Stereotactic Radiosurgery with Volumetric Modulated Arc Radiotherapy: Final Results of a Multi-arm Phase I Trial (DESTROY-2).

AIMS: To present the final results of a phase I trial on stereotactic radiosurgery (SRS) delivered using volumetric modulated arc therapy (VMAT) in patients with primary or metastatic tumors in different extracranial sites. MATERIALS AND METHODS: The DESTROY-2 trial, planned as a prospective dose escalation study in oligometastatic (one to five lesions) cancer patients relied on the delivery of a single high dose of radiation utilizing high-precision technology. The primary study endpoint was the definition of the maximum tolerated dose (MTD) of SRS-VMAT. The secondary objectives of the study were the evaluation of safety, efficacy, and long-term outcomes. All patients consecutively observed at our radiotherapy unit matching the inclusion criteria were enrolled. Each enrolled subject was included in a different phase I study arm, depending on the tumor site and the disease stage (lung, liver, bone, other), and sequentially assigned to a particular dose level. RESULTS: Two hundred twenty seven lesions in 164 consecutive patients (male/female: 97/67, median age: 68 years; range: 29-92) were treated. The main primary tumors were: prostate cancer (60 patients), colorectal cancer (47 patients), and breast cancer (39 patients). The maximum planned dose level was achieved in all study arms, and the MTD was not exceeded. 34 Gy, 32 Gy, 24 Gy, and 24 Gy were established as the single-fraction doses for treating lung, liver, bone, and other extracranial lesions, respectively. The prescribed BED 2Gyα/ß:10 to the planning target volume ranged from 26.4 Gy to 149.6 Gy. Twenty-seven patients (16.5%) experienced grade 1-2 and only one grade 3 acute toxicity, which was a pulmonary one. In terms of late toxicity, we registered only 5 toxicity>G2: a G3 gastro-intestinal one, three G3 bone toxicity, and a G3 laryngeal toxicity. The overall response was available for 199 lesions: 107 complete response (53.8%), 50 partial response (25.1%), and 31 stable disease (15.6%), leading to an overall response rate of 94.5%. Progression was registered only in 11 cases (5.5%). The overall response rate in each arm ranged from 88.6% to 96.4%. The overall two-year local control, distant metastasis free survival, disease free survival, and overall survival were 81.7%, 33.0%, 25.4%, and 78.7% respectively. CONCLUSION: In conclusion, the planned doses of 34 Gy, 32 Gy, 24 Gy, and 24 Gy were successfully administered as single-fractions for the treatment of lung, liver, bone, and other extracranial lesions, respectively, in a prospective SRS dose-escalation trial. No dose-limiting toxicities were registered, and minimal acute and late toxicity were reported. New indications for SRS are currently being studied in oligoprogressive patients receiving targeted drugs or in combination with immunotherapy. The DESTROY-2 trial represents, in our opinion, a credible starting point for future modern radiosurgery trials.

Contouring of emerging organs-at-risk (OARS) of the female pelvis and interobserver variability: A study by the Italian association of radiotherapy and clinical oncology (AIRO).

