Costs of Definitive Chemoradiation, Surgery, and Adjuvant Radiation Versus De-Escalated Adjuvant Radiation per MC1273 in HPV+ Cancer of the Oropharynx.

PURPOSE: De-escalated treatment for human papillomavirus (HPV)+ oropharynx squamous cell carcinoma (OPSCC) has shown promising initial results. Health-care policy is increasingly focusing on high-value care. This analysis compares the cost of care for HPV+ OPSCC treated with definitive chemoradiation (CRT), surgery and adjuvant radiation (RT), and surgery and de-escalated CRT on MC1273. METHODS AND MATERIALS: MC1273 is a prospective, phase 2 study evaluating adjuvant CRT to 30 to 36 Gy plus docetaxel for HPV+ OPSCC after surgery for high-risk patients. Matched standard-of-care control groups were retrospectively identified for patients treated with definitive CRT or adjuvant RT. Standardized costs were evaluated before radiation, during treatment (during RT), and at short-term (6 month) and long-term (7-24 month) follow-up periods. RESULTS: A total of 56 definitive CRT, 101 adjuvant RT, and 66 MC1273 patients were included. The CRT arm had more T3-4 disease (63% vs 17-21%) and higher N2c-N3 disease (52% vs 20-24%) vs both other groups. The total treatment costs in the CRT, adjuvant RT, and MC1273 groups were $47,763 (standard deviation [SD], $19,060], $57,845 (SD, $17,480), and $46,007 (SD, $9019), respectively, and the chemotherapy and/or RT costs were $39,936 (SD, $18,480), $26,603 (SD, $12,542), and $17,864 (SD, $3288), respectively. The per-patient, per-month, average short-term follow-up costs were $3860 (SD, $10,525), $1072 (SD, $996), and $972 (SD, $833), respectively, and the long-term costs were $978 (SD, $2294), $485 (SD, $1156), and $653 (SD, $1107), respectively. After adjustment for age, T-stage, and N-stage, treatment costs remained lower for CRT and MC1273 versus adjuvant RT ($45,450 and $47,114 vs $58,590, respectively; P < .001), whereas the total per-patient, per-month follow-up costs were lower in the MC1273 study group and adjuvant RT versus CRT ($853 and $866 vs $2030, respectively; P = .03). CONCLUSIONS: MC1273 resulted in 10% and 20% reductions in global costs compared with standard-of-care adjuvant RT and definitive CRT treatments. Substantial cost savings may be an added benefit to the already noted low toxicity and maintained quality of life of treatment per MC1273.

Avoidance of Overtreatment of Rectal Cancer by Selective Chemoradiotherapy: Results of the Optimized Surgery and MRI-Based Multimodal Therapy Trial.

BACKGROUND: Neoadjuvant chemoradiotherapy (nCRT) in patients with rectal cancer carries a high risk of adverse effects. The aim of this study was to examine the selective application of nCRT based on patient risk profile, as determined by MRI, to find the optimal range between undertreatment and overtreatment. STUDY DESIGN: In this prospective multicenter observational study, nCRT before total mesorectal excision (TME) was indicated in high-risk patients with involved or threatened mesorectal fascia (≤1 mm), or cT4 or cT3 carcinomas of the lower rectal third. All other patients received primary surgery. RESULTS: Of the 1,093 patients, 878 (80.3%) were treated according to the protocol, 526 patients (59.9%) underwent primary surgery, and 352 patients (40.1%) underwent nCRT followed by surgery. The 3-year locoregional recurrence (LR) rate was 3.1%. Of 604 patients with clinical stages II and III, 267 (44.2%) had primary surgery; 337 (55.8%) received nCRT followed by TME. The 3-year LR rate was 3.9%, without significant differences between groups. In patients with clinical stages II and III who underwent primary surgery, 27.3% were diagnosed with pathological stage I. CONCLUSIONS: The results justify the restriction of nCRT to high-risk patients with rectal cancer classified by pretreatment MRI. Provided that a high-quality MRI diagnosis, TME surgery, and standardized examination of the resected specimen are performed, nCRT, with its adverse effects, costs, and treatment time can be avoided in more than 40% of patients with stage II or III rectal cancer with minimal risk of undertreatment. (clinicaltrials.gov NCT325649).

