Search Results (96)

Background/Objectives: Lung cancer is the leading cause of cancer-related mortality worldwide. Accurate radiotherapy (RT) planning alongside chemotherapy and immunotherapy is critical for improving treatment outcomes for inoperable non-metastatic cases. Conventional computed tomography (CT)-based planning may be inadequate for accurately identifying tumor margins and the location of nodal disease. We investigated whether ¹⁸F-labeled fluorodeoxyglucose positron emission tomography (¹⁸F-FDG PET-CT) imaging can assist in target volume delineation for primary, nodal, and metastatic disease in the RT planning and overall therapeutic planning of patients. Methods: In this single-center, prospective study, we recruited 34 patients with histologically confirmed locally advanced non-small-cell lung carcinoma (NSCLC). All patients underwent ¹⁸F-FDG PET-CT-based RT simulation. Two sequential RT plans were created by the same radiation oncologist: one based on CT alone and the other PET-CT. Planning target volumes (PTVs) and PET-CT-guided adjustments were analyzed to assess their impact. Standardized protocols for immobilization, imaging, target delineation, and dose prescription were applied. Results: A total of 34 patients (31 males and 3 females) were recruited in the study. ¹⁸F-FDG PET-CT detected distant metastases in 7/34 (20.6%) patients, altering the overall therapeutic plan in 4/34 (11.8%) and allowing radical RT in 3 of them who had oligometastatic disease (8.8%). It modified RT planning in 26/34 (76.5%) patients and clarified malignancy in atelectatic areas. Nodal involvement was identified in 3/34 patients (8.8%) and excluded in 3/34 cases, avoiding unnecessary nodal irradiation. Additional involved nodes were revealed in 12/34 (35.3%) patients, requiring dose escalation. Overall, changes to the tumor PTV were made in 23/30 (76.6%) and to the nodal PTV in 19/30 (63.3%) cases (p < 0.0001). Primary tumor and nodal PTVs increased in 20/34 (66.7%) and 13/34 (43.3%), respectively. Conclusions: ¹⁸F-FDG PET-CT significantly improves RT planning by more precisely defining tumor and nodal volumes, identifying undetected lesions, and guiding dose adaptation. Larger long-term studies are required to confirm potential locoregional control and survival improvements. Full article

In this work, the effects of heavy ion strike position, incident angle, linear energy transfer (LET) value, ambient temperature, bias conditions, and the synergistic effects of total dose irradiation on the single-event transient (SET) in silicon-germanium heterojunction bipolar transistors on silicon-on-insulator (SiGe-on-SOI HBTs) were investigated using TCAD simulations. It was demonstrated that, compared to the bulk SiGe HBT, the SiGe-on-SOI HBT exhibits lower transient current and less charge collection, indicating better resistance to SET. The SET response is more pronounced when heavy ions strike vertically from the emitter and base regions. Transient current and collected charge escalate with increasing incident angle, demonstrating a strong linear correlation with LET values. As the temperature decreases, the peak transient current increases, while the pulse duration decreases and the total collected charge diminishes. After total dose irradiation, the peak transient current in the SiGe-on-SOI HBT decreases, whereas the damage was more severe in the absence of irradiation. Under collector positive bias and positive bias, significant SET responses were observed, while cutoff bias and substrate bias exhibited better resistance to SET damage. These findings provide critical insights into radiation-hardened design strategies for the SiGe-on-SOI HBT. Full article

