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Abstract Background Radiation therapy plays a central role in the management of many childhood malignancies and Helical Tomotherapy (HT) provides potential to decrease toxicity by limiting the radiation dose to normal structures. The aim of this article was to report preliminary results of our clinical experience with HT in pediatric malignancies. Methods In this study 66 consecutive patients younger than 14 years old, treated with HT at our center between January 2006 and April 2010, have been included. We performed statistical analyses to assess the relationship between acute toxicity, graded according to the RTOG criteria, and several clinical and treatment characteristics such as a dose and irradiation volume. Results The median age of patients was 5 years. The most common tumor sites were: central nervous system (57%), abdomen (17%) and thorax (6%). The most prevalent histological types were: medulloblastoma (16 patients), neuroblastoma (9 patients) and rhabdomyosarcoma (7 patients). A total of 52 patients were treated for primary disease and 14 patients were treated for recurrent tumors. The majority of the patients (72%) were previously treated with chemotherapy. The median prescribed dose was 51 Gy (range 10-70 Gy). In 81% of cases grade 1 or 2 acute toxicity was observed. There were 11 cases (16,6%) of grade 3 hematological toxicity, two cases of grade 3 skin toxicity and one case of grade 3 emesis. Nine patients (13,6%) had grade 4 hematological toxicity. There were no cases of grade 4 non-hematological toxicities. On the univariate analysis, total dose and craniospinal irradiation (24 cases) were significantly associated with severe toxicity (grade 3 or more), whereas age and chemotherapy were not. On the multivariate analysis, craniospinal irradiation was the only significant independent risk factor for grade 3-4 toxicity. Conclusion HT in pediatric population is feasible and safe treatment modality. It is characterized by an acceptable level of acute toxicity that we have seen in this highly selected pediatric patient cohort with clinical features of poor prognosis and/or aggressive therapy needed. Despite of a dosimetrical advantage of HT technique, an exhaustive analysis of long-term follow-up data is needed to assess late toxicity, especially in this potentially sensitive to radiation population.

Brain metastases are not currently an incurable situation and can now be controlled with current treatments, surgery, radiation, and systemic therapies. Radiation therapy is the treatment of choice. It can be administered with other therapies, and even with several techniques of radiotherapy. Due to the greater efficiency and control of extracerebral disease with chemotherapy, radiation, or targeted therapies, it is necessary in brain metastases to achieve more tumor responses with fewer secondary side effects. Radiosurgery and hypofractionated stereotactic radiotherapy achieve these objectives. Whole brain radiotherapy still seems to have a role in certain tumor indications and according to the number and origin of brain metastases. Technical improvements of traditional radiotherapy treatment and combinations of focal therapies make the treatment of brain metastasis one of the most exciting in the current oncology settings. [ABSTRACT FROM AUTHOR]

Stereotactic radiosurgery (SRS) is an effective treatment for incompletely resected or recurrent pituitary adenomas characterized by high rates of local control and endocrinological remission. The SRS-associated morbidity is usually considered minimal, but could not be neglected. It is mainly related to new pituitary hormone deficit, and seemingly caused by un-intentional inclusion of the hypothalamus, pituitary stalk and gland in the high-dose irradiation area. We report long-term clinical outcomes of 30 pituitary adenoma patients who received SRS in our institution. Dose was generally prescribed to the 90% isodose line and ranged from 10 to 16 Gy (mean and median 14 Gy). Selection of prescription dose was based on a tumor location and proximity to adjacent radiation-sensitive structures and previous radiotherapy. The length of follow-up varied from 15 to 230 months (mean 102.6 months, median 90 months). Overall, in 28 patients (93%) control of tumor growth was observed during the follow-up. In 19 patients (63%) tumor size was considered stable after SRS, in 9 patients (30%) tumor reduced in size and in 2 patients (7%) tumor progression was observed. Among 26 patients with functioning pituitary adenomas 17 patients (65,4%) had normalization and 4 patients (15,3%) had improvement of endocrinological function. Persistent hypersecretion was observed in 5 patients (19,3%) with functioning pituitary adenomas. New hypopituitarism after SRS treatment was observed in 4 patients (13.3%). The median maximum dose to hypothalamus, pituitary stalk and pituitary gland was 2.33 Gy (range 0.78-6.22 Gy), 11.20 Gy (range 3.17-15.49 Gy) and 12.83 Gy (range 5.00-15.24 Gy), respectively. SRS allows to effectively control tumor growth in 90-100% of patients and in the great part of patients a relatively rapid endocrinological remission is observed. Doses to the structures of hypothalamic-pituitary axis might have influence on the development of radiation-induced hypopituitarism. Every effort should be made to spare these structures as much as possible. [ABSTRACT FROM AUTHOR]

