Dosimetric Comparison Between Proton and Photon Radiation Therapies for Pediatric Neuroblastoma.

Purpose: The aim of this study is to determine the most beneficial radiation treatment technique for pediatric patients with thoracic and abdominal neuroblastoma (NBL), through a dosimetric comparison between photon Volumetric Modulated Arc Therapy and proton Intensity-Modulated Proton Therapy treatment plans. Materials and Methods: A retrospective analysis was conducted on a multicentre case series of 19 patients with thoracic and/or abdominal NBL who underwent radiation therapy, following the recommendations of the European protocol for high-risk NBL (HR-NBL2/SIOPEN). The prescribed dose was 21.6 Gy in 12 fractions (1.8 Gy/fraction) delivered over the preoperative disease volume. The dose volume histograms were analyzed for each patient, and a Wilcoxon signed-rank test with a significance level of 0.01 was employed to assess statistical differences between the dosimetric parameters investigated. Two homogeneity indices (HI and newHI) were compared to evaluate the uniformity in dose, delivered to the adjacent vertebrae (VBs_Adj). Results: Both radiation techniques conform to the protocol regarding CTV/PTV coverage for every location. Proton therapy resulted in statistically significant dose sparing for the heart and lungs in supradiaphragmatic locations and for the contralateral kidney, liver, spleen, and bowel in subdiaphragmatic locations. For both techniques, sparing the non-adjacent vertebrae (VBs_NAdj) results more challenging, although promising results were obtained. Furthermore, the dose delivered to the VBs_Adj was not statistically different, in terms of homogeneity, for the 2 radiation techniques that both met the protocol's requirements. Conclusion: This dosimetric analysis highlights the potential of protons to reduce radiation dose to healthy tissue. These findings apply to all the investigated patients, regardless of primary tumor location, making proton therapy a valuable option for the treatment of neuroblastoma. However, a multidisciplinary assessment of each case is essential to ensure the selection of the most effective and suitable treatment modality.

The prognostic value of FIGO staging defined by combining MRI and [18F]FDG PET/CT in patients with locally advanced cervical cancer.

The last version of the FIGO classification recommended imaging tools to complete the clinical assessment of patients with cervical cancer. However, the preferable imaging approach is still unclear. We aimed to explore the prognostic power of Magnetic Resonance Imaging (MRI), contrast-enhanced Computed Tomography (ceCT), and [18F]-Fluorodeoxyglucose Positron Emission Tomography ([18F]FDG-PET)/CT in patients staged for locally advanced cervical cancer (LACC, FIGO stages IB3-IVA). Thirty-six LACC patients (mean age 55.47 ± 14.01, range 31-82) were retrospectively enrolled. All of them underwent MRI, ceCT and [18F]FDG-PET/CT before receiving concurrent chemoradiotherapy. A median dose of 45 Gy (range 42-50.4; 25-28 fractions, 5 fractions per week, 1 per day) was delivered through the external-beam radiation therapy (EBRT) on the pelvic area, while a median dose of 57.5 Gy (range 16-61.1; 25-28 fractions, 5 fractions per week, 1 per day) was administered on metastatic nodes. The median doses for brachytherapy treatment were 28 Gy (range 28-30; 4-5 fractions, 1 every other day). Six cycles of cisplatin or carboplatin were administered weekly. The study endpoints were recurrence-free survival (RFS) and overall survival (OS). Metastatic pelvic lymph nodes at MRI independently predicted RFS (HR 13.271, 95% CI 1.730-101.805; P = 0.027), while metastatic paraaortic lymph nodes at [18F]FDG-PET/CT independently predicted both RFS (HR 11.734, 95% CI 3.200-43.026; P = .005) and OS (HR 13.799, 95% CI 3.378-56.361; P < 0.001). MRI and [18F]FDG-PET/CT findings were incorporated with clinical evidences into the FIGO classification. With respect to the combination of clinical, MRI and ceCT data, the use of next-generation imaging (NGI) determined a stage migration in 10/36 (27.7%) of patients. Different NGI-based FIGO classes showed remarkably different median RFS (stage IIB: not reached; stage IIIC1: 44 months; stage IIIC2: 3 months; P < 0.001) and OS (stage IIB: not reached; stage IIIC1: not reached; stage IIIC2: 14 months; P < 0.001). A FIGO classification based on the combination of MRI and [18F]FDG-PET/CT might predict RFS and OS of LACC patients treated with concurrent chemoradiotherapy.

Neoadjuvant Chemotherapy Followed by Radical Surgery versus Concurrent Chemo-Radiotherapy in the Treatment of Locally Advanced Cervical Cancer: A Multicenter Retrospective Analysis.

