bluuebunny/crossref_metadata_2025 huggingface dataset:
Functional and psychological evaluation after exclusive chemoradiation therapy in oral and oropharyngeal cancer
Authors: Zanon C. , Airoldi M. , Garzaro M. , Raimondo L.
Published: August 2020

e17012

Purpose: The treatment of head and neck tumours often negatively affects speech, swallowing, body image and quality of life (QoL). Aim of this study was the evaluation of the impact of exclusive chemoradiation therapy (CH-RT) on QoL and psychological functioning. Patients and Methods: Twenty-eight patients, affected by a carcinoma of the oral cavity and oropharynx received exclusive CH-RT. Late effects of CH-RT and psycho-oncological assessment included: Radiation Therapy Oncology Group (RTOG) - European Organisation for Research and Treatment of Cancer (EORTC) late radiation morbidity scoring system, DISCHE morbidity recording scheme, Hospital Anxiety and Depression Scale (HADS), Montgomery Asberg Depression Rating Scale (MADRS), Mini Mental Adjustment to Cancer (MINI MAC), and EORTC QoL Head and Neck 35. Results: After a median follow-up of 42 months (range 12–60 months) moderate-severe late toxicity was as follows: taste impairment (89.20%), salivary function (82.12%), subcutaneous tissue (7.08%). Concerning dysphagia 39% of patients complained some discomfort, 28% had a more severe toxicity whereas 7% could not have an oral feeding; patients with severe dysphagia showed higher levels of anxiety (p < 0.05): dysphagia influences the QoL, fatigue and physical-social functioning. Rates of depression and anxiety were generally low: 78.6% of our sample did not show clinical relevant anxious symptoms and 82.1% of patients did not reach the threshold of an overt depression. Just a fair concordance in rate of depression between self- and hetero-evaluated scale was observed, with higher rates relieved by MADRS compare to HADS depression subscale using 8 or 10 cut-off (Cohen's k test = 0.401) Conclusions: Our data suggest low rates of anxiety and depression, in patients treated with CH-RT, with a different evaluation between self-evaluative and hetero-evaluative scales.

No significant financial relationships to disclose.
A six-panel PCR of both plasma and blood for EBV-DNA as tumor marker for nasopharyngeal carcinoma patients treated in the United States
Authors: Weiss J. , Xavier M. , Tsai D. , Arnoldi S. , Sherman E.
Published: August 2020

e17014

Background: Studies of plasma from nasopharyngeal carcinoma (NPC) patients from endemic regions demonstrate that circulating DNA derived from EBV may be used as a tumor marker, but data from non-endemic regions or in whole blood are limited. Methods: ViraCor Laboratories (Lee's Summit, MO) performed PCR for EBNA, EBER, and LMP on both plasma and whole blood of 11 NPC patients undergoing therapy at the Hospital of the University of Pennsylvania. Results were correlated with disease status via review of chart records and imaging reports. Results: 7 of 11 patients tested were positive for circulating EBV derived DNA. 2 patients were treated with induction chemotherapy with suppression to 0 copies of circulating DNA for all plasma measures, but not whole blood measures (LMP 0, EBER 100 and EBNA 200 copies for one patient and LMP 100, EBNA 100 and EBER 300 copies for the other). The first of these patients remains free of disease but the other retains a large mass believed to be active disease, but which has not grown over 8 months following therapy. 5 patients, including the 2 patients treated with induction therapy, were treated with chemoradiotherapy. PCR following therapy was negative on all plasma measures for the 4 patients who remain free of disease (at intervals of 7, 12, 13 and 16 months). 2 of these patients retained low-level EBV on at least 1 whole-blood measure–1 for EBNA alone (100 copies) and the other for both EBER and EBNA (300 and 100 copies). 2 patients were treated for metastatic disease. 3 episodes of progression were all accompanied by increases in plasma EBV (EBNA from 13,700 to 21,100 with EBER 1600 to 9400 and EBNA 1800 to 2200 to 3000 with EBER 100 to 100 to 500). Conclusions: This pilot data on a population treated in the United States is consistent with larger data sets obtained in endemic regions demonstrating that EBV is an effective tumor marker for prognosis and to follow therapy. It is the first to demonstrate greater specificity of plasma measures over whole blood measures, and it raises the hypothesis that whole blood measures may be more sensitive. Further prospective study is warranted in non-endemic populations both to validate the measure and to facilitate translational research into biologic factors driving the behavior of these tumors.

[Table: see text]
Use of tumor volume as measured on F18FDG-PET/CT scan as a predictive biomarker for head and neck cancer
Authors: Choi Y. , Song M. , Seol Y. , Kwon B. , Shin H. , Chung J. , Lee J. , Lee B. , Kim S. , Sohn C. , Cho G.
Published: August 2020

e17019

Background: Functional imaging, PET and its fusion with anatomical modalities, PET/CT promise to improve detection and characteristic disease. The objective of this study was to evaluate metabolic tumor volume as measured on F-18 FDG-PET/CT and its association with treatment response and prognosis in patients with head and neck cancer. Methods: The study population consisted of patients received neoadjuvant chemotherapy for a maximum of three cycles followed by radiation therapy. Before treatment patients were taken FDG-PET/CT scan, SUVmax, tumor volume, metastasis were recorded. Results: We enrolled 59 patients with stage III ann IV head and neck cancer. The median age was 66 years (range 47–81). There were 32 patients with stage III and 27 with stage IV. The mean SUVmax was 8.8 (range, 1.478). The mean tumor volume was 21.3 cm3 (range, 0.2–170). There was no correlation between tumor volume and SUVmax (correlation coefficient 0.295). Higher SUVmax was not associated with an increased risk of lymph node and distant metastasis at diagnosis (p = 0.968). But higher tumor volume was associated with an increased risk of lymph node and distant metastasis at diagnosis (p = 0.063). The metabolic tumor volume as measured on PET/CT scans was predictor of treatment response and disease -free survival. The response rate were 84% (21/25) for an SUVmax <5.5, 55% (19/34) for an SUVmax > 5.5 (p = 0.038). The disease free survival were 31.1month for an SUVmax <5.5, 4.6months for an SUVmax > 5.5 (p = 0.025). Conclusions: The metabolic tumor volume as measured on F-18FDG-PET/CT is a predictive biomarker of treatment response and disease free survival for patients with head and neck cancer.

