; null response rate (RR) = 5%; alternative RR = 20%). Results: The median age of 32 enrolled pts was 63 yrs (35–81), 20 (63%) were male, 12 (38%) were female. Histological subtypes include papillary: 19 pts (59%); follicular- 9 pts (28%), medullary- 2 pts (6%) and anaplastic-2 pts (6%). 25 pts (78%) had prior surgery, 19 pts (59%) had prior 131I treatment, 15 pts (47%) had prior RT, 6 pts (19%) had prior Adriamycin. Best response as assessed by RECIST criteria is PR in 3 pts with 38%-48% regression and additional unconfirmed PRs in 3 pts. Two pts (follicular) have PR>12 mos. Response assessments are ongoing. 12 patients have discontinued treatment: 6 pts (19%)-progression, 3 pts-adverse events (AEs) and 3 pts-other. Twenty pts (63%) remain on study. The range for time on study is (6, 469) days. Median progression free survival has not been reached. Preliminary safety data for 17 pts indicate most common treatment emergent AEs as fatigue (9 pts), nausea (5 pts), proteinuria ( 5pts ), dizziness (4pts). Gr. 3 AEs include proteinuria ( 2pts ), cough (1pt), dyspnea (1 pt), abdominal pain (1pt), dysphagia (1pt), fatigue (1pt), muscle weakness (1pt), anorexia (1pt). Gr. 2 hypertension was observed in 2 pts. Conclusions: AG-013736 has substantial anti-tumor activity in advanced thyroid cancer. Therapy is well tolerated with manageable toxicity. Further investigation in this setting is warranted.

[Table: see text]
A phase I, open-label study of lapatinib plus chemoradiation in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN)
Authors: Harrington K. J. , Bourhis J. , Nutting C. M. , Rosine D. , Theodosiou A. M. , Gardiner S. , Berger M. S. , Beelen A. P. , Stead A. G. , El-Hariry I. A.
Published: March 2020

5553

Background: Lapatinib is a selective and potent dual, competitive inhibitor of EGFR and ErbB2. A high level of expression of EGFR is reported in SCCHN (ranging from 55% to 90%), which is a negative prognostic factor, whereas ErbB2 expression ranges between 40% to 60%. The rationale for EGFR inhibition in combination with fractionated radiotherapy is to enhance radiosensitivity and inhibit cellular proliferation, including accelerated repopulation, during treatment. Methods: Patients (pts) with locally advanced SCCHN were enrolled at escalating dose levels of lapatinib (500–1,500 mg/d) in combination with radiotherapy (66–70 Gy/6–7 weeks given 5 days a week in 2 Gy daily fractions) and intravenous cisplatin (100 mg/m2, days 1, 22 and 43 of radiotherapy). Each cohort was to include 3 pts, with expansion to 6 in the event of dose-limiting toxicity (DLT). Main eligibility criteria were confirmed SCCHN, excluding nasopharynx, stage III, IVa,b, and adequate organ function. Regular safety assessments were performed during therapy and follow-up period. Cardiac assessments using MUGA or ECHO scans were also performed. Results: Seventeen pts were treated (500 mg - 7; 1,000 mg - 7; 1,500 mg - 3; expanded cohort of 9 additional pts is currently recruiting). The most common side effects were Grade 1-3 dysphagia, mucositis and dermatitis, typically observed with cisplatin and radiotherapy in this population. Lapatinib-related adverse events were minor. In the 500mg cohort: 2 pts had diarrhea (Gr 1), 1 pt had tinnitus (Gr 1); in the 1,000mg cohort: 2 pts had nausea (Gr 2) and vomiting (Gr 2), 1 pt had transient elevated liver enzymes (Gr 3); in the 1,500mg cohort 2 pts had nausea (Gr 1) and 3 pts vomiting (1 pt Gr 1, and 2 pts Gr 2). One DLT was reported both at 500 mg and 1,000 mg dose levels; no further DLT were reported at the final 1,500 mg dose level. The optimally tolerated regimen was lapatinib 1,500 mg OD, given concurrently with conventional radiotherapy and cisplatin. Preliminary evidence of clinical activity was encouraging. Conclusions: The combination of lapatinib and concomitant chemoradiation is well tolerated, has demonstrated encouraging clinical activity in this population of locally advanced SCCHN patients, and warrants phase II studies in this disease.