Purpose: To provide straightforward instructions for daily practice in delineating emerging organs-at-risk (OARs) of the female pelvis and to discuss the interobserver variability in a two-step multicenter study. Methods and materials: A contouring atlas with anatomical boundaries for each emerging OAR was realized by radiation oncologists and radiologists who are experts in pelvic imaging, as per their knowledge and clinical practice. These contours were identified as quality benchmarks for the analysis subsequently carried out. Radiation oncologists not involved in setting the custom-built contouring atlas and interested in the treatment of gynecological cancer were invited to participate in this 2-step trial. In the first step all participants were supplied with a selected clinical case of locally advanced cervical cancer and had to identify emerging OARs (Levator ani muscle; Puborectalis muscle; Internal anal sphincter; External anal sphincter; Bladder base and trigone; Bladder neck; Iliac Bone Marrow; Lower Pelvis Bone Marrow; Lumbosacral Bone Marrow) based on their own personal knowledge of pelvic anatomy and experience. The suggested OARs and the contouring process were then presented at a subsequent webinar meeting with a contouring laboratory. Finally, in the second step, after the webinar meeting, each participant who had joined the study but was not involved in setting the benchmark received the custom-built contouring atlas with anatomical boundaries and was requested to delineate again the OARs using the tool provided. The Dice Similarity Coefficient (DSC) and the Jaccard Similarity Coefficient (JSC) were used to evaluate the spatial overlap accuracy of the different volume delineations and compared with the benchmark; the Hausdorff distance (HD) and the mean distance to agreement (MDA) to explore the distance between contours. All the results were reported as sample mean and standard deviation (SD). Results: Fifteen radiation oncologists from different Institutions joined the study. The participants had a high agreement degree for pelvic bones sub-structures delineation according to DICE (IBM: 0.9 ± 0.02; LPBM: 0.91 ± 0.01). A moderate degree according to DICE was showed for ovaries (Right: 0.61 ± 0.16, Left: 0.72 ± 0.05), vagina (0.575 ± 0.13), bladder sub-structures (0.515 ± 0.08) and EAS (0.605 ± 0.05), whereas a low degree for the other sub-structures of the anal-rectal sphincter complex (LAM: 0.345 ± 0.07, PRM: 0.41 ± 0.10, and IAS: 0.4 ± 0.07). Conclusion: This study found a moderate to low level of agreement in the delineation of the female pelvis emerging OARs, with a high degree of variability among observers. The development of delineation tools should be encouraged to improve the routine contouring of these OARs and increase the quality and consistency of radiotherapy planning.

Stereotactic Body Reirradiation in Gynaecological Cancer: Outcomes and Toxicities from a Single Institution Experience.

AIMS: To report toxicity profile, outcomes and quality of life (QoL) data in patients with recurrent gynaecological cancer who underwent stereotactic body radiotherapy (SBRT) retreatment. MATERIALS AND METHODS: Data from patients' folders were retrospectively extracted, focusing on the primary neoplasm, previous systemic therapies and previous radiotherapy. Concerning SBRT, the total dose (five daily fractions) was delivered with a linear accelerator using intensity-modulated radiotherapy techniques. Acute and late toxicities were assessed by the CTCAE 4.03 scale. QoL was evaluated according to the Cancer Linear Analogue Scale [CLAS1 (fatigue), CLAS2 (energy level), CLAS3 (daily activities)]. RESULTS: Between December 2005 and August 2021, 23 patients (median age 71 years, range 48-80) with 27 lesions were treated. Most patients had endometrial (34.8%), ovarian (26.1%) and cervical cancer (26.1%) as the primary tumour. The most common SBRT schedules in five fractions were 30 Gy (33.3%), 35 Gy (29.6%) and 40 Gy (29.6%). The median follow-up was 32 months (range 3-128). There were no patients reporting acute or late toxicities higher than grade 2, except for a bone fracture. One- and 2-year local control was 77.9% and 70.8%, respectively. One- and 2-year overall survival was 82.6% and 75.1%, respectively. The overall response rate was 96.0%. Regarding QoL, no statistically significant difference was identified between the baseline and follow-up values: the median CLAS1, CLAS2 and CLAS3 scores for each category were 6 (range 4-10) at baseline and 6 (range 3-10) 1 month after SBRT. CONCLUSIONS: This preliminary experience suggests that SBRT retreatment for recurrent gynaecological cancer is a highly feasible and safe treatment with limited side-effects and no short-term QoL impairment.

Volumetric Intensity-Modulated Arc Stereotactic Radiosurgery Boost in Oligometastatic Patients with Spine Metastases: a Dose-escalation Study.