No significant financial relationships to disclose.
Capecitabine and cisplatyl as neoadjuvant treatment of locally advanced nasopharyngeal carcinoma
Authors: Kerboua E.
Published: August 2020

e17036

Background: The main objective of this study is to evaluate the activity and safety of capecitabine (X) and cisplatyl (C) in patients (pts) with locally advanced nasopharyngeal carcinoma(NPC). Capecitabine was reported to have single-agent activity in advanced/metastatic NPC. Combination of X and C should provide a convenient and active regimen. Methods: Pts with undifferentiated NPC type were enrolled from July 2007 to September 2008. They received X 1,000 mg/m2orally bid on days 1–14 + C 75/m2 IV day 1 q 3W, Three cycles were administered in a neoadjuvant setting before radiotherapy. The primary endpoint was overall response rate (ORR). Results: Forty-one (41) pts have been enrolled 28 male/13 female with locally advanced NPC: 15 pts (36,6% ) were stage III (UICC 1997) 26 pts (63,3%) stage IV (n = 6 IVA and n = 20 IVB). All pts were evaluated for safety and 36 pts for response. ORR was 86% with 63,8% (n = 23) complete response (CR), 22,2% (n = 8) partial response (PR), 2 progression disease (PD) and 2 stable disease (SD). The most common grade 3/4 adverse events were diarrhea 4,8% (n = 2), neutropenia 7,3% (n = 3), thrombocytopenia 7,3% (n = 3), vomiting 9,7% (n = 4) . Two pts died from sepsis that was probably treatment-related. A hand-foot syndrome was observed in 25% of pts (grade 1/2). Conclusions: Preliminary results show that X plus C provide an active regimen with an acceptable tolerability profile as neoadjuvant chemotherapy for locally advanced NPC. This regimen requires a shorter hospital stay and is more convenient for pts compared with the gold standard 5-FU plus cisplatyl.

No significant financial relationships to disclose.
Weekly cetuximab and paclitaxel combination in metastatic/recurrent squamous cell cancer carcinoma of the head and neck (SCCHN): Clinical experience of a single institution
Authors: Diaz de Corcuera I. , Serrano C. , Pérez J. , Quispe I. , Arguis M. , Muñoz E. , Benavente S. , Martínez P. , Parera M. , del Campo J. M.
Published: August 2020

e17043

Background: Results of a recent phase III randomized study with cetuximab and platin-5FU chemotherapy support its use in recurrent/metastatic SCCHN. However, many patients (pts) are not able to be treated with platin combinations. Paclitaxel (P) and cetuximab (C) have shown an encouraging activity in a similar patients subset. We review the data of the patients treated with this schedule in our centre. Methods: From our database, we conducted a retrospective study of 20 patients with recurrent SCCHN who did not meet criteria for platin therapy and were treated with weekly P (80 mg/m2) and C (initially 400 mg/m2 followed by 250 mg/m2) until progression or intolerable toxicity. We have collected data regarding previous treatments, response rate (RR), progression free survival (PFS), overall survival (OS) and toxicity. Results: From January 2007 to November 2008, 20 patients were included (18 male, 2 female) with a median age of 63 (50–81). Oral cavity (35%) and oropharynx (25%) were the most frequent locations. Most of the pts (13/20) had been treated with previous chemotherapy combinations (range 1–3 lines). All pts were evaluable for response and toxicity. Overall RR was 45% (1CR, 8 PR) and 35% of the pts (7/10) had SD. Response in radiated areas were 35% (6/17). With a median follow up of 10 months the median PFS and OS were 6.5 and 7 months respectively. Main related toxicities (Gr 2/3) were acne-like rash (30%), asthenia (15%), anemia (10%), and mucositis (10%). Conclusions: Our analysis confirms that weekly paclitaxel-cetuximab is an effective and safety combination in metastatic/recurrent SCCHN. Treatment is very well tolerated and could be a good alternative to platin-based chemotherapy in unfit patients for this therapy.

