The 2022 Assisi Think Tank Meeting: White paper on optimising radiation therapy for breast cancer.

The present white paper, referring to the 4th Assisi Think Tank Meeting on breast cancer, reviews state-of-the-art data, on-going studies and research proposals. <70% agreement in an online questionnaire identified the following clinical challenges: 1: Nodal RT in patients who have a) 1-2 positive sentinel nodes without ALND (axillary lymph node dissection); b) cN1 disease transformed into ypN0 by primary systemic therapy and c) 1-3 positive nodes after mastectomy and ALND. 2. The optimal combination of RT and immunotherapy (IT), patient selection, IT-RT timing, and RT optimal dose, fractionation and target volume. Most experts agreed that RT- IT combination does not enhance toxicity. 3: Re-irradiation for local relapse converged on the use of partial breast irradiation after second breast conserving surgery. Hyperthermia aroused support but is not widely available. Further studies are required to finetune best practice, especially given the increasing use of re-irradiation.

Correlation of [18F] FDG-PET/CT with dosimetry data: recurrence pattern after radiotherapy for head and neck carcinoma.

OBJECTIVE: To analyze the pattern of failure in relation to pre-treatment [18F] FDG-PET/CT uptake in head and neck squamous cell carcinoma (HNSCC) patients treated with definitive radio-chemotherapy (RT-CHT). METHODS AND MATERIALS: From 2012 to 2016, 87 HNSCC patients treated with definitive RT-CHT, with intensity modulated radiation therapy with simultaneous integrated boost, underwent pre-treatment [18F] FDG-PET/CT (PETpre), and MRI/CT for radiotherapy (RT) planning purposes. Patients with local recurrence, received [18F] FDG-PET/CT, (PETrec) at the time of the discovery of recurrence. In these patients, the metabolic target volume (MTV), MTVpre and MTVrec were segmented on PET images by means of an adaptive thresholding algorithm. The overlapping volume between MTVpre and MTVrec (MTVpre&rec) was generated and the dose coverage of MTVrec and MTVpre&rec was checked on the planning CT using the D99 and D95 dose metrics. The recurrent volume was defined as: ''In-Field (IF)'', "Marginal recurrence" or ''Out-of-Field (OF)'' if D95 was respectively equal or higher than 95%, D95 was between 95 and 20% or the D95 was less than 20% of prescribed dose. RESULTS: We found 10/87 patients (11.5%) who had recurrence at primary site. Mean MTVpre was 12.2 cc (4.6-28.9 cc), while the mean MTVrec was 4.3 cc (1.1-12.7 cc). Two recurrences resulted 100% inside MTVpre, 4 recurrences were mostly inside (61-91%) and 4 recurrences were marginal to MTVpre (1-33%). At dosimetric analysis, five recurrences (50%) were IF, 4 (40%) marginal and one (10%) OF. The mean D99 of the overlapping volumes MTVpre&rec was 68.1 Gy (66.5-69.2 Gy), considering a prescription dose of 70 Gy to the planning target volume (PTV). CONCLUSION: Our study shows that the recurrence may originate from the volume with the highest FDG-signal. Tumor relapse in the high-dose volume support the hypothesis that an intensification of the dose on these volumes could be further assessed to prevent local relapse.

The spine instability neoplastic score (SINS) in the assessment of response to radiotherapy for bone metastases

Background. Vertebral metastases are often causing pain and spine instability. Radiotherapy is of significant benefit for painful spine metastases but the response can be very variable. The spine instability neoplastic score (SINS) is a recent classification system for diagnosis of spinal instability caused by vertebral metastases. We analysed the degree of pain relief, the need of drug therapy and the imaging features and the SINS before and after radiotherapy. In particular, we investigated the possible correlation of spine instability defined by pre-treatment SINS with pretreatment pain and with response to radiotherapy. Material/methods. This study included 121 patients with spine metastases treated with palliative 3D conformal radiotherapy. Pain “at rest” and “breakthrough pain”, need for drug therapy in terms of "anti-inflammatory", "weak opioid", "strong opioid", imaging studies and SINS were assessed before and after radiotherapy. Statistical analysis was performed by the correlation coefficient of Spearman and Kruskal-Wallis test. Results. Pain relief after radiotherapy was observed in 50.4 and 57.8% of patients in terms of pain at rest and breakthrough pain, respectively. The correlation between pain before radiotherapy and SINS was not statistically significant for both pain at rest (p = 0.4) and breakthrough pain (p = 0.49). The correlation between pain response after radiotherapy and SINS was statistically significant for both pain at rest (p = 0.007) and breakthrough pain (p = 0.047). Discussion/conclusion. The degree of instability, classified according to SINS, resulted to be predictive factor for pain response after radiotherapy. SINS might become a valid tool to identify those patients who can benefit the most from radiotherapy (AU)