[Table: see text]
Phase I/II study of erlotinib combined with cisplatin and radiotherapy for locally advanced squamous cell carcinoma of the head and neck (SCCHN)
Authors: Herchenhorn D. , Dias F. L. , Ferreira C. G. , Bezerra M. , Fonseca A. J. , Mora P. , Pineda R. M. , Fontão K. , Knust R. E. , Martins R. G.
Published: March 2020

5575

Background: Erlotinib has single agent activity in SCCHN. Preclinical data indicates synergy with both cisplatin and radiotherapy (RT). Methods: This phase I/II study included patients (pts) with stages III and IV SCCHN. Pts received therapy with RT 70.2 Gy for 8 weeks and cisplatin (C) 100 mg/m2, 3 doses every 3 weeks, both starting on Day 8. Erlotinib (E) was started on Day 1 and continued until the end of RT. Phase I doses were escalated in cohorts of 3 pts/dose level: level 1–50 mg, level 2–100 mg and level 3–150 mg. In case of grade IV toxicity leading to RT interruption, 3 additional pts were included in the same dose level. Frozen tissue for molecular studies was collected before and after treatment. Results: Phase I was completed with 9 patients. No patient had RT interruption due to grade IV toxicity. Consequently 150 mg/day was established as the phase II dose. Twelve patients have been included in the phase II part of the trial. Final toxicity data is available for 13 patients (9 from phase I and 4 from phase II). Median age was 58 years, 10 pts had laryngeal carcinoma (stage III 4pts, IVA 3 pts, IVB 3 pts) and 3 oropharyngeal carcinoma (stage III 1pt, IVA 1pt, IVB 1 pt). The dose of C was reduced or held in 3 pts due to ototoxicity (2 pts) and neutropenia (1 pt). Other grade III or IV toxicity included dermatitis (8 pts), skin rash (3 pts), respiratory infection (2 pts), nausea (2 pts), neutropenia (2 pts), mucositis (2 pts) and cutaneous infection (1 pt). Response was accessed by direct visualization/biopsy and CT/MRI scans. Among the 13 patients who have completed treatment, 11 (84.6%) achieved complete pathological response, 1 had residual disease and 1 disease progression. Conclusions: This trial establishes the standard dose of erlotinib, 150 mg/day, as safe to be combined with full dose cisplatin and radiotherapy, in locally advanced SCCHN. Accrual for the phase II study is ongoing and additional response and toxicity data will be presented at the meeting.

No significant financial relationships to disclose.
Combination therapy of docetaxel, carboplatin or paclitaxel, carboplatin for patients with metastatic/recurrent carcinoma of the head and neck (SCCHN)
Authors: Bickmann A. , Holzgraefe M. , Wolf M. , Schröder M.
Published: March 2020

5576

Background: The five-year survival for patients with recurrent disease has not been significantly increased in the last years. Despite aggressive initial management of the primary tumor, patients suffer from locoregional recurrence in up to 50% and distant metastasis is seen in about 25% of cases. Materials and Methods: 96 patients with recurrent or metastatic carcinoma of the head and neck received therapy as follows. From August 1996 to May 2000, 52 patients received chemotherapy with paclitaxel 100 mg/m2 in combination with carboplatin AUC2. Between May 2000 and October 2004, 44 patients with recurrent or metastatic disease were treated with docetaxel 35 mg/m2 in combination with carboplatin AUC2. Both chemotherapy regimens were administered weekly for a maximum of six cycles. Results: Most of the patients underwent a combination first line therapy with CT/Surg/RT (48%/47.7%) or CT/RT (36%/23%) before suffering from rec. disease. After recurrence local, regional or distant, we observed 9.6% complete response for the combination-therapy with paclitaxel/carboplatin and 25% with docetaxel/carboplatin, partial response in 38.5% and 34.1% of the patients, yielding an overall response rate of 48.1% with weekly paclitaxel/carboplatin and 59.1% with weekly docetaxel/carboplatin. Stable disease was documented for 25% of the patients treated with paclitaxel/carboplatin and 18.2% after treatment with docetaxel/carboplatin. Median survival was measured after first diagnosis of recurrence or metastatic disease. We observed a median survival of 10.9 month for the group treated with paclitaxel/carboplatin and 37 month for patients treated with docetaxel/carboplatin. Therapy with both treatment-options was well tolerated, all 96 patients received six cycles. Most frequent toxicity was leucopenia (Grade I/II/III: paclitaxel 12%/27%/15%; docetaxel 25%/23%/16%). Conclusions: Chemotherapy for recurrent carcinoma of the head and neck with weekly docetaxel/carboplatin is well tolerated and effective. The toxicitiy profile makes this combination favourable for an outpatient setting.

No significant financial relationships to disclose.
Phase II study of combretastatin A4 phosphate (CA4P) in patients with advanced anaplastic thyroid carcinoma (ATC)
Authors: Cooney M. M. , Savvides P. , Agarwala S. , Wang D. , Flick S. , Bergant S. , Bhakta S. , Lavertu P. , Ortiz J. , Remick S.
Published: March 2020