No significant financial relationships to disclose.
Role of concurrent chemoradiotherapy in organ preservation for locally advanced head and neck cancer
Authors: Savaraj N. , Dinh V. , Chua L. , Bustillo P. , Nissim K.
Published: August 2020

e17044

Background: Optimal management for head and neck cancer is controversial. Standard of care has been surgery followed by radiotherapy, but is done with the risk of organ resection. The VA larynx study, EORTC 24891, and 91–11 US Intergroup trial have shown that chemoradiotherapy is comparable to surgery with radiotherapy in laryngeal cancers while preserving organ function. It is unclear, though, whether this could be accomplished in other tumor sites without sacrificing locoregional control and/or survival. Methods: We performed a retrospective chart review of patients who were treated at the Miami VA Medical Center with chemoradiotherapy for advanced staged head and neck cancers from 1996 to 2008. The majority of patients (84%) received 5FU and cisplatin. The choice of chemoradiotherapy was either determined by patients’ choice or their comorbidities, such as pulmonary disease and cardiac disease, precluded them from undergoing major surgery. Primary endpoints included death, relapse rates, and disease-free survival; secondary endpoints were toxicities associated with treatment and diminished organ function. Results: A total of 62 patients were included. Out of these patients, 52% had stage III disease and 50% had primary sites in the oropharynx; the remaining included larynx and hypopharynx. 20% of patients required salvage neck dissection. Complications included severe mucositis (69%), dysphagia (19% short term, 34% long term), hoarseness (13%), and dry mouth (24%). 27% had relapse of disease and median time for disease-free survival was 26 months. A total of 35 patients had died with a 2-year survival rate of 59.6%. Overall survival was best for laryngeal and oropharyngeal cancer (63 and 46 months, respectively) compared to hypopharyngeal cancer (22 months). Conclusions: Concurrent chemoradiotherapy is a valid option for treatment of locally advanced head and neck cancers especially for laryngeal and possibly oropharyngeal primaries with significant but tolerable toxicities. Although organ preservation is possible for the majority of patients with locally advanced head and neck cancer, however, the poor survival seen in hypopharyngeal cancer needs further investigation.

No significant financial relationships to disclose.
Function preservation with multimodality treatment in locally advanced oral tongue cancer
Authors: Hussain R. , Jamshed A. , Rehman K. , Iqbal H. , Azhar R. , Faruqui Z. , Ahmed Q.
Published: August 2020

e17051

Background: Total or near total glossectomy with postoperative radiation is a standard treatment option for locally advanced squamous cell carcinoma oral tongue (LASCCOT). However, the procedure is controversial due to dismal cure rates and major functional deficits that impact on speech, deglutition and quality of life. We evaluated function preservation and survival outcome in LASCCOT treated with induction chemotherapy, limited surgery, and postoperative radiation/chemoradiation. Methods: We retrospectively identified 15 patients with LASCCOT treated with induction chemotherapy, limited surgery and postoperative radiation/chemoradiation at our institution between 04/07 - 04–08. M67%:F33% median age 50 years. Pretreatment AJCC stage as assessed on MRI was T2N+ (tumour crossing midline) 13%, T3N0 20%, T3N+ 47%, and T4N+ 20%. Prior to surgery induction chemotherapy, consisting of cisplatin 75 mg/m2 day 1 and gemcitabine 1 mg/m2 day 1 and 8 every three weeks for 2 cycles was given. Four to six weeks following second cycle of chemotherapy local excision of residual primary tumor with ipsilateral modified neck dissection was performed. Postoperative radiation dose was 60Gy/30 fractions. Post therapy pathological stage was ypT0N0 20%, ypT1N0 20%, ypT1N+ 40%, ypT2N+ 13%, and ypT3N+ 7%. Patients with ypN+ disease received concomitant 3 weekly cisplatin 75 mg/m2 with radiation. Results: Overall and disease free survival at 20 months was 60%. Twelve patients (80%) are alive and 3 patients (20%) have died of disease at 9, 14 and 14 months (locoregional failure 1 and distant metastasis 2 patients). In patients alive without disease assessment of deglutition and speech at the time of last follow up showed all patients on full oral diet with spontaneous intelligible speech. Conclusions: Multimodality treatment with induction chemotherapy, limited surgery and post operative radiation/chemoradiation may allow selected LASCCOT patients to avoid morbid surgery and preserve tongue function without compromising survival. This approach merits further investigation in clinical trials.

No significant financial relationships to disclose.
Concurrent hypofractionated chemoradiation (CRT) for head and neck squamous cancer with weekly cisplatin: A Lancashire experience
Authors: Sivaramalingam M. , Mehta A. , Wong H. , Sidek N.
Published: August 2020

e17052

Background: Concurrent chemoradiation with intravenous cisplatin is the standard treatment for locally advanced head and neck cancer. We evaluated the use of hypofractionated radiotherapy and weekly concomitant cisplatin in our center. Methods: We retrospectively analysed 37 patients treated at our centre from August 2005 to November 2007. They received weekly concurrent chemoradiation with cisplatin 30 mg/m2 with radiotherapy 65Gy in 30 fractions. We analysed tumour sites, changes in weight as an indirect measure of nutritional status, calculated creatinine clearance to assess nephrotoxicity, sites of recurrence, progression free survival and overall survival. The minimum follow up was 6 months. Results: Our study population comprised of 61% of T4 disease while 25% of our patients had T3 disease. Nearly a third of our patients underwent radical neck dissection prior to concurrent chemoradiation. We found that 80% of our patients had completed the full course of concurrent chemoradiation. More than 50% of patients had oropharyngeal cancer while 25% hypopharyngeal cancer. Majority of patients lost weight during treatment. The mean weight loss was 3.56 kilograms, despite 90% having had prophylactic enteral feeding tubes. Eleven patients maintained their weight while on treatment. There were 11 recurrences: 5 were at the primary site, 4 had distant metastasis, 1 had combination of primary site and nodal drainage and 1 patient had only nodal relapse. Lung was the most common site of distant metastasis amongst the 4 patients. While a proportion of patients had a fall in creatinine clearance, the values did not drop below the accepted 50 mL/min.Two-year progression free survival was 68% and overall survival at 24 months was 68.7%. Conclusions: Weekly intravenous cisplatin when combined with radiotherapy 65Gy in 30 fractions was effective in treating head and neck cancer. The nephrotoxicity was within acceptable limits. Many patients lost weight with this treatment despite having prophylactic enteral feeding tubes. Our survival figures were encouraging and similar to other reports in the literature.