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Prediction of local and metastatic recurrence in solitary fibrous tumor: construction of a risk calculator in a multicenter cohort from the French Sarcoma Group (FSG) database.

BACKGROUND: Solitary fibrous tumors (SFT) are rare unusual ubiquitous soft tissue tumors that are presumed to be of fibroblastic differentiation. At present, the challenge is to establish accurate prognostic factors. PATIENTS AND METHODS: A total of 214 consecutive patients with SFT diagnosed in 24 participating cancer centers were entered into the European database (www.conticabase.org) to perform univariate and multivariate analysis for overall survival (OS), local recurrence incidence (LRI) and metastatic recurrence incidence (MRI) by taking competing risks into account. A prognostic model was constructed for LRI and MRI. Internal and external validations of the prognostic models were carried out. An individual risk calculator was carried out to quantify the risk of both local and metastatic recurrence. RESULTS: We restricted our analysis to 162 patients with local disease. Twenty patients (12.3%) were deceased at the time of analysis and the median OS was not reached. The LRI rates at 10 and 20 years were 19.2% and 38.6%, respectively. The MRI rates at 10 and 20 years were 31.4% and 49.8%, respectively. Multivariate analysis retained age and mitotic count tended to significance for predicting OS. The factors influencing LRI were viscera localization, radiotherapy and age. Mitotic count, tumor localization other than limb and age had independent values for MRI. Three prognostic groups for OS were defined based on the number of unfavorable prognostic factors and calculations were carried out to predict the risk of local and metastatic recurrence for individual patients. CONCLUSION: LRI and MRI rates increased between 10 and 20 years so relapses were delayed, suggesting that long-term monitoring is useful. This study also shows that different prognostic SFT sub-groups could benefit from different therapeutic strategies and that use of a survival calculator could become standard practice in SFTs to individualize treatment based on the clinical situation.

The spine instability neoplastic score (SINS) in the assessment of response to radiotherapy for bone metastases.

BACKGROUND: Vertebral metastases are often causing pain and spine instability. Radiotherapy is of significant benefit for painful spine metastases but the response can be very variable. The spine instability neoplastic score (SINS) is a recent classification system for diagnosis of spinal instability caused by vertebral metastases. We analysed the degree of pain relief, the need of drug therapy and the imaging features and the SINS before and after radiotherapy. In particular, we investigated the possible correlation of spine instability defined by pre-treatment SINS with pretreatment pain and with response to radiotherapy. MATERIAL/METHODS: This study included 121 patients with spine metastases treated with palliative 3D conformal radiotherapy. Pain "at rest" and "breakthrough pain", need for drug therapy in terms of "anti-inflammatory", "weak opioid", "strong opioid", imaging studies and SINS were assessed before and after radiotherapy. Statistical analysis was performed by the correlation coefficient of Spearman and Kruskal-Wallis test. RESULTS: Pain relief after radiotherapy was observed in 50.4 and 57.8% of patients in terms of pain at rest and breakthrough pain, respectively. The correlation between pain before radiotherapy and SINS was not statistically significant for both pain at rest (p = 0.4) and breakthrough pain (p = 0.49). The correlation between pain response after radiotherapy and SINS was statistically significant for both pain at rest (p = 0.007) and breakthrough pain (p = 0.047). DISCUSSION/CONCLUSION: The degree of instability, classified according to SINS, resulted to be predictive factor for pain response after radiotherapy. SINS might become a valid tool to identify those patients who can benefit the most from radiotherapy.

Best practices for the management of local-regional recurrent chordoma: a position paper by the Chordoma Global Consensus Group.

