Patient and family financial burden associated with cancer treatment in Canada: a national study.

GOAL: To determine patient-reported financial and family burden associated with treatment of cancer in the previous 28 days across Canada. METHODS: A self-administered questionnaire (P-SAFE v7.2.4) was completed by 901 patients with cancer from twenty cancer centres nationally (344 breast, 183 colorectal, 158 lung, 216 prostate) measuring direct and indirect costs related to cancer treatment and foregone care. Monthly self-reported out-of-pocket-costs (OOPCs) included drugs, homecare, homemaking, complementary/ alternative medicines, vitamins/supplements, family care, accommodations, devices, and "other" costs. Travel and parking costs were captured separately. Patients indicated if OOPC, travel, parking, and lost income were a financial burden. RESULTS: Mean 28-day OOPCs were CA$518 (US Purchase Price Parity [PPP] $416), plus CA$179 (US PPP $144) for travel and CA$84 (US PPP $67) for parking. Patients self-reporting high financial burden had total OOPCs (33%), of CA$961 (US PPP $772), while low-burden participants (66%) had OOPCs of CA$300 (US PPP $241). "Worst burden" respondents spent a mean of 50.7% of their monthly income on OOPCs (median 20.8%). Among the 29.4% who took time off work, patients averaged 18.0 days off. Among the 26.0% of patients whose caregivers took time off work, caregivers averaged 11.5 days off. Lastly, 41% of all patients had to reduce spending. Fifty-two per cent of those who reduced spending were families earning < CA$50,000/year. CONCLUSIONS: In our Canadian sample, high levels of financial burden exist for 33% of patients, and the severity of burden is higher for those with lower household incomes.

Non-operative management for oral cavity carcinoma: Definitive radiation therapy as a potential alternative treatment approach.

PURPOSE: To determine the outcomes of oral cavity squamous cell cancer (OSCC) patients treated with non-surgical approach i.e. definitive intensity-modulated radiation therapy (IMRT). METHODS: All OSCC patients treated radically with IMRT (without primary surgery) between 2005-2014 were reviewed in a prospectively collected database. OSCC patients treated with definitive RT received concurrent chemotherapy except for early stage patients or those who declined or were unfit for chemotherapy. The 5-year local, and regional, distant control rates, disease-free, overall, and cancer-specific survival, and late toxicity were analyzed. RESULTS: Among 1316 OSCC patients treated with curative-intent; 108 patients (8%) received non-operative management due to: medical inoperability (n = 14, 13%), surgical unresectability (n = 8, 7%), patient declined surgery (n = 15, 14%), attempted preservation of oral structure/function in view of required extensive surgery (n = 53, 49%) or extensive oropharyngeal involvement (n = 18, 17%). Sixty-eight (63%) were cT3-4, 38 (35%) were cN2-3, and 38 (35%) received concurrent chemotherapy. With a median follow-up of 52 months, the 5-year local, regional, distant control rate, disease-free, overall, and cancer-specific survival were 78%, 92%, 90%, 42%, 50%, and 76% respectively. Patients with cN2-3 had higher rate of 5-year distant metastasis (24% vs 3%, p = 0.001), with detrimental impact on DFS (p = 0.03) and OS (p < 0.02) on multivariable analysis. Grade ≥ 3 late toxicity was reported in 9% of patients (most common: grade 3 osteoradionecrosis in 6%). CONCLUSIONS: Non-operative management of OSCC resulted in a meaningful rate of locoregional control, and could be an alternative curative approach when primary surgery would be declined, unsuitable or unacceptably delayed.

Stereotactic body radiation therapy for hepatocellular carcinoma with Macrovascular invasion.

BACKGROUND: In patients with hepatocellular carcinoma (HCC), macrovascular invasion (MVI) is associated with a poor prognosis. The purpose of this study is to describe long-term outcomes of patients with HCC and MVI treated with stereotactic body radiation therapy (SBRT). METHODS: Patients with HCC and MVI who were treated with SBRT from January 2003 to December 2016 were analyzed. Patients who had extrahepatic disease or previous liver transplant were excluded. Demographical, clinical, and treatment variables were analyzed. RESULTS: 128 eligible patients with HCC and MVI were treated with SBRT. Median age was 60.5 years (39 to 90 years). Baseline Child-Pugh (CP) score was A5 in 67%, A6 in 20%. Median SBRT dose was 33.3 Gy (range: 27 to 54 Gy) in 5 fractions. Local control at 1 year was 87.4% (95% CI 78.6 to 96.1%). Median overall survival (OS) was 18.3 months (95% CI 11.2 to 21.4 months); ECOG performance status > 1 (HR:1.85, p = 0.0138) and earlier treatment era (HR: 2.20, p = 0.0015) were associated with worsening OS. In 43 patients who received sorafenib following SBRT, median OS was 37.9 months (95% CI 19.5 to 54.4 months). Four patients developed GI bleeding possibly related to SBRT at 2 to 8 months, and 27% (31/112 evaluable patients) had worsening of CP class at three months after SBRT. CONCLUSIONS: SBRT was associated with encouraging outcomes for patients with HCC and MVI, especially in those patients who received sorafenib after SBRT. Randomized phase III trials of SBRT with systemic and/or regional therapy are warranted and ongoing.

