Does free nicotine replacement improve smoking cessation rates in cancer patients?

Background: Cigarette smoking is carcinogenic and has been linked to inferior treatment outcomes and complication rates in cancer patients. Here, we report the results of an 18-month pilot smoking cessation program that provided free nicotine replacement therapy (nrt). Methods: In January 2017, the smoking cessation program at our institution began offering free nrt for actively cigarette-smoking patients with cancer. The cost of 4 weeks of nrt was covered by the program, and follow-up was provided by smoking cessation champions. Results: From January 2017 to June 2018, 8095 patients with cancer were screened for cigarette use, of whom 1135 self-identified as current or recent smokers. Of those 1135 patients, 117 enrolled in the program and accepted a prescription for nrt. The rates of patient referral and patients attending a referral appointment were significantly higher in 2018-2018 than they had been in 2015-2016 (100% vs. 80.3%, p < 0.001, and 27.6% vs. 11.3%, p < 0.001, respectively). Median follow-up was 9.0 months (25%-75% interquartile range: 5.7-11.6 months). Of the patients who accepted nrt and who also had complete data (n = 71), 25 (35.2%) reported complete smoking cessation, and 32 (45.1%) reported only decreased cigarette smoking. On univariable analysis, no factors were significantly predictive of smoking cessation, although initial cigarette use (>10 vs. ≤10 initial cigarettes) was significantly predictive of smoking reduction (odds ratio: 5.04; 95% confidence interval: 1.46 to 17.45; p = 0.011). Conclusions: This pilot study of free nrt demonstrated rates of referral and acceptance of nrt that were improved compared with historical rates, and most referred patients either decreased their use of cigarettes or quit entirely.

Predictive factors for persistent and late radiation complications in breast cancer survivors.

PURPOSE: With improved diagnostic techniques and treatments of breast cancer, overall survival times are longer, giving more opportunity for normal tissue complications of treatment to manifest. Radiation late effects (RLEs) could have profound long-term impacts on the quality of life of the survivors. The aim of this study was to identify predictive factors influencing timing and types of complications in patients referred to the Adult Radiation Late Effects Clinic (ARLEC). METHODS: In a period of 16 years, 296 breast cancer patients were referred to the ARLEC. The clinical records were retrospectively studied to collect epidemiologic, medical and treatment data. Associations were sought between candidate predictive factors and time to the first complication after radiation treatment (RT) completion (primary outcome), and pain or swelling (secondary outcomes) using univariable and multivariable linear and logistic regression analyses. All analyses were performed in SAS, version 9.4. RESULTS: All patients were female with a mean age of 56.3 years. The first treatment-related complication occurred after a median of 3 months. Patients were followed at ARLEC for a median of 18 months. Older age and delay from surgery to RT (S-RT delay) were associated with earlier onset of complications (both p < 0.001). The most common complications were breast pain (62.1%) and swelling (45.9%). Histology and RT boost were associated with pain (p = 0.035 and 0.013). RT boost and S-RT delay on the other hand were associated with swelling (p = 0.013 and 0.005). CONCLUSIONS: Clinical factors identified could help recognize the patients at high risk for developing RLEs and alert physicians to initiate earlier diagnostic and therapeutic measures.

Personalizing post-treatment cancer care: a cross-sectional survey of the needs and preferences of well survivors of breast cancer.

Background: Improved treatments resulting in a rising number of survivors of breast cancer (bca) calls for optimization of current specialist-based follow-up care. In the present study, we evaluated well survivors of bca with respect to their supportive care needs and attitudes toward follow-up with various care providers, in varying settings, or mediated by technology (for example, videoconference or e-mail). Methods: A cross-sectional paper survey of well survivors of early-stage pT1-2N0 bca undergoing posttreatment follow-up was completed. Descriptive and univariable logistic regression analyses were performed to examine associations between survivor characteristics, supportive care needs, and perceived satisfaction with follow-up options. Qualitative responses were analyzed using conventional content analysis. Results: The 190 well survivors of bca who participated (79% response rate) had an average age of 63 ± 10 years. Median time since first follow-up was 21 months. Most had high perceived satisfaction with in-person specialist care (96%, 177 of 185). The second most accepted model was shared care involving specialist and primary care provider follow-up (54%, 102 of 190). Other models received less than 50% perceived satisfaction. Factors associated with higher perceived satisfaction with non-specialist care or virtual follow-up by a specialist included less formal education (p < 0.01) and more met supportive care needs (p < 0.05). Concerns with virtual follow-up included the perceived impersonal nature of virtual care, potential for inadequate care, and confidentiality. Conclusions: Well survivors of bca want specialists involved in their follow-up care. Compared with virtual follow-up, in-person follow-up is perceived as more reassuring. Certain survivor characteristics (for example, met supportive care needs) might signal survivor readiness for virtual or non-specialist follow-up. Future work should examine multi-stakeholder perspectives about barriers to and facilitators of shared multimodal follow-up care.