Chordomas are rare, malignant bone tumors of the skull-base and axial skeleton. Until recently, there was no consensus among experts regarding appropriate clinical management of chordoma, resulting in inconsistent care and suboptimal outcomes for many patients. To address this shortcoming, the European Society of Medical Oncology (ESMO) and the Chordoma Foundation, the global chordoma patient advocacy group, convened a multi-disciplinary group of chordoma specialists to define by consensus evidence-based best practices for the optimal approach to chordoma. In January 2015, the first recommendations of this group were published, covering the management of primary and metastatic chordomas. Additional evidence and further discussion were needed to develop recommendations about the management of local-regional failures. Thus, ESMO and CF convened a second consensus group meeting in November 2015 to address the treatment of locally relapsed chordoma. This meeting involved over 60 specialists from Europe, the United States and Japan with expertise in treatment of patients with chordoma. The consensus achieved during that meeting is the subject of the present publication and complements the recommendations of the first position paper.

Quality of life in patients treated by adjuvant radiotherapy for endometrial and cervical cancers: correlation with dose-volume parameters

Introduction: Modern multidisciplinary cancer treatments aim at obtaining minimal influence on patients’ quality of life (QoL). The purpose of this study was to assess QoL and correlate it with dose-volume parameters of organ at risks (OARs) in patients who received adjuvant radiotherapy for endometrial and cervical cancers. Materials and methods: We administered the EORTC QLQ-C30 and EN24 or CX24 questionnaires to 124 patients, 100 with endometrial cancer and 24 with cervical cancer treated with postoperative radiotherapy ± chemotherapy in regular follow-up. Bladder function, fecal incontinence or urgency and sexual functioning were investigated and correlated with dose-volume parameters of OAR by multiple linear regression analysis. This correlation was assessed by R2 value. Results: QoL was very high in the majority of patients (82.3 % of patients). Few patients referred urinary incontinence (3.2 %) or abdominal discomfort of high grade (4.0 %). We found a significant correlation between bladder V40, i.e., absolute percentage of bladder volume that received a dose of 40 Gy, and global health status (p < 0.05, R 2 = 0.17), urinary urgency (p < 0.05, R 2 = 0.24), urinary incontinence (p < 0.05, R 2 = 0.23) and dyspareunia (p < 0.05, R 2 = 0.04). We found also a correlation between global health status and mean dose to vagina (p < 0.05, R 2 = 0.17) and between maximum dose to lumbo-sacral plexus and abdominal pain (p < 0.05, R 2 = 0.07). Conclusions: Women treated with surgery and adjuvant radiotherapy for endometrial and cervical cancers have good QoL with minimal limitations of daily activities. QoL was correlated with dose-volume parameters such as bladder V40, mean dose to vagina, maximum dose to trigone and LSP

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Common European Mitochondrial Haplogroups in the Risk for Radiation-induced Subcutaneous Fibrosis in Breast Cancer Patients.

AIMS: The contribution of mitochondrial DNA (mtDNA) variations to clinical radiosensitivity is largely unknown. In the present study, we evaluated the association between mtDNA haplogroups and the risk of radiation-induced subcutaneous fibrosis after postoperative radiotherapy in breast cancer patients. MATERIALS AND METHODS: Subcutaneous fibrosis was scored according to the Late Effects of Normal Tissue-Subjective Objective Management Analytical (LENT-SOMA) scale in 286 Italian breast cancer patients who received radiotherapy after breast-conserving surgery. Eight mtDNA single nucleotide polymorphisms that define the nine major haplogroups in the European population were determined by polymerase chain reaction restriction fragment length polymorphism analysis on genomic DNA extracted from peripheral blood. RESULTS: In a Kaplan-Meier analysis evaluated by the Log-rank test, carriers of haplogroup H were found to be at lower risk of grade ≥2 subcutaneous fibrosis (P = 0.018) compared with all other haplotypes combined. In the multivariate Cox regression analysis adjusted for clinical factors (body mass index, breast diameter, adjuvant treatment, dose per fraction, radiation type and acute skin toxicity), haplogroup H emerged as a protective factor for moderate to severe radiation-induced fibrosis at a nominal significance level (hazard ratio: 0.50, 95% confidence interval 0.27-0.92, P = 0.027), which did not survive correction for multiple testing. CONCLUSIONS: Our results suggest a protective effect of the mitochondrial haplogroup H in the development of radiation-induced fibrosis in breast cancer patients. However, the loss of statistical significance after correction for multiple comparisons and the lack of an independent validation cohort make our findings preliminary, requiring further confirmation in large-scale prospective studies.