A scoping review of rehabilitation interventions for survivors of head and neck cancer.

Purpose: The objectives of this scoping review were to summarize, understand, and disseminate findings from a broad body of literature on rehabilitation interventions used with survivors of head and neck cancer. Method: Searches were conducted in six databases. Inclusion criteria were studies of adult head and neck cancer survivors with a predefined primary rehabilitation outcome as a result of an intervention. Excluded were studies not written in English, opinion papers, or studies where the intervention was not carried out by a rehabilitation healthcare service. A second level, full-text review of the studies was conducted. A thematic analysis was used to examine and combine study findings. Results: A total of 3804 results were retrieved from all sources resulting in 39 papers that were analyzed. The thematic analysis of the included papers represented interventions focusing on swallowing and nutrition, speech, physical therapy, assistive devices, complementary and alternative modalities, comprehensive interdisciplinary programs, and preventive rehabilitation programs. Conclusion: This review has provided an overview of the scope of rehabilitation interventions available for survivors of head and neck cancer and preliminary information about their efficacy. This is foundational information for the development and refinement of rehabilitation interventions and programs for head and neck cancer survivors. Implications for Rehabilitation The existing evidence suggests that survivors of head and neck cancer can benefit from early screening of potential rehabilitation needs and being involved in preventive rehabilitation programs pre-surgery when possible. Rehabilitation programs should consider swallowing interventions for patients as evidence reports improved swallowing function, decreased pain and discomfort, and reduced duration of feeding tube use. Rehabilitation programs should consider nutritional interventions after radiotherapy: Patients benefited from stabilized weights, improved nutritional status, and an improved quality of life. Physical exercise interventions demonstrated improvements in physical function, muscular endurance, range of motion, overall quality of life, and showed reductions in pain, and fatigue.

Effect of Intensity Modulated Radiation Therapy With Concurrent Chemotherapy on Survival for Patients With Cervical Esophageal Carcinoma.

PURPOSE: We evaluated the effect of consecutive protocols on overall survival (OS) for cervical esophageal carcinoma (CEC). METHODS AND MATERIALS: All CEC cases that received definitive radiation therapy (RT) with or without chemotherapy from 1997 to 2013 in 3 consecutive protocols were reviewed. Protocol 1 (P1) consisted of 2-dimensional RT of 54 Gy in 20 fractions with 5-fluorouracil plus either mitomycin C or cisplatin. Protocol 2 (P2) consisted of 3-dimensional conformal RT (3DRT) of ≥60 Gy in 30 fractions plus elective nodal irradiation plus cisplatin. Protocol 3 (P3) consisted of intensity modulated RT (IMRT) of ≥60 Gy in 30 fractions plus elective nodal irradiation plus cisplatin. Multivariable analyses were used to assess the effect of the treatment protocol, RT technique, and RT dose on OS, separately. RESULTS: Of 81 cases (P1, 21; P2, 23; and P3, 37), 34 local (P1, 11 [52%]; P2, 12 [52%]; and P3, 11 [30%]), 16 regional (P1, 6 [29%]); P2, 3 [13%]; and P3, 7 [19%]), and 34 distant (P1, 10 [48%]; P2, 9 [39%]; and P3, 15 [41%]) failures were identified. After adjusting for age (P=.49) and chemotherapy (any vs none; hazard ratio [HR] 0.5, 95% confidence interval [CI] 0.3-0.9; P=.023), multivariable analysis showed P3 had improved OS compared with P1 (HR 0.4, 95% CI 0.2-0.8; P=.005), with a trend shown for benefit compared with P2 (HR 0.6, 95% CI 0.3-1.0; P=.061). OS between P1 and P2 did not differ (P=.29). Analyzed as a continuous variable, higher RT doses were associated with a borderline improved OS (HR 0.97, 95% CI 0.95-1.0; P=.075). IMRT showed improved OS compared with non-IMRT (HR 0.57, 95% CI 0.3-0.8; P=.008). CONCLUSIONS: The present retrospective consecutive cohort study showed improved OS with our current protocol (P3; high-dose IMRT with concurrent high-dose cisplatin) compared with historical protocols. The outcomes for patients with CEC remain poor, and novel approaches to improve the therapeutic ratio are warranted.