OBJECTIVES: This study aims to evaluate oncological outcomes in women affected by locally advanced cervical cancer (LACC) treated by neoadjuvant chemotherapy before radical surgery (NACT + RS) or concurrent chemo-radiotherapy (CCRT). METHODS: This was a multicenter retrospective analysis of data related to women with LACC (FIGO stage IB2-IVA), who were treated by NACT + RS or CCRT between November 2006 and January 2018. The first endpoints were the evaluation of disease-free survival (DFS) and overall survival (OS); univariate and multivariate analyses were performed for identifying the prognostic factors independently associated with these oncological outcomes. RESULTS: Overall, 106 women were included in the analysis; 55 of them (51.9%) underwent NACT + RS and 51 (48.1%) CCRT, respectively. Patients in the NACT + RS group had a significant better five-year DFS and five-year OS than those in the CCRT group (77.4% vs. 33.4%, p < .001 and 93.8% vs. 56.5%, p = .003). In the multivariate analyses, treatment choice (NACT + RS or CCRT) was the only independent prognostic factor for predicting both DFS (HR = 3.954; 95 CI = 1.898-8.236; p < 0.001) and OS (HR = 5.330; 95 CI = 1.563-18.178; p = 0.008). CONCLUSIONS: This retrospective study demonstrated an improved survival outcome for patients undergoing NACT + RS compared with those undergoing CCRT. Our findings seem to support the use of NACT before RS as an effective alternative option to CCRT standard therapy.

Correlation of multimodal 18F-DOPA PET and conventional MRI with treatment response and survival in children with diffuse intrinsic pontine gliomas.

To evaluate the contribution of 18F-dihydroxyphenylalanine (DOPA) PET in association with conventional MRI in predicting treatment response and survival outcome of pediatric patients with diffuse intrinsic pontine gliomas (DIPGs). Methods: We retrospectively analyzed 19 children with newly diagnosed DIPGs who underwent 18F-DOPA PET/CT and conventional MRI within one week of each other at admission and subsequent MRI follow-up. Following co-registration and fusion of PET and MRI, 18F-DOPA uptake avidity and extent (PET tumor volume and uniformity) at admission, along with MRI indices including presence of ring contrast-enhancement, tumor volume at admission and at maximum response following first-line treatment, were evaluated and correlated with overall survival (OS). The association between 18F-DOPA uptake tumor volume at admission and MRI tumor volume following treatment was evaluated. Statistics included Wilcoxon signed-rank and Mann-Whitney U tests, Kaplan-Meier OS curve and Cox analysis. Results: DIPGs with a 18F-DOPA uptake Tumor/Striatum (T/S) ratio >1 presented an OS ≤ 12 months and lower degree of tumor volume reduction following treatment (p = 0.001). On multivariate analysis, T/S (p = 0.001), ring enhancement (p = 0.01) and the degree of MRI tumor volume reduction (p = 0.01) independently correlated with OS. In all patients, areas of increased 18F-DOPA uptake overlapped with regions demonstrating more prominent residual components/lack of response following treatment. Conclusions:18F-DOPA PET provides useful information for evaluating the metabolism of DIPGs. T/S ratio is an independent predictor of outcome. 18F-DOPA uptake extent delineates tumoral regions with a more aggressive biological behaviour, less sensitive to first line treatment.

Radiation-Induced Moyamoya Syndrome in Children with Brain Tumors: Case Series and Literature Review.

BACKGROUND: Over the last decades, significant advancements have been achieved in the treatment of pediatric brain tumors as a result of radiation therapy (RT). With the increasing diffusion of this treatment, iatrogenic damage to cerebrovascular tissues contouring the radiation target volume has become the subject of debate, especially radiation-induced moyamoya syndrome (RIMS). METHODS: A systematic literature search was performed on the association between moyamoya vasculopathy and cranial irradiation in children. Large case series of patients with moyamoya were analyzed and clinicoradiologic data were collected reviewing pediatric patients treated with RT for primary brain tumors at our institution. RESULTS: The risk of developing RIMS is higher in younger children, in patients with optic pathway glioma, and in those receiving higher radiation doses. Headache is the most common presenting symptom and cerebral infarction is frequent. The preferred surgical techniques were pial synangiosis and encephaloduroarteriosynangiosis. In our case series, surgical revascularization led to neovascularization, with clinical improvement or stability in all patients. Medical therapy did not significantly affect the clinical course. CONCLUSIONS: Pediatric patients receiving involved field RT for the treatment of brain tumors have an increased risk of developing RIMS. Prompt diagnosis and early surgical revascularization play a pivotal role in decreasing the clinical impact of this complication. The use of new techniques, such as the intensity-modulated RT, and the increasing dose saving for the organs at risk, are essential to prevent iatrogenic vasculopathy. The combination of appropriate medical therapy and surgery will improve patient management and clinical outcome.