Building a New Model of Care for Rapid Breast Radiotherapy Treatment Planning: Evaluation of the Advanced Practice Radiation Therapist in Cavity Delineation.

AIMS: Breast radiotherapy treatment is commonly managed by a multidisciplinary team to ensure optimal delivery of care. We sought a new model of care whereby a clinical specialist radiation therapist (CSRT) delineates the cavity target for whole breast radiotherapy treatment planning and the radiation oncologist validates the contour during final plan review. This study evaluated the radiation oncologist's acceptance of these contours and identified characteristics of cavities suitable for CSRT-directed contouring. MATERIALS AND METHODS: Following specialised breast oncology education and training by the radiation oncologist, the CSRT prospectively delineated cavities in 30 tangential breast radiotherapy cases and consulted the radiation oncologist in 'complex' cases but directed 'non-complex' cases for treatment planning. Changes to CSRT contours were evaluated using the conformity index. Breast density, time since surgery and cavity location, size and visualisation score [CVS: range 1 (no visible cavity) to 5 (homogenous cavity)] were captured. RESULTS: Of the 30 CSRT delineated cavities contours, the CSRT directed 20 (66.7%) cases for planning without radiation oncology review; 19 were accepted (without changes) by the radiation oncologist upon final plan review and one was changed by the radiation oncologist (conformity index = 0.93) for boost treatment and did not affect the tangential treatment plan. Ten (33.3%) cases, all CVS ≤ 3, were reviewed with the radiation oncologist before planning (conformity index = 0.88 ± 0.12). CVS was inversely correlated with breast density and cavity size (P < 0.01). CONCLUSIONS: The CSRT delineated cavities appropriate for clinical radiotherapy treatment planning in women with well-visualised cavities, whereas 'complex' cases with dense breast parenchyma, CVS ≤ 3, and/or cases needing boost radiotherapy treatment required review with the radiation oncologist before planning.

The Brain Metastases Symptom Checklist as a novel tool for symptom measurement in patients with brain metastases undergoing whole-brain radiotherapy.

PURPOSE: We evaluated the feasibility, reliability, and validity of the Brain Metastases Symptom Checklist (bmsc), a novel self-report measure of common symptoms experienced by patients with brain metastases. METHODS: Patients with first-presentation symptomatic brain metastases (n = 137) referred for whole-brain radiotherapy (wbrt) completed the bmsc at time points before and after treatment. Their caregivers (n = 48) provided proxy ratings twice on the day of consultation to assess reliability, and at week 4 after wbrt to assess responsiveness to change. Correlations with 4 other validated assessment tools were evaluated. RESULTS: The symptoms reported on the bmsc were largely mild to moderate, with tiredness (71%) and difficulties with balance (61%) reported most commonly at baseline. Test-retest reliability for individual symptoms had a median intraclass correlation of 0.59 (range: 0.23-0.85). Caregiver proxy and patient responses had a median intraclass correlation of 0.52. Correlation of absolute scores on the bmsc and other symptom assessment tools was low, but consistency in the direction of symptom change was observed. At week 4, change in symptoms was variable, with improvements in weight gain and sleep of 42% and 41% respectively, and worsening of tiredness and drowsiness of 62% and 59% respectively. CONCLUSIONS: The bmsc captures a wide range of symptoms experienced by patients with brain metastases, and it is sensitive to change. It demonstrated adequate test-retest reliability and face validity in terms of its responsiveness to change. Future research is needed to determine whether modifications to the bmsc itself or correlation with more symptom-specific measures will enhance validity.

Adjuvant sunitinib following chemoradiotherapy and surgery for locally advanced esophageal cancer: a phase II trial.

