International Journal of Radiation Oncology Biology Physics最新文献

Purpose: Patterns of failure and salvage therapy options for patients with anal squamous cell carcinoma (ASCC) who recur after definitive-intent intensity-modulated radiotherapy (IMRT) with concurrent chemotherapy are not well described.

Patients and methods: We identified consecutive patients with ASCC treated with definitive-intent IMRT between July 2005 and December 2019. Relevant patient and tumor parameters, disease outcomes (locoregional failure (LRF), distant failure (DF), progression-free survival (PFS), colostomy-free survival (CFS), and overall survival (OS)), patterns of failure, and salvage therapies were collected. Failures were analyzed by competing risks methods, whereas survival endpoints were estimated by Kaplan-Meier method. Univariate and multivariate analyses were performed. Landmark analyses were conducted by considering whether patients had LRF within 12 months from completing IMRT.

Results: 375 patients were identified with a median follow-up of 6 years. Stage breakdown was 15%, 23%, and 62% for AJCC stage 0-I, II, and III, respectively. Six-year rates of LRF, DF, PFS, CFS, and OS were 12%, 13%, 73%, 76%, and 80%, respectively. Disease recurred in 74 patients. Among the 45 patients with LRF, 39 (87%) failed within the anorectum, with 25 anal canal, 6 anal margin, and 8 rectal recurrences. Only 4 (9%) patients had isolated nodal failure. Patients experiencing LRF had worse six-year OS than patients without LRF (44% versus 86%, P<0.0001). Approximately 30% of patients who underwent salvage therapy were alive ten years after recurrence, compared with none of the patients who were managed with chemotherapy alone or best supportive care.

Conclusions: This large ASCC cohort managed with definitive-intent IMRT demonstrated excellent rates of locoregional control and survival. Isolated regional nodal failures were uncommon, whereas the majority of LRFs occurred within the anorectum, despite dose escalation by tumor stage. We observed poor outcomes for patients experiencing locoregional disease recurrence, even after aggressive salvage treatment.

Purpose/objective(s): Dose-escalated radiotherapy is increasingly used in the treatment of pancreatic cancer, however approaches to target delineation vary widely. We present the first North American cooperative group consensus contouring atlas for dose-escalated pancreatic cancer radiotherapy.

Materials/methods: An expert international panel comprising 15 radiation oncologists, 2 surgeons and 1 radiologist were recruited. Participants used MimCloud software to contour high and low risk clinical target volumes (CTV) on three pancreatic cancer cases: a borderline resectable head tumor, a locally advanced head tumor, and a medically inoperable tail tumor. Simultaneous truth and performance level estimation (STAPLE) volumes were created, and contours were analyzed using Dice similarity coefficients.

Results: The contoured gross tumor volume (GTV) for the borderline head, locally advanced head, and unresectable tail tumor cases were 156.7, 58.2 and 9.0 cc, respectively, and the Dice similarity coefficients (SD) for the high- and low-risk CTV ranged from 0.45 to 0.82. Consensus volumes were agreed upon by authors. High-risk CTVs comprised the tumor plus abutting vessels. Low-risk CTVs started superiorly at (tail tumors) or 1 cm above (head tumors) the celiac takeoff and extended inferiorly to the superior mesenteric artery (SMA) at the level of the first jejunal takeoff. For head, neck, and proximal body tumors, the lateral volume encompassed the entire pancreas head and 5-10 mm around the celiac, superior mesenteric artery (SMA), superior mesenteric vein (SMV), including the common hepatic artery and medial portal vein, consistent with a "Triangle" volume-based approach. For distal body and tail tumors, the entire tail was included, along with the splenic vessels and the takeoffs of celiac artery.

Conclusion: Through multidisciplinary collaboration, we created consensus contouring guidelines for dose-escalated pancreatic cancer radiotherapy. These volumes include not only gross disease, but also routine elective coverage, and can be used to standardize practice for future trials seeking to define the role of dose escalated radiotherapy in pancreatic cancer.