Introduction: Long-term analysis of PACIFIC revealed the clinical benefit of chemoradiotherapy combined with Durvalumab for unresectable non-small-cell lung cancer (NSCLC) stage III. ALLSTAR is a prospective registry aimed at validating the PACIFIC regimen in daily practice in Austria. Patients and Methods: Patients were eligible if they had pathologically confirmed unresectable NSCLC III with a curative treatment option. The endpoints for this analysis were overall survival (OS), updated local control (LC), and progression-free survival (PFS). Results: The 2- and 3-year LC rates in patients who received total radiation doses > 66 Gy were 80% and 75%, respectively, which were superior to the standard treatment (65% and 54%; p-value 0.085). This benefit was even more pronounced in Durvalumab patients with 2- and 3-year LC rates of 82% and 79% with >66 Gy (p-value 0.068). The 2- and 3-year OS with Durvalumab was 71% and 63%, respectively, compared to 58% and 44% without Durvalumab (HR 0.552; 95%-CI 0.347–0.881; p-value 0.011). Patients who were treated with Durvalumab also had a significantly longer 2- and 3-year PFS (56% and 48%) than those without (35% and 20%; HR 0.469; 95%-CI 0.312–0.707; p-value < 0.001). Pulmonary side effects were observed in 66/188 (35%) patients, with one case of grades 4 and 5 each. Oesophageal toxicity grade 1–3 occurred in 93/188 (49%) cases. Conclusion: The updated ALLSTAR analysis demonstrated sustained benefit of Durvalumab for OS and PFS, as well as a possible long-term benefit of radiation dose escalation > 66 Gy on LC. Full article

Background/Objectives: Current evidence suggests that patients with unresectable non-small cell lung cancer (NSCLC) whose tumours harbour driver mutations do not benefit from immune checkpoint inhibition. Kirsten rat sarcoma virus mutations (KRASmts), however, seem to be the exceptions to the rule. To this end, we compared KRASmt patients who were treated with immunotherapy to those without. Methods: ALLSTAR is a nationwide registry for patients with histologically verified non-operable NSCLC aged 18 or older having a curative treatment option. This report presents a subcohort of KRASmt patients who were recruited between 2020/03 and 2023/04. The diagnostic work-up included ¹⁸F-FDG-PET-CT scan and contrast-enhanced cranial CT or—preferably—MRI. Patients were treated with chemoradiotherapy (CRT) either followed by immune checkpoint inhibition (ICI) or not. Results: Thirty-two KRASmt patients with a median follow-up of 25.9 months were included in this analysis. After CRT, 27/32 (84%) patients received ICI. The 2-year overall survival rate in KRASmt patients who received immunotherapy was significantly better compared to those without ICI (N = 32; 84% versus 20%; p < 0.001). Likewise, the 2-year progression-free-survival with immunotherapy was also significantly better than in those without ICI (N = 32; 75% versus 20%; p < 0.001). Of the 12/32 patients (38%) who had received radiation doses > 66 Gy, none had a locoregional relapse, whereas in the other 20 patients, 5 (25%) events occurred (p-value = 0.116). Conclusions: Since KRASmt patients could benefit from ICI treatment, immunotherapy should be offered to these patients, similar to those without actionable genetic drivers. Additionally, radiation dose escalation > 66 Gy may also improve locoregional control in this subset of patients. Full article

Unresectable stage III non-small-cell lung cancer (NSCLC) remains a clinical challenge, due to the need for optimal local and systemic control. The management of unresectable Stage III NSCLC has evolved with advancements in radiation therapy (RT), systemic therapies, and immunotherapy. For patients with locally advanced NSCLC who are not surgical candidates, concurrent chemoradiotherapy (CRT) has modest survival outcomes, due to both local progression and distant metastasis. Efforts to enhance outcomes have led to dose-escalation trials, advances in modern RT techniques such as intensity-modulated RT (IMRT) and proton beam therapy (PBT), and the integration of adaptive RT to optimize target coverage while sparing organs at risk. Concurrent and consolidative immunotherapy, particularly with PD-L1 inhibitors, has shown promise, as evidenced by the PACIFIC trial, which demonstrated improved progression-free survival (PFS) and overall survival (OS) with durvalumab following CRT. Ongoing trials are now investigating novel immunotherapy combinations and targeted therapies in this setting, including dual checkpoint inhibition, DNA repair inhibitors, and molecularly targeted agents like osimertinib for EGFR-mutated NSCLC. Emerging biomarkers, such as circulating tumor DNA and radiomics, offer potential for personalizing treatment and predicting outcomes. Additionally, PBT and MR-guided adaptive RT have shown the potential to reduce toxicities while maintaining efficacy. Integrating these novel approaches may offer opportunities for optimizing treatment responses and minimizing adverse effects in this challenging patient population. Further investigation into patient stratification, biomarker-driven therapy, and refined therapeutic combinations is essential to improve long-term outcomes in unresectable Stage III NSCLC. This narrative review explores the current management strategies for unresectable Stage III NSCLC, from a radiation oncology perspective. Full article

