International Journal of Radiation Oncology Biology Physics最新文献

Purpose: To establish an ultra-high dose rate (UHDR) radiation system using a synchrotron proton beam accelerator and to compare the effects by irradiation positions on cultured cells and chick embryos.

Methods and materials: Protons for UHDR were obtained by applying high-frequency power at much higher levels than usual to extract all protons within approximately 50 ms. Subsequently, monitoring with a Faraday cup was performed immediately after synchrotron extraction and the waveform was adjusted accordingly. Four cultured tumor lines, two normal cell lines, and chick embryos were used. Ultra-high dose-rate radiation (UHDR-RT) at 6-18 Gy (200-300 Gy/s, single exposure) and conventional dose-rate radiation (Conv-RT) at 6-18 Gy (3 Gy/s) were administered to the 1-cm spread-out Bragg peak (SOBP) and the plateau region preceding SOBP. Following irradiation, disparities in cell growth rates and cell cycle progression were assessed, and cell survival was evaluated via colony assay. Chick embryos were also examined for survival.

Results: UHDR-RT was achieved at a range of 40 to 800 Gy/s, encompassing both plateau and peak phases. In vitro studies demonstrated similar cell-killing effects between UHDR-RT and Conv-RT in cancer cells. Significant apoptotic effects and G2 arrest were observed during the cell cycle under peak UHDR-RT conditions. The FLASH effect was not observed in normal single cells under normal atmospheric conditions. Stronger cell-killing effects were noted in V79 spheroids exposed to peak UHDR-RT than peak Conv-RT. Moreover, in chick embryos, an increase in survival rate, indicative of the FLASH effect, was observed.

Conclusions: The FLASH effect was also achieved with UHDR-RT using a synchrotron proton beam accelerator in chick embryos. The cell-killing effects in cancer cells were higher with peak UHDR-RT which may be due to the higher linear energy transfer at the SOBP.

Background: Symptomatic locoregionally advanced breast cancer (SLABC) can cause troublesome pain or wound complications that negatively impact quality of life. Although palliative radiotherapy (RT) can minimize tumor-related symptoms, how best to tailor RT to achieve the most meaningful and durable response is not well defined.

Methods: This is a single-institution, multi-site retrospective review of patients with SLABC treated between 2016 and 2023 with palliative RT to symptomatic disease in the breast, chest wall, and/or regional lymph node basins. Overall survival (OS), locoregional control (LC), clinical and radiographic treatment response, overall pain scores, and treatment-related toxicities were analyzed.

Results: 164 patients with a median age of 57 years were analyzed with a median follow-up time of 4.97 months. 86% had distant metastases. The most common presenting symptom was pain (87%), followed by ulcerating or fungating lesion (76%) and discharge (45%). The median cumulative biologically effective dose to the gross tumor volume (BED_GTV) was 69 Gy. The 1-year OS and LC rates were 37% and 63%, respectively. Eighty-one percent experienced improvement in symptoms within 3 months after RT, the odds of which increased per Gy BED_GTV (OR 1.029, p=0.003). Acute toxicities were associated with number of fractions and BED_GTV (both p<.001), but not with concurrent systemic therapy nor reirradiation (both p>.05). Trends in pain scores showed a significant change in pain trajectory that was sustained during the first year after RT. OS and LC were not different among patients who received 1 vs 2-10 vs >10 fractions, and between ≤70 vs >70 Gy BED_GTV.

Conclusion: In this large series of patients with SLABC, palliative RT was effective at relieving locoregional symptoms with acceptable toxicity, with the likelihood of symptom improvement associated with radiation dose. Survival of these patients remains poor, highlighting the importance of palliative care strategies that minimize overall symptom burden while maximizing quality of life.

Purpose: This study aimed to analyze the incidence of cancer therapy-related cardiovascular toxicity (CTRCVT) and identify the radiation dosimetric and clinical risk factors for these events in patients with HER2-positive breast cancer.