Accelerated partial breast irradiation via the mammosite catheter: preliminary reports of a single-institution experience.

Several studies have shown that the majority of in-breast recurrences following lumpectomy are at or near the original tumor site while ipsilateral breast recurrences further a field occur rarely. This suggests that the radiation dose could be delivered exclusively to the tumor bed, allowing larger fractions to be used without increasing toxicity and shortening the total treatment time. We investigated the use of the MammoSite irradiation system with a view to analyzing complications, cosmesis and patient comfort. Between 2004 and 2007 intracavity brachytherapy was given to 30 patients using the MammoSite device. The reference isodose was prescribed to the lumpectomy cavity with a 1 cm margin. Geometric parameters and anatomic position of the applicator after implantation were checked via CT, x-ray and ultrasound. Analysis was done for patient quality of life, cosmesis, early and late complications. Forty-nine patients received a proposal for MammoSite brachytherapy. Nine declined, 40 enrolled while 10 were excluded for various reasons (Table 5). A total of 30 patients were actually treated to 34 Gy (2 x 3.4 Gy) in 5 days. We observed 3 cases (10%) of infection within 3 months of implantation. Symptomatic seroma was seen in five patients (16.6%) at 6 months, in three (10%) at 12 months, and in just one patient (3.3%) at 18 months. Good to excellent cosmetic results were achieved in 75% by patient and physician ratings. Accelerated partial breast irradiation using the MammoSite catheter produces favorable short-term outcomes, limited toxic effects on skin, and optimal cosmetic results. Patient tolerance for the treatment is very high. Critical issues may regard the importance of good cavity conformance and adequate balloon-skin distance in avoiding possible dose excesses to the skin. For a selected patient group, this could be a valid alternative to conventional whole breast irradiation.

Repeated Stereotactic Radiosurgery in Brain Metastases: A Case Report.

The aims of radiation therapy of brain metastases include maintaining neurocognitive function and control of disease and, hopefully, improvement of survival. We present a case report with a very long survival in which the role of repeated stereotactic radiosurgery (SRS) was investigated for a patient with a recurrent brain metastasis from non-small cell lung cancer in the same area. Stereotactic re-irradiation was successful and well-tolerated with no neurological toxicity after 16 months.

Neuroendocrine late effects after tailored photon radiotherapy for children with low grade gliomas: Long term correlation with tumour and treatment parameters.

PURPOSE: To evaluate neuroendocrine late effects in paediatric patients with low grade glioma (LGG) who underwent radiotherapy. METHODS AND MATERIAL: We performed a retrospective evaluation of 40 children with LGG treated from July 2002 to January 2015 with external radiotherapy. Tumour locations were cerebral hemisphere (n=2); posterior fossa (n=15); hypothalamic-pituitary axis (HPA, n=15); spine (n=5). Three patients presented a diffuse disease. We looked for a correlation between endocrine toxicity and tumour and treatment parameters. The impact of some clinical and demographic factors on endocrinal and neuro toxicity was evaluated using the log-rank test. RESULTS: The median follow-up was 52months (range: 2-151). Median age at irradiation was 6. The dose to the HPA was significantly associated with endocrine toxicity (P value=0.0190). Patients who received chemotherapy before radiotherapy and younger patients, showed worse performance status and lower IQ. The 5-year overall survival (OS) and progression free survival (PFS) rates were 94% and 73.7%, respectively. CONCLUSION: Radiotherapy showed excellent OS and PFS rates and acceptable late neuroendocrine toxicity profile in this population of LGG patients treated over a period of 13years. In our experience, the dose to the HPA was predictive of the risk of late endocrine toxicity.

Complete response in a patient with gynecological hidradenocarcinoma treated with exclusive external beam radiotherapy and brachytherapy: a case report.

Hidradenocarcinoma (HC) is a very rare disease. This case report illustrates a successful treatment of a 60-year-old woman with vulvo-vaginal localization of hidradenocarcinoma treated with external beam radiotherapy delivered by helical tomotherapy with a simultaneous integrated boost (SIB), followed by brachytherapy. External beam radiotherapy dose prescription was 50.4 Gy in 28 fractions, five fractions per week to whole pelvis (planning target volume 1 - PTV1), 60.2 Gy in 28 fractions to SIB1 (fundus of uterus and right inguinal node), and 58.8 Gy in 28 fractions to SIB2 (lower/middle third of vagina, paraurethral region and right inguinal lymph nodes). Brachytherapy dose prescription was 28 Gy in 4 fractions for cervix, fundus of uterus and upper third of vagina (HR-CTV1), and 22 Gy in 4 fractions to middle third of vagina and paraurethral region (HR-CTV2). D90 for whole treatment was 91.9 Gy and 86.0 Gy for HR-CTV1 and HR-CTV2, respectively. Patient remained 12-months disease-free without treatment related side effects.