Objectives: To analyze the results of interstitial (IRT) high-dose-rate (HDR) brachytherapy (BT) in the primary treatment of patients with unresectable superior sulcus tumors (SST) combined with external beam radiotherapy (EBRT). Methods: Between 2013 and 2023, seven patients with unresectable SST were treated with combined BT and EBRT with or without concomitant chemotherapy. The patients’ median age was 64 years (range, 49–79 years) and median tumor volume was 146.8 cm³ (range, 29.3–242.3 cm³). A median BT dose of 8 Gray (Gy) (range, 5–10 Gy) was prescribed and delivered in a single fraction. A median EBRT dose of 54 Gy (range, 30–59 Gy) was prescribed and administered normofractionated (single dose: 1.8 Gy). Results: We report the results of seven patients with SST treated with combined BT and EBRT and followed for a median of 38 months. The overall clinical response rate was 83.33% with five out of six patients achieving local control, while one out of six (16.66%) showed local and general progression. No deaths were attributed to the treatment itself; rather, one patient died during the course of therapy as a result of systemic progression. The most common radiation-related adverse events were grade I–II fatigue and mild paresthesia. No severe toxicity (CTCAE ≥ III°) was observed with interstitial high-dose-rate (HDR) BT combined with EBRT. Conclusions: For patients with unresectable superior sulcus tumors, interstitial HDR BT in combination with EBRT is a feasible treatment option that offers the potential for local control and long-term survival. The findings of this study should be validated in a larger patient cohort. Full article

While the cure rate of cancer in children has markedly improved in the last few decades, late effects continue to be a problem in survivors. Radiotherapy, which is a major component of treatment in many cancers, is one of the major agents responsible for late toxicity. In the past decade, radiotherapy has been omitted in patients achieving excellent response to chemotherapy, such as in Hodgkin lymphoma and some Wilms tumors with lung metastases. Likewise, response to chemotherapy has been used to determine whether lower doses of radiation can be delivered in intracranial germinoma and pediatric nasopharyngeal carcinoma. Molecular subtyping in medulloblastoma is currently being employed, and in WNT-pathway M0 tumors, the reduction in radiotherapy dose to the craniospinal axis and tumor bed is currently being investigated. Finally, dose escalation was recently evaluated in patients with rhabdomyosarcoma > 5 cm who do not achieve a complete response to initial 9 weeks of chemotherapy as well as for unresectable Ewing sarcoma patients to improve local control. Full article