AIMS: To report the final results of a dose-escalation study of volumetric intensity-modulated arc stereotactic radiosurgery (VMAT-SRS) boost after three-dimensional conformal radiation therapy in patients with spine metastases. MATERIALS AND METHODS: Oligometastatic cancer patients bearing up to five synchronous metastases (visceral or bone, including vertebral ones) and candidates for surgery or radiosurgery were considered for inclusion. 25 Gy was delivered in 10 daily fractions (2 weeks) to the metastatic lesion, affected vertebrae and adjacent ones (one cranial and one caudal vertebra). Sequentially, the dose to spinal metastases was progressively increased (8 Gy, 10 Gy, 12 Gy) in the patient cohorts. Dose-limiting toxicities were defined as any treatment-related non-hematologic acute adverse effects rated as grade ≥3 or any acute haematological toxicity rated as ≥ 4 by the Radiation Therapy Oncology Group scale. RESULTS: Fifty-two lesions accounting for 40 consecutive patients (male/female: 29/11; median age: 71 years; range 40-85) were treated from April 2011 to September 2020. Most patients had a primary prostate (65.0%) or breast cancer (22.5%). Thirty-two patients received 8 Gy VMAT-SRS boost (total BED α/ß10: 45.6 Gy), 14 patients received 10 Gy (total BED α/ß10: 51.2 Gy) and six patients received 12 Gy (total BED α/ß10: 57.6 Gy). The median follow-up time was over 70 months (range 2-240 months). No acute toxicities > grade 2 and no late toxicities > grade 1 were recorded. The overall response rate based on computed tomography/positron emission tomography-computed tomography/magnetic resonance was 78.8%. The 24-month actuarial local control, distant metastases-free survival and overall survival rates were 88.5%, 27.1% and 90.3%, respectively. CONCLUSION: A 12 Gy spine metastasis SRS boost following 25 Gy to the affected and adjacent vertebrae was feasible with an excellent local control rate and toxicity profile.

Stereotactic radiosurgery for bone metastases in oligometastatic prostate cancer patients: DESTROY-2 clinical trial subanalysis.

INTRODUCTION: Aim of this analysis was to report toxicity and clinical outcomes in oligorecurrent prostate cancer (PCa) patients treated with single fraction stereotactic radiosurgery (SRS) for bone metastases. METHODS: We separately analyzed clinical data of PCa patients with bone oligometastases enrolled in a prospective phase I trial (DESTROY-2). DESTROY-2 was based on SRS delivered using volumetric modulated arc therapy in patients with primary or metastatic tumors in several extra-cranial body sites. Acute and late toxicity, biochemical tumor response, local control (LC), distant metastases-free (DPFS), progression-free (PFS), time to next-line systemic treatment-free (NEST-FS), and overall survival (OS) were calculated. RESULTS: Data on 37 PCa patients, carrying out 50 bone metastases, candidates for curative-intent treatment and treated with SRS at our Institution were collected. SRS dose ranged between 12 and 24 Gy. One grade 1 acute skin toxicity in one patient treated on the hip (24 Gy) and one grade 1 late skin toxicity in a patient with a scapular lesion (24 Gy) were recorded. No cases of bone fracture were registered in the treated population. With a median follow-up of 25 months (range 3-72 months) 2-year actuarial LC, DPFS, PFS, and OS were 96.7%, 58.1%, 58.1%, and 95.8%, respectively. Median and 2-year NEST-FS were 30 months (range 1-69 months) and 51.2%, respectively. CONCLUSIONS: Data analysis showed few toxicity events, high local control rate and prolonged NEST-FS after linear accelerator-based radiosurgery of bone oligometastases from PCa. The possibility of postponing systemic treatments in patients with oligometastatic PCa by means of SRS should be taken into account. Further prospective studies on larger series are needed to confirm the reported results.

Stereotactic body radiotherapy to lymph nodes in oligoprogressive castration-resistant prostate cancer patients: a post hoc analysis from two phase I clinical trials.