Pediatric craniospinal irradiation with conventional technique or helical tomotherapy: impact of age and body volume on integral dose.

PURPOSE: The use of helical tomotherapy (HT) for craniospinal irradiation (CSI) in pediatric patients remains an issue of discussion. In this study, we evaluated the integral dose (ID) to organs at risk (OARs) and to the whole body delivered with conventional 3-dimensional conformal radiotherapy (3D-CRT) and HT for pediatric patients and made a comparison according to different whole body volumes. METHODS: We selected 10 pediatric patients with different body volumes and of different ages undergoing CSI. Plans for 3D-CRT and HT were developed for each patient. The ID to OARs and to the whole body were compared and statistical analyses were performed to determine differences. RESULTS: We noticed that variations of ID depend on the different anatomical location of the organs relatively to the target, with lower ID to OARs opposed to the target and increased ID to lateral organs: ID tomotherapy/3D-CRT ratio was higher in lungs, kidneys, and mammary region, while it was lower in heart, liver, thyroid, and esophagus. The ID of the body increased with large volumes both in HT and in 3D-CRT plans, but in tomotherapy plans ID increased significantly more with large volumes than with small ones. CONCLUSIONS: While there are no differences in using tomotherapy or 3D-CRT with small body volumes, we found a difference with large volumes (≥20,000 mL vs ≤20,000 mL). Therefore, for very small patients, the use of intensity-modulated radiotherapy provided with tomotherapy to reduce the dose to OARs can be reconsidered.

Survey on gynecological cancer treatment by Piedmont, Liguria, and Valle d'Aosta group of AIRO (Italian Association of Radiation Oncology).

PURPOSE: We focused the attention on radiation therapy practices about the gynecological malignancies in Piedmont, Liguria, and Valle d'Aosta to know the current treatment practice and to improve the quality of care. MATERIAL AND METHODS: We proposed a cognitive survey to evaluate the standard practice patterns for gynecological cancer management, adopted from 2012 to 2014 by radiotherapy (RT) centers with a large amount of gynecological cancer cases. There were three topics: 1. Taking care and multidisciplinary approach, 2. Radiotherapy treatment and brachytherapy, 3. Follow-up. RESULTS: Nineteen centers treated gynecological malignancies and 12 of these had a multidisciplinary dedicated team. Radiotherapy option has been used in all clinical setting: definitive, adjuvant, and palliative. In general, 1978 patients were treated. There were 834 brachytherapy (BRT) treatments. The fusion between diagnostic imaging (magnetic resonance imaging - MRI, positron emission tomography - PET) and computed tomography (CT) simulation was used for contouring in all centers. Conformal RT and intensity modulated radiation therapy (IMRT) were the most frequent techniques. The image guided radiation therapy (IGRT) was used in 10/19 centers. There were 8 active BRT centers. Brachytherapy was performed both with radical intent and as boost, mostly by HDR (6/8 centers). The doses for exclusive BRT were between 20 to 30 Gy. The doses for BRT boost were between 10 and 20 Gy. Four centers used CT-MRI compatible applicators but only one used MRI for planning. The BRT plans on vaginal cuff were still performed on traditional radiographies in 2 centers. The plan sum was evaluated in only 1 center. Only 1 center performed in vivo dosimetry. CONCLUSIONS: In the last three years, multidisciplinary approach, contouring, treatment techniques, doses, and control systems were similar in Liguria-Piedmont and Valle d'Aosta. However, the technology implementation didn't translate in a real treatment innovation so far.

Radiosurgery with Helical Tomotherapy: Outcomes for Patients with One or Multifocal Brain Metastasis.