Cost-effectiveness analysis of endocrine therapy alone versus partial-breast irradiation alone versus combined treatment for low-risk hormone-positive early-stage breast cancer in women aged 70 years or older.

PURPOSE: We performed a cost-effectiveness analysis of three strategies for the adjuvant treatment of early breast cancer in women age 70 years or older: an aromatase inhibitor (AI-alone) for 5 years, a 5-fraction course of accelerated partial-breast irradiation using intensity-modulated radiation therapy (APBI-alone), or their combination. METHODS: We constructed a patient-level Markov microsimulation from the societal perspective. Effectiveness data (local recurrence, distant metastases, survival), and toxicity data were obtained from randomized trials when possible. Costs of side effects were included. Costs were adjusted to 2019 US dollars and extracted from Medicare reimbursement data. Quality-adjusted life-years (QALY) were calculated using utilities extracted from the literature. RESULTS: The strategy of AI-alone ($12,637) was cheaper than both APBI-alone ($13,799) and combination therapy ($18,012) in the base case. All approaches resulted in similar QALY outcomes (AI-alone 7.775; APBI-alone 7.768; combination 7.807). In the base case, AI-alone was the cost-effective strategy and dominated APBI-alone, while combined therapy was not cost-effective when compared to AI-alone ($171,451/QALY) or APBI-alone ($107,932/QALY). In probabilistic sensitivity analyses, AI-alone was cost-effective at $100,000/QALY in 50% of trials, APBI-alone in 28% and the combination in 22%. Scenario analysis demonstrated that APBI-alone was more effective than AI-alone when AI compliance was lower than 26% at 5 years. CONCLUSIONS: Based on a Markov microsimulation analysis, both AI-alone and APBI-alone are appropriate options for patients 70 years or older with early breast cancer with small cost differences noted. A prospective trial comparing the approaches is warranted.

Relapsed Wilms' tumor in pediatric patients: challenges in low- to middle-income countries-a single-center experience.

BACKGROUND: Wilms' tumor (WT) affects one in 10,000 children and accounts for 5% of all childhood cancers. Although the overall relapse rate for children with WT has decreased to less than 15 %, the overall survival for patients with recurrent disease remains poor at approximately 50 %. The aim of the study to evaluate the outcome of relapsed Wilms' tumor pediatric patients treated at the National Cancer Institute (NCI), Egypt, between January 2008 and December 2015. RESULTS: One hundred thirty (130) patients diagnosed with WT during the study period, thirty (23%) patients had relapsed. The median follow up period was 22.3 months (range 3.6-140 months). The Overall Survival (OS) was 30.9% while the event-free survival (EFS) was 29.8% at a 5-year follow up period. Median time from diagnosis to relapse was 14.4 months. A second complete remission was attained in 18/30 patients (60%). The outcome of the 30 patients; 11 are alive and 19 had died. Three factors in our univariate analysis were prognostically significant for survival after relapse. The first was radiotherapy given after relapse (p = 0.012). The 5-year EFS and OS for the group that received radiotherapy were 41.9% versus 16.7% and 11.1% respectively for those that did not. The second was the state of lymph nodes among patients with local stage III (p = 0.004). Lastly, when risk stratification has been applied retrospectively on our study group, it proved to be statistically significant (p = 0.029). CONCLUSION: Among relapsed pediatric WT, radiotherapy improved survival at the time of relapse and local stage III with positive lymph nodes had the worst survival among other stage III patients.

A contemporary analysis of racial disparities in recommended and received treatment for head and neck cancer.