Introduction: This systematic review evaluated whether curative intent hypofractionated radiation therapy improved survival (primary endpoint) as compared to standard conventionally fractionated radiation therapy for stage III non-small cell lung cancer (NSCLC) patients. Toxicity was also examined as a secondary endpoint. Methods: Electronic bibliographic databases were searched from 1 January 1990 to 31 March 2024. Phase II and phase III trials were included to assess survival (primary outcome) and toxicity (secondary outcome) for newly diagnosed stage III NSCLC patients. Results: Eight phase II trials (n = 349 participants), 3 randomized phase II trials (n = 382 participants), and 5 randomized phase III trials (n = 811 participants), for a total of 1542 participants, were identified. The published trials were heterogeneous, with a wide variety of dose prescriptions. A wide range of survivals (median survival 13.6 months–42.5 months) and toxicities such as grade 3 or higher esophagitis (0–42%) and grade 3 or higher pneumonitis (0–18%) were reported. Conclusions: There is no level 1 evidence to date that suggests that any hypofractionated regimen (dose escalated or not) improves survival as compared to conventionally fractionated radiation. The published phase III trials have been powered for superiority (not equivalence) for the hypofractionated arm. Toxicity with hypofractionated regimens may be similar to conventionally fractionated regimens when normal tissue radiotherapy constraints are kept within tolerance limits. It is unclear how the use of systemic therapy may negatively affect radiation toxicity with hypofractionated radiation therapy. Full article

Intensity-modulated radiation therapy (IMRT) improves disease control and reduces treatment-related toxicity in patients with localized nasopharyngeal carcinoma (NPC). However, due to the proximity of the auditory apparatus to the treatment volume and the frequent incorporation of cisplatin-based chemotherapy, treatment-related sensorineural hearing loss (SNHL) remains a common debilitating complication among NPC survivors. The reported crude incidence of SNHL following IMRT for NPC varies widely at 1–46% due to differences in auditory assessment methods and thresholds, follow-up durations, chemotherapy usage, and patient compositions. International guidelines and radiation dosimetric studies have recommended constraining the cochlear mean dose to less than 44–50 Gy, but the risk of SNHL remains high despite adherence to these constraints. Potential strategies to improve hearing outcomes in NPC survivors include cautious de-escalation of radiotherapy dose and volume, individualization of cochlear constraints, optimization of radiotherapy planning techniques, and the use of substitutes or alternative schedules for cisplatin-based chemotherapy. The addition of immune checkpoint inhibitors to chemoradiotherapy did not impact ototoxicity. Prospective studies that employ both objective and patient-reported auditory outcomes are warranted to test the long-term benefits of various approaches. This article aims to provide a comprehensive review of the incidence and radiation dose–toxicity relationship of SNHL in NPC survivors and to summarize potential strategies to optimize hearing outcomes in relation to nuances in radiotherapy planning and the selection of systemic therapy. Full article

Background and Objectives: The recently published Spine Stereotactic Radiosurgery (SSRS) ESTRO guidelines advise against treating spinal metastatic disease with a single dose equal to or smaller than 18 Gy, prioritizing local control over the potential for complications. This study aims to assess the necessity and validity of these higher dose recommendations by evaluating the outcomes and experiences with lower radiation doses. Materials and Methods: A retrospective evaluation of SSRS patients treated at a single institute was conducted. The outcomes and complications of this cohort were compared to the current literature and the data supporting the new ESTRO guidelines. Results: A total of 149 treatment sessions involving 242 spinal levels were evaluated. The overall local control rate was 91.2%. The mean radiation dose for the local control group compared to the local failure group was similar (17.5 vs. 17.6 Gy, not significant). The overall complication rate was 6%. These results are consistent with previous publications evaluating SSRS for metastatic spinal disease. Conclusions: SSRS dose escalation may increase local control efficacy but comes with a higher risk of complications. The evidence supporting the strong recommendations in the recent ESTRO guidelines is not robust enough to justify a universal application. Given the palliative nature of treatment for metastatic patients, dose determination should be individualized based on patient conditions and preferences, with a detailed discussion about the risk–benefit ratio of increased doses and the level of evidence supporting these recommendations. Full article

