Purpose Chemoradiotherapy and adjuvant immunotherapy have become the standard of care for patients with unresectable stage III non-small cell lung cancer (NSCLC). In elderly patients, chemoradiotherapy is often considered too burdensome and is therefore frequently omitted or discontinued. We retrospectively analysed the long-term results of concurrent daily low-dose cisplatin and radiotherapy (CCRT) in patients with unresectable stage III NSCLC, with a particular focus on age. Methods Between 2005 and 2015, 154 consecutive patients with unresectable NSCLC received CCRT consisting of daily low-dose cisplatin (6 mg/m2) administered concurrently with 24 fractions of 2.75 Gy to a total dose of 66 Gy over 5 weeks. Disease recurrence, metastases and treatment complications were assessed by clinical examination and radiological imaging (CT, PET-CT, MRI). Observed survival, disease-free survival (DFS) and complication rates were estimated using the Kaplan-Meier (KM) method; Cox regression model was used to examine differences between non-elderly patients (age ≤70.0 years; n=106) and elderly patients (>70.0 years; n=48). Relative survival (RS) rates were calculated to adjust for age- and sex-specific background mortality . Results The median follow-up for survival was 34 months (range, 1-204 months), and for recurrence, metastasis and complication 29 months (range, 1-140 months). The observed KM survival rates at 1, 5 and 10 years were 79%, 39% and 19%, respectively. Median survival was 33 months. In non-elderly patients (≤ 70.0 years), the KM survival rates were 78%, 38% and 24% (median 35 months); in elderly patients (>70.0 years), the rates were 81%, 42% and 10% (median 31 months) (p= 0.1). The RS rates at 1, 5 and 10 years for non-elderly patients were 79%, 39% and 26% (median 35 months), for the elderly patients 84%, 48% and 13% (median 35 months; p = 0.5). Disease Free Survival at 1, 5, and 10 years were 67%, 43% and 40%. Worse ECOG scale, no surgery and a large treated volume of positive lymph nodes (GTV lymph nodes) were significant risk factors for poor survival. Local tumour volume and no surgery were an independent risk factors for distant metastasis. Age and surgery were significant risks for recurrence. A large treated volume of the positive lymph nodes treated was a significant risk factor for treatment complications. Conclusion CCRT with daily low-dose cisplatin and high-dose RT in elderly patients with unresectable stage III NSCLC is not associated with significantly more toxicity than in non-elderly patients, resulting in a favourable long-term tumour control and survival. Despite more co-morbidity and a shorter survival in elderly patients, the age- and sex-adjusted relative survival is similar to that of non-elderly patients .
Background Oral mucositis (OM) is a debilitating complication of radiotherapy. Although benzydamine has been shown to reduce radiation-induced oral mucositis (RIOM) severity at low to moderate doses (<50 Gy), evidence regarding its effectiveness at higher doses remains limited. This pilot, open-label, randomized clinical trial evaluated the effect of 0.15% benzydamine hydrochloride oral spray on OM progression and severity after OM onset during high-dose radiotherapy (>50 Gy). Methods A total of 35 patients with head and neck cancer who developed OM during high-dose radiotherapy (>50 Gy) without concurrent chemotherapy were enrolled (benzydamine group: n = 18, mean age 56.4 ± 12.0 years; control group: n = 17, mean age 52.8 ± 17.1 years) following specialist-confirmed OM onset, approximately two weeks after radiotherapy initiation. Tumor subsites included nasopharyngeal carcinoma, tongue, tonsillar, and other tumors. OM severity was assessed according to World Health Organization (WHO) criteria over six weeks. Patients with WHO grade 1–2 mucositis were randomized to benzydamine spray plus standard care or standard care alone; all were included in the intention-to-treat analysis. Results Grade 3 or higher mucositis at week 6 occurred in 11.1% of the benzydamine group compared with 70.6% of the control group (p < 0.001; OR = 0.052; 95% CI, 0.006–0.268). The group-by-time interaction significantly improved CLMM fit over the main-effects model (AIC = 304.7 vs. 332.9; p < 0.001), and was significant (OR = 0.267; 95% CI, 0.157–0.457; p < 0.001), indicating less pronounced OM progression over time in the benzydamine group. These results were consistent with a sensitivity analysis conducted on the 29 patients who completed the full follow-up period. Conclusion The present findings suggest that benzydamine may reduce OM progression and severity after OM onset in patients undergoing high-dose radiotherapy. This clinical trial was retrospectively registered in a public trials registry.
