Incidence of and risk factors for non-hematologic toxicity with combined radiotherapy and CDK4/6 inhibitors in metastatic breast cancer using dose-volume parameters analysis: a multicenter cohort study.

BACKGROUND: There is a lack of data on combined radiotherapy (RT) and cyclin-dependent kinase 4 and 6 inhibitor (CDK4/6i) risk factors and toxicity. This study aimed to assess the incidence of and risk factors for non-hematologic toxicities in patients treated with combined RT and CDK4/6i using dose-volume parameter analysis. METHODS: We conducted a retrospective multicenter cohort study of patients with metastatic breast cancer receiving RT within 14 days of CDK4/6i use. The endpoint was non-hematologic toxicities. Patient characteristics and RT treatment planning data were compared between the moderate or higher toxicities (≥ grade 2) group and the non-moderate toxicities group. RESULTS: Sixty patients were included in the study. CDK4/6i was provided at a median daily dose of 125 mg and 200 mg for palbociclib and abemaciclib, respectively. In patients who received concurrent RT and CDK4/6i (N = 29), the median concurrent prescribed duration of CDK4/6i was 14 days. The median delivered RT dose was 30 Gy and 10 fractions. The rate of grade 2 and 3 non-hematologic toxicities was 30% and 2%, respectively. There was no difference in toxicity between concurrent and sequential use of CDK4/6i. The moderate pneumonitis group had a larger lung V20 equivalent dose of 2 Gy per fraction and planning target volume than the non-moderate pneumonitis group. CONCLUSIONS: Moderate toxicities are frequent with combined RT and CDK4/6i. Caution is necessary concerning the combined RT and CDK4/6i. Particularly, reducing the dose to normal organs is necessary for combined RT and CDK4/6i.

Quality Indicators in Palliative Radiation Oncology: Development and Pilot Testing.

PURPOSE: A quality indicator (QI) is a valuable tool to evaluate the quality of health care systems. In palliative radiation oncology, only a few related QIs have been developed to date. In this study, we sought to develop and pilot test QIs that assess the quality of care in palliative radiation therapy. METHODS AND MATERIALS: A modified Delphi method was used to establish consensus with an expert panel. The panel consisted of 8 radiation oncologists who have expertise in palliative radiation oncology and 1 expert on Delphi methodology. Online panel meetings and e-mail surveys were conducted to develop QIs on palliative radiation therapy for bone and brain metastases. Feasibility of measurement was assessed though pilot surveys that were conducted by radiation oncologists at 5 facilities. RESULTS: After 3 online meetings and 2 e-mail surveys, we developed 4 QIs on bone metastases and 3 QIs on brain metastases. Two email surveys and 2 pilot surveys confirmed the validity of QIs and the feasibility of measurement, respectively. CONCLUSIONS: We developed valid and feasible QIs on palliative radiation therapy for bone and brain metastases. Our work may contribute to reduce the evidence-practice gaps in palliative radiation oncology.

Palliative brachytherapy and external beam radiotherapy for dysphagia from esophageal cancer: a nationwide survey in Japan.

BACKGROUND: International guidelines recommend brachytherapy for patients with dysphagia from esophageal cancer, whereas brachytherapy is infrequently used to palliate dysphagia in some countries. To clarify the availability of palliative treatment for dysphagia from esophageal cancer and explain why brachytherapy is not routinely performed are unknown, this study investigated the use of brachytherapy and external beam radiotherapy for dysphagia from esophageal cancer. METHODS: Japanese Radiation Oncology Study Group members completed a survey and selected the treatment that they would recommend for hypothetical cases of dysphagia from esophageal cancer. RESULTS: Of the 136 invited facilities, 61 completed the survey (44.9%). Four (6.6%) facilities performed brachytherapy of the esophagus, whereas brachytherapy represented the first-line treatment at three (4.9%) facilities. Conversely, external beam radiotherapy alone and chemoradiotherapy were first-line treatments at 61 and 58 (95.1%) facilities, respectively. In facilities that performed brachytherapy, the main reason why brachytherapy of the esophagus was not performed was high invasiveness (30.2%). Definitive-dose chemoradiotherapy with (≥50 Gy) tended to be used in patients with expected long-term survival. CONCLUSIONS: Few facilities routinely considered brachytherapy for the treatment of dysphagia from esophageal cancer in Japan. Conversely, most facilities routinely considered external beam radiotherapy. In the future, it will be necessary to optimize external beam radiotherapy.