No significant financial relationships to disclose.
Impact of setup error on integral dose in head and neck cancer treated with intensity modulated radiation therapy
Authors: Prabhakar R. V. , Haresh K. P. , Laviraj M. A. , Rath G. K. , Julka P. K.
Published: August 2020

e17056

Background: Intensity modulated radiation therapy (IMRT) has been widely used in the treatment of head and neck cancer and has the potential of escalating the dose with less morbidity. Integral dose is a concern in radiotherapy especially with IMRT as it may lead to an increase in second malignancies. Setup error is another important issue in radiotherapy which affects the final treatment outcome. In this study, the effect of setup error on non-target integral dose (NTID) for head and neck cancer treated with IMRT has been studied. Methods: Twelve patients of carcinoma of nasopharynx treated by IMRT with simultaneous integrated boost technique were included. The dose to the gross tumor volume (PTV70), CTV1 (PTV59.4) and CTV2 (PTV54) were planned for 70 Gy, 59.4 Gy and 54 Gy respectively in 33 fractions. All the patients were planned with nine equally spaced beams. The IMRT plan was generated in Eclipse treatment planning system using sliding window technique. Keeping it as the base plan, the patient setup error was simulated in the treatment planning system for 3 mm, 5 mm and 10 mm by shifting the isocenter in all three dimensions viz. anterior, posterior, superior, inferior, right lateral and left lateral. NTID was calculated from the following relation NTID = (non-target tissue volume X mean non-target tissue dose)/1000. Paired sample t-test was performed to compare NTID for different shifts with no shift (statistical significance: p < 0.05). Results: The mean NTID for no shift was 120.75 ± 22.85 (median: 116.59). The mean NTID with isocenter shift along the anterior direction were 119.87 ± 22.80, 119.24 ± 22.80, 117.97 ± 22.52 for 3 mm, 5 mm and 10 mm respectively. Similarly, the NTID for the posterior shifts were 121.59 ± 22.96, 122.08 ± 23.07 and 123.26 ± 23.34 for 3 mm, 5 mm and 10 mm respectively. The anterior and posterior setup error showed statistically significant difference (p < 0.0001) for NTID compared to no shift whereas lateral, superior and inferior setup errors were found to be statistically insignificant. Conclusions: Setup error is an important issue in radiotherapy. Our study shows that setup error along the posterior direction significantly increases NTID. Hence, the setup error along the posterior direction may increase the risk of second malignances in IMRT.

No significant financial relationships to disclose.
Cost-effectiveness of capecitabine in combination with oxaliplatin (XELOX) compared with FOLFOX for the treatment of metastatic colorectal cancer: A Canadian evaluation
Authors: Belovich D. , Hux M. , Douglas P. , Maroun J. A. , Sommer N.
Published: August 2020

e17502

Background: Capecitabine is an oral fluoropyrimidine used to treat patients with metastatic colorectal cancer (mCRC). Recent trials in 1st- and 2nd-line treatment have shown that capecitabine in combination with oxaliplatin (XELOX) is non-inferior to FOLFOX4 in terms of progression-free survival, overall survival and response rates. XELOX offers patients the advantage of treatment every 3 weeks rather than every 2 weeks without the need for lengthy infusions. This analysis evaluated the cost- effectiveness of replacing FOLFOX4 with XELOX for 1st- and 2nd-line treatment of mCRC from both Canadian healthcare system payor and societal perspectives. Methods: Based on evidence of non-inferiority of XELOX vs. FOLFOX4, cost-minimization analyses (CMA) were conducted using phase III clinical trial data. The CMA compared total cost associated with chemotherapy medications, administration of chemotherapy, and treatment related toxicities. For the societal perspective, patients’ costs and time were also included. The costs (or savings) were compared for 1st-line XELOX vs. FOLFOX4 and 2nd-line XELOX vs. FOLFOX4. Due to variation in Canadian clinical practice, sensitivity analyses using the FOLFOX6 regimen as a comparator were performed. Results: Cost savings per patient for XELOX vs. FOLFOX4 from a healthcare system payor perspective and a societal perspective are shown in the Table . XELOX was also associated with cost savings when compared with the simplified administration regimen of FOLFOX6. Reduced costs for chemotherapy administration and costs for patients’ time and travel primarily related to fewer clinic visits offset the increased drug acquisition cost of the XELOX regimen. Conclusions: Replacing FOLFOX with XELOX is associated with cost savings from the healthcare system payor and societal perspectives while preserving clinical efficacy.

[Table: see text]

[Table: see text]
The economic implications of rasburicase treatment in adult tumor lysis syndrome patients
Authors: Eaddy M. , O’Day K. , Tangirala K. M. , Seal B.
Published: August 2020