Purpose Intravascular brachytherapy (IVBT) has a well-proven activity against coronary restenosis of a native vessel or a single bare metal stent. However, its effectiveness for multiple recurrent same-vessel in-stent restenoses (ISRs) is unproven. The objective of this study was to determine if IVBT prolongs the ISR-free interval in recalcitrant lesions. Methods and Materials ISR-free intervals before and after IVBT for individual patients were compared. T1 was the ISR-free interval prior to IVBT, and T2 was the ISR-free interval after IVBT. Accrual was sought from patients with a prior ISR-free interval of less than 2 years. Standard radiation techniques were used, with doses of 18, 23, or 34 Gy prescribed at 2 mm from the radiation source. ISR-free intervals before (T1) and after IVBT (T2) were compared. Results Twenty-six vessels in 19 patients were studied. ISR-free intervals prior to IVBT ranged from 25 to 317 days (median, 96 days) compared with ISR-free intervals after IVBT that ranged from 30 to 612 days (median, 350 days; P < .001; log-rank test). Conclusion The results support the use of IVBT to prolong the ISR-free interval in recalcitrant ISRs.
Background Whole-gland salvage high dose-rate (HDR) prostate brachytherapy is an emerging option for radiorecurrent prostate cancer. However, long-term prospective data remains limited. This report presents the long-term results of our prospective study on the toxicities, health-related quality of life and efficacy of whole-gland HDR prostate brachytherapy. Methods Patients with biopsy-confirmed, MR-visible local recurrent prostate cancer after previous external-beam radiotherapy (EBRT) were eligible. Patients underwent MR-assisted, ultrasound-based whole-gland HDR prostate brachytherapy with a prescription dose of 21Gy to the entire prostate and 27Gy to the MR-defined intraprostatic target volume (TV) divided over two implants separated by 1-2 weeks. Adjuvant androgen deprivation therapy (ADT) was not used. Results 30 patients were enrolled in the study. Median follow-up from salvage HDR was 72.0 months (10.7-121.5). Most patients (93%) had initial EBRT doses at conventional fractionation. The pre-HDR median PSA was 3.67ng/mL (0.56-11.01). Seven (23.3%) were staged with PSMA-PET. Four (13%) required temporary urinary catheterization. There was only 1 (3.3%) grade 3-5 toxicity – a late grade 3 GU toxicity. The PSA progression-free survival and freedom from ADT rates were 73.0% and 93.0% at 3 years, and 24.8% and 69.6% at 5 years, respectively. Of the 26 patients who had a post-HDR MRI (median 415 days), 9 (35%) had persistent disease. Of the 23 (77%) patients who had PSA relapse, 18 (78%) patients had disease at the TV confirmed by MRI, PSMA-PET, or targeted biopsy. Conclusion Whole-gland salvage HDR brachytherapy with intra-prostatic boost is well tolerated. Progression after salvage treatment was associated with local failure.