Background: Radiation therapy plays a central role in the management of many childhood malignancies and Helical Tomotherapy (HT) provides potential to decrease toxicity by limiting the radiation dose to normal structures. The aim of this article was to report preliminary results of our clinical experience with HT in pediatric malignancies.Methods: In this study 66 consecutive patients younger than 14 years old, treated with HT at our center between January 2006 and April 2010, have been included. We performed statistical analyses to assess the relationship between acute toxicity, graded according to the RTOG criteria, and several clinical and treatment characteristics such as a dose and irradiation volume.Results: The median age of patients was 5 years. The most common tumor sites were: central nervous system (57%), abdomen (17%) and thorax (6%). The most prevalent histological types were: medulloblastoma (16 patients), neuroblastoma (9 patients) and rhabdomyosarcoma (7 patients). A total of 52 patients were treated for primary disease and 14 patients were treated for recurrent tumors. The majority of the patients (72%) were previously treated with chemotherapy. The median prescribed dose was 51 Gy (range 10-70 Gy). In 81% of cases grade 1 or 2 acute toxicity was observed. There were 11 cases (16,6%) of grade 3 hematological toxicity, two cases of grade 3 skin toxicity and one case of grade 3 emesis. Nine patients (13,6%) had grade 4 hematological toxicity. There were no cases of grade 4 non-hematological toxicities. On the univariate analysis, total dose and craniospinal irradiation (24 cases) were significantly associated with severe toxicity (grade 3 or more), whereas age and chemotherapy were not. On the multivariate analysis, craniospinal irradiation was the only significant independent risk factor for grade 3-4 toxicity.Conclusion: HT in pediatric population is feasible and safe treatment modality. It is characterized by an acceptable level of acute toxicity that we have seen in this highly selected pediatric patient cohort with clinical features of poor prognosis and/or aggressive therapy needed. Despite of a dosimetrical advantage of HT technique, an exhaustive analysis of long-term follow-up data is needed to assess late toxicity, especially in this potentially sensitive to radiation population. [ABSTRACT FROM AUTHOR]

