Purpose To report long-term tumor control, toxicity, and functional outcomes after a second course of fractionated radiation therapy for recurrent craniopharyngioma previously treated with radiation therapy. Methods and Materials We identified all patients with craniopharyngioma with recurrent or progressive disease, unsuitable for further medical management or re-resection, who underwent 2 courses of fractionated photon radiation therapy at a single institution between 1998 and 2024. Reirradiation was delivered to 54 Gy in 30 fractions with full overlap of the initial target; dose constraints to optic nerves, chiasm, and brainstem were Dmax/D0.03cc (Maximum Dose or Dose to 0.03 cubic centimetres) ≤54 Gy. Outcomes were summarized descriptively. Results Six patients received reirradiation a mean of 9.8 years (range, 5.6-20.5) after initial radiation therapy (50-54 Gy in 25-30 fractions). Median follow-up after reirradiation was 4.1 years (range, 0.4-8.8). At the last follow-up, 4 patients were alive, all with local disease control (2 with radiological regression, 2 with stable disease). Two deaths occurred (1 due to progressive disease and 1 due to functional decline with stable imaging). Visual outcomes were heterogeneous: 1 patient maintained intact vision; others had intermittent diplopia, bitemporal hemianopsia, or unilateral blindness with contralateral impairment. Endocrinopathy was frequent: 3 of 4 survivors had pan-hypopituitarism; 1 had partial deficits (hypothyroidism/amenorrhea). Functional status was impaired in survivors, with the inability to work or study due to fatigue, visual loss, or cognitive issues. Additional toxicities included posttreatment seizures requiring hospitalization (n = 1) and transient dexamethasone for headache (n = 1). Conclusions In carefully selected patients lacking other curative options, modern highly conformal reirradiation can achieve meaningful local control after prior high-dose radiation therapy, but carries an additive risk of visual, endocrine, and functional morbidity. Decisions should be individualized within a multidisciplinary team to identify appropriate cases for reirradiation and to ensure thorough long-term follow-up to manage delayed toxicity.
Purpose: Concomitant chemoradiation therapy (cCRT) is a standard-of-care treatment option for locally advanced non-small cell lung cancer, improving locoregional control (LRC) and overall survival (OS). However, many patients are unfit for cCRT and receive sequential chemoradiation therapy (sCRT); in this setting, hypofractionated radiation therapy may reduce treatment time, counter tumor repopulation, and improve access. Methods and Materials: We retrospectively analyzed outcomes and prognostic factors among 131 patients with locally advanced non-small cell lung cancer treated at a single high-volume cancer center with 1 of 3 approaches: cCRT with conventional fractionation (CONV-C; n = 52), sCRT with conventional fractionation (CONV-S; n = 37), or sCRT with hypofractionation (HYPO-S; n = 42). Results: After a median follow-up of 19.6 months, OS, progression-free survival, and distant failure-free survival were comparable among groups. LRC was significantly higher with HYPO-S (62.0%) than with CONV-S (34.8%; p = .009) and similar to CONV-C (62.0%). In multivariate analysis, LRC with HYPO-S remained comparable to CONV-C ( p = .576), whereas CONV-S was associated with inferior LRC compared with HYPO-S (hazard ratio, 2.257; 95% CI, 1.046-4.867; p = .038). Toxicity profiles were acceptable, with no significant differences in rates of grade ≥2 esophagitis or pneumonitis across groups. Conclusions: Sequential hypofractionated chemoradiation therapy achieved LRC and OS comparable to cCRT and superior LRC compared with sequential conventional schedules, without increased toxicity. These findings support broader adoption of HYPO-S as a resource-efficient, clinically effective strategy for patients ineligible for cCRT, particularly in low-income and middle-income health care systems.