5580

Background: CA4P is the first tubulin-binding vascular disrupting agent tested in the clinic. Phase I studies were devoid of significant myelosuppression, DLT included cardiovascular side effects, and there was demonstrable activity in ATC (Cancer Res 2002; 62:3408; Clin Cancer Res 2004; 10:96). Methods: Patients with metastatic ATC, good performance status, normal ECG and cardiac function, and no prior therapy for disseminated disease were eligible for study. CA4P at a dose of 45 mg/m2 was administered as 10-minute IV infusion on days 1, 8 and 15 every 28 days (1 cycle) until progression of disease. Results: A total of 18 patients (pts) (11M/7F), median age 62 (range 40–71 yrs), received a total of 55.67 cycles of treatment. Therapy was well tolerated with mild to moderate nausea, vomiting, headache, and tumor pain (3 pts with grade 3) all of which essentially resolved within first 24 hrs. There was no clinically meaningful myelosuppression or cardiac toxicity. No objective responses were seen; 6 pts with stable disease and 12 pts progressed. Median progression free survival (PFS) was 7.4 wks (range 2–84+ wks); with 28% of pts progression free > 3.0 mos. (12.0+, 14.3, 15.3, 25.6 and 84.0+ wks). Pts without bulky disease tended to do better. Fourteen pts have died; 4 are alive; and 2 are alive and on-study at 12.0+ and 84.0+ wks. Median survival is on the order of approximately 20 wks. Conclusions: Approximately a quarter of patients treated with single-agent CA4P experience greater than 3 mos. freedom from progression. Combined modality strategies with CA4P and either chemotherapy and other targeted agents or with radiation are warranted. [Supported in part by a clinical grant from OXiGENE, Inc., Waltham, MA and NIH grant nos. M01 RR-00080].

No significant financial relationships to disclose.
Phase III adjuvant trial of concurrent epirubicin/taxane vs. sequential epirubicin/cyclophosphamide followed by taxane for node positive breast cancer
Authors: Lambert-Falls R. , Deutsch M. A. , Desch C. , Zhou K. , Perez E.
Published: March 2020

573

Background: This study evaluates whether concurrent epirubicin/taxane (ET) improves disease-free survival (DFS) at 3 yrs compared to the sequential combination of epirubicin/cyclophosphamide followed by a taxane (EC>T) in pts with operable node (+) breast cancer. Methods: Eligible pts were randomized to receive either ET (E 75 mg/m 2) for 8 cycles q21 days or EC>T (E 90 mg/m 2, C 600 mg/m2) for 4 cycles, followed by 4 cycles of a taxane q21 days. Choice of T (paclitaxel 175 mg/m2 or docetaxel 75 mg/m 2) was at the physician’s discretion. The primary endpoint is DFS. A 0.10 increase in the probability of DFS at 3 yrs for the ET arm would be considered clinically relevant. To detect 82 events, 300 subjects per arm are required to provide 90% power at 5% significance level. Results: 617 pts were enrolled from Nov 2000 to June 2003; 308 pts received ET and 309 pts received EC>T. Both treatment arms were well balanced with respect to age, nodal+, ER status, Her-2+ and PS; median age 52.5 (42%<50 years old); 70% ER+; 61% LN (1–3); 16% Her-2+; 87% PS 0. Total of 2206 cycles of treatment were given to ET compared 2314 cycles of treatment to EC>T. At 30 months of median follow-up there were DFS 102 events occurred; 47 events in ET arm (16%) and 55 events in EC>T arm (18%); 63 total deaths; 29 deaths in ET arm and 34 deaths in EC>T arm. The most common toxicities include alopecia (50%), fatigue (31%), nausea and vomiting (30%), dyspepsia (27%), febrile neutropenia (15%), constipation (12%), diarrhea (10%), arthralgia (11%), stomatitis (10%). In cardiac safety f/u, only one pt in ET arm remained LVEF drop >15. Conclusions: Epirubicin can be combined with taxanes in both sequential and concurrent therapies and both regimens are effective and well tolerated. The study is sponsored by Pfizer Inc.

No significant financial relationships to disclose.
Update of cardiac dysfunction on NSABP B-31, a randomized trial of sequential doxorubicin/cyclophosphamide (AC)→paclitaxel (T) vs. AC→T with trastuzumab (H)
Authors: Geyer C. E. , Bryant J. L. , Romond E. H. , Ewer M. S. , Keefe D. L. , Shannon R. P. , Levine T. B. , Rastogi P. , Swain S. M. , Wolmark N.
Published: March 2020

581

Trastuzumab (H) has been shown to improve 3-year disease-free survival (DFS) and overall survival (OS) in HER2 positive, node-positive breast cancer patients when combined with paclitaxel (T) following AC (Romond NEJM 2005:353;1673–1684). Cardiac dysfunction is the major toxicity associated with the addition of H to AC→T. The 3-year cumulative incidence of cardiac events (class III/IV CHF or cardiac death) with AC→TH was 4.1% compared to 0.8% with AC→T (Tan-Chiu JCO 2005:23;7811–7819). An updated analysis of cardiac safety on B-31 with an additional full year of follow-up is planned for March 2006 and will be presented.