Concurrent chemo-radiotherapy in elderly patients: tolerance and compliance in a series of 137 patients.

INTRODUCTION: Aggressive cancer treatment is a challenge in elderly patients. The present study aims to assess tolerance in terms of acute toxicity and compliance of concurrent chemo-radiotherapy (cCRT) in a series of patients aged ≥70 years. MATERIALS AND METHODS: Clinical records of patients aged ≥70 years who underwent cCRT between January 2005 and December 2013 were reviewed. Concurrent CRT had curative intent in 134 patients (97.8 %) and palliative intent in 3 patients (2.2 %). Chemotherapy (CT) drugs and schedule were selected according to tumor histology. Radiotherapy median dose was 45.0 Gy (range 11-70 Gy) for curative purposes and 54 Gy (range 40-56 Gy) for palliative purposes. Incidence of acute toxicity and compliance to cCRT were analyzed and correlated with age, Karnofsky Performance Status (KPS), and Charlson Comorbidity Index (CCI). RESULTS: Overall, 137 patients, 82 males (60 %) and 55 females (40 %), median age 74 years (range 70-90 years) were analyzed. Concurrent CRT schedule was completed by 132 patients (96.4 %). Thirty-one of these patients (23.5 %) temporarily interrupted treatment. Hematological toxicity with grade ≥1 was observed in 25 patients (18.2 %), gastrointestinal toxicity in 55 (40.1 %), and genitourinary in 13 (9.5 %). Mucositis with grade ≥1 was recorded in 19 patients (13.9 %). No statistical significant correlation between KPS, CCI, and toxicity was found. A correlation trend between mucositis and patient age (p = 0.05) was observed. CONCLUSION: Concurrent CRT for elderly was feasible and quite well tolerated. Great attention in prescribing CT dose should be paid to limit acute toxicity.

Quality of life in patients treated by adjuvant radiotherapy for endometrial and cervical cancers: correlation with dose-volume parameters.

INTRODUCTION: Modern multidisciplinary cancer treatments aim at obtaining minimal influence on patients' quality of life (QoL). The purpose of this study was to assess QoL and correlate it with dose-volume parameters of organ at risks (OARs) in patients who received adjuvant radiotherapy for endometrial and cervical cancers. MATERIALS AND METHODS: We administered the EORTC QLQ-C30 and EN24 or CX24 questionnaires to 124 patients, 100 with endometrial cancer and 24 with cervical cancer treated with postoperative radiotherapy ± chemotherapy in regular follow-up. Bladder function, fecal incontinence or urgency and sexual functioning were investigated and correlated with dose-volume parameters of OAR by multiple linear regression analysis. This correlation was assessed by R (2) value. RESULTS: QoL was very high in the majority of patients (82.3 % of patients). Few patients referred urinary incontinence (3.2 %) or abdominal discomfort of high grade (4.0 %). We found a significant correlation between bladder V40, i.e., absolute percentage of bladder volume that received a dose of 40 Gy, and global health status (p < 0.05, R (2) = 0.17), urinary urgency (p < 0.05, R (2) = 0.24), urinary incontinence (p < 0.05, R (2) = 0.23) and dyspareunia (p < 0.05, R (2) = 0.04). We found also a correlation between global health status and mean dose to vagina (p < 0.05, R (2) = 0.17) and between maximum dose to lumbo-sacral plexus and abdominal pain (p < 0.05, R (2) = 0.07). CONCLUSIONS: Women treated with surgery and adjuvant radiotherapy for endometrial and cervical cancers have good QoL with minimal limitations of daily activities. QoL was correlated with dose-volume parameters such as bladder V40, mean dose to vagina, maximum dose to trigone and LSP.

Could machine learning improve the prediction of pelvic nodal status of prostate cancer patients? Preliminary results of a pilot study.