The prognosis of prostate cancer (PC) is generally favorable but the incidence of metastases is relatively high after the treatment of the primary tumor, especially in high-risk patients. Fractionated stereotactic body radiotherapy (SBRT) or single fraction stereotactic body radiosurgery (SRS) are emerging treatment options in this setting. However, data on SBRT/SRS in patients with metastatic castration-resistant PC (mCRPC) are largely lacking, particularly in subjects with nodal lesions. Therefore, we evaluated outcomes and toxicity recorded in mCRPC patients with nodal oligoprogression. Patients included in this analysis had ≤ 5 metastatic sites without visceral lesions and underwent SBRT/SRS on nodal metastases. Thirty-eight patients carrying out 61 nodal metastases were analyzed. The median SRS dose was 20 Gy (range 12-24 Gy) and the most common schedule was 20 Gy (44.8%). The median SBRT dose was 45 Gy (range 20-50 Gy) and the most common regimen was 45 Gy in 5 fractions (37.9%). Thirty-seven patients (97.4%) showed only grade 0-1 acute toxicity while one patient reported grade 2 dysphagia. In terms of late toxicity, one grade 2 laryngeal, one grade 1 skin and one grade 1 gastrointestinal toxicities were recorded. Two-year actuarial local control (LC), distant progression-free survival, progression-free survival (PFS) and overall survival were 94.0, 47.2, 47.2, and 90.2%, respectively. Two-year next line systemic therapy-free survival (NEST-FS) was 67.7%. In conclusion, the efficacy in terms of LC of SBRT/SRS in patients with nodal metastases from PC was confirmed. Moreover, this analysis suggests the efficacy in terms of PFS and NEST-FS also in the setting of oligoprogressive PC. In fact, about one-third of patients were free from progressive disease and two-third of subjects did not require hormonal therapy switch or discontinuation three years after treatment.

The role of brachytherapy (interventional radiotherapy) for primary and/or recurrent vulvar cancer: a Gemelli Vul.Can multidisciplinary team systematic review.

OBJECTIVE: The aim of our systematic review was to assess the role of interventional radiotherapy (IRT, brachytherapy) in the management of primary and/or recurrent vulvar carcinoma. EVIDENCE ACQUISITION: A systematic research using PubMed, Scopus and Cochrane library was performed. ClinicalTrials.gov was searched for ongoing or recently completed trials, and PROSPERO was searched for ongoing or recently completed systematic reviews. Only full-text English-language articles related to IRT for treatment of primary or recurrent VC were identified and reviewed. Conference paper, survey, letter, editorial, book chapter and review were excluded. Time restriction (1990-2018) as concerns the years of the publication was considered. EVIDENCE SYNTHESIS: Primary disease: the median 5-year LC was 43.5% (range 19-68%); the median 5-year DFS was 44.5% (range 44-81%); the median 5-year OS was 50.5% (range 27-85%). Recurrent disease: the median 5-year DFS was 64% (range 56-72%) and the median 5-year OS was 45% (range 33%-57%). Acute ≥ grade 2 toxicity was reported in three patients (1.6%). The severe late toxicity rates (grade 3-4) ranged from 0% to 14.3% (median 7.7%). CONCLUSION: IRT as part of primary treatment for primary and/or recurrent vulvar cancer is associated with promising clinical outcomes.

Minimally Invasive Approaches in Locally Advanced Cervical Cancer Patients Undergoing Radical Surgery After Chemoradiotherapy: A Propensity Score Analysis.

PURPOSE: Chemoradiation (CT/RT) followed by radical surgery (RS) may play a role in locally advanced cervical cancer (LACC) patients with suboptimal response to CT/RT or in low-income countries with limited access to radiotherapy. Our aim is to evaluate oncological and surgical outcomes of minimally invasive radical surgery (MI-RS) compared with open radical surgery (O-RS). PATIENTS AND METHODS: Data for stage IB2-IVA cervical cancer patients managed by CT/RT and RS were retrospectively analyzed. RESULTS: Beginning with 686 patients, propensity score matching resulted in 462 cases (231 per group), balanced for FIGO stage, lymph node status, histotype, tumor grade, and clinical response to CT/RT. The 5-year disease-free survival (DFS) was 73.7% in the O-RS patients and 73.0% in the MI-RS patients (HR 1.034, 95% CI 0.708-1.512, p = 0.861). The 5-year locoregional recurrence rate was 12.5% (O-RS) versus 15.2% (MI-RS) (HR 1.174, 95% CI 0.656-2.104, p = 0.588). The 5-year disease-specific survival (DSS) was 80.4% in O-RS patients and 85.3% in the MI-RS group (HR 0.731, 95% CI 0.438-1.220, p = 0.228). Estimated blood loss was lower in the MI-RS group (p < 0.001), as was length of hospital stay (p < 0.001). Early postoperative complications occurred in 77 patients (33.3%) in the O-RS group versus 88 patients (38.1%) in the MI-RS group (p = 0.331). Fifty-six (24.2%) patients experienced late postoperative complications in the O-RS group, versus 61 patients (26.4%) in the MI-RS group (p = 0.668). CONCLUSION: MI-RS and O-RS are associated with similar rates of recurrence and death in LACC patients managed by surgery after CT/RT. No difference in early or late complications was reported.