Phase I trial of radiation therapy and sorafenib in unresectable liver metastases.

BACKGROUND AND PURPOSE: To determine maximum tolerated dose (MTD) and toxicities of sorafenib combined with stereotactic radiotherapy (SBRT) or whole liver radiotherapy (WLRT) in patients with liver metastases. MATERIAL AND METHODS: Eligible patients had unresectable liver metastases. Sorafenib dose was escalated in 2 strata: I - SBRT: effective liver volume irradiated (Veff)<80% (30-60Gy in 6 fractions); II - WLRT: Veff>80% (21.6Gy in 6 fractions). Four weeks of sorafenib, with radiotherapy during weeks 2-3, was delivered at 3 escalating dose levels (200-400mg twice daily). Dose limiting toxicity was defined as any grade 3+ liver toxicity, or grade 4+ treatment-related toxicity. RESULTS: Thirty-three patients were treated: 18 in stratum I (median dose 42Gy), 15 in stratum II. The MTD was not reached. Grade 3+ toxicity was seen in 33% of patients, at a median of 10days. Two deaths from non-classic liver toxicity occurred post WLRT in stratum II. The median overall survival was 22.3 and 5.7months for strata I and II respectively. CONCLUSIONS: Sorafenib and 21.6Gy in 6 fraction WLRT resulted in unacceptably high rates of liver toxicity. Although sorafenib combined with SBRT was tolerable, the observed efficacy does not merit further clinical evaluation.

Phase 1/2 Study of the Addition of Cisplatin to Adjuvant Chemotherapy With Image Guided High-Precision Radiation Therapy for Completely Resected Gastric Cancer.

PURPOSE: Locoregional recurrence is common after surgery for gastric cancer. Adjuvant therapy improves outcomes but with toxicity. This phase 1/2 study investigated infusional 5-fluorouracil (5-FU) in combination with biweekly cisplatin delivered concurrently with image guided high-precision radiation therapy. METHODS AND MATERIALS: Eligible patients had completely resected stage IB to IV (Union for International Cancer Control TNM 6th edition) nonmetastatic gastric adenocarcinoma. Treatment constituted 12 weeks of infusional 5-FU (200 mg/m2/day) with cisplatin added in a standard 3 + 3 dose escalation protocol (0, 20, 30, and 40 mg/m2) during weeks 1, 3, 5, and 7, and an additional week 9 dose in the final cohort. Radiation therapy (45 Gy in 25 fractions) was delivered during weeks 3 to 7. Maximum tolerated dose (MTD) was determined in phase 1 and confirmed in phase 2. RESULTS: Among the 55 patients (median age, 54 years; range 28-77 years; 55% male), the median follow-up time was 3.0 years (range, 0.3-5.3 years). Five patients in phase 1 experienced dose-limiting toxicity, and MTD was determined as 4 cycles of 40 mg/m2 cisplatin. Twenty-seven patients were treated at MTD. Acute grade 3 to 4 toxicity rate was 37.0% at MTD and 29.1% across all dose levels. No treatment-related deaths occurred. Fourteen patients experienced recurrent disease. The 2-year overall survival (OS) and relapse-free survival were 85% and 74%, respectively. Median OS has not been reached. Quality of life (QOL) was impaired during treatment, but most scores recovered by 4 weeks. CONCLUSION: Cisplatin can be safely delivered with 5-FU-based chemoradiation therapy. Acute toxicity was acceptable, and patient-reported QOL showed the regimen was tolerable. Outcomes are encouraging and justify further study of this regimen.

E-Mail Communication Practices and Preferences Among Patients and Providers in a Large Comprehensive Cancer Center.

PURPOSE: Little is known about how electronic mail (e-mail) is currently used in oncology practice to facilitate patient care. The objective of our study was to understand the current e-mail practices and preferences of patients and physicians in a large comprehensive cancer center. METHODS: Separate cross-sectional surveys were administered to patients and physicians (staff physicians and clinical fellows) at the Princess Margaret Cancer Centre. Logistic regression was used to identify factors associated with current e-mail use. Record review was performed to assess the impact of e-mail communication on care. RESULTS: The survey was completed by 833 patients. E-mail contact with a member of the health care team was reported by 41% of respondents. The team members contacted included administrative assistants (52%), nurses (45%), specialist physicians (36%), and family physicians (18%). Patient factors associated with a higher likelihood of e-mail contact with the health care team included younger age, higher education, higher income, enrollment in a clinical trial, and receipt of multiple treatments. Eighty percent of physicians (n = 63 of 79) reported previous contact with a patient via e-mail. Physician factors associated with a greater likelihood of e-mail contact with patients included older age, more senior clinical position, and higher patient volume. Nine hundred sixty-two patient records were reviewed, with e-mail correspondence documented in only 9% of cases. CONCLUSION: E-mail is commonly used for patient care but is poorly documented. The use of e-mail in this setting can be developed with appropriate guidance; however, there may be concerns about widening the gap between certain groups of patients.