e17503

Background: Rasburicase is a recombinant urate-oxidase enzyme used to reduce high levels of plasma uric acid (UA) resulting from tumor lysis syndrome (TLS). Rasburicase reduces UA levels within 4 hours of administration, minimizing risk of serious complications from TLS. Treatment pattern analyses indicate rasburicase is often used in combination with allopurinol; however, no studies have evaluated clinical and economic consequences of this pattern of care. The purpose of the study was to compare hospitalization costs, length of stay (LOS), and duration of critical care in patients receiving rasburicase with or without allopurinol. Methods: Patients in the Premier hospital database administered rasburicase or combination therapy within 2 days of hospital admission were eligible for study inclusion. Patients were excluded if they were <18 years of age or received hemodialysis on admission. Patients were propensity score matched to rasburicase patients based on gender, race, hospital type, provider type, payer type, admission source, use of electrolyte modification therapy, critical care admission, and comorbid diagnoses. Differences in health care costs, LOS, and duration of subsequent critical care were assessed using exponentially distributed generalized linear models with a log link function. Projection weights are used to produce national projected patient counts. Results: There were 280 rasburicase and 310 combination patients matched in the analysis. Mean age of the sample was 65.2, with 31% being female. There were no statistical differences in matched covariates across the cohorts. Rasburicase patients incurred an average total cost of $39,474 per hospitalization compared to $52,047 for combination patients (p = 0.0029). Rasburicase patients also had a lower LOS (10.5 days) compared to combination therapy (16.4 days, p < 0.0001). Duration of critical care was similar in both cohorts (rasburicase = 1.4 days vs 1.8 days, p = 0.1222). Conclusions: Combination therapy of rasburicase and allopurinol resulted in higher total hospitalization costs and longer LOS compared to rasburicase monotherapy.

[Table: see text]
Initial results of a new clinical trial matching service to increase patient participation
Authors: Gansler T. , Comis R. , Sharpe K. , Tis L. , Jin M. , Dahlquist K. , Kepner J. , Hao Y. , Cressman G. , Naples K.
Published: August 2020

e17504

Methods: Data from CTMS constituents and follow-up information describing enrollment status and barriers to trial participation are reviewed. Results: During 15 months of operation the CTMS provided information to 10,997 individuals; 7,521 (68.39%) used the website only, and 3,476 (31.61%) also contacted the ACS call center. Among 981 of the 3,476 (28.22% the basis of analyses below) who consented to and could be reached for follow-up and who answered the question on enrollment status, 119 (12.13%) enrolled in a CT. Trial phase was known for 74 enrollees (phase I: 17 [22.97%]; II: 36 [48.65%]; III: 21 [28.38%]; IV: 0 [0%]). Enrollment was negatively (p < 0.05) associated with poor ECOG functional status and black race, and was positively related to disease stage. Among the 757 individuals with available disease site and enrollment information, those with stomach cancer accounted for the most enrollments (25, 24.75% of all enrollments); followed by melanoma (12, 11.88%) and kidney, renal pelvis, bladder, ureter and urethra (also 12, 11.88%), and breast cancer (11, 10.89%). The highest enrollment rates (% enrollees among individuals with available follow-up) were for multiple myeloma/plasma cell disorders (4/14, 28.57%), melanoma (12/49, 24.49%), primary CNS malignancy (5/31, 16.13%), and soft tissue sarcoma (6/45, 13.33%). The following barriers were significantly associated with non-enrollment: ‘I cannot travel to clinical trial site,‘ ‘I cannot find a clinical trial using the modality or treatment I want,‘ ‘My physical activity level is too low,‘ and ‘I do not have measurable disease or am cancer-free.‘ Conclusions: 12% of CTMS participants with available follow-up data for enrollment status participated in a CT. Several determinants of CT participation were identified. Strategies for eliminating racial disparities, facilitating transportation, and increasing participation among patients with earlier stage disease and more common tumor types must be developed and implemented.

No significant financial relationships to disclose.
Assessing compliance with practice treatment guidelines by treatment centers and the reasons for noncompliance
Authors: Biagi J. J. , Wong R. , Brierley J. , Rahal R. , Ross J.
Published: August 2020

e17506

Background: Cancer Care Ontario (CCO) is the chief advisor on cancer care to the government of Ontario, a province with a population of more than 12 million. One of the many roles of CCO is to develop evidence based consensus-derived treatment practice guidelines for all major cancer types, through its Program in Evidence-based Care (PEBC). To determine province-wide compliance with these guidelines, a pilot project assessed the proportion of patients with stage III colon cancer (CC) treated in concordance with the corresponding treatment guideline. Initial results are made available to the regional cancer centers (RCC) in the province and to the public through web based Cancer Systems Quality Index (CSQI, http://www.cancercare.on.ca/qualityindex2007/ ). Methods: The guideline (http://www.cancercare.on.ca/pdf/pebc2–29s.pdf) states that patients with resected stage 3 CC will have adjuvant fluoropyrimidine-based chemotherapy within eight weeks of resection. Patients at each of 11 RCC who presented in 2007/2008 with stage III CC and the proportion treated according to the guidelines were identified. Individual charts of those patients who were not treated according to guideline were reviewed to determine the reason. Results: Across eight RCC with complete chart results to date 376 patients with stage 3 CC were identified, 244 (65%, range 47% to 72%) treated in concordance with the guideline, including 13% treated with capecitabine and 6% on clinical trials. The reasons for non-concordance of the 132 remaining cases were: age and co morbid conditions 48 (13%), patient choice 36 (10%), referred for treatment outside the RCC system 16 (4%), stage incorrect and other 32 (9%). Conclusions: Adjuvant chemotherapy treatment of stage III CC at the RCC across the Province of Ontario was concordant with the guideline in the majority of patients, and appropriate clinical reasons for non-compliance were identified. Data from all 11 RCC will be presented along with concordance within the eight-week time frame stated in the guideline . Refinement in province-wide data collection and interpretation will allow results from this pilot to be expanded to other PEBC practice guidelines for dissemination through the CSQI.