Proteomic analysis of plasma exosomes from Cystic Echinococcosis patients provides in vivo support for distinct immune response profiles in active vs inactive infection and suggests potential biomarkers.

The reference diagnostic method of human abdominal Cystic Echinococcosis (CE) is imaging, particularly ultrasound, supported by serology when imaging is inconclusive. However, current diagnostic tools are neither optimal nor widely available. The availability of a test detecting circulating biomarkers would considerably improve CE diagnosis and cyst staging (active vs inactive), as well as treatments and follow-up of patients. Exosomes are extracellular vesicles involved in intercellular communication, including immune system responses, and are a recognized source of biomarkers. With the aim of identifying potential biomarkers, plasma pools from patients infected by active or inactive CE, as well as from control subjects, were processed to isolate exosomes for proteomic label-free quantitative analysis. Results were statistically processed and subjected to bioinformatics analysis to define distinct features associated with parasite viability. First, a few parasite proteins were identified that were specifically associated with either active or inactive CE, which represent potential biomarkers to be validated in further studies. Second, numerous identified proteins of human origin were common to active and inactive CE, confirming an overlap of several immune response pathways. However, a subset of human proteins specific to either active or inactive CE, and central in the respective protein-protein interaction networks, were identified. These include the Src family kinases Src and Lyn, and the immune-suppressive cytokine TGF-ß in active CE, and Cdc42 in inactive CE. The Src and Lyn Kinases were confirmed as potential markers of active CE in totally independent plasma pools. In addition, insights were obtained on immune response profiles: largely consistent with previous evidence, our observations hint to a Th1/Th2/regulatory immune environment in patients with active CE and a Th1/inflammatory environment with a component of the wound healing response in the presence of inactive CE. Of note, our results were obtained for the first time from the analysis of samples obtained in vivo from a well-characterized, large cohort of human subjects.

Concurrent chromothripsis events in a case of TP53 depleted acute myeloid leukemia with myelodysplasia-related changes.

Acute myeloid leukemia with myelodysplasia-related changes (AML-MRC) is a heterogeneous hematological disorder defined by morphological, genetic, and clinical features. Patients with AML-MRC often show cytogenetic changes, which are associated with poor prognosis. Straightforward criteria for AML-MRC diagnosis and a more rigorous characterization of the genetic abnormalities accompanying this disease are needed. Here we describe an informative AML-MRC case, showing two separate, but concurrent, chromothripsis events, occurred at the onset of the tumor, and originating an unbalanced t(5;7) translocation and a derivative chromosome 12 with a highly rearranged short arm. Conversely, despite chromothripsis has been often associated with genomic amplification in cancer, in this case a large marker chromosome harboring amplified sequences from chromosomes 19 and 22 arose from a stepwise mechanism. Notably, the patient also showed a TP53 mutated status, known to be associated with an increased susceptibility towards chromothripsis and a poor prognosis. Our results indicate that multiple chromothripsis events may occur early in neoplastic transformation and act in a synergistic way with progressive chromosomal alterations to determine a dramatic impact on disease outcome, as suggested by the gene expression profile analysis.

The Role of Radiotherapy in Extramammary Paget Disease: A Systematic Review.