Background and Objectives: Despite rapid advances in targeted therapies for renal cell carcinoma (RCC), bone metastases remain a major problem that significantly increases morbidity and reduces patients’ quality of life. Conventional fractionated radiotherapy (CF-RT) is known to be an important local treatment option for bone metastases; however, bone metastases from RCC have traditionally been considered resistant to CF-RT. We aimed to investigate the effectiveness of CF-RT for symptomatic bone metastasis from RCC and identify the predictive factors associated with treatment outcomes in the targeted therapy era. Materials and Methods: Between January 2011 and December 2023, a total of 73 lesions in 50 patients treated with a palliative course of CF-RT for symptomatic bone metastasis from RCC were evaluated, and 62 lesions in 41 patients were included in this study. Forty-five lesions (72.6%) were treated using targeted therapy during CF-RT. The most common radiation dose fractionations were 30 gray (Gy) in 10 fractions (50%) and 39 Gy in 13 fractions (16.1%). Results: Pain relief was experienced in 51 of 62 lesions (82.3%), and the 12-month local control (LC) rate was 61.2%. Notably, 72.6% of the treatment course in this study was combined with targeted therapy. The 12-month LC rate was 74.8% in patients who received targeted therapy and only 10.9% in patients without targeted therapy (p < 0.001). Favorable Eastern Cooperative Oncology Group performance status (p = 0.026) and pain response (p < 0.001) were independent predictors of improved LC. Radiation dose escalation improved the LC in radiosensitive patients. A consistent treatment response was confirmed in patients with multiple treatment courses. Conclusions: CF-RT enhances pain relief and LC when combined with targeted therapy. Patients who responded well to initial treatment generally showed consistent responses to subsequent CF-RT for additional painful bone lesions. CF-RT could therefore be an excellent complementary local treatment modality for targeted therapy. Full article

Objectives: We investigated spatial patterns between primary and recurrent tumor sites and assessed long-term toxicity after dose escalation stereotactic body radiation therapy (SBRT) to the dominant intra-prostatic nodule (DIN). Materials and methods: In 33 patients with intermediate–high-risk prostate cancer (PCa), doses up to 50 Gy were administered to the DIN. Recurrence sites were determined and compared to the original tumor development sites through multiparametric MRI and ⁶⁸Ga-labeled prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (⁶⁸Ga-PSMA-PET/CT) images. Overlap rates, categorized as 75% or higher for full overlap, and 25–74% for partial overlap, were assessed. Long-term toxicity is reported. Results: All patients completed treatment, with only one receiving concomitant androgen deprivation therapy (ADT). Recurrences were diagnosed after a median of 33 months (range: 17–76 months), affecting 13 out of 33 patients (39.4%). Intra-prostatic recurrences occurred in 7 patients (21%), with ≥75% overlap in two, a partial overlap in another two, and no overlap in the remaining three patients. Notably, five patients with intra-prostatic recurrences had synchronous bone and/or lymph node metastases, while six patients had isolated bone or lymph node metastasis without intra-prostatic recurrences. Extended follow-up revealed late grade ≥ 2 GU and GI toxicity in 18% (n = 6) and 6% (n = 2) of the patients. Conclusions: Among patients with intermediate–high-risk PCa undergoing focal dose-escalated SBRT without ADT, DIN recurrences were infrequent. When present, these recurrences were typically located at the original site or adjacent to the initial tumor. Conversely, relapses beyond the DIN and in extra-prostatic (metastatic) sites were prevalent, underscoring the significance of systemic ADT in managing this patient population. Advances in knowledge: Focal dose-escalated prostate SBRT prevented recurrences in the dominant nodule; however, extra-prostatic recurrence sites were frequent. Full article

Radiotherapy is an essential component of the treatment regimens for many cancer patients. Despite recent technological advancements to improve dose delivery techniques, the dose escalation required to enhance tumor control is limited due to the inevitable toxicity to the surrounding healthy tissue. Therefore, the local enhancement of dosing in tumor sites can provide the necessary means to improve the treatment modality. In recent years, the emergence of nanotechnology has facilitated a unique opportunity to increase the efficacy of radiotherapy treatment. The application of high-atomic-number (Z) nanoparticles (NPs) can augment the effects of radiotherapy by increasing the sensitivity of cells to radiation. High-Z NPs can inherently act as radiosensitizers as well as serve as targeted delivery vehicles for radiosensitizing agents. In this work, the therapeutic benefits of high-Z NPs as radiosensitizers, such as their tumor-targeting capabilities and their mechanisms of sensitization, are discussed. Preclinical data supporting their application in radiotherapy treatment as well as the status of their clinical translation will be presented. Full article