We tested and compared performances of Roach formula, Partin tables and of three Machine Learning (ML) based algorithms based on decision trees in identifying N+ prostate cancer (PC). 1,555 cN0 and 50 cN+ PC were analyzed. Results were also verified on an independent population of 204 operated cN0 patients, with a known pN status (187 pN0, 17 pN1 patients). ML performed better, also when tested on the surgical population, with accuracy, specificity, and sensitivity ranging between 48-86%, 35-91%, and 17-79%, respectively. ML potentially allows better prediction of the nodal status of PC, potentially allowing a better tailoring of pelvic irradiation.

Interstitial brachytherapy for eyelid carcinoma. Outcome analysis in 60 patients.

BACKGROUND: Eyelid cancer is a therapeutic challenge due to the cosmetic and functional implications of this anatomical region and the objectives of therapy are tumor control, functional and cosmetic outcome. AIM: The present study was performed to analyze local control, toxicity, functional and cosmetic results in patients with eyelid carcinoma treated by interstitial brachytherapy. MATERIAL AND METHODS: In this study 60 patients with eyelid carcinoma were treated by interstitial brachytherapy using iridium ((192)Ir) wires with a linear activity of 1.2-1.7 mCi/cm. The prescription dose was 51-70 Gy (mean 65 Gy, median 66 Gy). RESULTS: Of the 60 patients 51 (85.0 %) had received no prior treatment, 4 (6.7 %) had received previous surgery with positive or close margins and 5 (8.3 %) had suffered local recurrence after surgery. Of the tumors 52 (86.7 %) were basal cell carcinoma, 7 (11.7 %) squamous cell carcinoma and 1 (1.7 %) Merkel cell carcinoma. Clinical stage of the 51 previously untreated tumors was 38 T1N0, 12 T2N0 and 1 T3N0. Mean follow-up was 92 months (range 6-253 months). Local control was maintained in 96.7 % of patients. Late effects higher than grade 2 were observed in 3.0 % of cases. Functional and cosmetic outcomes were optimal in 68.4 % of patients. CONCLUSION: Interstitial brachytherapy for carcinoma of the eyelid can achieve local control, cosmetic and functional results comparable to those of surgery.

Initial clinical experience with scanned proton beams at the Italian National Center for Hadrontherapy (CNAO).

We report the initial toxicity data with scanned proton beams at the Italian National Center for Hadrontherapy (CNAO). In September 2011, CNAO commenced patient treatment with scanned proton beams within two prospective Phase II protocols approved by the Italian Health Ministry. Patients with chondrosarcoma or chordoma of the skull base or spine were eligible. By October 2012, 21 patients had completed treatment. Immobilization was performed using rigid non-perforated thermoplastic-masks and customized headrests or body-pillows as indicated. Non-contrast CT scans with immobilization devices in place and MRI scans in supine position were performed for treatment-planning. For chordoma, the prescribed doses were 74 cobalt grey equivalent (CGE) and 54 CGE to planning target volume 1 (PTV1) and PTV2, respectively. For chondrosarcoma, the prescribed doses were 70 CGE and 54 CGE to PTV1 and PTV2, respectively. Treatment was delivered five days a week in 35-37 fractions. Prior to treatment, the patients' positions were verified using an optical tracking system and orthogonal X-ray images. Proton beams were delivered using fixed-horizontal portals on a robotic couch. Weekly MRI incorporating diffusion-weighted-imaging was performed during the course of proton therapy. Patients were reviewed once weekly and acute toxicities were graded with the Common Terminology Criteria for Adverse Events (CTCAE). Median age of patients = 50 years (range, 21-74). All 21 patients completed the proton therapy without major toxicities and without treatment interruption. Median dose delivered was 74 CGE (range, 70-74). The maximum toxicity recorded was CTCAE Grade 2 in four patients. Our preliminary data demonstrates the clinical feasibility of scanned proton beams in Italy.

Clinical and technical characteristics of intraoperative radiotherapy. Analysis of the ISIORT-Europe database.