OBJECTIVE/PURPOSE: Extramammary Paget disease (EMPD) is a rare neoplasm of the skin generally affecting the anogenital area. Because of the low-frequency of the disease, no specific guidelines about the treatment strategy are available. Surgery is the recommended therapy for resectable and localized disease, but several other local treatments have been reported such as radiotherapy (RT). Most articles report small retrospective studies, referring to patients treated decades ago with large heterogeneity in terms of RT dose and technique. The aim of this study was to systematically review the main experiences in RT for the treatment of EMPD in the past 30 years. MATERIALS AND METHODS: A systematic search of the bibliographic databases PubMed and Scopus from January 1986 to January 2017 was performed including studies published in English, Italian, Spanish, French, and German language. RESULTS: According to the search strategy, 19 full-text articles, published from 1991 to 2015, fulfilled inclusion criteria and were included in the final review. All articles were retrospective analyses with no randomized controlled trials. These studies evaluated 195 EMPD patients treated with RT, delivered in several settings. A large variability in terms of RT doses, fractionation, clinical setting, and techniques was found.Radiotherapy was administered as definitive treatment for primary or recurrent disease after surgery in 18 studies with doses ranging from 30 to 80.2 Gy delivered in 3 to 43 fractions. Radiotherapy was administered as postoperative adjuvant treatment in 9 articles with doses ranging between 32 and 64.8 Gy in 20 to 30 fractions. Two studies reported the RT use in preoperative neoadjuvant setting with doses ranging between 40 and 43.30 Gy, and 2 experiences reported the RT treatment for in situ EMPD, using 39.6 to 40 Gy. Adverse events were reported in almost all but 2 articles and were grade 2 or lower.The 18 studies evaluating RT as definitive treatment for primary or recurrent disease after surgery reported a complete response rate ranging from 50% to 100%, with a variable rate of local relapse or persistent disease ranging from 0% to 80% of cases. The 9 studies evaluating RT as postoperative adjuvant treatment reported a local relapse or persistent disease rate of 0% to 62.5%. A dose-response relationship was reported suggesting doses greater than or equal to 60 Gy for gross tumor volume treatment. Local control, disease-free survival, and overall survival at 12, 20, and 60 months have been retrieved for available data, respectively.In patients with EMPD and concurrent underlying internal malignancy, the prognosis was often worsened by the latter. In this setting, literature analysis showed a potential RT palliative role for symptoms control or local control maintenance.Derma tumor invasion greater than 1 mm and lymph node metastases were reported to be important prognostic factors for distant metastases or death. CONCLUSIONS: To date, literature highlights the role of RT in the management of EMPD, but with low level of evidences.

Clinical outcome of recurrent locally advanced cervical cancer (LACC) submitted to primary multimodality therapies.

OBJECTIVES: Recurrence of disease represents a clinical challenge in cervical cancer patients, especially when all available treatment modalities have been used in the primary setting. The aim of this study was to analyze the patterns of recurrence and their association with clinical outcome in locally advanced cervical cancer (LACC) patients submitted to primary chemoradiation (CTRT) followed by radical surgery (RS). METHODS: This study was conducted on 364 LACC patients treated with CTRT plus RS since January 1996 to July 2012. For each relapse, information on date of clinical/pathological recurrence, and pattern of disease presentation were retrieved. Post-relapse survival (PRS) was recorded from the date of recurrence to the date of death for disease or last seen. Survival probabilities were compared by the log rank test. Cox's regression model with stepwise variable selection was used for multivariate prognostic analysis for PRS. RESULTS: Within a median follow-up of 42months, 75 recurrences (20.6%) and 54 disease-associated deaths (14.8%) were recorded. By analysing the pattern of relapse, most of the recurrences were outside the irradiated field (n=43, 57.3%) and the most frequently observed site was visceral (n=16, 21.3%). Among the parameters of the recurrence associated with PRS including the pattern of recurrence, the size of recurrence, SCC-Ag serum levels at recurrence, and secondary radical surgery, only the last one retained an independent predictive role in reducing the risk of death (p=0.037). CONCLUSIONS: The feasibility of secondary radical resection positively impacts on PRS of LACC patients submitted to multimodality primary treatments.

Stereotactic radiosurgery (SRS) with volumetric modulated arc therapy (VMAT): interim results of a multi-arm phase I trial (DESTROY-2).