[Table: see text]
Relationship between numeracy and breast cancer patients’ estimates of adjuvant treatment benefit
Authors: Lipkus I. M. , Kimmick G. G. , Chui S. Y. , Fifield D. L. , Werner L. A. , Marcom P. K.
Published: March 2020

586

Background: Based on clinical anecdotes and existing literature, the general population has trouble understanding and making use of statistical information. We explored the accuracy of breast cancer patients’ (pts) estimates of treatment outcomes (probabilities of remaining cancer free versus recurring) relative to data provided by ‘Adjuvant! Online‘ decision aid program, and whether accuracy differed by pts numeracy skills (i.e. use of mathematical concepts and operations). Methods: 43 ER+ women with early stage, node-negative breast cancer were recruited (mean age 56, 72% Caucasian). After signing an informed consent and completing an assessment of numeracy (Lipkus et al., 2001), pts discussed case-specific Adjuvant! print-outs with an oncologist. Pts then estimated their chances of being cancer free after receiving no further treatment, hormonal therapy only, chemotherapy only, or both. Pts also were asked to select the treatment option that afforded their best chance of remaining cancer free. Results: Compared to the estimates provided by Adjuvant! Online, pts underestimated their chance of being cancer free after receiving no further treatment (M=62 vs. 48 out of 100), hormonal therapy only (M=72 vs. 45), chemotherapy only, (M=71 vs.42), and combined therapy (M=78 vs. 54). 63% correctly selected the treatment option that afforded the highest estimate of being cancer free. More numerate patients were more likely to correctly specify which treatment option provided the best chance of being cancer free (OR=0.67, 95% CI: 0.50, 0.89, p<.006); and less likely to give personal estimates of being cancer free inconsistent with estimates provided by Adjuvant! for hormonal therapy (OR=0.17, 95% CI: 0.04, 0.72, p<.02), chemotherapy (OR=0.62, 95% CI: 0.39, 0.99, p<.05) and combined therapy (OR=0.44, 95% CI: 0.23, 0.85, p<.02). Conclusions: Findings suggest that pt numeracy skills are important in comprehending statistical data about adjuvant treatment outcomes. Numeracy skills may have implications for how statistical information about treatment is presented and discussed, affecting processes of informed decision-making and pt quality of life.

No significant financial relationships to disclose.
Conditional survival for patients with colon cancer: An analysis of National Surgical Adjuvant Breast and Bowel Project (NSABP) trials C-03 through C-06
Authors: Wang S. J. , Zamboni B. A. , Wieand H. S. , Yothers G. , Dignam J. J. , Raich P. C. , O’Connell M. J. , Wolmark N. , Thomas C. R.
Published: March 2020

6005

Background: Survival for cancer patients is usually only reported as survival from time of diagnosis to some time landmark (e.g., 5 yrs). For pts surviving one or more years after diagnosis, however, their survival probability changes, and is more accurately depicted by conditional survival (CS), defined as the probability of surviving for an additional fixed time interval given that the pt has already survived a period of time. The purpose of this study was to determine the 5-yr CS of colon cancer pts in 4 NSABP trials. Methods: We analyzed long-term overall survival data from the 5587 colon cancer pts who were enrolled in fluorouracil (or equivalent) arms of NSABP trials C-03 through C-06. We computed observed 5-yr overall CS for pts who had already survived without disease from 0 to 5 yrs after diagnosis, and stratified the results by age, sex, race, stage, number of positive nodes, number of nodes resected, tumor location, and performance status. Results: The Table below shows the 5-yr overall CS for all pts and for selected subgroups for different survival times since diagnosis. As disease-free survival time since diagnosis increased, 5-yr observed overall CS increased from 76% to 90% at 5 yrs. For pts under age 50, CS increased from 78% to 95% at 5 yrs, but for pts > 70 yrs, CS remained fairly constant (71–82%). For pts with > 10 positive nodes, CS increased from 37% to 81% at 5 yrs, but did not change appreciably for node-negative pts (87–92%). Dukes’ C pts saw an increase in CS from 68% to 88% at 5 yrs, while CS for Dukes’ B pts did not change appreciably. Conclusion: Projected survival probability generally increases with time for colon cancer pts who remain disease-free for a period of time after diagnosis, and conditional survival can provide more informative prognostic information for these pts. An additional effect is that prognostic factors that are important at baseline become less important for conditional survival as the disease-free period increases.

[Table: see text]

No significant financial relationships to disclose.
A timing and process flow analysis of opening clinical trials within an oncology cooperative group setting: The case of the CALGB
Authors: Dilts D. M. , Sandler A. B. , Baker M. , Cheng S. , McGuire S. , Menon G. , Wu A. , Karas K. , Sawyer D. , Schilsky R. L.
Published: March 2020