The prognosis for locally advanced esophageal cancer is poor despite the use of trimodality therapy. In this phase II study, we report the feasibility, tolerability and efficacy of adjuvant sunitinib. Included were patients with stage IIa, IIB or III cancer of the thoracic esophagus or gastroesophageal junction. Neoadjuvant therapy involved Irinotecan (65 mg/m2 ) + Cisplatin (30 mg/m2 ) on weeks 1 and 2, 4 and 5, 7 and 8 with concurrent radiation (50Gy/25 fractions) on weeks 4-8. Sunitinib was commenced 4-13 weeks after surgery and continued for one year. Sixty-one patients were included in the final analysis, 36 patients commenced adjuvant sunitinib. Fourteen patients discontinued sunitinib due to disease recurrence (39%) within the 12-month period, 12 (33%) discontinued due to toxicity, and 3 (8%) requested cessation of therapy. In the overall population, median survival was 26 months with a 2 and 3-year survival rate of 52% and 35%, respectively. The median survival for the 36 patients treated with sunitinib was 35 months and 2-year survival probability of 68%. In a historical control, a prior phase II study with the same trimodality therapy (n = 43), median survival was 36 months, with a 2-year survival of 67%. Initiation of adjuvant sunitinib is feasible, but poorly tolerated, with no signal of additional benefit over trimodality therapy for locally advanced esophageal cancer.

A Canadian national expert consensus on neoadjuvant therapy for breast cancer: linking practice to evidence and beyond.

BACKGROUND: Use of the neoadjuvant approach to treat breast cancer patients has increased since the early 2000s, but the overall pathway of care for such patients can be highly variable. The aim of our project was to establish a multidisciplinary consensus among clinicians with expertise in neoadjuvant therapy (nat) for breast cancer and to determine if that consensus reflects published methods used in randomized controlled trials (rcts) in this area. METHODS: A modified Delphi protocol, which used iterative surveys administered to 85 experts across Canada, was established to obtain expert consensus concerning all aspects of the care pathway for patients undergoing nat for breast cancer. All rcts published between January 1, 1967, and December 1, 2012, were systematically reviewed. Data extracted from the rcts were analyzed to determine if the methods used matched the expert consensus for specific areas of nat management. A scoring system determined the strength of the agreement between the literature and the expert consensus. RESULTS: Consensus was achieved for all areas of the pathway of care for patients undergoing nat for breast cancer, with the exception of the role of magnetic resonance imaging in the pre-treatment or preoperative setting. The levels of agreement between the consensus statements and the published rcts varied, primarily because specific aspects of the pathway of care were not well described in the reviewed literature. CONCLUSIONS: A true consensus of expert opinion concerning the pathway of care appropriate for patients receiving nat for breast cancer has been achieved. A review of the literature illuminated gaps in the evidence about some elements of nat management. Where evidence is available, agreement with expert opinion is strong overall. Our study is unique in its approach to establishing consensus among medical experts in this field and has established a pathway of care that can be applied in practice for patients receiving nat.

Lymphoepithelioma-like carcinoma of the breast: a diagnostic and therapeutic challenge.

We present a patient with lymphoepithelioma-like carcinoma (LELC) of the breast whose diagnosis is illustrative of the pathology nuances that must be taken into account to successfully reach correct identification of the disease. We also present an overview of our patient's proposed treatment in the context of 16 other reported LELC cases. Although LELC cases are rare, a sufficient number have been reported to discern the natural history of this pathologic entity and to undertake a review of those cases and of the application of oncologic first principles in their management. Given the potential for locoregional spread and distant metastases in LELC, adjuvant therapy has a role in the treatment of this entity.

Caught in the middle: case study of a brachial (sentry) lymph node recurrence after resection and locoregional breast radiotherapy.

To reduce local recurrence, adjuvant locoregional radiotherapy is given routinely for post-mastectomy breast patients with 4 or more positive lymph nodes. Most institutions adopt a 3- or 4-field radiotherapy technique, in which the field and shielding placements are informed by bony anatomic landmarks viewed on digitally reconstructed radiographs.Here, we report on a 40-year-old woman who underwent a lumpectomy with axillary node dissection, followed by chemotherapy, completion mastectomy, and adjuvant locoregional radiotherapy (50 Gy in 25 fractions) for a multicentric pT1cN2aM0 invasive ductal carcinoma of the right breast. At 9 months after radiotherapy, she presented with a palpable brachial lymph node, a major draining node of the upper extremity, in the axilla, abutting the previous anterior supraclavicular and axillary radiation fields. This occurrence highlights the potential superolateral border of the level i axillary nodal chain and its relationship to the upper extremity lymphatics via the brachial ("sentry") node. Adapting the delineated nodal target volume in locoregional radiotherapy of the breast for disease with extensive nodal involvement or other high-risk pathologic indications may be warranted in certain situations. Careful imaging and an informed discussion with the patient is needed before deciding to treat the sentry node and including the acromial-clavicular joints, balanced with the potential increased risk of lymphedema.