BACKGROUND: Racial disparities in squamous cell carcinoma of the head and neck (HNSCC) negatively affect non-Hispanic black (NHB) patients. This study was aimed at understanding how treatment is prescribed and received across all HNSCC subsites. METHODS: With the National Cancer Database, patients from 2004 to 2014 with surgically resectable HNSCCs, including tumors of the oral cavity (OC), oropharynx (OP), hypopharynx (HP), and larynx (LX), were studied. The treatment received was either upfront surgery or nonsurgical treatment. Treatment patterns were compared according to race and subsite, and how these differences changed over time was evaluated. RESULTS: NHB patients were less likely than non-Hispanic white (NHW) patients to receive surgery across all subsites (relative risk [RR] for OC, 0.87; RR for OP, 0.75; RR for HP, 0.73; RR for LX, 0.87; all P values <.05). They were also more likely to refuse a recommended surgery (RR for OC, 1.50; RR for OP, 1.23; RR for HP, 1.23; RR for LX, 1.34), and this difference was significant except for HP. NHB patients were more likely to not be offered surgery across all subsites (RR for OC, 1.38; RR for OP, 1.07; RR for HP, 1.05; RR for LX, 1.03; all P values <.05). Rates of surgery increased and rates of not being offered surgery declined for both NHB and NHW patients from 2004 to 2014, but the absolute disparities persisted in 2014. CONCLUSIONS: Across all HNSCC subsites, NHB patients were less likely than NHW patients to be recommended for and receive surgery and were more likely to refuse surgery. These differences have closed over time but persist. Enhanced shared decision making may improve these disparities.

Economic Analysis of Adjuvant Chemoradiotherapy Compared with Chemotherapy in Resected Pancreas Cancer.

BACKGROUND: Population-based survival and costs of pancreas adenocarcinoma patients receiving adjuvant chemoradiation and chemotherapy following pancreaticoduodenectomy are poorly understood. METHODS: This retrospective cohort study used linked administrative and pathological datasets to identify all patients diagnosed with pancreas adenocarcinoma and undergoing pancreaticoduodenectomy in Ontario between April 2004 and March 2014, who received postoperative chemoradiation or chemotherapy. Stage and margin status were defined by using pathology reports. Kaplan-Meier and Cox proportional hazards regression survival analyses were used to determine associations between adjuvant treatment approach and survival, while stratifying by margin status. Median overall health system costs were calculated at 1 and 3 years for chemoradiation and chemotherapy, and differences were tested using the Kruskal-Wallis test. RESULTS: Among 709 patients undergoing pancreaticoduodenectomy for pancreas cancer during the study period, the median survival was 21 months. Median survival was 19 months for chemoradiation and 22 months for chemotherapy. Patients receiving chemoradiation were more likely to have positive margins: 47.7% compared with 19.2% in chemotherapy. After stratifying by margin status and controlling for confounders, adjusted hazard ratio of death were not statistically different between chemotherapy and chemoradiation [margin positive, hazard ratio (HR) = 0.99, 95% confidence interval (CI) = 0.88-1.27; margin negative, HR 0.95, 95% CI 0.91-1.18]. Overall 1-year health system costs were significantly higher for chemoradiation (USD $70,047) than chemotherapy (USD $54,005) (p ≤ 0.001). CONCLUSIONS: Chemotherapy and chemoradiation yielded similar survival, but chemoradiation resulted in higher costs. To create more sustainable healthcare systems, both the efficacy and costs of therapies should be considered.

The Financial Impact of Fractionation Scheme and Treatment Planning Method for Rectal Cancer in the United States.