6015

Background: Cooperative oncology groups are major sponsors of Phase III clinical trials, yet the number of steps and times required to setup and open such a trial have yet to be studied. This study assesses these items in the Cancer and Leukemia Group B (CALGB) for all Phase III studies opened in a 3 year period. Methods: Step 1: headquarters and statistical center staff were interviewed to discover the detailed steps required for a study to transit from initial concept submission by a potential study chair to final activation of the study. The formal procedures manuals were also reviewed. All study records and draft protocol documents were inspected to verify and identify additional setup steps. Finally, data was collected through direct contact with study chairs and disease committee chairs. Step 2: timing data for each of the major functions or processes were collected. All times are from initial initiation of the function to the final completion of the task. Times represent calendar time. Step 3: creation of stream-lined process flows, currently underway. Members from the CALGB and the Vanderbilt Center for Management Research in Healthcare (cmrhc.org) will spend 2 days creating a process to significantly reduce the time and the number of steps to opening a trial. Results: A total of 13 Phase III studies were activated during the 3 years study period. 372 processes are required to open a Phase III at CALGB, which include 314 work steps, 43 major decision points. Interesting, most of the decision points (63%) are external to CALGB. There are 23 processing loops that require repeating processes. The process map, which lists all processes, is a chart 243.5” × 41 in 8 pt font (or about the length of a 20 passenger bus). Median calendar days to activate a Phase III study at CALGB is 767 days (min = 488, max = 1,441). The three functions requiring the greatest median days are protocol development (477), forms development (434), and regulatory affairs (350). Conclusion: It can require years to open a Phase III study at a major cooperative oncology group. Using process redesign techniques, we expect to be able to significantly streamline the process. Support provided by the NCI.

No significant financial relationships to disclose.
Measuring chemotherapy safety in a community oncology practice: Results of a three-year prospective study
Authors: Jacobson J. O. , Krzyzanowska M. K. , Schwartz J. H. , Maloney B. , Lavino A. , Treacy J.
Published: March 2020

6019

Background: Chemotherapy administration is associated with a risk for severe toxicity and mortality. Limited data are available to assess these risks outside of clinical trials or administrative databases. We sought to determine the risk of chemotherapy administration in a community-based oncology practice, to identify potential risk factors, and to look for trends over time. Methods: The North Shore Medical Center Cancer Center (NSCC) is a community-based cancer facility in Peabody, MA. In 1/03, we began a prospective study to identify and categorize all adult patients admitted to hospital with severe chemotherapy toxicity and to compare them to all chemotherapy recipients. Consecutive cases admitted to hospital from NSCC were reviewed in a monthly multidisciplinary peer review meeting. Admissions deemed to be treatment-related were entered into a toxicity database. Results: Between 1/1/03 and 11/30/05, 2206 courses of chemotherapy were administered to 1574 patients resulting in 12,380 treatment-months of therapy. 162 patients required 174 hospital admissions, for an annualized risk of treatment-related hospitalization (TRH) of 16.6% and a mean length of stay of 7.0 days. Mean age of cases was similar for those admitted for toxicity compared to all chemotherapy patients (65.3 versus 64.6 yrs.). GI toxicity and infection (principally fever and neutropenia) accounted for 77% of TRH. Between 2003 and 2005, the risk of a TRH declined for colorectal cancer cases while it increased for breast cancer and lung cancer cases. There were 14 treatment-related deaths (TRD) for an annualized risk of 1.1%. TRD’s were infectious in 9, GI in 4 and cardiac in 1. Median age was 67, similar to the entire cohort. TRD occurred early (median 28 days from the inception of chemotherapy, range 1–120 days). Significant comorbidity was identifiable in 12 of 14 cases. 10 of 14 cases were being treated palliatively. Conclusions: These prospectively collected data confirm that chemotherapy administration in a community-based practice can be associated with a low risk of severe toxicity and a very low risk of mortality. TRH and TRD could become standard measures of quality care for cancer facilities.

No significant financial relationships to disclose.
Trastuzumab for all? A decision analysis examining tradeoffs between efficacy and cardiac toxicity of adjuvant therapy in HER2 positive breast cancer
Authors: Gupta A. K. , Mekan S. F. , Eckman M. H.
Published: March 2020

6022

Background: Early results from three randomized trials showed that adjuvant trastuzumab (T) results in significant reduction in recurrence rates in high risk HER2 positive breast cancer patients (pts). However, the long term survival benefits and the balance of risk and benefit of adjuvant T in pts with lower risk of cancer recurrence and a higher risk of cardiac toxicity (elderly and pre-existing heart disease) remain undetermined. Methods: We evaluated these tradeoffs through a Markov state transition decision analytic model to simulate the survival benefits in a variety of subpopulations of HER2 positive cancer pts. Efficacy and cardiac toxicity of T were based on B-31 and N9831 trials. Outcomes were expressed in quality adjusted life years (QALYs) and 10 year survival rates. We explored a number of prototypic scenarios that varied in age, risk of cancer recurrence, and cardiac toxicity rates. Our base case focused on a 50 year-old, 2 cm, node positive, ER/PR negative pt with a 6% cumulative risk of cardiac toxicity. Results: Survival rates and the cardiac death rates for the base case and a hypothetical elderly pt with low risk of cancer recurrence are illustrated in the table . One-way sensitivity analyses on the base case, across a wide range of values for age (50–80); hazard ratio for T efficacy (0.48 to 0.95); annual cancer recurrence risk (0.5–5%) and cardiac toxicity (4–60%) demonstrated that adjuvant T was the more effective strategy. Conclusions: The addition of T in HER2 positive cancer is more effective than standard chemotherapy alone in most cases, including elderly pts with node negative disease and those with increased risk of cardiac toxicity. However, the incremental benefit decreases with advancing age, higher risk of cardiac toxicity and in pts with lower risk of recurrence. This model is a useful clinical tool to quantify risks and benefits of adjuvant T and in predicting long term survival in different subpopulations of HER2 positive breast cancer pts.