Purpose: Prior evidence suggests a progression-free survival (PFS) benefit from adding metastasis-directed therapy (MDT) to standard-of-care (SOC) systemic therapy for patients with some oligometastatic solid tumors. Randomized trials testing this hypothesis in breast cancer have yet to be published. We sought to determine whether adding MDT to SOC systemic therapy improves PFS in oligometastatic breast cancer.

Methods: EXTEND is a multicenter phase II randomized basket trial testing the addition of MDT to SOC systemic therapy in patients with ≤5 metastases (NCT03599765). Patients were randomized 1:1 to MDT (definitive local treatment to all sites of disease, plus SOC systemic therapy) or to SOC systemic therapy only. Primary endpoint was PFS, and secondary endpoints included overall survival (OS), time to subsequent line of systemic therapy, and time to the appearance of new metastases. Exploratory analyses included quality of life (QOL) and systemic immune response measures.

Results: From September 2018 through July 2022, 22 and 21 patients were randomized to the MDT and no-MDT arms, respectively. At a median follow-up of 24.8 months, PFS was not improved with the addition of MDT to SOC systemic therapy (median PFS 15.6 months MDT vs 24.9 months no-MDT [hazard ratio {HR} 0.91; 95% CI 0.34-2.48, p=0.86]). Similarly, MDT did not improve OS, time to subsequent line of systemic therapy, or time to the appearance of new metastases (all p>0.05). No significant differences were found in QOL measures, systemic T-cell activation, or T-cell stimulatory cytokine concentration.

Conclusion: Among patients with oligometastatic breast cancer, the addition of MDT to SOC systemic therapy did not improve PFS. These findings suggest that MDT may have no systemic benefit in otherwise unselected oligometastatic breast cancer patients, although this trial was limited by a heterogenous and small sample size and overperformance of both treatment arms.

Radiotherapy, including conventionally fractionated external beam radiation therapy, stereotactic radiosurgery, and fractionated stereotactic radiotherapy, is a cornerstone in the interdisciplinary management of meningiomas. Recent advances in radiation oncology and also in other fields, such as neuropathology and imaging, have various implications for meningioma radiotherapy. This review aims to summarize current and anticipated developments, as well as active clinical trials related to the use of radiotherapy for meningiomas. In imaging, positron emission tomography has proven valuable for assessing the spatial extension of meningiomas and may enhance target delineation, treatment response monitoring, and recurrence assessment after radiotherapy. Particle therapy, including protons and carbon ions, as well as stereotactic radiosurgery and radiotherapy, allow for conformal treatments that permit dose escalation in selected patients with high-grade meningiomas. Additionally, emerging integrated molecular and genetic classifications offer superior risk stratification and may refine patient selection for radiotherapy. However, there is a paucity of active meningioma trials directly investigating or refining the use of radiotherapy. In summary, significant advances in functional imaging, molecular and genetic diagnostics, and radiation treatment techniques hold the potential to improve patient outcomes and to avoid over- and undertreatment. Collaborative efforts and further clinical trials are essential to optimize meningioma radiotherapy.

Purpose: Palliative radiation therapy (RT) is effective for multiple myeloma (MM) but may cause cytopenia. Bone marrow volume receiving 10 Gy (BMV10Gy) has been associated with hematologic toxicity (HT) in cervical cancer, but no studies have investigated this in MM. We hypothesized that absolute BMV10Gy is associated with acute HT in MM patients receiving palliative RT.

Materials and methods: This single institution retrospective analysis evaluated 125 MM patients who received palliative RT between 2007 and 2023 and had ≥2 weeks of follow-up laboratory data. Laboratory values were recorded pre-RT, post-RT, and at nadir within 90 days of completing RT. Clinical HT was defined as new transfusion/growth factor, admission for HT, and/or systemic therapy pause/discontinuation. BM was defined as a bone volume within the RT field. BMV5-40Gy (cubic centimeter [cm³]) was recorded for each treatment. Logistic regressions were performed with clinical HT as the primary endpoint.