Improving observer variability in target delineation for gastro-oesophageal cancer--the role of (18F)fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography.

AIM: To evaluate the effect of the addition of fused positron emission tomography-computed tomography (PET-CT) imaging vs computed tomography alone in the identification of the gross tumour volume (GTV) in patients with gastro-oesophageal carcinoma. MATERIALS AND METHODS: Ten patients with gastro-oesophageal cancer referred for radiation therapy underwent both (18F)fluoro-2-deoxy-d-glucose-PET (FDG-PET) and computed tomography in the treatment position. Image sets were anonymised and co-registered. Six radiation oncologists independently defined the GTV, first using the computed tomography data alone supplemented by standardised clinical and diagnostic imaging information, and second, using co-registered computed tomography and FDG-PET data (PET-CT). The standard deviation for both GTV length and volume (excluding involved lymph nodes) was taken as a measurement of inter-observer and intra-observer variability. Computer software that calculates volume overlap between contours was also used to generate an observer agreement index to compare intra- and inter-observer variability. RESULTS: The addition of FDG-PET imaging decreased the median standard deviation for tumour length from 10 mm (range 8.1-33.3, mean 12.4 mm) for computed tomography alone to 8mm (range 4.4-18.1, mean 8.1 mm) for PET-CT (P = 0.02). Eight of the 10 patients showed an increase in volume of overlap between observers with the addition of FDG-PET imaging to the contouring process (P = 0.05). The average observer agreement index in PET-CT was 72.7% compared with 69.1% when using computed tomography alone. There was significantly less intra-observer variability in all measures when PET-CT was used. The median standard deviation in length improved from 5.3 to 1.8 mm, the median standard deviation in volume improved from 4.5 to 3 cm3 and the median observer agreement index improved from 76.2 to 78.7% when computed tomography alone was compared with PET-CT. The corresponding P values were 0.001, 0.033 and 0.022, respectively. CONCLUSIONS: The addition of FDG-PET to computed tomography-based planning for the identification of primary tumour GTV in patients with gastro-oesophageal carcinoma decreases both inter-observer and intra-observer variability.

Prognostic factors in brain metastases: can we determine patients who do not benefit from whole-brain radiotherapy?

AIMS: Whole-brain radiotherapy (WBRT) is a standard treatment recommendation for patients with brain metastases. The goal of treatment is symptom control, which in the short run can be often achieved by steroids. Patients with a short life expectancy may not derive benefit from the addition of radiation. The ability to identify this group would aid the decision of whether to recommend WBRT. MATERIALS AND METHODS: Data on all patients referred for WBRT to palliative radiotherapy teams at two comprehensive cancer centres were prospectively collected over a 2-year period. The most frequent radiation dose and fractionation was 2000 cGy in 5 fractions over 1 week. Multivariate logistic regression analysis using forward stepwise selection process was used to develop a prediction model for early death (before 8 weeks). The variables considered were sex, performance status, primary disease, weight loss, age, time from primary diagnosis to brain metastases diagnosis, number of metastatic sites and Radiation Therapy Oncology Group (RTOG) recursive partitioning analysis (RPA) status. RESULTS: Two hundred and seventy-five patients with brain metastases were assessed. The median follow-up was 19 weeks, and estimated median overall survival was 5.3 months. Multivariate regression revealed Eastern Cooperative Oncology Group (ECOG) performance status and number of metastatic sites to be significant predictors of early death. The odds ratios were 2.38 (95% confidence interval [CI] 1.77-3.19) and 1.39 (95% CI 1.07-1.81), respectively. Sixty-eight per cent of patients could be correctly classified; however, 55% would have been incorrectly predicted to die early. CONCLUSIONS: Poor performance status and number of metastatic sites are useful predictors of early death. A regression model was highly predictive overall, but this was primarily due to a high negative predictive value of 86%. The ability to predict patients who would die early (positive predictive value) was only 45%. Thus, despite the understanding that we are over-treating a subset of patients, further research is required to identify patients who do not require radiotherapy.