No significant financial relationships to disclose.
Characteristics of elderly metastatic prostate cancer (M1 PC) long-term survivors in the SEER Medicare database receiving androgen-deprivation therapy (ADT)
Authors: Obeidat N. A. , Mullins C. D. , Onukwugha E. , Seal B. , Hussain A.
Published: August 2020

e17513

Background: ADT remains standard treatment for pts with M1 PC, with radiation (RT) and chemotherapy (CT) providing additional palliation. This population-based analysis evaluated if long-term survivors (LT) receiving ADT possessed different characteristics relative to short-term survivors (ST). Methods: Pts age >/= 66y in SEER Medicare diagnosed with M1 PC between 1998 and 2002 and receiving ADT with or without subsequent CT were identified. Median overall survival (OS) for the sample was used as a cut-off to categorize ST and LT pts. Within these categories, demographic, and clinical characteristics were evaluated. Results: 2,665 ADT pts were first identified who had median OS of 26 months (95% CI 24.0 - 27.0). 1,349 pts died at </= 26 months (ST pts), while 1,245 pts survived or were lost to follow-up beyond 26 months (LT pts). Median time to first treatment with ADT was 1 mo in both ST and LT groups. Within this 66y+ population, LT pts were younger (p < 0.0001), more likely to be married (p = 0.0277), and were comprised of lower % of non-Hispanic white pts and higher % of ‘other’ races, but comparable % of African American and White-Hispanics (p = 0.0005). Distributional differences in PSA were detected, but interpreting the results was difficult due to missing or unknown information. Both ST and LT pts received RT and prostatectomy at similar rates, but LT pts had less comorbidities (p = 0.0008), and were more likely to receive CT (p = 0.0026). Conclusions: Long-term survivors were found to have demographic and clinical characteristics that differed from short-term survivors. Evidence regarding how these characteristics simultaneously impact the type and timing of treatment as well as survival deserve more exploration.

[Table: see text]
Barriers to cancer clinical trial enrollment in Latinos
Authors: Lopez A.
Published: August 2020

e17519

Background: Cancer clinical trials (CCT) improve cancer outcomes. Nonmajority participants in CCT make up no more than 1% of all participants. Latinos would be included in this 1% or less. Specific barriers and facilitators to Latino accruement to CCT have not been well elucidated. The principal objective of this study was to identify barriers and facilitators to the enrollment of Latinos in CCT. Methods: Cancer patients were randomly invited to participate in a survey while they waited for their oncology appointment. The surveys had been developed, piloted and validated with a different population of Latino cancer survivors. All instruments were translated in standard fashion and recruiters were bilingual, bicultural Latino. Survey instruments addressed knowledge, attitudes and beliefs re: participation in CCT. Assessments were made by age, gender, education, ethnicity (Latino and non-Latino), language, place of residence, having been offered a CCT, and previous participation in a CCT. Answers were evaluated with bivariate analyses and multiple logistic regressions. In the bivariate analysis the chi-squared test was used to evaluate significant differences between groups. To determine the effect of each of the variables and the most significant predictors, multiple logistic regression models were constructed. Results: Sample characteristics: 64% male and 36% females; mean age 59.66; 18% Latinos and 82% non-Latinos; 67% urban and 31% rural. 83% of the participants spoke at least some English at home whereas 4% spoke only Spanish. From the total sample 22% had previously participated in a CCT and 30% had been offered a CCT. Significant differences were noted in knowledge of CCT by age (to age 70), ethnicity (non-Latino), language (English speakers), education (some college), and having been offered or participated in a CCT (p < 0.05). There were no significant differences by sex and residence. Greatest predictors of CCT knowledge were ethnicity and education l:evel; however, no significant differences were noted by ethnicity or education level in interest in CCT participation. Conclusions: These data suggest that interventions to improve knowledge of CCT may ameliorate the disparity of CCT enrollment by Latinos.

No significant financial relationships to disclose.
Treatment center (TC) variability in survival of patients (pts) with colorectal cancer (mCRC) treated with bevacizumab (BV): A subanalysis from the BRiTE Observational Study (OCS)
Authors: Barron H. V. , Purdie D. M. , Feng S. , Sing A. P.
Published: August 2020

e17532

Background: Treatment options and overall survival (OS) rates for pts with mCRC have increased markedly over the past decade. However, the variability in OS across TCs, and possible contributing factors (measured and unmeasured), remain unclear. We present an analysis from the BRiTE OCS assessing variability in OS as a function of TC, and sought to identify site factors that may predict better outcomes. Methods: BRiTE enrolled 1,953 pts with mCRC receiving a first-line BV-based regimen, from 248 U.S. sites, mostly community practices (Grothey et al. J Clin Oncol. 2008 26:5326). A Cox proportional hazard model was used to identify predictors of OS (age, PS, albumin, alkaline phosphatase, site of primary tumor) and calculate the expected number of deaths (E) compared to the observed number of deaths (O) within each TC. The ratio O/E was calculated and its distribution is presented. Sites with high O/E (top 25%) vs low O/E (lowest 25%) were titled “worst” (W) and “best” (B), respectively. B and W sites were compared by type (academic vs community, hospital vs clinic, urban vs rural), number of pts treated, choice of first-line chemotherapy, postprogression (PD) therapy, and duration of BV. TCs with ≥3 pts were included in the analysis (198). Results: Significant variation in the O/E ratio was observed across TCs ( Table ). The differences between W and B TCs were that pts at W TCs were less likely to receive a first-line oxali containing regimen (65% vs 67%), had shorter overall duration of BV (8 m vs 12 m) and were less likely to use BV following PD (33% vs 39%). Measured site, pt, and treatment variables explained ∼7% of the variability in O/E, suggesting most TC variability was due to unmeasured factors. Conclusions: Significant variability in OS exists across BRiTE TCs, which appears partly related to the specific therapies received by pts. Further work is needed to determine whether W TCs can be optimized and improve outcomes in pts with mCRC.