[Table: see text]

No significant financial relationships to disclose.
Socioeconomic and demographic factors associated with use of sentinel node biopsy and adjuvant biologic response modifiers in melanoma
Authors: Lange J. R. , Chang D. , Palis B. E. , Balch C. M.
Published: March 2020

6027

Background: Cancer management may be influenced by factors other than disease characteristics. Little is known about the association of demographic and socioeconomic factors with melanoma care. Methods: The National Cancer Data Base, a hospital-based registry, was queried on reported use of adjuvant biologic response modifiers (BRM) for patients with resected regional metastases and the use of sentinel node biopsy (SNBx) for patients with clinical stage I and II melanoma in patients ages 1–69 between 1994 and 2003. Independent variables were age, sex, race, severity of disease, income, insurance type, U. S. Census region and type of treating facility. Analysis was performed by forward stepwise logistic regression. Results: Between 1994 and 2003, 37.8% of 10,790 patients with resected node-positive melanoma received BRM. Between 1998 and 2002, 61,251 patients with clinical stage I and II melanoma had a SNBx in 13.2%, 46.2%, 55.9%, and 41.7% of those with T1, T2, T3, and T4 tumors, respectively. In multivariate analysis, geographic variance in use of BRM and SNBx was striking ( Table ). Insurance type (commercial vs. others) and facility type (teaching/research vs. others) were also significantly associated with these modalities. Use of BRM was also associated with age, number of positive nodes and earlier treatment year, but not with sex, income or race. Use of SNBx was also associated with T stage, later treatment year, age and income, but not with sex or race. Conclusions: BRM and SNBx use varied significantly with geographic region, insurance type, and type of treating facility; this may have implications for provider education and public policy.

[Table: see text]

No significant financial relationships to disclose.
Randomized clinical trials in oncology stopped early for benefit (RCTSEB)
Authors: Segota E. , Soares H. P. , Djulbegovic B. , Kumar A. , Bassler D. , Guyatt G. H.
Published: March 2020

6039

Background: Randomized clinical trials (RCT) that stop earlier than planned because of apparent benefit often receive great attention. However, how often these early results get confirmed by other subsequent meta-analysis/randomized studies, and how often results get included in clinical guidelines is not known. We conducted systematic review of oncologic RCTSEB to further determine if the results from RCTSEB are confirmed by the subsequent studies and/or included in guidelines. Methods: RCT of any intervention reported as having stopped early because of the results favoring the intervention were previously identified (JAMA.2005;294:2203).Trials with interventions in prevention and treatment of solid and hematologic malignancies were included for this review. Citation search was conducted by two reviewers to identify meta-analysis (MA), systematic reviews (SR) and RCTs that used similar trial design as the RCTSEB. National Comprehensive Cancer Guidelines were reviewed to identify the impact of the results on recommendations on clinical practice. Results: 33 trials were identified, and 5 were excluded because they did not fit the inclusion criteria. MA/SR were available for the assessment of interventions reported in 15/28 RCTSEB. Results of subsequent MA confirmed 12/15 findings, while 3 trials were contradicted. Of the remaining 13 trials, for 7 there was at least one subsequent RCT identified. 6/7 were confirmed as beneficial in the subsequent RCTs and 1 was contradicted. For 6/28 RCTSEB we did not find any subsequent MA/SR/RCTS. We also looked at the inclusion of interventions from RCTSEB in the clinical guidelines. 18/28 interventions from RCTSEB were mentioned in the formulation of clinical guidelines.16/18 were recommended as true positive recommendations. The other 2 interventions which were addressed in the guidelines were either not confirmed (n = 1) or incorrectly recommended (n = 1). Conclusions: In this set of oncology of RCTSEBs the findings were subsequently confirmed in 64% (18/28) cases. Guidelines developers used 2/28 (7%) of RCTSEB for which reliable confirmatory data were available. However, caution should be applied in the interpretation of our results because the same RCTSEB was also included in confirmatory MAs which possibly could have introduced bias.