A phase II study of palliative radiotherapy combined with zoledronic acid hydrate for metastatic bone tumour from renal cell carcinoma.

PURPOSE: Palliative radiotherapy is the standard of care for bone metastases. However, skeletal-related events, defined as a pathologic fracture, paraplegia, surgery or radiotherapy for local recurrence, or severe pain in previously irradiated bone with radio-resistant histology type still present high incidence. The primary objective of this study was to determine whether zoledronic acid hydrate and palliative radiotherapy could prevent local skeletal-related events. METHODS: Eligible patients with bone metastases from renal cell carcinoma were treated with zoledronic acid hydrate every 3 or 4 weeks and concurrent palliative radiotherapy of 30 Gy in 3 Gy fractions. The criteria for radiotherapy were established by the treating physician, but patients with complicated bone metastases (impending pathological fracture or spinal cord compression) which needed immediate surgery were excluded. The primary endpoint was the local skeletal-related event-free survival rate at 1 year. RESULTS: Twenty-seven patients were included in the study. The median age was 65 (range, 50-84) years. Radiotherapy dose was 30 Gy for all patients except 1 whose radiotherapy was terminated due to brain metastasis progression at 18 Gy. Zoledronic acid hydrate was administered in a median of 12 (range, 0-34) times. The median follow-up period was 12 months and 19 months in patients who were still alive. Of 27 patients in the efficacy analysis, the 1-year local skeletal-related event-free rate was 77.6% (80% confidence interval, 66.2-89.0). Common grade 3 toxicities were hypocalcemia (1 [4%]), sGPT level increase (1 [4%]) and sGOT level increase (1 [4%]). There was no grade 4 or 5 toxicity. CONCLUSION: Zoledronic acid hydrate administration and palliative radiotherapy were a well-tolerated and promising treatment reducing skeletal-related events for bone metastases from renal cell carcinoma.

Predicting prognosis of short survival time after palliative whole-brain radiotherapy.

Using existing prognostic models, including the Graded Prognostic Assessment (GPA), it is difficult to identify patients with brain metastases (BMs) who are not likely to survive 2 months after whole-brain radiotherapy (WBRT). The purpose of this study was to identify a subgroup of patients who would not benefit clinically from WBRT. We retrospectively reviewed the records of 111 patients with BMs who were ineligible for surgery or stereotactic irradiation and who underwent WBRT between March 2013 and April 2016. Most patients were scheduled to receive a total dose of 30 Gy in 10 fractions. Non-small cell lung cancer represented the most common primary cancer type (67%), followed by breast cancer (12%). Median survival time (MST) was 109 days (range, 4-883). Univariate analysis identified five factors significantly associated with poor prognosis: performance status (PS) 2-4, perilesional edema, elevated serum lactate dehydrogenase (LDH), using steroids during WBRT, and presence of hepatic metastases. Multivariate analysis confirmed elevated LDH (>300 IU/l) as an independent predictor. MST for LDH >300 IU/l (n = 30) and LDH ≤300 IU/L (n = 87) cohorts were 47 days and 148 days, respectively (P < 0.001). MSTs for GPA 0-1 patients (n = 85) with and without elevated LDH were 37 days and 123 days, respectively (P < 0.001). More than half of the patients with GPA 0-1 and elevated LDH died within two months. Adding elevated LDH to the GPA will permit identification of patients with BMs who have extremely unfavorable prognoses.

Symptomatic Radiation Pneumonitis After Accelerated Partial Breast Irradiation Using Three-dimensional Conformal Radiotherapy.