BACKGROUND: A joint analysis of clinical data from centres within the European section of the International Society of Intraoperative Radiation Therapy (ISIORT-Europe) was undertaken in order to define the range of intraoperative radiotherapy (IORT) techniques and indications encompassed by its member institutions. MATERIALS AND METHODS: In 2007, the ISIORT-Europe centres were invited to record demographic, clinical and technical data relating to their IORT procedures in a joint online database. Retrospective data entry was possible. RESULTS: The survey encompassed 21 centres and data from 3754 IORT procedures performed between 1992 and 2011. The average annual number of patients treated per institution was 42, with three centres treating more than 100 patients per year. The most frequent tumour was breast cancer with 2395 cases (63.8 %), followed by rectal cancer (598 cases, 15.9 %), sarcoma (221 cases, 5.9 %), prostate cancer (108 cases, 2.9 %) and pancreatic cancer (80 cases, 2.1 %). Clinical details and IORT technical data from these five tumour types are reported. CONCLUSION: This is the first report on a large cohort of patients treated with IORT in Europe. It gives a picture of patient selection methods and treatment modalities, with emphasis on the main tumour types that are typically treated by this technique and may benefit from it.

Dysphagia after definitive radiotherapy for head and neck cancer. Correlation of dose-volume parameters of the pharyngeal constrictor muscles.

BACKGROUND: Dysphagia is a complication of head and neck cancer patients undergoing radiotherapy (RT). We analysed frequency and severity of swallowing dysfunction and correlated these findings with dose-volume histograms (DVHs) of the pharyngeal constrictor muscles. METHODS: A total of 50 patients treated by radical RT were enrolled. DVHs of constrictor muscles were correlated with acute and late dysphagia and with the items of three quality of life questionnaires. RESULTS: Mean dose to superior and middle constrictor muscles (SCM, MCM), partial volume of SCM and MCM receiving a dose ≥ 50 Gy dose to the whole constrictor muscles ≥ 60 Gy and tumour location were associated to late dysphagia at univariate analysis. Mean dose to the MCM was the only statistically significant predictor of late dysphagia at the multivariable analysis. CONCLUSION: The study shows a significant relationship between long-term dysphagia and mean doses to SCM, MCM, whole constrictor muscles, and oropharyngeal tumour. This finding suggests a potential advantage in reducing the RT dose to swallowing structures to avoid severe dysphagia.

Perfusion computed tomography assessments of peri-enhancing brain tissue in high-grade gliomas.

PURPOSE: This study was undertaken to identify tumoural infiltration of peri-enhancing brain tissue in patients with glioblastoma by means of perfusion computed tomography (PCT) parameters, cerebral blood volume (CBV) and permeability surface (PS). MATERIALS AND METHODS: Eight patients with surgically treated glioblastoma who were eligible for radiotherapy and nine patients with brain metastases from lung and breast cancer underwent CT before and after injection of contrast medium. CBV and PS were calculated in the contrast-enhancing lesion area, in the area of perilesional oedema and in the normal-appearing white matter (NAWM), normalised to contralateral symmetrical areas. RESULTS: No significant differences were found for normalised CBV (nCBV) and nPS in NAWM regions between metastasis and glioma. Significant differences in nPS (p<0.005) were found between the typically vasogenic oedema surrounding the metastases and signal alteration surrounding the glial neoplasm. On the contrary, no significant differences were detected in the same areas for nCBV. CONCLUSIONS: PCT can analyse the histopathological substrate underlying the hypodense peritumoural halo and differentiate between vasogenic oedema and neoplastic infiltration on the basis of the PS parameter. In our study, PS was more informative than CBV. These findings can be used to integrate plans for radiation therapy and/or surgery.

Primary pineal tumors: outcome and prognostic factors - a study from the Rare Cancer Network (RCN)