Introduction: Adjuvant radiotherapy improves locoregional control after breast cancer surgery, but dose prescription remains based mainly on clinicopathological risk rather than individual tumor radiosensitivity. The radiation sensitivity index (RSI) and genomic-adjusted radiation dose (GARD) provide a framework for biologically guided radiotherapy personalization. In the neoadjuvant setting, however, radiosensitivity measured on the diagnostic biopsy may not reflect the residual disease ultimately targeted by adjuvant radiotherapy.Materials and Methods: We analyzed matched pre-treatment and post-treatment RNA sequencing data from two public cohorts of hormone receptor-positive, HER2-negative (HR+/HER2-) breast cancer treated with neoadjuvant chemotherapy. The discovery cohort included 16 matched pairs from GSE191127, and the validation cohort included 14 matched HR+/HER2- pairs from GSE309004. RSI was computed using a ten-gene rank-based model. ΔRSI was defined as RSI_post - RSI_pre. Immune fractions were inferred using quanTIseq, and GARD was calculated for START-B, RTOG 1005, and FAST-Forward adjuvant radiotherapy schedules.Results: In the discovery cohort, mean RSI increased from 0.602 to 0.677 after neoadjuvant chemotherapy, with 12 of 16 patients (75%) showing a post-treatment increase. In the validation cohort, mean RSI increased from 0.489 to 0.593 (Wilcoxon p = 0.014), with 11 of 14 patients (78.6%) showing an increase. In the pooled cohort, mean ΔRSI was +0.089, and 23 of 30 patients (76.7%) showed increased RSI after chemotherapy (Wilcoxon p = 0.005). Higher pre-treatment M2 macrophage fraction correlated with larger ΔRSI. RSI changes translated into heterogeneous GARD modifications across fractionation schedules.Conclusion: Neoadjuvant chemotherapy is associated with a reproducible increase in RSI in HR+/HER2- breast cancer, suggesting that residual tumors may become more radioresistant at the genomic level after systemic therapy. Post-neoadjuvant RSI warrants prospective evaluation for individualized adjuvant radiotherapy strategies.
Purpose Prostate stereotactic ablative body radiotherapy (SABR) is now a standard-of-care radiation therapy option for prostate cancer based on high-level clinical trial evidence. As part of the Australia and New Zealand (ANZ) prostate SABR guideline development process, the Royal Australian and New Zealand College of Radiologists has commissioned a pattern-of-practice survey on contemporaneous prostate SABR practice. Methods and Materials We conducted a cross-sectional survey among ANZ genitourinary radiation oncologists (ROs), focusing on patient selection, contouring, treatment planning, and delivery of prostate SABR. Results A total of 53 ROs across ANZ responded to the survey (response rate: 28%). Of the 41 ROs currently offering prostate SABR, 95%, 90%, 35%, 5%, and 0% offer prostate SABR as standard-of-care options to individuals with favorable intermediate risk, unfavorable intermediate risk, favorable high risk (NINJA/ TROG18.01 trial eligible), very high risk, and node-positive prostate cancer, respectively. Most ROs (86%) routinely use fiducial markers. All ROs routinely request planning magnetic resonance imaging for contouring. Clinical target volume contouring ranged from prostate alone (26%) to prostate plus proximal 1 cm of the seminal vesicles (81%). Planning target volume margins ranged from 3 to 5 mm. An anisotropic 5 mm margin with 3 mm posteriorly was most common (56%). Nineteen (45%) ROs provide a focal boost to the intraprostatic lesion. The most common dose fractionation was 36.25 Gy to the planning target volume and 40 Gy to the clinical target volume over 5 fractions, delivered as 2 (50%) to 3 fractions (76%) per week. The majority of ROs offer prostate SABR on standard computed tomography-linear accelerator (LINAC) (88%), with several ROs also treating patients with CyberKnife (10%) and magnetic resonance-LINAC (5%). Of the ROs who use standard computed tomography-LINAC, 84% use intrafraction motion monitoring. Twelve (23%) ROs do not offer prostate SABR. The main barrier cited was a lack of expertise (42%). Conclusions This ANZ-wide prostate SABR pattern-of-practice survey demonstrated some variations in practice, providing contemporary insight into how prostate SABR is delivered across ANZ and highlighting barriers to wider adoption.