Results: Around 105 (84%) patients received concurrent systemic therapy. Median BMV10Gy was 266 cm³ (IQR, 157-501 cm³). Median RT equivalent dose in 2 Gy fractions was 26 Gy (IQR, 23-33 Gy). On univariable analysis, BMV5Gy, BMV10Gy, and BMV15Gy were significantly associated with clinical HT (P = .014, P = .018, P = .050, respectively), while RT equivalent dose in 2 Gy fractions dose was not (P = .997). On multivariable analysis, BMV10Gy was significantly associated with clinical HT (P = .049) after adjusting for dose, number of lesions treated, lesion location (spine, pelvis, limb, and soft tissue), and systemic therapy class. Disease course (number of prior systemic therapies) was significantly associated with clinical HT on univariable and multivariable analysis, with late relapsed/refractory patients (≥3 prior systemic therapies) having 9.6 higher odds of clinical HT compared to newly diagnosed patients (P < .001).

Conclusions: To our knowledge, this is the first study to associate the volume of irradiated BM with acute HT in MM. In addition to BMV5-15Gy, number of prior relapses and systemic therapy lines were significantly associated with HT. Disease history should be evaluated, and RT field volumes were minimized for patients with poor bone marrow reserve (eg, late relapsed/refractory disease).

Purpose: The addition of immunotherapy (IO) after concurrent chemoradiation therapy (CCRT) for unresectable non-small cell lung cancer (NSCLC) has become common practice in eligible patients. Approaches to further improve outcomes and reduce treatment-related toxicity for these patients are needed. This study evaluates the risk of radiation pneumonitis after CCRT and its correlation with the radiation dose distribution, IO regimen (nivolumab vs nivolumab plus ipilimumab), and patient demographics across BTCRC-LUN16-081.

Methods and materials: Patients with unresectable stage III NSCLC after completion of CCRT were enrolled in BTCRC-LUN16-081, a randomized phase 2 trial to assess the efficacy and tolerability of consolidative nivolumab versus nivolumab plus ipilimumab for 6 months. Radiation dose parameters, patient demographics, and toxicity events were evaluated among treatment arms for risk and severity of pneumonitis.

Results: One hundred-five patients were enrolled into 2 treatment arms; 54 patients received nivolumab alone, and 51 patients received nivolumab plus ipilimumab. Of these, 104 patients had dose-volume histogram information available. Within this cohort, 65 patients (62.5%) had stage IIIA, and 39 patients (37.5%) had stage IIIB NSCLC disease, per the American Journal Committee on Cancer, seventh edition. During the study, 29 patients (27.9%) were diagnosed with grade 2 or greater pneumonitis. Using logistic regression and evaluating different cutoffs for percentage of normal lung volume receiving at least 20 gy (V20), patients with V20 > 23% demonstrated significantly higher grade 2 or greater pneumonitis rates (37.1% vs 16.2%, P = .031). No significant difference in rates of pneumonitis between arms was identified. Traditional lung dose-volume histogram cutoffs (percentage of normal lung volume receiving at least 5 gy (V5) > 65%, V20 > 35%, and mean > 20 Gy) were not associated with pneumonitis.

Conclusions: In patients receiving nivolumab or nivolumab plus ipilimumab after definitive CCRT, lung V20 > 23% was associated with an increased risk of grade 2 or greater pneumonitis. Radiation dose constraints for lungs in patients receiving consolidative IO after CCRT should continue to be evaluated and optimized when feasible.

Purpose: Long treatment sessions are a limitation within MRIgART. This work aims for significantly enhancing the delivery efficiency on the MR-linac by introducing dedicated optimization and delivery techniques for VMAT. VMAT plan and delivery quality during MRIgART is compared to step-and-shoot IMRT for prostate SBRT.

