Dose-response of localized renal cell carcinoma after stereotactic body radiation therapy: A meta-analysis.

BACKGROUND: Stereotactic ablative radiation therapy (SBRT) is an emerging treatment option for primary renal cell carcinoma (RCC), particularly in patients who are unsuitable for surgery. The aim of this review is to assess the effect of increasing the biologically equivalent dose (BED) via various radiation fractionation regimens on clinical outcomes. METHODS: A literature search was conducted in PubMed (Medline), EMBASE, and the Cochrane Library for studies published up to October 2023. Studies reporting on patients with localized RCC receiving SBRT were included to determine its effectiveness on local control, progression-free survival, and overall survival. A random effects model was used to meta-regress clinical outcomes relative to the BED for each study and heterogeneity was assessed by I2. RESULTS: A total of 724 patients with RCC from 22 studies were included, with a mean age of 72.7 years (range: 44.0-81.0). Local control was excellent with an estimate of 99 % (95 %CI: 97-100 %, I2 = 19 %), 98 % (95 %CI: 96-99 %, I2 = 8 %), and 94 % (95 %CI: 90-97 %, I2 = 11 %) at one year, two years, and five years respectively. No definitive association between increasing BED and local control, progression-free survival and overall survival was observed. No publication bias was observed. CONCLUSIONS: A significant dose response relationship between oncological outcomes and was not identified, and excellent local control outcomes were observed at the full range of doses. Until new evidence points otherwise, we support current recommendations against routine dose escalation beyond 25-26 Gy in one fraction or 42-48 Gy in three fractions, and to consider de-escalation or compromising target coverage if required to achieve safe organ at risk doses.

Common Iliac Node-Positive Prostate Cancer Treated With Curative Radiation Therapy: N1 or M1a?

PURPOSE: Common iliac (CI) nodes are staged as (oligo)metastatic M1a for prostate cancer. Whether outcomes of pelvic node-positive (cN1) differ from CI node-positive (CI-M1a) prostate cancer after curative treatment is unclear. The present study compares outcomes in patients treated with radical whole pelvic radiation therapy (RT) and long-term androgen deprivation therapy (ADT). METHODS AND MATERIALS: Patients with a node-positive adenocarcinoma prostate were identified, either CI-M1a or cN1, from a prospectively maintained database. More than 75% of patients were staged with Gallium (Ga) 68 prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) at the time of diagnosis. All patients received long-term ADT and moderately or extremely hypofractionated RT to the prostate and pelvis, including the CI region. At the time of biochemical failure (BCF), restaging was done with Ga68-PSMA-PET/CT to establish the patterns of failure. The CI-M1a cohort was classified as proximal or distal CI nodal location, and studied for outcomes. RESULTS: Of the 130 patients analyzed, 87 had cN1 and 43 had CI-M1a stage disease. The median duration of ADT before RT was 7 months, and total duration was at least 24 months. The majority of patients (65%) had Gleason grade group IV to V, and 75% had ≥T3 disease. After a median follow up of 61 months, BCF in the 2 groups was similar (cN1: n = 21 of 87; 24.1%; CI-M1a: n = 11 of 43; 25.6%; P = .86). At the time of BCF, restaging Ga68-PSMA-PET/CT located distant metastases in 20 of 32 patients (63%; 57% in cN1 and 73% in CI-M1a; P = .47). In addition, the 5-year biochemical failure-free (cN1: 77.4%; CI-M1a: 70.4%; P = .43), distant metastasis-free (cN1: 86.9%; CI-M1a: 79.4%; P = .23), and overall (cN1: 92.6%; CI-M1a 90.1%; P = .80) survival were similar in the 2 groups. Outcomes within CI-M1a were similar for proximal versus distal CI nodal location and 5-year biochemical failure-free survival (73.6% vs 58.6%; P = .81). CONCLUSIONS: Patients with oligometastatic CI-M1a and cN1 prostate cancer showed similar outcomes when treated with curative whole pelvic RT and long-term ADT. The treatment for these oligometastatic patients should be prospectively evaluated.

Serial Bone Density Changes in Women Undergoing Pelvic (Chemo) Radiation: Results From the PARCER Trial.

PURPOSE: Pelvic irradiation leads to substantial dose to the pelvic girdle. However, bone density loss as a function of radiation therapy dose and time has not been investigated. This study was undertaken to evaluate such a dose-response relationship. METHODS AND MATERIALS: Women undergoing pelvic radiation therapy for cervix cancer within a phase 3 trial were included. The study necessitated 2 computed tomography imaging sets acquired at least 12 months apart in patients with no evidence of relapse. All images were transferred to the treatment planning system to determine radiation dose and Hounsfield unit (HU). Across the entire lumbopelvic region (lumbar 1-5 [L1-5] vertebrae, pubic symphysis, femur, acetabulum, greater trochanter, and anterior-superior iliac spine) multiple regions were defined to measure radiation therapy dose and HU. Bone health was categorized as normal if >130 HU, osteopenic at 110 to 130 HU, and osteoporotic <110 HU at baseline and follow-up. Univariate analysis was performed to test the effect of various factors on HU. Further interaction among radiation therapy dose, time, and HU was assessed using a linear mixed model. RESULTS: Overall, 132 of 300 patients were eligible. The median age was 49 (42-56) years. With a prescription dose of 50 Gy, the L1 and L2 vertebrae received a median dose of 1.2 and 4 Gy, respectively, and L3-5 received 10 to 50 Gy. At 24 months, median HU loss at L4-5 was 45 HU (interquartile range, 34-77 HU). Out of the 132 patients, at baseline 96% had normal bone health. However, at the last follow-up, 3% of patients had normal bone health, 12% developed osteopenia, and 85% developed osteoporosis (P < .001). There were no patient- or treatment-related factors predicted for HU loss on univariate analysis. HU loss >60 to 70 was observed at >45 Gy at L5 vertebra (60-70 HU, P < .02) and >15 Gy at L4 vertebra (33 HU; P = .04). CONCLUSIONS: Dose-response relationship is observed between radiation dose and bone mineral density loss. Prospective studies are needed to corroborate these observations and design future interventions.

Improving Outcomes in Chronic Myeloid Leukemia Over Time in the Era of Tyrosine Kinase Inhibitors.

Most patients with chronic myeloid leukemia (CML) receiving treatment with BCR-ABL1 tyrosine kinase inhibitors (TKIs) will achieve favorable responses. Moreover, TKI therapy enables patients to experience long-term survival, with survival rates similar to those of individuals without CML. This enhanced survival has resulted from the availability of multiple BCR-ABL1 TKIs with efficacy, not only in frontline treatment, but, importantly, also in second- and third-line treatment. We have reviewed the changes in long-term outcomes in the era of TKI therapy and how these changes have affected treatment practices. We discuss the development of imatinib, the first BCR-ABL1 TKI, followed by newer TKIs, including nilotinib, dasatinib, bosutinib, and ponatinib. We consider the key studies that led to their development as frontline or later-line therapies, their safety profiles, and their effect on improving patient outcomes. With these improved outcomes, the definition of an optimal response has become more stringent, and treatment monitoring strategies have changed. Second-line patient populations have evolved from those with resistance to, or intolerance of, imatinib to those with moderate responses to, or low-grade adverse events with, imatinib. Although all TKIs are associated with high survival rates, newer TKIs have been associated with lower disease progression rates and, importantly, deeper treatment responses and, potentially, a greater chance of future treatment-free remission. Finally, we consider the unmet needs of patients with CML, including the challenges remaining for those without optimal responses during TKI therapy and new therapies and strategies to identify such patients at diagnosis.