To evaluate the feasibility and report the preliminary results for stereotactic radiosurgery (SRS) treatments of single or multiple brain metastases delivered with helical tomotherapy (HT) by means of the InterFix™ Radiosurgery kit. Between September 2010 and August 2012, thirty patients underwent SRS for treatment of 46 brain metastases with a median prescription dose of 20 Gy (range 15-21 Gy). Clinical response was assessed with 2-3 month intervals by magnetic resonance imaging (MRI). Dose distribution indexes were computed and compared with published data for SRS performed with dedicated machines. After a median follow-up of 14 months (range 4-31) the estimated overall survival (OS) rate was 70% at 6 months, 60% at 12 months and 44% at 18 months. Local control (LC) was 72% at 6 months, 65% at 12 months and 50% at 18 months. Acute toxicity as headache and epileptic crisis occurred in only two patients. The mean values of conformity, homogeneity and gradient score indexes were 1.36, 1.04 and 50 respectively. HT-SRS for single or multiple brain metastases appears a reliable technique with encouraging clinical outcomes and competitive dosimetrical results.

Mono-institutional Italian experience with a double-lumen balloon-brachytherapy device for early breast cancer: results at a 5-year minimum follow-up.

AIMS AND BACKGROUND: To report the 5-year minimum follow-up in low-risk breast cancer patients treated with a double-lumen balloon-brachytherapy device in one mono-institutional Italian experience. Local control data and cosmetic outcomes were collected and analyzed. METHODS: Between October 2004 and December 2007, we treated 30 early stage breast cancer patients who underwent conservative surgery followed by adjuvant accelerated partial breast irradiation with a double-lumen balloon-brachytherapy system. Eligibility criteria for the protocol were based on the indications of the American Brachytherapy Society and the American Society of Breast Surgeons. The device was placed inside the lumpectomy cavity during surgery by open technique in all the patients. Computed tomography images and standard X-ray were used for treatment planning. The total irradiation dose was 34 Gy in 10 fractions of 3.4 Gy (twice daily) over 5 days to the lumpectomy cavity. RESULTS: Median follow-up was 80.5 months (range, 60-98). No patient developed local recurrence or distant metastasis. At the end of treatment, there was evidence of a symptomatic seroma in 83% of the total patients, with a yearly decreasing trend. However, the incidence of mild and moderate fibrosis progressively increased. Seventy-seven percent of the patients were satisfied with their cosmetic results. CONCLUSIONS: Our findings reinforce the hypothesis that an accelerated double-lumen balloon-breast brachytherapy catheter in selected low-risk patients is safe, and a favorable cosmetic outcome can be achieved.

Two different hypofractionated breast radiotherapy schedules for 113 patients with ductal carcinoma in situ: preliminary results.

AIM: To assess local control and cosmetic outcomes for two different hypofractionated radiotherapy schedules after breast-conserving surgery for ductal carcinoma in situ (DCIS). PATIENTS AND METHODS: A total of 113 breast-conserving operated patients with DCIS were treated from August 2006 to August 2011: 41 women received 46 Gy in 20 fractions of 2.3 Gy four times a week, for five weeks; the other 72 patients received 39 Gy in 13 fractions of 3 Gy four times a week for 3.5 weeks. Both schedules involved a concomitant boost to the tumor bed, with dose adjustment according to the surgical margins. RESULTS: The median follow-up is 30.5 months. Overall, the treatments were well-tolerated. The most common acute effect was erythema: grade 1 in 56.1% and 31.9% in the longer and in the shorter hypofractionated treatment, grade 2 in 9.8% and 0% of cases respectively. Late toxicity of fibrosis occurred at grade 1 in 19.6% and 15.3% respectively and at grade 2 in 0% and 2.8%. CONCLUSION: These results suggest that patients with DCIS can be safely treated with a shorter radiotherapy regimen.

Adjuvant hypofractionated radiotherapy with weekly concomitant boost for women with early breast cancer: the clinical experience at Genoa university.

UNLABELLED: The aim of this investigation was to evaluate the feasibility of a shortened whole-breast irradiation schedule with a concomitant boost delivered to the tumor bed once-a-week in patients with early breast cancer submitted to conservative surgery. PATIENTS AND METHODS: Patients with pT1 and pT2 M0 carcinoma of the breast were selected. The basic course consisted of 4600 cGy to the whole breast in 20 fractions, 4 times a week, for 5 weeks. Once a week, a concomitant boost of 120 cGy was delivered to the lumpectomy area. RESULTS: From March 2007 to August 2008, we assessed this radiotherapy schedule in 377 patients. According to the RTOG/EORTC Toxicity Criteria, at treatment completion, 85% of patients showed G0-1, 12% G2 and 3% G3 skin toxicity. At 24 months, late toxicity was G0 in 92%, G1 in 7% and G2 in 1%; cosmesis was excellent or good in 95% of patients. To date, at a median follow-up of 33 months, no patient has yet experienced local relapse. CONCLUSION: A shortened whole-breast irradiation schedule with a weekly concomitant boost may be an alternative option with acceptable toxicity and excellent cosmesis.