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Medical costs of sorafenib compared with sunitinib in treatment of patients <65 years with renal cell carcinoma: A retrospective claims database analysis
Authors: Quinn D. , Barghout V. , Moyneur E.
Published: August 2020

e17536

Background: Sorafenib (SR) and sunitinib (SU) are FDA approved (12/05 and 1/06, respectively) tyrosine kinase inhibitors for patients (pts) with advanced renal cell carcinoma (RCC). Little is known of their cost impact. We conducted this study to quantify overall direct costs (inpatient, outpatient, pharmacy) for each treatment in privately insured pts (<65 y). Given differences between private and public insurer payment scales, pts ≥65 y were not included in this study but are the subject of a planned further analysis. Methods: A retrospective US claims-based study was conducted using data covering all US census regions for ≥18 million lives from MarketScan MedStat (1/02–12/07). Inclusion criteria were ≥2 RCC claims (ICD-9 189.0, 198.0), continuous health care coverage, >180 days of coverage before RCC diagnosis. SR and SU pts were identified based on oral therapy after initial RCC-related claim (intent-to-treat). Observation period was from first drug-dispensing date until ≤12 mo or first of therapy switch, nephrectomy, disenrollment, or study end (12/31/07). Univariate and multivariate Tobit analyses were conducted; control factors included age, sex, region, plan type, comorbidity, prior Tx/procedures, and time since RCC Dx. Results: Of 10,462 RCC pts identified, 144 and 220 received initial therapy with SR and SU, respectively. In the 180 days before RCC diagnosis, total direct medical costs, baseline demographics, and comorbidities were similar between groups. The univariate incremental total monthly medical cost for SU was $2,049 (P<.001) more than for SR, representing yearly costs for SU $24,588 more than for SR. Multivariate analyses for incremental total monthly costs for SU also remained significant at $1,399 (P<.001). Conclusions: Retrospective analysis of this US claims database for RCC pts <65 treated first with SR showed statistically significant lower total medical costs (particularly inpatient costs) than for pts treated first with SU.

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NCCN Chemotherapy Order Templates: Enhancing patient safety through standardization
Authors: Li E. C. , Hinkel J. M. , Gallagher L. , DeVader S. R. , Vandergrift J. L. , Lepisto E. M.
Published: August 2020

e17537

Background: NCCN Chemotherapy Order Templates (COT), which delineate antineoplastics and associated supportive care agents, monitoring and safety parameters, and instructions for self-administered agents, were launched in 2008 to complement the NCCN Clinical Practice Guidelines in Oncology and NCCN Drugs and Biologics Compendium for nine cancers. Through COT, NCCN sought to enhance patient safety by reducing medication errors, anticipating and managing adverse events, and standardizing care. NCCN developed and distributed a survey to evaluate the reception, use, and impact of COT on oncology practice. Methods: The survey included multiple-choice questions with filtering logic. Questions included 5-point Likert scale. The survey was emailed on December 18, 2008 to a convenience sample of 10,183 registered users of NCCN.org who had clicked at least once to the COT; 110 (1%) survey emails were undeliverable. 734 (7%) responded by 1/5/09 and 588 (6%) completed the survey (80% completion rate). 28 (<1%) recipients opted out of participating. Results: 476 (64%) respondents were providers, including MDs (47%), mid-level (8%) and nurses (10%); 11% were pharmacists. Of the 734 respondents, 465 (63%) had used COT. Among the 465 users, the median number COT accessed was 2 (range 0 - 9) with physicians accessing more than other providers (p = 0.002). Breast cancer COT were accessed most (68%). COT were used as a reference (52%) and for setting up chemotherapy orders (42%). 292 users (63%) agreed that COT impacted patient safety; with MDs more likely to agree (p = 0.001) compared to other providers. Of these, 89% responded that COT made chemotherapy ordering safer. 271 users (58%) agreed that using NCCN COT in practice impacted the ordering of supportive care agents. Among providers, MDs were more likely to agree (p = 0.002). Of those who agreed, 86% responded that COT made it more likely that appropriate supportive care orders were included. Conclusions: Adding NCCN Chemotherapy Order Templates to the core NCCN content was done to make the NCCN Clinical Practice Guidelines in Oncology more accessible to providers. Survey results indicate that COT users feel that template use improves the safety of chemotherapy and supportive care agents. Throughout 2009, NCCN will continue to develop COT to cover most cancers.

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Treatment patterns of docetaxel and paclitaxel in patients with early-stage breast cancer in a community oncology center
Authors: Tangirala M. , Lei C. , Joel H. , Christiansen N. , Sullivan S.
Published: August 2020

