Indirect costs associated with out-of-country referral for proton therapy: a survey of adult and pediatric patients in Alberta, Canada

Background Patients in Alberta, Canada are referred to the United States (US) for proton treatment. The Alberta Ministry of Health pays for the proton treatment and the cost of flights to and from the United States. This study aimed to determine the out-of-pocket expenses incurred by patients or patients’ families. Methods An electronic survey was sent to 59 patients treated with proton therapy between January 2008 and September 2019. Survey questions asked about expenses related to travel to the US and those incurred while staying in the US, reimbursement of expenses, and whether any time away from work was paid or unpaid leave. Results Seventeen respondents (response rate, 29%) reported expenses of flights for family members (mean, CAD 1886; range CAD 0–5627), passports/visas and other travel costs (mean, CAD 124; range CAD 0–546), accommodation during travel to the US (mean, CAD 50; range CAD 0–563), food during travel to the US (mean, CAD 89; range CAD 0–338), accommodation in the US (rented home/apartment mean, CAD 7394; range CAD 3075-13,305; hotel mean, CAD 4730; range CAD 3564-5895; other accommodation mean CAD 2660; range CAD 0–13,842), transportation in the US (car mean, CAD 2760; range CAD 0–7649; bus/subway mean, CAD 413; range CAD 246–580), and food in the US (mean, CAD 2443; range 0–6921). Expenses were partially reimbursed or covered by not-for-profit organizations or government agencies for some patients (35%). Patients missed a mean of 59 days of work; accompanying family members missed an average of 34 days. For 29% this time away from work was paid, but unpaid for 71% of respondents. Conclusions Multiple factors contributed to the expenses incurred including age of the patient, number of accompanying individuals, available accommodation, mode of transportation within the US, and whether the patient qualified for financial support. Added to this burden is the potential loss of wages for time away from work. The study showed a large variation in indirect costs for each family and supports actively seeking more opportunities for financial support for families with children with cancer.

Beam-Specific Spot Guidance and Optimization for PBS Proton Treatment of Bilateral Head and Neck Cancers

Purpose A multi-field optimization (MFO) technique that uses beam-specific spot placement volumes (SPVs) and spot avoidance volumes (SAVs) is introduced for bilateral head and neck (H&N) cancers. These beam-specific volumes are used to guide the optimizer to consistently achieve optimal organ-at-risk (OAR) sparing with target coverage and plan robustness. Materials and Methods Implementation of this technique using a 4-beam, 5-beam, and variant 5-beam arrangement is discussed. The generation of beam-specific SPVs and SAVs derived from target and OARs are shown. The SPVs for select fields are further partitioned into optimization volumes for uniform dose distributions that resemble those of single-field optimization (SFO). A conventional MFO plan that does not use beam-specific spot placement guidance (MFOcon) and an MFO plan that uses only beam-specific SPV (MFOspv) are compared with current technique (MFOspv/sav), using both simulated scenarios and forward-calculated plans on weekly verification computed tomography (VFCT) scans. Results Dose distribution characteristics of the 4-beam, 5-beam, and variant 5-beam technique are demonstrated with discussion on OAR sparing. When comparing the MFOcon, MFOspv, and MFOspv/sav, the MFOspv/sav is shown to have superior OAR sparing in 9 of the 14 OARs examined. It also shows clinical plan robustness when evaluated by using both simulated uncertainty scenarios and forward-calculated weekly VFCTs throughout the 7-week treatment course. Conclusion The MFOspv/sav technique is a systematic approach using SPVs and SAVs to guide the optimizer to consistently reach desired OAR dose values and plan robustness.

Targeting the DNA replication stress phenotype of KRAS mutant cancer cells

Mutant KRAS is a common tumor driver and frequently confers resistance to anti-cancer treatments such as radiation. DNA replication stress in these tumors may constitute a therapeutic liability but is poorly understood. Here, using single-molecule DNA fiber analysis, we first characterized baseline replication stress in a panel of unperturbed isogenic and non-isogenic cancer cell lines. Correlating with the observed enhanced replication stress we found increased levels of cytosolic double-stranded DNA in KRAS mutant compared to wild-type cells. Yet, despite this phenotype replication stress-inducing agents failed to selectively impact KRAS mutant cells, which were protected by CHK1. Similarly, most exogenous stressors studied did not differentially augment cytosolic DNA accumulation in KRAS mutant compared to wild-type cells. However, we found that proton radiation was able to slow fork progression and preferentially induce fork stalling in KRAS mutant cells. Proton treatment also partly reversed the radioresistance associated with mutant KRAS. The cellular effects of protons in the presence of KRAS mutation clearly contrasted that of other drugs affecting replication, highlighting the unique nature of the underlying DNA damage caused by protons. Taken together, our findings provide insight into the replication stress response associated with mutated KRAS, which may ultimately yield novel therapeutic opportunities.

SWK-11. ASSESSMENT OF THE INDIRECT COSTS ASSOCIATED WITH PROTON THERAPY TREATMENT FOR ALBERTA PATIENTS REFERRED OUT OF COUNTRY

BACKGROUND Proton therapy for benign and malignant tumors has dosimetric and clinical advantages over photon therapy. Patients in Alberta, Canada are referred to the United States for proton treatment. The Alberta Heath Care Insurance Plan (AHCIP) pays for the proton treatment and the cost of flights to and from the United States (direct costs). This study aimed to determine the out-of-pocket expenses incurred by patients or their families (indirect costs). METHODS Invitation letters linked to an electronic survey were mailed to patients treated with protons between 2008 and 2018. Expenses for flights for other family members, accommodations, transportation, food, passports, insurance, and opportunity costs including lost wages and productivity were measured. RESULTS Fifty-nine invitation letters were mailed. Seventeen surveys were completed (28.8% response rate). One paper survey was mailed at participant request. Nine respondents were from parent/guardian, 8 from patients. All patients were accompanied to the US by a family member/friend. Considerable variability in costs and reimbursements were reported. Many of the accompanying family/friends had to miss work; only 3 patients themselves reported missed work. Time away from work varied, and varied as to whether it was paid or unpaid time off. CONCLUSIONS Respondents incurred indirect monetary and opportunity costs which were not covered by AHCIP when traveling out of country for proton therapy. Prospective studies could help provide current data minimizing recall bias. These data may be helpful for administrators in assessing the societal cost of out-of-country referral of patients for proton therapy.