Prevalence and nature of survivorship needs in patients with head and neck cancer.

BACKGROUND: The purpose of this study was to determine the number, type, and predictors of patients with head and neck cancer unmet survivorship needs. METHODS: This study accrued patients with head and neck cancer at any time point in their survivorship course, and they completed a survey, including demographic information and the Cancer Survivors' Unmet Needs Measure (CaSUN). RESULTS: The median age of the 158 participants was 64 years. Ninety-six patients (61%) reported at least one unmet need on the CaSUN and 6 patients had a very high number of needs between 31 and 35. The mean number of unmet needs was 5.8 ± 8.9. Comprehensive Cancer Care was the most common domain of unmet need (n = 69; 45%). Younger age, earlier survivorship phase, and worse quality of life were associated with increased survivorship unmet needs on multivariable analysis. CONCLUSION: A high proportion of patients with head and neck cancer have unmet needs. These data can guide the development of head and neck survivorship programs. © 2016 Wiley Periodicals, Inc. Head Neck 38: 1097-1103, 2016.

Phase 1 Trial of Sorafenib and Stereotactic Body Radiation Therapy for Hepatocellular Carcinoma.

PURPOSE: To determine the maximally tolerated dose of sorafenib delivered before, during, and after stereotactic body radiation therapy (SBRT) in hepatocellular carinoma (HCC). METHODS AND MATERIALS: Eligible patients had locally advanced Child-Pugh class A HCC, showed Eastern Cooperative Oncology Group performance status 0-1, and were ineligible for standard local-regional therapies. Sorafenib was dose escalated in 2 strata: (1) low effective irradiated liver volume (veff) < 30% and (2) high veff 30%to 60%. Sorafenib (400 mg daily = dose level 1) was administered for 12 weeks, with 6 fractions SBRT delivered weeks 2 and 3, and escalation to full dose (400 mg twice daily) after 12 weeks as tolerated. Standard 3 + 3 cohorts with dose escalation of sorafenib were planned. RESULTS: Sixteen patients (4 low veff, median dose 51 Gy; 12 high veff, median dose 33 Gy) were treated at 2 sorafenib dose levels. Of those patients 75% were had Barcelona Clinic Liver Cancer stage C, and 63% had main branch portal vein invasion. In the low veff stratum, no dose-limiting toxicities (DLTs) were observed in 4 patients treated with SBRT and sorafenib 400 mg. Inb the high veff stratum: 2 of 3 evaluable patients treated with sorafenib 400 mg experienced DLT (grade 3 large bowel bleed and grade 4 bowel obstruction 51 and 27 days, respectively, after SBRT). One of 6 evaluable patients at dose level -1 (200 mg once daily) experienced a grade 3 tumor rupture at week 5. Median overall survival and in-field local progression have not been reached. Worsening of Child-Pugh liver function class was seen in 6 of 12 patients in the high veff stratum. CONCLUSIONS: Significant toxicity was observed in the high veff stratum, and concurrent SBRT with sorafenib is not recommended outside a clinical trial.

Hyperfractionated, accelerated radiotherapy for locally advanced head and neck cancer: quality of life in a prospective phase I/II trial.

BACKGROUND AND PURPOSE: Quality of life (QOL) was measured prospectively in a dose escalation study of twice daily hyperfractionated, accelerated radiotherapy for locally advanced head and neck cancer (HNC). MATERIALS AND METHODS: Patients with squamous cell HNC (TNM stage III/IV larynx or pharynx, or hypopharynx any stage) received 40 fractions of twice daily RT at 3 dose levels: (L1) 60Gy, 1.5Gy/fraction; (L2) 62Gy, 1.55Gy/fraction; and (L3) 64Gy, 1.6Gy/fraction. QOL was measured on the FACT-H&N at baseline, 6 and 12 months. RESULTS: Mean QOL scores were: baseline 104, 6 months 108, 12 months 112. At all time points, QOL scores were lower in patients with more advanced T-category. A mixed-model analysis of determinants of QOL showed no dose effect among L1 (n=22), L2 (n=26) or L3 (n=123). QOL improved significantly with time from diagnosis, however post-treatment QOL was lower and improved more slowly in patients who had feeding tubes. CONCLUSIONS: Post-RT QOL improved from baseline by a statistically and clinically significant amount. Hyperfractionated, accelerated RT provides favorable QOL outcomes, and is a viable alternative to chemoradiation for patients with locally advanced HNC.