Purpose This study aims to evaluate the safety and efficacy of high-dose carbon ion reirradiation (CIR) in patients with recurrent pelvic sarcomas. Methods and Materials This retrospective study included 46 patients treated with high-dose CIR for locoregional recurrences of pelvic sarcomas between 2013 and 2023 at the National Center for Oncological Hadrontherapy, Pavia, Italy. Clinical outcomes, toxicity, and cumulative doses were analyzed. Results The median prescribed total dose of CIR was 60 GyRBE (range, 45-73.6 GyRBE). The maximum cumulative equivalent dose in 2 Gy fractions to the target volume reached 284 Gy, with a median of 153 Gy. The median follow-up was 32.5 months. The 1-, 2-, and 3-year locoregional progression-free survival rates were 79.1%, 43.9%, and 25.1%, respectively, with a mean time to locoregional relapse of 18.9 months. The 1-, 2-, and 3-year overall survival rates were 100%, 93.9%, and 83.1%, respectively. At last follow-up, grade 3 neuropathy occurred in 6.5% of the patients, grade 3 anorectal dysfunction in 8.7%, and grade 3 skin toxicity in 6.5%. Conclusions High-dose CIR is a feasible salvage strategy for recurrent pelvic sarcoma, offering promising outcomes and manageable toxicity in carefully selected patients. Prospective studies are warranted to refine dose-response models and validate long-term efficacy.
Purpose:Patients with recurrent meningiomas treated with prior radiation therapy have limited treatment options. This study aims to evaluate the efficacy and tolerability of reirradiation with temporally-modulated pulsed radiation therapy (TMPRT) in a cohort of patients with recurrent meningioma. Methods and Materials:We retrospectively identified 26 patients with recurrent meningioma treated with TMPRT from 2003 to 2025 at a single institution. All patients had radiographic or pathologic evidence of progression, were not candidates for radiosurgery or surgery, had previously received conventionally fractioned radiation therapy, and were retreated with temporally-modulated pulsed radiation therapy. Radiographic progression was assessed using Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Acute and late toxicities were graded based on Common Terminology Criteria for Adverse Events (CTCAE) 5.0. Overall survival and progression-free survival (PFS) were estimated using the Kaplan-Meier method. Results:Median follow-up was 61.9 months. Median TMPRT dose was 54 Gy in 2 Gy fractions. Median planning treatment volume was 193 cm3. PFS at 6 months was 77% (95% CI, 56%-89%) and median PFS was 27.2 months (95% CI, 7.5-46.5 months). Median overall survival was 27.2 months (95% CI, 16.4-73.9 months). Three patients (12%) experienced grade ≥3 acute toxicity, 3 patients (12%) experienced grade ≥3 late toxicity. Conclusions:TMPRT was effective and generally well-tolerated in a cohort of patients with recurrent meningioma previously treated with radiation therapy. This represents the largest-volume reported reirradiation meningioma cohort, and suggests that TMPRT may safely expand the role of photon reirradiation to a patient population with limited local treatment options.
Purpose The 2024 and 2025 international consensus guidelines redefined the anterior border of the level IVa elective nodal volume for nasopharyngeal carcinoma (NPC). This study aimed to provide the first dosimetric validation of this anatomical refinement by quantifying its impact on thyroid and larynx doses, and translating these reductions into clinically interpretable normal tissue complication probability (NTCP) estimates. Methods and Materials Thirty patients with NPC treated with helical tomotherapy were selected to represent a full spectrum of lower cervical nodal involvement. For each patient, two comparative treatment plans for different nodal clinical target volume (CTVn) definitions were generated: (1) CTVn based on 2018 guidelines, defining the level IVa anterior border at the anterior edge of the sternocleidomastoid muscle; and (2) CTVn based on 2024/2025 guidelines, shifting this border to the posterior edge of the infrahyoid ribbon muscles. Plans were optimized to minimize thyroid and larynx doses while maintaining equivalent target coverage. Dosimetric parameters and NTCP for hypothyroidism and laryngeal edema were compared using paired analyses. Results The updated CTVn delineation significantly reduced thyroid Dmean from 48.5 Gy to 44.8 Gy (p < 0.001) and thyroid V50 from 59.9% to 46.3% (p < 0.001). Larynx Dmean decreased from 25.9 Gy to 21.7 Gy (p < 0.001). The NTCP for hypothyroidism was reduced from 43.9% to 34.9% (p < 0.001), corresponding to a 20.5% relative risk reduction. Target coverage and doses to other organs at risk remained comparable between plans. Conclusions Adopting the updated 2024/2025 international consensus guidelines for level IVa delineation significantly reduces radiation dose to the thyroid and larynx without compromising target coverage. This translates into a clinically meaningful reduction in the risk of primary hypothyroidism, supporting the widespread implementation of these guidelines to improve survivorship outcomes in patients with NPC.