e17550

Background: Docetaxel and paclitaxel have been widely used in treating breast cancer (BC). This study aimed to describe real-world treatment patterns of two taxanes in early-stage BC. Methods: Georgia Oncology Specialist Database (GOSD) was used and contained chemotherapy, medical and pharmacy claims, and lab results for nearly 170,000 patients with various types of cancer (2003–2008). Patients with stage I-III BC receiving doxirubicin-cyclophosphamide-taxane (ACT) were identified, and their pre-taxane and on-taxane periods (from first to last dose of docetaxel/paclitaxel) were examined. Number of cycles was compared using Student's t-test. Taxane dose schedule and the use of other chemotherapy in pre- and on-taxane periods were compared using Chi-Square test. A similar analysis was replicated using Pharmetrics database (2003–2008) in BC patients on ACT regimen with prior mastectomy. Results: In GOSD, 79 docetaxel (7.9%, 58.2%, 34.2% in stage I, II, III, respectively) and 139 paclitaxel (10.8%, 64.7%, 25.5% in stage I, II, III, respectively) patients were identified. Compared with paclitaxel, docetaxel patients completed more cycles (4.9 vs. 3.9, p < 0.001), were less frequently on weekly schedule, and more frequently on every-two-week (Q2w) or every-three-week (Q3W) schedules (2.5% vs. 15.2%, 27.9% vs. 62.6%, and 41.8% vs. 0%; p < 0.001). 22.8% of docetaxel patients received AC followed by docetaxel (AC>T) and 77.22% received ACT concurrently, while 100% of paclitaxel patients were on AC>T regimen. In Pharmetrics data, compared with paclitaxel (n = 211), docetaxel patients (n = 96) completed more cycles (11.3 vs. 4.6, p < 0.001), were less frequently on weekly, while more frequently on Q2W and Q3W schedules (3.1 vs. 9.5%, 9.4% vs. 62.6%, and 59.4% vs. 4.7%; p < 0.001). While 97.6% of paclitaxel patients were on AC>T regimen, AC>T and ACT regimens were evenly split among docetaxel patients (49% vs. 51%). Conclusions: Docetaxel and paclitaxel have different treatment patterns in real-world clinical practice. The patterns in a community oncology center appear to be consistent with national data. A potential limitation of this study is that the potential selection bias may not be fully adjusted.

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Improving the efficiency and effectiveness of clinical research regulatory review processes: Lessons from the Six Sigma Body of Knowledge
Authors: Stahl D. C. , Song C. J. , Figlin R. A.
Published: August 2020

e17554

Background: The duration and complexity of regulatory review processes are increasingly associated with the slow pace and high cost of clinical trials. To evaluate and minimize the impact of these factors, City of Hope (COH), a NCI-designated Comprehensive Cancer Center, developed a strategic initiative to improve the efficiency and effectiveness of its clinical research review processes. The ongoing initiative is supported by Six Sigma-based techniques for problem identification and process optimization that have been successfully applied in other industries. Methods: The Six Sigma process improvement methodology known as DMAIC (Define, Measure, Analyze, Improve, and Control) was applied to five different clinical trial submission types (new study submissions, amendments, continuations, internal adverse events, external adverse events) reviewed by the COH Institutional Review Board (IRB), Cancer Protocol Review and Monitoring Committee (CPRMC), and Data and Safety Monitoring Board (DSMB). A consistent set of metrics and expectations were created for each review process to evaluate pre-review queue times, review process durations, submissions returned for corrections, and submissions returned with conditional approvals. Results: Over 7,900 submissions received during a 15 month period were evaluated quarterly to identify opportunities for improvement and the effects of previously implemented solutions. Multiple root causes for submission defects and delays were identified, including: (1) staffing and training deficiencies, (2) suboptimal workload distribution, (3) unclear policies and processes, (4) submission standardization opportunities, and (5) workflow automation and other information technology opportunities. Ongoing remediation efforts have yielded substantial improvements. Conclusions: Although Six Sigma process improvement techniques were originally developed for manufacturing applications, they can be applied in a clinical research setting to improve regulatory review processes. The methodology was most effectively introduced incrementally via application to specific problems rather than a traditional top-down implementation. Support provided by NCI P30 CA33572.

No significant financial relationships to disclose.
Effect of geographic distance from a cancer centre on choice of systemic therapy in metastatic colorectal cancer
Authors: Seal M. D. , Pond G. R. , Wilkieson T. , Hotte S. J.
Published: August 2020

e17559

Background: There is little data on whether geographic distance from patient residence to a treatment facility is a predictor of systemic therapy utilization or clinical trial (CT) enrollment. Therefore a retrospective chart review was undertaken to investigate this variable. Methods: Consecutive patients with metastatic colorectal cancer (mCRC) assessed by a medical oncologist at the Juravinski Cancer Centre (JCC), Ontario during 2006 were selected. Patients with pathology other than adenocarcinoma and those with complete surgical resection of metastases were excluded. Distance and time to JCC were calculated using online mapping software. The study received full ethics approval. Results: 276 patients were included with full data available on 169 patients. Median travel time and distance to JCC were 23.0 minutes (min) and 19.2 kilometers (km), respectively. The maximum travel time was 120 min and 87% of patients lived within 60 min of JCC. Distance and time were highly correlated (p<0.0001). Overall, 43% of patients had discussed a CT with their oncologist and 20% enrolled in a CT. Patients living >50 km from JCC were less likely to discuss a CT (38%) or participate in a CT (15%) than patients who lived 25–50 km (39% and 19%) or <25 km (47% and 23%) from JCC. These trends did not attain statistical significance (odds ratio [OR] = 0.88, 95% CI = 0.66–1.17, p = 0.39 for CT discussion, OR = 0.76, 95% CI = 0.54–1.08, p = 0.13 for CT enrollment). Distance was not a statistically significant (p = 0.42) predictor of number of treatment regimens, however, 44% of patients <25 km from JCC received 3 or more lines of treatment compared with 33% of patients ≥25 km away. No association with survival was observed. Conclusions: Patients with mCRC living ≥25 km from JCC received fewer systemic regimens and were less likely to discuss or enter a CT. These trends were not statistically significant. Data collection is ongoing to increase the power of this study.

No significant financial relationships to disclose.