Human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC) presents unique challenges and opportunities for treatment, particularly regarding de-escalation strategies to reduce treatment morbidity without compromising oncological outcomes. This paper examines the role of Transoral Robotic Surgery (TORS) as a de-escalation strategy in managing HPV-related OPSCC. We conducted a comprehensive literature review from January 2010 to June 2023, focusing on studies exploring TORS outcomes in patients with HPV-positive OPSCC. These findings highlight TORS’s potential to reduce the need for adjuvant therapy, thereby minimizing treatment-related side effects while maintaining high rates of oncological control. TORS offers advantages such as precise tumor resection and the ability to obtain accurate pathological staging, which can guide the tailoring of adjuvant treatments. Some clinical trials provide evidence supporting the use of TORS in specific patient populations. The MC1273 trial demonstrated promising outcomes with lower doses of adjuvant radiotherapy (RT) following TORS, showing high locoregional tumor control rates and favorable survival outcomes with minimal side effects. ECOG 3311 evaluated upfront TORS followed by histopathologically directed adjuvant therapy, revealing good oncological and functional outcomes, particularly in intermediate-risk patients. The SIRS trial emphasized the benefits of upfront surgery with neck dissection followed by de-escalated RT in patients with favorable survival and excellent functional outcomes. At the same time, the PATHOS trial examined the impact of risk-adapted adjuvant treatment on functional outcomes and survival. The ongoing ADEPT trial investigates reduced-dose adjuvant RT, and the DART-HPV study aims to compare standard adjuvant chemoradiotherapy (CRT) with a reduced dose of adjuvant RT in HPV-positive OPSCC patients. These trials collectively underscore the potential of TORS in facilitating treatment de-escalation while maintaining favorable oncological and functional outcomes in selected patients with HPV-related OPSCC. The aim of this scoping review is to discuss the challenges of risk stratification, the importance of HPV status determination, and the implications of smoking on treatment outcomes. It also explores the evolving criteria for adjuvant therapy following TORS, focusing on reducing radiation dosage and volume without compromising treatment efficacy. In conclusion, TORS emerges as a viable upfront treatment option for carefully selected patients with HPV-positive OPSCC, offering a pathway toward treatment de-escalation. However, selecting the optimal candidate for TORS-based de-escalation strategies is crucial to fully leverage the benefits of treatment de-intensification. Full article

The purpose of this study was to determine the maximum tolerated dose (MTD) for stereotactic body radiation therapy (SBRT) in the treatment of non-metastatic prostate cancer. This study was a phase 1 dose escalation trial conducted in Japan. Patients with histologically proven prostate cancer without lymph nodes or distant metastases were enrolled. The prescribed doses were 42.5, 45, or 47.5 Gy in five fractions. Dose-limiting toxicity (DLT) was defined as grade (G) 3+ gastrointestinal or genitourinary toxicity within 180 days after SBRT completion, and a 6 plus 6 design was used as the method of dose escalation. A total of 16 patients were enrolled, with 6 in the 42.5 Gy group and 10 in the 45 Gy group. No DLT was observed in the 42.5 Gy group. In the 45 Gy group, one patient experienced G3 rectal hemorrhage, and another had G4 rectal perforation, leading to the determination of 42.5 Gy as the MTD. None of the patients experienced biochemical recurrence or death during the follow-up period. We concluded that SBRT for non-metastatic prostate cancer at 42.5 Gy in five fractions could be safely performed, but a total dose of 45 Gy increased severe toxicity. Full article