Background Radiation-induced intestinal injury (RIII) is a serious complication of radiotherapy without effective therapies. The alarmin S100A8/A9, a biomarker of gastrointestinal inflammation, is highly elevated following abdominal irradiation (ABI). However, it remains unclear whether it functions as an active driver of RIII pathogenesis. Objective The study aims to assess the effects of S100A8/A9 on the pathogenesis of RIII. Our goal is to identify its dynamic alteration during RIII and determine whether it can be used as a therapeutic target in the injury and repair phases of acute RIII. Methods C57BL/6J mice were subjected to ABI, and S100A8/A9 expression was analyzed by qRT-PCR and immunofluorescence at multiple time points (days 1, 4, and 8) during RIII. The small-molecule inhibitor Paquinimod (Paq) was used to block S100A9 in vivo, and recombinant proteins S100A8/A9 were used in IEC-6 cells and organoids for in vitro validation. Epithelial regeneration was tracked through lineage tracing assays using Lgr5-eGFP-IRES-CreERT2; R26-CAG-LSL-tdTomato mice. Results S100A8/A9 expression in the mouse intestine was obviously upregulated post-ABI in a time-dependent manner, which started to increase from day 1 and reached the peak on day 4. The increased S100A8/A9 was primarily released from neutrophils infiltrated into the intestinal crypts. Inhibition of S100A8/A9 with Paq substantially alleviated irradiation-induced epithelial apoptosis, oxidative stress, and inflammatory responses, while enhancing crypt regeneration and restoration of intestinal barrier integrity. Mechanistically, S100A8/A9 exacerbated irradiation-induced intestinal injury via binding to TLR4 and RAGE receptors, and subsequently activating NF-κB and MAPK signaling pathways. Conclusion This study identifies S100A8/A9 as a critical pathogenic contributor to acute RIII and provides strong evidence supporting S100A8/A9 as a potential therapeutic target for RIII.
Purpose This study aimed to predict deep-inspiration breath-hold (DIBH) intolerance during abdominal cancer radiotherapy and its impact on residual motion, based on patient characteristics and DIBH performance at simulation. Methods We retrospectively studied 82 patients on voluntary DIBH for abdominal cancers between January and July 2022. DIBH was performed using infrared markers to track abdominal wall motion. The anteroposterior motion during simulation was recorded as a reference trace based on which a gate window was set. DIBH intolerance was defined as modification of the gate window or conversion to free breathing during the treatment course. Predictive features included reference trace characteristics (breath hold level (BHL), DIBH stability & reproducibility, free breathing amplitude, period, baseline drift) and baseline clinical characteristics (age, performance status, comorbidities, anxiety, preferred language). Univariate tests and random forest multivariate modeling were used for analysis, with model performance assessed using 10-fold cross-validation. The association between predicted intolerance and residual fiducial motion during treatment in a subset of 15 patients, was also investigated. Results A statistically significant association was found between BHL at simulation and DIBH intolerance (4% false discover rate). A 1 mm increase in BHL increased intolerance risk by 7%. The multivariate model, combining trace and clinical characteristics, predicted DIBH intolerance with a median area under the curve of 0.63. Reference trace characteristics showed higher predictive importance than clinical characteristics. The predicted intolerance risk increased sharply for BHL > 25 mm. Residual motion was significantly higher for the patient intolerant of DIBH (p = 0.02). A moderate positive correlation (r = 0.46, p = 0.08) was observed between the model prediction and residual motion during treatment. Conclusion Coaching patients to reach appropriate BHL is critical to DIBH tolerability and to reduce residual motion. The multivariate model suggests a limited but potential framework for predicting intolerance risk.
