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Purpose: Total body irradiation (TBI) is a common part of the myelo- and immuno-ablative conditioning regimen prior to an allogeneic hematopoietic stem cell transplantation (allo-HSCT). Due to concerns regarding acute and long-term complications, there is currently a decline in otherwise successfully established TBI-based conditioning regimens. Here we present an analysis of patient and treatment data with focus on survival and long-term toxicity.
Methods: Patients with hematologic diseases who received TBI as part of their conditioning regimen prior to allo-HSCT at Frankfurt University Hospital between 1997 and 2015 were identified and retrospectively analyzed.
Results: In all, 285 patients with a median age of 45 years were identified. Median radiotherapy dose applied was 10.5 Gy. Overall survival at 1, 2, 5, and 10 years was 72.6, 64.6, 54.4, and 51.6%, respectively. Median follow-up of patients alive was 102 months. The cumulative incidence of secondary malignancies was 12.3% (n = 35), with hematologic malignancies and skin cancer predominating. A TBI dose ≥ 8 Gy resulted in significantly improved event-free (p = 0.030) and overall survival (p = 0.025), whereas a total dose ≤ 8 Gy and acute myeloid leukemia (AML) diagnosis were associated with significantly increased rates of secondary malignancies (p = 0.003, p = 0.048) in univariate analysis. No significant correlation was observed between impaired renal or pulmonary function and TBI dose.
Conclusion: TBI remains an effective and well-established treatment, associated with distinct late-toxicity. However, in the present study we cannot confirm a dose–response relationship in intermediate dose ranges. Survival, occurrence of secondary malignancies, and late toxicities appear to be subject to substantial confounding in this context.
Purpose: As the population ages, the incidence of rectal cancer among elderly patients is rising. Due to the risk of perioperative morbidity and mortality, alternative nonoperative treatment options have been explored in elderly and frail patients who are clinically inoperable or refuse surgery.
Methods: Here we present technical considerations and first clinical experience after treating a cohort of six rectal cancer patients (T1‑3, N0‑1, M0; UICC stage I-IIIB) with definitive external-beam radiation therapy (EBRT) followed by image-guided, endorectal high-dose-rate brachytherapy (HDR-BT). Patients were treated with 10–13 × 3 Gy EBRT followed by HDR-BT delivering 12–18 Gy in two or three fractions. Tumor response was evaluated using endoscopy and magnetic resonance imaging of the pelvis.
Results: Median age was 84 years. All patients completed EBRT and HDR-BT without any high-grade toxicity (> grade 2). One patient experienced rectal bleeding (grade 2) after 10 weeks. Four patients (67%) demonstrated clinical complete response (cCR) or near cCR, there was one partial response, and one residual tumor and hepatic metastasis 8 weeks after HDR-BT. The median follow-up time for all six patients is 42 weeks (range 8–60 weeks). Sustained cCR without evidence of local regrowth has been achieved in all four patients with initial (n)cCR to date.
Conclusion: Primary EBRT combined with HDR-BT is feasible and well tolerated with promising response rates in elderly and frail rectal cancer patients. The concept could be an integral part of a highly individualized and selective nonoperative treatment offered to patients who are not suitable for or refuse surgery.
Purpose: Dosimetric treatment planning evaluations concerning patient-adapted moulds for iridium-192 highdose-rate brachytherapy are presented in this report.
Material and methods: Six patients with perinasal skin tumors were treated with individual moulds made of biocompatible epithetic materials with embedded plastic applicators. Treatment plans were optimized with regard to clinical requirements, and dose was calculated using standard water-based TG-43 formalism. In addition, retrospective material-dependent collapsed cone calculations according to TG-186 protocol were evaluated to quantify the limitations of TG-43 protocol for this superficial brachytherapy technique.
Results: The dose-volume parameters D90, V100, and V150 of the planning target volumes (PTVs) for TG-43 dose calculations yielded 92.2% to 102.5%, 75.1% to 93.1%, and 7.4% to 41.7% of the prescribed dose, respectively. The maximum overall dose to the ipsilateral eyeball as the most affected organ at risk (OAR) varied between 8.9 and 36.4 Gy. TG-186 calculations with Hounsfield unit-based density allocation resulted in down by –6.4%, –16.7%, and –30.0% lower average D90, V100, and V150 of the PTVs, with respect to the TG-43 data. The corresponding calculated OAR doses were also lower. The model-based TG-186 dose calculations have considered reduced backscattering due to environmental air as well as the dose-to-medium influenced by the mould materials and tissue composition. The median PTV dose was robust within 0.5% for simulated variations of mould material densities in the range of 1.0 g/cm³ to 1.26 g/cm³ up to 7 mm total mould thickness.
Conclusions: HDR contact BT with individual moulds is a safe modality for routine treatment of perinasal skin tumors. The technique provides good target coverage and OARs’ protection, while being robust against small variances in mould material density. Model-based dose calculations (TG-186) should complement TG-43 dose calculations for verification purpose and quality improvement.
Background: Facial skin cancer lesions in close proximity to critical organs require further development of radiotherapeutic techniques for highly conformal treatment, especially when treating elderly frail patients. We report on our treatment technique and first clinical experience for patients with perinasal/periorbital skin cancer treated with individualized epithetic mold high-dose-rate brachytherapy (BRT).
Methods: From January 2019, patients with complex shaped or unfavorably located skin cancer not eligible for surgery or external beam radiotherapy (RT) were screened for mold-based BRT. Six patients were identified. Toxicity and clinical response were documented during therapy and posttreatment follow-up.
Results: Median patient age was 80 years (74–92 years). Median prescription dose was 42 Gy (range, 33–44 Gy) delivered in once-daily fractions of 3 or 4 Gy. Two patients had treatment interruptions caused by acute conjunctivitis grade 2 and a nontreatment-related cardiac event, respectively. At a median follow-up of 335 days (96–628 days), no ≥ grade 2 late toxicity was documented with all patients showing complete clinical response.
Conclusions: High-dose-rate BRT with individualized epithetic molds for perinasal/periorbital skin cancer is a well-tolerated and safe treatment option for patients not eligible for primary surgery or definitive external beam RT because of comorbidities or tumor location.