PURPOSE: To better define outcome and prognostic factors in primary pineal tumors. MATERIALS AND METHODS: Thirty-five consecutive patients from seven academic centers of the Rare Cancer Network diagnosed between 1988 and 2006 were included. Median age was 36 years. Surgical resection consisted of biopsy in 12 cases and resection in 21 (2 cases with unknown resection). All patients underwent radiotherapy and 12 patients received also chemotherapy. RESULTS: Histological subtypes were pineoblastoma (PNB) in 21 patients, pineocytoma (PC) in 8 patients and pineocytoma with intermediate differentiation in 6 patients. Six patients with PNB had evidence of spinal seeding. Fifteen patients relapsed (14 PNB and 1 PC) with PNB cases at higher risk (p = 0.031). Median survival time was not reached. Median disease-free survival was 82 months (CI 50 % 28-275). In univariate analysis, age younger than 36 years was an unfavorable prognostic factor (p = 0.003). Patients with metastases at diagnosis had poorer survival (p = 0.048). Late side effects related to radiotherapy were dementia, leukoencephalopathy or memory loss in seven cases, occipital ischemia in one, and grade 3 seizures in two cases. Side effects related to chemotherapy were grade 3-4 leucopenia in five cases, grade 4 thrombocytopenia in three cases, grade 2 anemia in two cases, grade 4 pancytopenia in one case, grade 4 vomiting in one case and renal failure in one case. CONCLUSIONS: Age and dissemination at diagnosis influenced survival in our series. The prevalence of chronic toxicity suggests that new adjuvant strategies are advisable (AU)

A treatment planning code for inverse planning and 3D optimization in hadrontherapy.

The therapeutic use of protons and ions, especially carbon ions, is a new technique and a challenge to conform the dose to the target due to the energy deposition characteristics of hadron beams. An appropriate treatment planning system (TPS) is strictly necessary to take full advantage. We developed a TPS software, ANCOD++, for the evaluation of the optimal conformal dose. ANCOD++ is an analytical code using the voxel-scan technique as an active method to deliver the dose to the patient, and provides treatment plans with both proton and carbon ion beams. The iterative algorithm, coded in C++ and running on Unix/Linux platform, allows the determination of the best fluences of the individual beams to obtain an optimal physical dose distribution, delivering a maximum dose to the target volume and a minimum dose to critical structures. The TPS is supported by Monte Carlo simulations with the package GEANT3 to provide the necessary physical lookup tables and verify the optimized treatment plans. Dose verifications done by means of full Monte Carlo simulations show an overall good agreement with the treatment planning calculations. We stress the fact that the purpose of this work is the verification of the physical dose and a next work will be dedicated to the radiobiological evaluation of the equivalent biological dose.

Threshold segmentation for PET target volume delineation in radiation treatment planning: the role of target-to-background ratio and target size.

A multivariable approach was adopted to study the dependence of the percentage threshold [TH(%)] used to define the boundaries of 18F-FDG positive tissue on emission scan duration (ESD) and activity at the start of acquisition (Aacq) for different target sizes and target-to-background (T/B) ratios. An anthropomorphic model, at least for counting rate characteristics, was used to study this dependence in conditions resembling the ones that can be encountered in the clinical studies. An annular ring of water bags of 3 cm thickness was fitted over an International Electro-technical Commission (IEC) phantom in order to obtain counting rates similar to those found in average patients. The scatter fraction of the modified IEC phantom was similar to the mean scatter fraction measured on patients, with a similar scanner. A supplemental set of microhollow spheres was positioned inside the phantom. The NEMA NU 2-2001 scatter phantom was positioned at the end of the IEC phantom to approximate the clinical situation of having activity that extends beyond the scanner field of view. The phantoms were filled with a solution of water and 18F (12 kBq/mL) and the spheres with various T/B ratios of 22.5, 10.3, and 3.6. Sequential imaging was performed to acquire PET images with varying background activity concentrations of about 12, 9, 6.4, 5.3, and 3.1 kBq/mL. The ESD was set to 60, 120, 180, and 240 s/bed. Data were fitted using two distinct multiple linear regression models for sphere ID < or = 10 mm and sphere ID > 10 mm. The fittings of both models were good with an R2 of 0.86 in both cases. Neither ESD nor Aacq resulted as significant predictors of the TH(%). For sphere ID < or =10 mm the target size was the most significant predictor of the TH(%), followed by the T/B ratio, while for sphere ID > 10 mm the explanatory power of the target size and T/B ratio were reversed, the T/B ratio being now the most important predictor of the TH(%). Both the target size and T/B ratio play a major role in explaining the variance of the TH(%), throughout the whole range of target sizes and T/B ratios examined. Thus, algorithms aimed at automatic threshold segmentation should incorporate both variables with a relative weight which critically depends on target size.