Background Localized radiation is a cornerstone therapy for early-stage mycosis fungoides (MF), with low-dose regimens achieving high response rates. However, the optimal fractionation schedule remains unclear. Single-fraction (8 Gy × 1) and split-fraction (4 Gy × 2) regimens are widely used, but comparative data are limited. Reducing treatment burden may be particularly important in rural settings, where travel distance can limit access. Objective To compare lesion-level response, recurrence, and durability between 8 Gy × 1 and 4 Gy × 2 low-dose radiation regimens in MF. Methods We performed a retrospective review of 136 lesions from 27 adults with biopsy-confirmed MF treated with localized electron beam radiation at a rural multidisciplinary cutaneous lymphoma clinic (2014–2025). Lesions were categorized as patch or plaque. The primary outcome was complete response (CR) at 6 months. Secondary outcomes included overall response rate (ORR), local recurrence, time to next therapy, and toxicity. Analyses included χ²/Fisher’s exact tests, Kaplan–Meier survival, Cox regression, and inverse-probability weighting (IPW). Results Of 136 lesions, 119 (87.5%) received 4 Gy × 2 and 17 (12.5%) received 8 Gy × 1. Six-month CR was 81.5% versus 82.4%, respectively (p = 1.0). ORR was 98.3% versus 100%, respectively (p = 1.0). Six-month local recurrence occurred in 3.4% versus 11.8% lesions (p = 0.17), and additional local treatment within 6 months was required in 12.6% versus 5.9% lesions (p = 0.69). No grade ≥2 toxicities occurred. Median patient travel distance was 86.2 miles vs 71.0 miles (p = 0.069). Multivariable and IPW analyses showed no association between regimen and CR at 6 months. Limitations Retrospective design and small single-fraction sample. Conclusions Single-fraction 8 Gy was associated with similar short-term outcomes and excellent tolerability, supporting its use as an effective, logistically advantageous option, particularly in rural practice.
Purpose: Malignant peripheral nerve sheath tumor (MPNST) is a rare, aggressive soft tissue sarcoma with highest incidence in patients with neurofibromatosis type 1 (NF1). Data on outcomes and second malignancies following radiation therapy (RT) are limited, particularly in patients with NF1. This study evaluated overall survival (OS), progression-free survival (PFS), local failure, and secondary malignancies in patients with localized resectable MPNST. Methods and Materials: Patients diagnosed with localized resectable MPNST between 2010 and 2024 were retrospectively identified. Survival was estimated using the Kaplan–Meier method, multivariable analysis was conducted using Cox proportional hazards modeling, and cumulative incidence was estimated using Fine and Gray model. Results: Sixty-eight patients met inclusion criteria; median age was 34 years, and 75% had NF1. Median follow-up was 43.5 months. RT was delivered in 61.8% of patients, primarily preoperatively (71.1%). RT was associated with improved 3-year OS (87.2% vs 51.5%, P = .039) and 3-year PFS (55.8% vs 41.5%, P = .017). On multivariable analysis, RT remained independently associated with improved PFS (HR, 0.34, P = .003) and OS (HR, 0.4, P = .034). Three-year local failure was for RT versus no RT was 26.3% versus 35.3% (P = .240). One secondary malignancy arose within a prior RT field 9.5 years after initial RT, and another at the RT field edge 8.6 years later. Conclusions: RT was independently associated with improved PFS and OS in patients with localized resected MPNST. These hypothesis-generating findings need validation in a larger cohort. The risk of RT-associated secondary malignancy was low, occurring beyond the median disease progression timeframe.
