S.A. Dudley

Cost-Effectiveness of Pertuzumab in Human Epidermal Growth Factor Receptor 2–Positive Metastatic Breast Cancer

PURPOSE The Clinical Evaluation of Pertuzumab and Trastuzumab (CLEOPATRA) study showed a 15.7-month survival benefit with the addition of pertuzumab to docetaxel and trastuzumab (THP) as first-line treatment for patients with human epidermal growth factor receptor 2 (HER2) -overexpressing metastatic breast cancer. We performed a cost-effectiveness analysis to assess the value of adding pertuzumab. PATIENT AND METHODS We developed a decision-analytic Markov model to evaluate the cost effectiveness of docetaxel plus trastuzumab (TH) with or without pertuzumab in US patients with metastatic breast cancer. The model followed patients weekly over their remaining lifetimes. Health states included stable disease, progressing disease, hospice, and death. Transition probabilities were based on the CLEOPATRA study. Costs reflected the 2014 Medicare rates. Health state utilities were the same as those used in other recent cost-effectiveness studies of trastuzumab and pertuzumab. Outcomes included health benefits expressed as discounted quality-adjusted life-years (QALYs), costs in US dollars, and cost effectiveness expressed as an incremental cost-effectiveness ratio. One- and multiway deterministic and probabilistic sensitivity analyses explored the effects of specific assumptions. RESULTS Modeled median survival was 39.4 months for TH and 56.9 months for THP. The addition of pertuzumab resulted in an additional 1.81 life-years gained, or 0.62 QALYs, at a cost of

Radiation Therapy for Colorectal Liver Metastases

472,668 per QALY gained. Deterministic sensitivity analysis showed that THP is unlikely to be cost effective even under the most favorable assumptions, and probabilistic sensitivity analysis predicted 0% chance of cost effectiveness at a willingness to pay of

Tracheal Diverticulum Following Paratracheal Hypofractionated Radiotherapy in the Setting of Prior and Subsequent Bevacizumab.

100,000 per QALY gained. CONCLUSION THP in patients with metastatic HER2-positive breast cancer is unlikely to be cost effective in the United States.

Fractionation of palliative radiotherapy in metastatic breast cancer: Selection and survival.

Purpose of ReviewThe purpose of the present study is to review the management of colorectal liver metastases (CLM) with radiation therapy (RT).Recent FindingsConventional RT is a local-regional modality that may provide symptomatic palliation, local control, and potential for prolongation of survival. Studies of RT to the liver contributed to understanding of the volume effect of liver toxicity and the potential for dose escalation to limited volumes. Stereotactic body radiation therapy (SBRT) delivers highly conformal ablative doses, providing high rates of local control without associated increases in toxicity. Radioembolization can provide local control for chemorefractory patients, but its added value in the first-line setting with modern systemic therapy remains an area of active investigation.SummarySBRT and radioembolization play key roles in the modern management of patients with CLM who are not eligible for surgery. Patients with limited burden of intrahepatic disease may be ideally suited for SBRT, while those with higher number (≥3) of CLM may be more appropriate for transarterial radioembolization.

Survival comparison of patients treated with one versus five fraction palliative radiotherapy.

We present the case of a 63-year-old woman with limited metastatic colorectal cancer to the lungs and liver treated with FOLFIRI-bevacizumab, followed by consolidative hypofractionated radiotherapy to right paratracheal metastatic lymphadenopathy. We treated the right paratracheal site with 60 Gy in 15 fractions (70 Gy equivalent dose in 2 Gy fractions). The patient tolerated the treatment well, and six months later started a five-month course of FOLFIRI-bevacizumab for new metastatic disease. She presented to our clinic six months after completing this, complaining of productive cough with scant hemoptysis, and was found to have localized tracheal wall breakdown and diverticulum in the region of prior high-dose radiation therapy, threatening to progress to catastrophic tracheovascular fistula. This was successfully repaired surgically after a lack of response to conservative measures. We urge caution in treating patients with vascular endothelial growth factor (VEGF) inhibitors in the setting of hypofractionated radiotherapy involving the mucosa of tubular organs, even when these treatments are separated by months. Though data is limited as to the impact of sequence, this may be particularly an issue when VEGF inhibitors follow prior radiotherapy.