No significant financial relationships to disclose.
Pre-operative breast magnetic resonance imaging (MRI) influences patient selection for partial breast irradiation
Authors: Vallow L. A. , Packianathan S. , Deperi E. R. , McDonough M. D. , Earle J. D. , Perez E. A.
Published: March 2020

604

Background:
Many patients with localized breast cancer undergo breast conservation therapy. Partial breast irradiation (PBI) is a technique that reduces irradiated tissue volume and decreases treatment time. Appropriate patient selection for this technique is critical. We studied the influence of pre-operative breast MRI on patient selection for PBI.
Methods:
Between 05/04 and 05/05, 231 women with newly diagnosed breast cancer underwent pre-operative bilateral breast MRI (median age = 64, range 34 to 89). Following initial clinico-pathologic review, patients were deemed to be eligible for PBI based on the NSABP B39 protocol if they satisfied its inclusion criteria (tumor size ≤3 cm, ≤3 positive nodes, negative surgical margins, lack of multicentric disease), derived through physical examination, mammography and/or ultrasonography. Breast MRI scans of all patients deemed eligible for PBI by these criteria were then reviewed to determine the impact of the MRI findings on their eligibility for PBI. Only patients who had pathological assessment to correlate with the MRI findings were included in the analysis.
Results:
Based on the NSABP B39 inclusion criteria, 186 patients (81%) were considered to be appropriate candidates for PBI without influence from MRI findings. Of these 186 women, MRI findings led to pathologically proven additional disease that altered the recommendations for PBI in 26 patients (14%). Mammographically occult, biopsy proven multicentic disease was detected in the ipsilateral breast in 13 patients (7%), whereas 5 women (2.7%) had mammographically occult, biopsy proven multicentric disease in the contralateral breast. In 8 patients (4.3%), pathological assessment confirmed more extensive local disease than was detected by breast MRI.
Conclusions:
Up to 14% of patients initially deemed eligible for PBI were later found to be ineligible because of breast MRI findings. Ipsilateral multicentric disease was identified in 7%, contralateral disease was discovered in 2.7%, and more extensive local disease was noted in 4.3%. Bilateral breast MRI complements other imaging modalities in determining eligibility for PBI by identifying mammographically occult disease in patients for whom PBI may be inappropriate.

No significant financial relationships to disclose.
The cost burden of trastuzumab and bevacizumab monoclonal antibody therapy in solid tumors: Can we afford it?
Authors: Drucker A. , Virik K. , Skedgel C. , Rayson D. , Sellon M. , Younis T.
Published: March 2020

6044

Background: Monoclonal antibodies (MAb), such as trastuzumab (TZ) and bevacizumab (BZ), have become an important yet expensive component of cancer treatment. The potential cost impact on health care budgets needs to be assessed in the context of its potential utilization. An estimate of the additional costs incurred by adopting TZ and BZ therapy in breast (BRC), lung (LUC) and colorectal (CRC) cancers was undertaken. Methods: The MAb costs per patient were estimated based on treatment indications, length of treatment, standard doses / schedules and local pharmacy data. Supportive medications, diagnostics and health resources utilization only required for the MAb therapy were also examined. This analysis was performed in Canadian dollars ($), and assumes complete drug delivery and uncomplicated cycles. Drug costs were based on average 2005 wholesale prices in Canada. The analysis took a direct payer perspective. We subsequently estimated the cost of MAb therapy per patient relative to the total costs of conventional cancer management without MAb therapy. Budget impact estimates on Canada’s health care system were then derived according to constructed schema, which accounts for absolute numbers of target patients and systemic therapy utilization. Results: The average costs of TZ per treated patient were $47,278 and $26,648 for adjuvant and metastatic BRC, respectively. For BZ, these were $47,250 and $38,500 for metastatic LUC and CRC, respectively. Other costs associated with MAb therapy were in the range of 3–6%. The predicted TZ drug costs in metastatic breast cancer were within 10% of the actual costs derived from pharmacy data. The potential life-time absolute costs to Canada’s health care system were approximately $118 million for TZ, and $262 million for BZ. This corresponds to an average of approximately 21% increase in the health care expenditure for BRC, LUC, and CRC. Conclusions: MAb therapy, such as TZ and BZ, may add a significant cost burden to Canada’s publicly funded health care system. The developed schema in this analysis may be of potential use to health care providers and policy makers in assessing the impact of MAb therapy on health care budgets.

No significant financial relationships to disclose.
Patient survival and health care utilization in Medicare beneficiaries diagnosed with cancer of unknown primary
Authors: Tong K. B. , Murtagh K. N. , Hubert H. , Santry B. , Layton A. J. , Anderson G. G.
Published: March 2020