Neoadjuvant radiotherapy has an established role in the treatment of locally advanced rectal cancer, improving the curability of the disease. Multiple randomized trials have showcased equal efficacy and tolerance between short-course radiotherapy (scRT) and long course chemo-radiotherapy (lcCRT). In the latest update of the RAPIDO randomized trial, patients treated with standard lcCRT displayed better locoregional control, despite the fact that total neoadjuvant therapy (TNT)/scRT was associated with higher pathological complete response (pCR) rates and lower incidence of metastases. Whether this finding reflects actual difference between the two RT schedules efficacy remains controversial. Assuming non-superiority of either schedule, radiobiological analysis of scRT reveals a lower biological dose delivered to the tumor compared to lcCRT. This suggests that additional factors, such as treatment acceleration counteracting rapid tumor repopulation or enhanced anti-tumor immunity, potentiate scRT efficacy. Recent clinical data from scRT/immunotherapy (IO)/TNT trials reinforce this hypothesis, demonstrating that anti-PD-1/PD-L1 monoclonal antibodies almost double the pCR rates achieved by scRT. This synergy seems notably limited in lcCRT/IO combinations, although the interpretability of these data is limited to cross-trial comparisons. Overall, the historical debate regarding the optimal RT schedule appears to be subsiding, giving way to a growing emphasis on IO/RT combinations, particularly as scRT/IO paradigms continue to yield highly promising outcomes. Biologically, this shift is supported by preclinical and clinical data suggesting a more potent anti-tumor immune response and reduced lymphotoxicity with larger RT fractions. Further clinical research through well-designed randomized trials could eventually validate this strategy, raising new questions about which immune pathways should be targeted next and whether surgery could be avoided altogether.
Purpose:Radiation therapy (RT) for head and neck cancer commonly causes fibrosis of the salivary gland (SG) and loss of secretory function. We previously demonstrated that transdermal injection of the copper chelator tetrathiomolybdate into irradiated submandibular glands reduced the early deposition of fibrillar collagen and preserved their integrity and function. Although these studies identified copper metabolism as a novel therapeutic target to control RT-induced damage to the SG, local delivery of copper chelators in human SG presents clinical hurdles including specialized personnel and equipment needed for administration together with the discomfort felt by patients upon receiving this treatment. To overcome these issues, the current study investigated whether systemic administration of tetrathiomolybdate (TTM) via drinking water could similarly reduce collagen deposition and preserve secretory function. Methods and Materials:Mice received TTM in drinking water (0.1 mg/mL) beginning 7 days before and continuing through 7 days after a single 15-Gy dose of RT to the neck. Systemic TTM exposure and copper bioavailability were assessed by measuring molybdenum and copper levels and serum ceruloplasmin activity. RT-induced SG injury was evaluated by collagen deposition, histopathology, epithelial integrity, and stimulated saliva secretion. Results:Systemically administered TTM reached the submandibular gland and reversibly reduced copper bioavailability, as demonstrated by increased molybdenum levels, reduced copper-to-molybdenum ratios, and suppression of serum ceruloplasmin activity. Moreover, TTM treatment attenuated RT-induced collagen deposition and epithelial damage and promoted recovery of ZO-1 expression. Finally, at 30 days after RT, stimulated saliva flow was significantly higher in TTM-treated irradiated mice than in irradiated mice receiving regular water. Conclusion:Systemic TTM administration reduces copper bioavailability, attenuates RT-induced collagen deposition and epithelial injury, and preserves SG secretory function. These findings support systemic copper chelation as a less invasive alternative to local TTM delivery for limiting RT-induced SG damage.
Postoperative stereotactic body radiation therapy (SBRT) for spinal metastases presents technical challenges, particularly in the presence of internal fixation devices. Titanium implants—the standard implant material—cause substantial imaging artifacts in computed tomography (CT) and magnetic resonance (MR) scans, which can lead to target and organ-at-risk contouring problems and compromise the accuracy of dose calculations. Meanwhile, carbon fiber-reinforced polyetheretherketone (Carbon/PEEK) implants have emerged as radiolucent alternatives with favorable imaging properties. This review summarizes the current evidence comparing titanium and Carbon/PEEK implants in the context of postoperative spine SBRT, focusing on differences in artifact size in CT and MR imaging, contouring accuracy, dose perturbation, dose calculation accuracy, image guided radiation therapy, radiation therapy robustness to setup error, and clinical outcomes in photon and proton therapies.