Purpose Despite advances in treatments, nearly half of the patients with head and neck squamous cell carcinoma (HNSCC) experience recurrence. Early recurrence detection is critical for enabling timely curative interventions and improving survival outcomes. Here, we evaluated circulating tumor DNA (ctDNA) testing post-definitive treatment to detect molecular residual disease (MRD) and predict outcomes in patients with HNSCC. Methods and Materials This retrospective study included a real-world cohort of 97 patients with stage I to IV HNSCC undergoing ctDNA testing using a personalized, tumor-informed assay (Signatera, Natera, Inc). Longitudinal plasma samples (n = 500) were collected pretreatment, in the early postdefinitive local treatment setting (within 3 months of completing definitive local treatment, before adjuvant treatment), and during postdefinitive treatment surveillance (after adjuvant therapy [if given] or postcompletion of definitive local treatment until recurrence). Results Median patient follow-up was 22 (2-56) months. ctDNA-based MRD positivity in the early postdefinitive local treatment setting was significantly associated with inferior progression-free survival (PFS) (hazard ratio [HR], 6.39; P = .0002) and overall survival (OS) (HR, 25.72; P = .003). Longitudinally, MRD positivity during the postdefinitive treatment surveillance window was associated with significantly shorter PFS (HR, 38.87; P < .0001) and OS (HR, 14.37; P = .014) and preceded radiographic progression by a median of 4.3 (0.62-21.91) months. The increased risk of recurrence for patients who were MRD-positive was observed across all pathologic stages, regardless of p16 status. In multivariate analysis, MRD positivity postdefinitive treatment was the only clinicopathologic factor significantly associated with PFS (HR, 38.29; P < .001). Conclusions In patients with stage I to IV HNSCC, ctDNA-based MRD positivity after definitive local therapy and adjuvant treatment is associated with disease recurrence and poor survival outcomes.
Purpose: Classical rapid access palliative radiation therapy (RAPRT) programs are typically organized as dedicated clinics designed to enable same-day consultation, simulation, treatment planning, and delivery of palliative radiation therapy. At our institution, urgent and expedited palliative radiation therapy is delivered through an integrated, nonclassical RAPRT model embedded in routine departmental practice. This study describes the implementation and performance of this model. Methods and Materials: We retrospectively reviewed patients treated by our RAPRT workflow between January 1, 2018, and December 31, 2024. Demographic, clinical, treatment-related, and workflow data were collected from the institutional oncology information system and clinical records. Workflow intervals were calculated using electronic timestamps. Results: A total of 775 patients received 848 treatment courses; 37% were hospitalized at the time of treatment. Fifty-six patients (7.2%) received >1 treatment course, and 15 required reirradiation. The median time from referral to radiation oncology consultation was 1 day (Q1, 1; Q3, 3). Median age was 63 years (Q1, 54; Q3, 73), and the most common primary tumors were lung (25%) and gastrointestinal cancers (17%). Poor performance status (Eastern Cooperative Oncology Group performance status 3-4) was observed in 40% of cases. The most common treatment sites were bone (47%) and thorax (19%). A single fraction was prescribed in 797 extracranial courses, representing 94% of all courses. Median total treatment process time was 109 minutes (Q1, 102; Q3, 165), and median time spent in the radiation therapy center was 207 minutes (Q1, 111; Q3, 250). Time to simulation and dosimetry time were the most time-consuming workflow steps, accounting for 24% and 31% of the total workflow duration, respectively. Conclusions: An integrated, nonclassical RAPRT model using existing departmental resources is feasible and can achieve rapid palliative radiation therapy timelines comparable to those reported by dedicated RAPRT programs. Robust information systems and coordinated electronic workflows are central to the efficient implementation of this model.
Purpose The benefit of proton beam therapy (PBT) for primary brain tumors compared with x-ray therapy has not been demonstrated by randomized controlled trials. We performed a model-based approach study to evaluate the potential benefit of PBT for brain tumors using the normal tissue complication probability (NTCP) models complying with the Radiotherapy Treatment plannINg study Guidelines (RATING). Methods and Materials Sixty-six patients with primary brain tumors treated with PBT were registered. We used 11 NTCP models, calculated NTCP for each adverse event, and estimated the PBT and intensity modulated radiation therapy (IMRT) plans for the entire patient population and for groups classified by pathology. Wilcoxon signed-rank tests were performed for statistically significant differences between the 2 modalities, and a 2-tailed test was considered significant when <.05. A reduction was considered clinically meaningful when the difference in NTCP between the 2 modalities (ΔNTCP) exceeded the prespecified threshold. Results Overall, PBT reduced NTCP from the cataracts, delayed recall, memory impairment, contralateral hearing impairment, and tinnitus. Patients with meningiomas and low-grade gliomas had similar tendencies. PBT was associated with a lower excess absolute risk of secondary cancer of the central nervous system in all patients. However, NTCPs for alopecia, blindness, and brain necrosis were higher in the PBT cohort, highlighting important clinical trade-offs. Thirty-one patients (47.0%) had at least 1 ΔNTCP above the specified threshold. Conclusions In this model-based planning comparison, PBT was associated with lower estimated NTCPs for selected endpoints compared with virtual IMRT, whereas IMRT showed advantages for alopecia, blindness, and brain necrosis. PBT may offer meaningful clinical benefits, particularly in reducing the excess absolute risk of secondary cancer for patients with long-term survival. In addition, the comparison based on Radiotherapy Treatment plannINg study Guidelines made the study more objective than similar previous studies.