Pembrolizumab (P) is approved in the first-line (1L) setting in patients with squamous cell carcinoma of the head and neck (SCCHN) with a CPS ≥ 1 and has shown promising activity in the locally-advanced (LA) setting. However, there are no alternatives for patients who are platinum-5FU (PF)-unfit and in need of a rapid tumor response. Taxanes are active agents in SCCHN that could effectively substitute 5FU as shown in Keynote-B10, Frail-Immune and DEPEND trials [1-3]. We evaluated the combination of pembrolizumab plus platinum and taxanes (PCT) +/- prophylactic (p) G-CSF in PF-unfit patients at our institution. Retrospective study of patients diagnosed with SCCHN and treated with PCT at Hospital Clínico Universitario San Carlos, Madrid (Spain). A descriptive study, as well as objective response rate (ORR), progression-free survival (PFS), overall survival (OS) and safety in the 1L and in the LA setting, were analyzed. Within the period August 2019 - October 2023, 18 patients (1L: n=6; LA: n=12) were identified. Among 1L: Male/Female: 2/4; age: 65y (56-86). Subsite: oral cavity (OC): n=5, larynx (n=1). Median CPS: 40 (5-80). No. combo PCT cycles: 6 (2-9). No. maintenance P cycles: 4 (1-8). ORR: 67% (2 CR, 2 PR, 2 SD). After a median follow-up (F-U) of 9 months (m) (1 -25), median PFS and OS were 8 m (4.7 - 11.3) and NR (NR-NR), respectively. pG-CSF in 4/6 pts. G3/4 toxicity: G3 neutropenia: 4/6, G3 thrombopenia: 1/6. There were no toxic deaths. Among LA: Male/Female: 8/4; age: 72y (47-96). P + wkCBDCA-paclitaxel: n=10/12; P + 3wkCBDCA-paclitaxel: n=1/12, P + 3wkCDDP-docetaxel: n=1/12. Subsite: oropharynx: n=3, OC: n=5, CUP: n=1, Sinonasal: n=3. Median CPS: 30 (3-100). No. combo PCT cycles: 3 (2-4). No. maintenance P cycles: 0 (0-4). ORR after PCT (n=10): 90% (4 CR, 5 PR, 1 PD). Post-PCT Tx: Surgery: n=3; CRTx: n=5; Maint P: n=6. After a median follow-up (F-U) of 4 m (0-34), median PFS and OS were 6 m (NR - NR) and NR (NR-NR), respectively. pG-CSF in 6/12 pts. G3/4 toxicity: G3 neutropenia: 6/12, G3 thrombopenia: 4/12, G3 pneumonia: 1/12, G3 IR-colitis: 1/12, G4 IR-transaminitis: 1/12. There were no toxic deaths. Updated results for the LA population (as of March 2024) will be presented at the meeting. PCT and particularly weekly PCT +/- pG-CSF is a highly effective and safe chemoimmunotherapy option for PF-unfit patients in need of a rapid response and a positive CPS, both in the 1L and LA settings. Trials with weekly PCT should be conducted in comorbid and/or elderly patients with LA and R/M SCCHN not candidates for high-dose CT and in need of rapid response. [ABSTRACT FROM AUTHOR]

Perioperative accelerated partial breast irradiation with multicatheter interstitial brachytherapy is an alternative to the postoperative option that offers advantages in terms of specificity and comfort for patients as it avoids a second procedure. Since the simulation CT scan is performed 48 hours after the intervention, immediate tissue changes as air gaps can occasionally be observed. To our knowledge, there is no literature published on this regard, so the aim of this study was to assess the impact of significant air gaps when planning and treating multicatheter perioperative breast cancer brachytherapy. Two consecutive cases with air gaps > 6 cc were included. For each case, a planning CT scan was performed 48 hours after the surgical procedure (tumorectomy + catheter insertion). Treatment planning was performed according to the department protocol and administered in an ultra-fractionated scheme: 3 fractions of 745 cGy every 12 hours. A second CT scan was performed right after the last treatment fraction, before the catheter removal. The air gaps have been contoured in both pre and post-treatment CTs and their volumes have been compared. The scans have been fused and the dosimetric differences have been evaluated. A total of 13 catheters have been analyzed in both scans. A volume reduction (-10% and -30% for each case) has been observed in the post-treatment air gap. Of the 13 catheters compared in the CT scans fusion, the catheter position displacement inside CTV was ≤ 1.5 mm in 12 of them (median displacement 1 mm), with one catheter displaced 2.7 mm in the post-treatment CT. Mean CTVD90 and V100 variation in the pre and post-treatment scans were -1.5 and -1.7% respectively. Dose variations in surrounding organs were: Skin Dmax -10 and -3%, Ribs Dmax +15 and +15% and Ipsilateral Lung Dmax +12 and +13%. Dosimetric disparities did not exceed tolerance and coverage limits in any case. With two cases analyzed, the volumetric reduction of the air gaps does not seem to affect the geometry of the implants, with most of the catheters remaining stable in their initial position. Discrete changes in the coverage parameters and doses to OARs fulfill the pre-established constraints. The confirmation of these results as well as the clinical relevance of these changes has to be examined in future studies including more patients. [ABSTRACT FROM AUTHOR]