Pre-treatment non-target lung FDG-PET uptake predicts symptomatic radiation pneumonitis following Stereotactic Ablative Radiotherapy (SABR)

201 Background: Various schedules of palliative radiotherapy (pRT) are prescribed for metastatic breast cancer (MBC) patients. Length of treatment can vary from a single day to three weeks. Single fraction pRT provides similar pain relief vs. multi-fraction pRT for bone metastases, but retreatment rates are higher. In the era of targeted and hormonal therapy, patients with MBC can survive many years after their initial diagnosis. We investigated whether patients with MBC who were prescribed single fraction pRT had poorer prognoses and experienced shorter survival than patients who were prescribed multi-fraction pRT. METHODS Patients at a single institution with MBC underwent pRT, with fractionation schedules including 8 Gy in 1 fraction (fx), 20 Gy in 5 fx, 30 Gy in 10 fx, 37.5 Gy in 15 fx between 2001-2015. 392 treatments were prescribed (109/241/29/13 in each regimen as above). Date of death was obtained from medical records, Social Security Death Index, or published obituaries. Patients who were alive or whose date of death could not be determined were censored at the date of their last encounter. Survival was calculated from the start of treatment to the date of death or censorship. RESULTS Patients treated with 37.5 Gy in 15 fx (MS 20 months, p = 0.002) or 30 Gy in 10 fx (MS 22 months, p = 0.03) experienced longer survival than patients treated with 8 Gy in 1 fx (MS 8 months). There was no significant survival difference between patients treated with 20 Gy in 5 fx (MS 18 months, p = 0.49) and patients treated with 8 Gy in 1 fx. There was no significant survival difference between patients treated by the three multi-fractionation schedules. CONCLUSIONS MBC patients who were prescribed 37.5 Gy and 30 Gy lived longer than patients who were prescribed 8 Gy of pRT. No statistically significant difference was found between patients who were prescribed 20 Gy compared to 8 Gy, possibly due to the lower number of patients who received these regimens. Single fraction pRT was more likely to be prescribed to patients who would ultimately have shorter survival. More research is needed, ideally across multiple institutions, to explore the correlation between physician estimation of patient survival and selection of pRT regimen for patients with MBC.

Automated Survival Prediction in Metastatic Cancer Patients Using High-Dimensional Electronic Medical Record Data

200 Background: Choice of fractionation scheme for palliative radiotherapy has received greater attention in recent years, particularly in the current healthcare environment where issues of cost and quality of life have taken on increasing importance. The ASTRO Choosing Wisely campaign recommends against routine use of extended fractionation schemes ( > 10 fractions) for palliation of bone metastases given equivalent pain relief between 30 Gy in 10 fractions and 8 Gy in 1 fraction, and strong consideration for use of 8 Gy in 1 fraction is urged for patients with a limited prognosis or transportation difficulties. We investigated whether there was a difference in survival between patients treated with an intermediate fractionation scheme (5 fractions) and patients who received single-fraction treatment. METHODS We identified 220 patients who received a total of 264 courses of palliative radiotherapy with either 8 Gy in 1 fraction (n = 91) or 20 Gy in 5 fractions (n = 173). Date of death was obtained from either the patients medical record, the Social Security Death Index, or publicly available obituaries. If none of these yielded a date of death, patients were censored at the date of their last clinical encounter. The majority of patients (n = 192) were treated for bone metastases. All primary sites were included, with the three most common histologies being lung, breast and prostate (n = 80, 31 and 16, respectively). RESULTS Overall, we found no significant survival difference between the two groups. Patients treated with 8 Gy in 1 fraction had a median survival of 146 days, whereas patients treated with 20 Gy in 5 fractions had a median survival of 183 days (p = 0.43). CONCLUSIONS Given no difference in survival between fractionation schemes of 20 Gy in 5 fractions and 8 Gy in 1 fraction, delivery of palliative radiation in a single fraction should be strongly considered. Previous studies have identified a higher re-treatment rate in single-fraction treatments, although closer analysis of this data revealed no difference in absolute pain scores prior to re-treatment. Thus, re-treatment for single-fraction radiotherapy may be due instead to a greater clinical willingness to re-treat as opposed to a greater clinical need.