AIM: To examine the relationship between symptomatic radiation pneumonitis and lung dose-volume parameters for patients receiving accelerated partial breast irradiation (APBI) using three dimensional-conformal radiotherapy (3D-CRT). PATIENTS AND METHODS: The prescribed radiation dose was 30 Gy in 5 fractions over 10 days. Toxicity was graded according to the Common Terminology Criteria for Adverse Events (version 4.0). RESULTS: Fifty-five patients were enrolled from August 2010 to October 2013 and the median follow-up time was 30 months (range=18-46 months). Three patients (5%) developed grade 2 symptomatic radiation pneumonitis after 3D-CRT APBI. Among 16 patients with ILV10Gy (% ipsilateral lung receiving ≥10 Gy) of 10% or higher, three patients (19%) developed symptomatic radiation pneumonitis. This trend was not observed in any of the patients with ILV10Gy less than 10% (p=0.005). CONCLUSION: High ILV10Gy might be associated with symptomatic radiation pneumonitis after 3D-CRT APBI.

Rectal Toxicity After Extremely Hypofractionated Radiotherapy Using a Non-Isocentric Robotic Radiosurgery System for Early Stage Prostate Cancer.

BACKGROUND: The aim of the study was to evaluate toxicity after extremely hypofractionated radiotherapy (EHF-RT) using a non-isocentric robotic radiosurgery system for early stage prostate cancer. METHODS: Eligibility criteria of this feasibility study were 50 - 84 years old, and low-risk to intermediate-risk disease. The prescribed dose to the iso-dose line of 95% of planning target volume was 35 Gy in five fractions over 2 weeks. The primary endpoint was the incidence of ≥ grade 2 acute toxicity which indicated symptoms requiring medications. RESULTS: We enrolled 20 patients from December 2012 to August 2014, and the median follow-up time was 30 months (range: 18 - 36). Sixteen patients had a short overall treatment time (OTT) of EHF-RT (9 - 10 days), and four patients had a long OTT (11 - 12 days) because of national holidays and patient's preference. The incidences of ≥ grade 2 acute toxicity in all sites, that in the rectum, and that in the genitourinary system, were 30%, 20%, and 10%, respectively. No patient developed severe acute toxicity (≥ grade 3). Among 16 patients with a short OTT of EHF-RT, four patients developed grade 2 acute rectal toxicity. Rectum-V28 Gy (rectal volume receiving ≥ 28 Gy) of 3.8 mL or higher had a tendency to increase grade 2 acute rectal toxicity (P = 0.058). One patient developed grade 3 late rectal toxicity and no patient developed severe late genitourinary toxicity. CONCLUSION: The incidences of ≥ grade 2 acute toxicity in all sites and that in the rectum after EHF-RT of 35 Gy in five fractions were 30% and 20%, respectively. High rectum-V28 Gy was associated with grade 2 acute rectal toxicity after EHF-RT for early prostate cancer.

Early onset recall pneumonitis during targeted therapy with sunitinib.

BACKGROUND: Sunitinib interacts with radiation therapy, leading to synergism of the toxicities of these treatments. Radiation recall pneumonitis is a rare but serious complication of targeted therapy with tyrosine kinase inhibitors. CASE PRESENTATION: The case of a patient with metastatic renal cell cancer (RCC) who developed recall pneumonitis on the first cycle of systemic sunitinib treatment is reported here. A 65-year-old man with RCC and bone metastasis underwent radiation therapy on his thoracic vertebrae (Th5-8) with a total dose of 24 Gy. Sunitinib (37.5 mg) was started 14 days after completing the radiation therapy. On the 14th day of sunitinib treatment, the patient developed progressive fever with worsening of dyspnea and general weakness. Treatment with pulse administration of prednisolone 1,000 mg for 3 days was initiated. Thereafter, the symptoms and the radiological findings regarding the interstitial filtration gradually improved over 7 days. CONCLUSION: To our knowledge, this is the first report of early onset recall pneumonitis during sunitinib therapy. At present, how sunitinib interacts with radiation therapy remains unclear. The possibility that tyrosine kinase inhibitor therapy, including with sunitinib, after radiation therapy may lead to adverse effects should be kept in mind.