BACKGROUND: Preoperative long-course chemoradiotherapy (CRT) and short-course radiotherapy (SCR) for locally advanced rectal cancer (LARC) were found to have equivalent outcomes in 3 randomized trials. SCR has not been widely adopted in the United States (US). Three-dimensional (3D) treatment planning is standard, whereas intensity-modulated radiotherapy (IMRT) is controversial. In this study, we assessed the economic impact of fractionation scheme and planning method for payers in the US. MATERIALS AND METHODS: We performed a population-based analysis of the total cost of radiotherapy for LARC in the US annually. The national annual target population was calculated using the Surveillance, Epidemiology, and End Results database. Radiotherapy costs were based on billing codes and 2018 pricing by Medicare's Hospital Outpatient Prospective Payment System. RESULTS: We estimate that 12,945 patients with LARC are treated with radiotherapy annually in the US. The cost of CRT with 3D or IMRT is US $15,882 and $23,745 per patient, respectively. With SCR, the cost with 3D or IMRT is $5,458 and $7,323 per patient, respectively. The use of SCR would lead to 53% to 77% annual savings of $106,168,871 to $232,105,727 compared with CRT. IMRT increases the total cost of treatment by 34% to 50%, and if adopted widely, would lead to an excess cost of $24,152,134 and $101,784,723 annually with SCR and CRT, respectively. CONCLUSIONS: SCR may have the potential to save approximately US $106 to t232 million annually in the US, likely without impacting outcomes. Lack of evidence showing benefit with costly IMRT should limit its use to clinical trials. It would be reasonable for public and private payers to consider which type of radiation is most suited to reimbursement.

Clinical and economic burden associated with stage III to IV triple-negative breast cancer: A SEER-Medicare historical cohort study in elderly women in the United States.

BACKGROUND: The current study was performed to describe patient characteristics, treatment patterns, survival, health care resource use (HRU), and costs among older women in the United States with advanced (American Joint Committee on Cancer stage III/IV) triple-negative breast cancer (TNBC) in the Surveillance, Epidemiology, and End Results (SEER)-Medicare database. METHODS: Women who were aged ≥66 years at the time of diagnosis and diagnosed with advanced TNBC between January 1, 2007, and January 1, 2011, in the SEER-Medicare database and who were followed for survival through December 31, 2013, were eligible. Patient demographic and clinical characteristics at the time of diagnosis, subsequent treatment patterns, and survival outcomes were analyzed. HRU and costs for the first 3 months after diagnosis, the last 3 months of life, and the time in between are summarized. All analyses were stratified by American Joint Committee on Cancer stage of disease. RESULTS: There were 1244 patients newly diagnosed with advanced TNBC; the majority were aged ≥75 years (61% with stage III disease and 57.4% with stage IV disease) and white (>70% of patients in both disease stage groups). The most common treatment approaches were surgery combined with chemotherapy for patients for stage III disease (50.6%) and chemotherapy alone or with radiotherapy for patients with stage IV disease (31.3%). Diverse chemotherapy regimens were administered for each line of therapy; nevertheless, the medications used were consistent with national guidelines. Patients with stage III and stage IV disease were found to have a similar mean number of hospitalizations and outpatient visits, but mean monthly costs were greater for patients with stage IV disease at all 3 time points. The mean cost per patient-month (in 2013 US dollars) was $4810 for patients with stage III disease and $9159 for patients with stage IV disease. CONCLUSIONS: Among older women with advanced TNBC, significant treatment variations and considerable HRU and costs exist. Further research is needed to find effective treatments with which to reduce the clinical and economic burden of this disease. Cancer 2018;124:2104-14. © 2018 American Cancer Society.

Cost-effectiveness analysis of PET-CT-guided management for locally advanced head and neck cancer.

BACKGROUND: A recent large United Kingdom (UK) clinical trial demonstrated that positron-emission tomography-computed tomography (PET-CT)-guided administration of neck dissection (ND) in patients with advanced head and neck cancer after primary chemo-radiotherapy treatment produces similar survival outcomes to planned ND (standard care) and is cost-effective over a short-term horizon. Further assessment of long-term outcomes is required to inform a robust adoption decision. Here we present results of a lifetime cost-effectiveness analysis of PET-CT-guided management from a UK secondary care perspective. METHODS: Initial 6-month cost and health outcomes were derived from trial data; subsequent incidence of recurrence and mortality was simulated using a de novo Markov model. Health benefit was measured in quality-adjusted life years (QALYs) and costs reported in 2015 British pounds. Model parameters were derived from trial data and published literature. Sensitivity analyses were conducted to assess the impact of uncertainty and broader National Health Service (NHS) and personal social services (PSS) costs on the results. RESULTS: PET-CT management produced an average per-person lifetime cost saving of £1485 and an additional 0.13 QALYs. At a £20,000 willingness-to-pay per additional QALY threshold, there was a 75% probability that PET-CT was cost-effective, and the results remained cost-effective over the majority of sensitivity analyses. When adopting a broader NHS and PSS perspective, PET-CT management produced an average saving of £700 and had an 81% probability of being cost-effective. CONCLUSIONS: This analysis indicates that PET-CT-guided management is cost-effective in the long-term and supports the case for wide-scale adoption.