Methods and materials: Ten prostate patients previously treated on a 1.5T MR-linac were retrospectively replanned to 36.25 Gy in five fractions using step-and-shoot IMRT and the clinical Hyperion optimizer within Monaco (Hyp-IMRT), the same optimizer with a VMAT technique (Hyp-VMAT), and a research-based optimizer with VMAT (OFL+PGD-VMAT). The plans were then adapted onto each daily MRI dataset using two different optimization strategies to evaluate the ATP workflow: "optimize weights" (IMRT-Weights and VMAT-Weights) and "optimize shapes" (IMRT-Shapes and VMAT-Shapes). Treatment efficiency was evaluated by measuring optimization time, delivery time, and total time (optimization + delivery). Plan quality was assessed by evaluating OAR sparing. Ten patient plans were measured using a modified linac control system to assess delivery accuracy via a gamma analysis (2%/2mm). Delivery efficiency was calculated as average dose rate divided by maximum dose rate.

Results: For Hyp-VMAT and OFL+PGD-VMAT the total time was reduced by 124 ± 140 seconds (p = .020) and 459 ± 110 seconds (p < 0.001), respectively as compared to the clinical Hyp-IMRT group. Speed enhancements were also measured for ATP with reductions in total time of 404 ± 55 (p<0.001) for VMAT-Weights as compared to the clinical IMRT-Shapes group. Bladder and rectum DVH points were within 1.3 % or 0.8 cc for each group. All VMAT plans had gamma passing rates greater than 96 %. The delivery efficiency of VMAT plans was 89.7 ± 2.7 % compared to 50.0 ± 2.2 % for clinical IMRT.

Conclusions: Incorporating VMAT into MRIgART will significantly reduce treatment session times while maintaining equivalent plan quality.

Purpose: This study aimed to assess the impact of tissue oxygen levels on transient oxygen consumption induced by ultra-high dose rate (UHDR) electron radiation in murine flank and to examine the effect of dose rate variations on this relationship.

Methods and materials: Real-time oximetry using the phosphorescence quenching method and Oxyphor PdG4 molecular probe was employed. Continuous measurements were taken during radiation delivery on a UHDR-capable Mobetron linear accelerator. Oxyphor PdG4 was administered into the subcutaneous tissue of the flank skin 1 hour before irradiation. Skin oxygen tension (pO₂) was manipulated by adjusting oxygen content in the inhaled gas mixture and/or by vasculature compression. A skin surface radiation dose of 19.8 ± 0.3 Gy was verified using a calibrated semiconductor diode dosimeter. Dose rate was varied across the UHDR range by changing linear accelerator cone length and pulse repetition frequency.

Results: The decrease in pO₂ per unit dose during radiation delivery, termed oxygen consumption g-value (g_O2, mmHg/Gy), was significantly influenced by tissue oxygen levels in the range 0 to 65 mmHg under UHDR conditions. Within the 0 to 20 mmHg range, g_O2 exhibited a sharp increase with rising baseline pO₂, plateauing at 0.26 mmHg/Gy. Dose rate variations (mean values, 25-1170 Gy/s; per pulse doses of 2.5-9.8 Gy) were explored by varying both cone length and pulse repetition frequency (10-120 Hz) with no significant changes in g_O2. Conventional dose rate irradiation resulted in no discernible changes in pO₂.

Conclusions: The results show significant differences in the radiation-chemical effects of UHDR radiation between hypoxic and well-oxygenated tissues. Similar trends between earlier published in vitro and in vivo experiments presented herein suggest the chemical mechanisms driving the dependencies of g_O2 on pO₂ are similar, potentially underpinning the FLASH effect. Importantly, significant variations in baseline pO₂ were observed in animals kept under identical conditions, underscoring the necessity to control and monitor tissue oxygen levels for preclinical investigations and future clinical applications of FLASH radiation therapy.