Accelerated partial breast irradiation (APBI) is a standard technique, and recent published studies in very accelerated programs (VAPBI) have reported promising preliminary data. We are conducting a Phase II trial evaluating the feasibility and outcomes of this technique in the perioperative setting. We are enrolling postmenopausal women with early-stage breast cancer who are candidates for breast conserving surgery. Inclusion criteria are: age ≥ 50 years, tumor size ≤3 cm, cN0, no evidence of distant metastases, hormonosensitive invasive tumors, her2 negative, ki67<20% and negative margins after lumpectomy. Patients with tumors close to the skin (≤5mm), lobular histology, a known mutation of BRCA, linfovascular invasion, with extensive intraductal carcinoma or multifocal tumors are not included. All cases were presented in a multidisciplinary committee and evaluated by a radiation oncologist prior to the surgery. Tumor bed is marked with radiopaque markers. Catheters are implanted with a free-hand technique intraoperatively once the pathologist rules out the axillary involvement and the negative margin status is confirmed. Forty-eight hours after the procedure, CT scan and 3D planning are performed and the final pathological report is obtained. Treatment is then administered, delivering 3 fractions of 7.45Gy in 1.5 days. Clinical and dosimetric data are prospectively collected (acute toxicity as per CTCAE, cosmetic assessment with De Wazer scale). Between November 2021 and December 2022, 31 patients were considered eligible of which 25 (80.6%) fulfilled inclusion criteria and were treated in a single institution. Patient, tumor and implant characteristics are shown in Table 1. Median duration of the catheter insertion was 15 minutes, and a median of seven catheters were implanted (range 5-9). Four patients presented acute toxicity, with three grade 1 hematomas and one grade 2 infection reported. No grade 3 or 4 complications have been described. The early cosmetic assessment was considered excellent or good in 23 patients and fair in 2. Perioperative VAPBI is feasible, safe and comfortable for patients. It allows treatment to be administered with geographic precision (as there is a direct visualization of the tumor bed), minimizing the number of catheters inserted and the CTV volume. Treatment is administered with definitive pathological results and in 1.5 days. Preliminary toxicity and cosmetic results are promising. Long-term control and late toxicity results will be reported with further follow-up. [ABSTRACT FROM AUTHOR]

To assess whether bladder neck (BN) dose has an impact on urinary toxicity in women diagnosed with endometrial cancer (EC) treated with high-dose-rate vaginal cuff brachytherapy (VBT). 98 patients diagnosed with FIGO Stage I EC treated with exclusive VBT after total hysterectomy and bilateral salpingo-oophorectomy ± lymph node dissection between 2016 and 2020 were retrospectively analyzed. Twenty-one Gy in 3 fractions were delivered to the upper 1/3 of the vagina (4 cm) at 5 mm depth. The BN was defined on CT as a 5-mm expansion around the urethra immediately inferior to the Foley balloon. Urinary toxicity was evaluated using the Common Terminology Criteria for Adverse Events (CTACE) version 4.0, and classified into acute (AUT) and chronic (CUT) according to whether they appeared before or after 6 months of VBT. Dysuria, urinary incontinence, urinary urgency, nocturia, bladder tenesmus, hematuria and BN dosimetric parameters per fraction were collected, including maximum dose (Dmax) D2cc, D1cc and D0.5cc. Descriptive analysis has been carried out and parametric tests such as chi-square have been used. The BN mean volume was 2.34 cc (SD +/- 0.17). With a median follow-up 39 months, 33 patients (33.3%) presented AUT and 36 (36.7%) CUT. Grade II AUT was observed in two patients (2%) and grade III in another two (2%). Grade II CUT was observed in six patients (6%) and grade III in three (3%). The most common symptom was incontinence. Twelve (12%) and 27 (27%) patients presented some grade of acute and chronic incontinence, respectively. Dmax > 4.6 Gy and D2cc, D1cc and D0.5cc > 3 Gy was significantly associated with CUT (p <0.04). Regarding symptoms, Dmax > 4.6 Gy, D1cc > 3 Gy, D2cc and D0.5cc > 2.2 Gy were related with chronic urgency and incontinence (p < 0.02 and 0.04, respectively). Our results suggest that dose to the bladder neck is related with chronic urinary toxicity, specially with urgency and incontinence, in EC patients treated with exclusive VBT. Larger sample size is needed to confirm the predictive value of this parameter. [ABSTRACT FROM AUTHOR]