A rectal cancer feasibility study with an embedded phase III trial design assessing magnetic resonance tumour regression grade (mrTRG) as a novel biomarker to stratify management by good and poor response to chemoradiotherapy (TRIGGER): study protocol for a randomised controlled trial.

BACKGROUND: Pre-operative chemoradiotherapy (CRT) for MRI-defined, locally advanced rectal cancer is primarily intended to reduce local recurrence rates by downstaging tumours, enabling an improved likelihood of curative resection. However, in a subset of patients complete tumour regression occurs implying that no viable tumour is present within the surgical specimen. This raises the possibility that surgery may have been avoided. It is also recognised that response to CRT is a key determinant of prognosis. Recent radiological advances enable this response to be assessed pre-operatively using the MRI tumour regression grade (mrTRG). Potentially, this allows modification of the baseline MRI-derived treatment strategy. Hence, in a 'good' mrTRG responder, with little or no evidence of tumour, surgery may be deferred. Conversely, a 'poor response' identifies an adverse prognostic group which may benefit from additional pre-operative therapy. METHODS/DESIGN: TRIGGER is a multicentre, open, interventional, randomised control feasibility study with an embedded phase III design. Patients with MRI-defined, locally advanced rectal adenocarcinoma deemed to require CRT will be eligible for recruitment. During CRT, patients will be randomised (1:2) between conventional management, according to baseline MRI, versus mrTRG-directed management. The primary endpoint of the feasibility phase is to assess the rate of patient recruitment and randomisation. Secondary endpoints include the rate of unit recruitment, acute drug toxicity, reproducibility of mrTRG reporting, surgical morbidity, pathological circumferential resection margin involvement, pathology regression grade, residual tumour cell density and surgical/specimen quality rates. The phase III trial will focus on long-term safety, regrowth rates, oncological survival analysis, quality of life and health economics analysis. DISCUSSION: The TRIGGER trial aims to determine whether patients with locally advanced rectal cancer can be recruited and subsequently randomised into a control trial that offers MRI-directed patient management according to radiological response to CRT (mrTRG). The feasibility study will inform a phase III trial design investigating stratified treatment of good and poor responders according to 3-year disease-free survival, colostomy-free survival as well as an increase in cases managed without a major resection. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT02704520 . Registered on 5 February 2016.

The relative cost of sentinel lymph node biopsy in early oral cancer.

INTRODUCTION: The European Sentinel Node (SENT) trial addressed the question of the clinically lymph node negative (cN0) neck in early oral squamous cell carcinoma (OSCC). Apart from reducing neck dissection numbers, sentinel lymph node biopsy (SLNB) may reduce treatment cost. Using a treatment model derived from SENT trial information, estimates were produced of relative treatment costs between patients managed through a traditional surgical or SLNB pathway. METHODS: The model created two management approaches, the traditional surgical pathway and SLNB pathway. Using SENT trial data regarding the proportion of patients with positive, negative and false negative SLNB's a relative cost ratio (RCR) for 100 hypothetical patients passing down each pathway was generated. RESULTS: From a cohort of 481 patients, 25% had a positive SLNB, 75% a negative result and 2.5% a false negative result. Treatment of 100 hypothetical patients using the SLNB pathway is 0.35-0.60 the cost of treating the same cohort using traditional surgery techniques. Even if 100% of SLNB's are positive the SLNB approach is 0.91 of the cost of the traditional surgical approach. CONCLUSION: The SLNB approach appears to be cheaper relative to the traditional surgical approach, especially when extrapolated to 100 hypothetical patients.