Conformal radiotherapy in the adjuvant treatment of gastric cancer: Review of 82 cases.

BACKGROUND: The Intergroup 0116 study showed a survival benefit with adjuvant chemoradiotherapy (CRT) for resected gastric cancer. We report our experience using conformal radiotherapy (RT). METHODS AND MATERIALS: Eighty-two patients with resected gastric or gastroesophageal junction (GEJ) adenocarcinoma, Stage IB to IV (M0), were treated with 45 Gy in 25 fractions using a 5-field conformal technique. Chemotherapy was in accordance with the Intergroup 0116 study, or infusional 5-fluorouracil and cisplatin in a phase I/II trial. RESULTS: Mean age was 56.4 years. Median follow-up was 22.8 months. Grade 3 or greater acute toxicity (National Cancer Institute Common Terminology Criteria of Adverse Events, version 3.0) was noted in 57% of patients (upper gastrointestinal tract 34%, hematologic 33%). One patient died of neutropenic sepsis. Radiation Therapy Oncology Group Grade 3 late toxicity included esophageal strictures (3 patients) and small bowel obstruction (1 patient). Full course CRT was completed by 67% of patients. Of 26 patients who relapsed, 20 died. Site of first relapse was available on 23 patients: 8 locoregional and distant, 4 locoregional alone, 11 distant alone. Overall and relapse-free survival were 69% and 54% at 3 years. CONCLUSION: Adjuvant CRT for gastric cancer, even with conformal RT, is associated with significant toxicity. Survival was comparable to that reported in the Intergroup 0116 study.

Preoperative radiation with concurrent chemotherapy for resectable rectal cancer: effect of dose escalation on pathologic complete response, local recurrence-free survival, disease-free survival, and overall survival.

PURPOSE: Three Phase II studies of preoperative radiotherapy and concurrent 5FU chemotherapy were undertaken. The primary endpoints were acute toxicity and pathologic complete response rate (pCR). Secondary endpoints were local recurrence-free survival (LRFS), disease-free survival (DFS), and overall survival (OS). METHODS AND MATERIALS: A total of 134 patients with adenocarcinoma of the rectum (clinical T3/T4 or N1/N2) were treated. The initial cohort received 40 Gy in 20 fractions, the second 46 Gy in 23 fractions, and the third 50 Gy in 25 fractions. 5FU (225 mg/m2/day) was given continuously throughout radiotherapy. A total of 121 patients underwent surgical resection. RESULTS: Treatment was well tolerated. Grade 3/4 acute toxicity was observed in 13%, 4%, and 14% of patients in the 40 Gy, 46 Gy, and 50 Gy cohorts, respectively (p = 0.20). pCR was documented in 15%, 23%, and 33% of patients, respectively (p = 0.07). The 2-year actuarial LRFS was 72%, 90%, and 89% (p = 0.02); DFS was 62%, 84%, and 78% (p = 0.02); and OS was 72%, 94%, and 92%, respectively (p = 0.03). CONCLUSIONS: All treatment schedules were well tolerated. There was a trend toward increased pCR with higher doses. A statistically significant increase in LRFS, DFS, and OS was seen with radiation doses of 46 Gy and greater, but there was no difference between 46 Gy and 50 Gy.

Survey of computer use for health topics by patients with head and neck cancer.

BACKGROUND: Computers are potentially powerful tools for patient education. E-health, which refers to health services and information delivered through the Internet, is a growing phenomenon within the health-care field. We sought to describe computer use and interest in e-health resources among patients with head and neck cancer. METHODS: A questionnaire was administered to 207 patients with head and neck cancer attending oncology follow-up clinics at a single comprehensive cancer center. RESULTS: Forty-eight percent had never used a computer; 43% used one more than once a week. E-health information had been sought by 31%. Likelihood to access e-health information increased with education and income but decreased with age (p < or = .05). CONCLUSIONS: Many patients with head and neck cancer welcome information technology, but most prefer more traditional sources of information. Interventions to improve computer access and/or skills are largely undesired. Individuals seem to either embrace technology or not. In this respect, patients with head and neck cancer are similar to, rather than unique from, other patients with cancer.