6064

Background: For patients presenting with cancer of unknown primary (CUP), identifying the site of origin can improve survival and treatment outcomes. We analyzed outcomes in patients who present with an initial diagnosis of malignant neoplasm without specification of site (ICD-9 199.0 and 199.1). Methods: Based on a 5% Medicare beneficiary sample from 2002 through 2004, we conducted a retrospective claims data analysis identifying patients who were cancer free in 2002 and who subsequently had a claim with a CUP diagnosis (ICD-9 199.0 or 199.1) in 2003. We evaluated survival and Medicare charges by procedure and diagnosis code for four consecutive quarters following CUP diagnosis. We assigned patients to one of two groups. The “differential” group consisted of CUP patients having a subsequent claim with a differential diagnosis code (ICD-9 140–229, excluding 199.0 and 199.1). The “unknown” group consisted of CUP patients with no later change in diagnosis. We applied chi-square and t-tests to examine differences in survival, resource utilization, and Medicare charges between groups. We developed Cox survival and linear regression models for multivariate analyses. Results: Of the 388 patients, 277 (71%) did not have a claim with a differential diagnosis during the follow-up period. Both groups were similar in race (80% white) gender (60% female) and age (range 70–79). The one-year mortality of the unknown group was 32.9% compared to 19.8% in the differential group (p=0.01). First quarter charges were higher for the unknown group: $2,549 vs. $1,683 (p < 0.001). Total allowed charges were higher for the differential group over the one-year follow up period: $7,493 vs. $5,540 (p < 0.05), even when adjusted for survival. Conclusions: Following a diagnosis of CUP, patients who obtain a differential diagnosis live longer and incur higher charges over time as a result of ongoing management and intervention. Improved diagnostic tests may affect patient survival and how Medicare resources are applied.

No significant financial relationships to disclose.
Agreement between physicians and patients about what constitutes shared decision making
Authors: Charles C. A. , Ellis P. M. , Dimitry S. J. , O’Brien M. A. , Whelan T. J.
Published: March 2020

6065

Background: Involving patients in making decisions about their own care is increasingly desirable for patients with serious illness. Shared decision making is one such model, the attributes of which have been well defined (Charles et al., Soc Sci Med,1997,1999). However, it is unclear whether physicians and patients agree on what constitutes a SDM interaction. Methods: Semi-structured interviews were undertaken with 21 medical and radiation oncologists and 14 cancer patients attending a regional cancer centre. Participants were asked what they thought it meant for the patient and physician to share in DM. Responses were compared to the theoretical constructs of SDM defined by Charles et al: information exchange (flow, direction, type, amount), deliberation, and who makes the decision. Two analysts independently reviewed the interviews for patient and physician definitions of SDM and compared these with the Charles et al. model of SDM using explicit classification decision rules. There were few discrepancies between analysts and agreement was reached in all cases. Results: 71% of physicians and 29% of patients described a two-way flow and direction of information exchange as necessary for SDM. Only 24% of physicians and 21% of patients described the exchange of both medical and personal information. All participants indicated that more than the minimum legally required amount of information was needed. 67% of physicians and 36% of patients described both patient and physician involvement in deliberation about treatment as a component of SDM. 48% of physicians and 21% of patients identified both patients and physicians are involved in deciding what treatment to implement in a shared approach. Overall, none of the participant definitions identified all the components of the SDM model. Physicians in their definitions, identified more components than did patients. Conclusions: Physicians appear to have a stronger understanding of the elements involved in SDM. These differences may lead to different expectations about patient involvement in DM. Physicians have a responsibility for ensuring that patients are invited to contribute to all components of SDM in the oncology consultation.

No significant financial relationships to disclose.
Structure of a physician assistant (PA)-managed survivorship practice within a multidisciplinary breast clinic
Authors: Moore B. A. , Northfelt D. W.
Published: March 2020

6087

Background: In the last two decades, success in breast cancer screening and treatment has resulted in evolution of a growing patient population with unique medical needs. The American Cancer Society currently estimates a 98% relative five-year survival rate for patients with localized breast cancer, 88% for all stages combined. Caring for survivors represents both opportunity and challenge for the medical community. The integrated team approach in a multidisciplinary breast center is the ideal model to incorporate PAs in providing comprehensive long-term surveillance and support in this setting. Methods: The core mission of a PA-managed survivorship practice is outlined as follows: Maximize health and quality of life in breast cancer survivors, recognizing physical, psychological and spiritual factors; Provide early detection of disease recurrence and/or new breast cancer occurrence in women with a breast cancer history; Aggressively manage and overcome problems resulting from breast cancer treatment; Aid women in understanding and overcoming risks, including genetic risks, for developing breast cancer. Evidenced-based algorithms defining standards of care create the foundation for clinical decision making and establish precedent for continuity of care. The scope of care is enhanced by opportunities to incorporate research and genetic counseling. Results: Of 205 patients seen between 9/1 and 12/31/2005, 48% were younger than 70, 55% were Stage I, 82% were less than 5 years post-treatment, 63% were on hormone therapy. Conclusions: With continued trends in breast cancer survival, specialized long-term surveillance and support is essential to providing quality, comprehensive care that addresses the unique medical needs of these patients. A PA-managed breast cancer survivorship practice within a multidisciplinary breast clinic not only provides forum for such endeavors, but also fosters opportunity for life-long partnership focusing on quality of life, health and well-being.

[Table: see text]

No significant financial relationships to disclose.