Materials and methods: Data from 1,378 patients who were treated with curative surgery and adjuvant trastuzumab for breast cancer were retrospectively analyzed. A total of 959 patients underwent postoperative radiation therapy (RT), while 419 patients were managed without RT (no-RT). CTRCVT were categorized according to the time of occurrence in relation to trastuzumab as follows: during trastuzumab cycles (CTRCVT-during T) or after completing trastuzumab (CTRCVT-after T). The cardiac radiation dose was extracted from the RT plan of each individual patient. The incidence of and contributing factors for CTRCVT-during T and -after T were evaluated.

Results: After a median follow-up of 95.8 months (range, 4.3-181.1 months), 69 patients (5.0%) had experienced CTRCVT. CTRCVT-during T was detected in 41 patients (3.0%), and the 8-year rate of CTRCVT-after T was 2.2%. Of the patients developing CTRCVT-during T, 27 (2.0%) discontinued trastuzumab. The cardiac radiation doses were significantly associated with the risk of both CTRCVT-during T (odds ratio, 1.087; P = 0.001) and -after T (hazard ratio, 1.177; P <0.001). The 8-year rates of CTRCVT-after T were not significantly different between the no-RT and RT groups (2.0% vs. 2.4%, P = 0.956). However, the rate was significantly higher in patients with heart V_25Gy ≥3% compared to those with heart V_25Gy <3% (5.7% vs. 1.5%, P = 0.019). Patients who received <17 cycles of trastuzumab had worse oncological outcomes than those who received ≥17 cycles.

Conclusions: Both CTRCVT-during T and -after T were associated with the cardiac radiation dose. Therefore, evaluation of the cardiac radiation dose is necessary to prevent early termination of trastuzumab treatment, which could lead to worse outcomes.

Purpose: Local and distant progression remain common following resection of resectable pancreatic ductal adenocarcinoma (PDAC) despite adjuvant multiagent chemotherapy. We report a prospective institutional phase I trial incorporating adjuvant GVAX vaccine, low-dose cyclophosphamide (Cy) and SBRT followed by FOLFIRINOX (FFX) among patients who underwent resection of high-risk PDAC.

Patients and methods: The study design was a modified 3+3. Cohort 1 received 5-fraction SBRT to 33 Gy to the tumor bed and 25 Gy to elective nodes followed by 6 cycles of full dose FFX. After toxicity review, cohort 2 had SBRT and were switched to modified FFX (mFFX). Cohort 3 had 1 cycle of Cy/GVAX followed by SBRT, mFFX, and 4 cycles of maintenance Cy/GVAX with 6-month Cy/GVAX boosts until progression.

Results: 19 patients were enrolled with a median follow-up of 36.2 months. To be eligible, patients were required to have close/positive margins (within ≤1 mm) (71%) and/or lymph node metastasis (79%). Overall, 63% of patients had both. In cohort 1, 67% of patients received 6 cycles of FFX; in cohort 2, 75% received 6 cycles of modified FFX. In cohort 3, 12 patients received the first dose of Cy/GVAX and SBRT with 10 individuals (83%) receiving 6 cycles of mFFX. Cohort 3 had acceptable levels of grade ≥3 thrombocytopenia, neutropenia, and diarrhea after two cycles of mFFX. Median OS/DFS for the overall cohort and cohort 3 was 36.2/18.2 months and 61.3/24.1 months, respectively. 1-year and 2-year OS for cohort 3 was 83%/75%, respectively. At last follow-up (median= x), 5 patients were alive (42%) in cohort 3.

Conclusion: This is the first prospective trial to evaluate adjuvant GVAX, Cy, SBRT, and mFFX in resected PDAC patients with high-risk features. This combination regimen was well tolerated with limited toxicity and promising survival outcomes, warranting future studies to validate this regimen in the adjuvant setting.

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.