AIMS: To present the interim results of a phase I trial on stereotactic radiosurgery (SRS) delivered using volumetric modulated arc therapy (VMAT) in patients with primary or metastatic tumours in different extracranial sites. MATERIALS AND METHODS: Patients were enrolled in different arms according to tumour site and clinical stage, and sequentially assigned to a given dose level. Acute toxicity, tumour response and early local control were investigated and reported. RESULTS: One hundred lesions in 65 consecutive patients (male/female: 30/35, median age: 66 years; range: 40-89) were treated. Of these 100 lesions, 21 were primary or metastatic lung tumours, 24 were liver metastases, 30 were bone metastases, 24 were nodal metastases and one was a primary vulvar melanoma. The prescribed dose ranged from 12 (BED(2Gy,α/ß:10) = 26.4 Gy) to 28 Gy (BED(2Gy,α/ß:10) = 106.4 Gy) to the planning target volume. Twenty-one patients (32.3%) experienced grade 1-2 acute toxicity, which was grade 2 in only two cases. The overall response rate based on computed tomography/magnetic resonance imaging was 52% (95% confidence interval 40.1-63.2%) and based on positron emission tomography scan was 90% (95% confidence interval 76.2-96.4%). As of November 2013, the median duration of follow-up was 11 months (range = 1-38). Recurrence/progression within the SRS-VMAT treated field was observed in nine patients (total lesions = 18): the inside SRS-VMAT field local control expressed on a per lesion basis was 87.8% at 12 months and 71.9% at 24 months. CONCLUSIONS: The maximum tolerable dose has not yet been reached in any study arm. SRS-VMAT resulted in positive early clinical results in terms of tumour response, local control rate and acute toxicity.

Clinical implications of different calculation algorithms in breast radiotherapy: a comparison between pencil beam and collapsed cone convolution.

BACKGROUND: This investigation focused on the clinical implications of the use of the Collapsed Cone Convolution algorithm (CCC) in breast radiotherapy and investigated the dosimetric differences as respect to Pencil Beam Convolution algorithm (PBC). MATERIAL AND METHODS: 15 breast treatment plans produced using the PBC algorithm were re-calculated using the CCC algorithm with the same MUs. In a second step, plans were re-optimized using CCC algorithm with modification of wedges and beam weightings to achieve optimal coverage (CCCr plans). For each patient, dosimetric comparison was performed using the standard tangential technique (SWT) and a forward-planned IMRT technique (f-IMRT). RESULTS: The CCC algorithm showed significant increased dose inhomogeneity. Mean and minimum PTV doses decreased by 1.4% and 2.8% (both techniques). Mean V95% decreased to 83.7% and 90.3%, respectively for the SWT and f-IMRT. V95% was correlated to the ratio of PTV and lung volumes into the treatment field. The re-optimized CCCr plans achieved similar target coverage, but high-dose volume was significantly larger (V107%: 7.6% vs 2.3% (SWT), 7.1% vs 2.1% (f-IMRT). There was a significantly increase in the ipsilateral lung volume receiving low doses (V5 Gy: 31.3% vs 26.2% in SWT, 27.0% vs 23.0% in f-IMRT). MUs needed for PTV coverage in CCCr plans were higher by 3%. CONCLUSIONS: The PBC algorithm overestimated PTV coverage in terms of all important dosimetric metrics. If previous clinical experience are based on the use of PBC model, especially needed is discussion between medical physicists and radiation oncologists to fully understand the dosimetric changes.

Successful treatment of a young patient with locally advanced clear cell adenocarcinoma of the uterine cervix undergoing chemoradiation followed by radical surgery.

Clear cell adenocarcinoma (CCAC) of the uterine cervix is a rare variant of cervical adenocarcinoma accounting for approximately 4-9% of this disease. Given the rarity of this pathological entity, the optimal treatment management is far from being defined. Earlier evidence suggested that the prognosis of patients bearing cervical CCAC is worse than with other histotypes, thus making the investigation of multimodal treatment strategies clinically worthwhile. Herein, we report the first case of locally advanced, large size cervical CCAC in a young woman who was triaged to concomitant chemoradiotherapy followed by radical surgery and experienced a pathologically assessed optimal response to this multimodal approach.

An in-vivo dosimetry procedure for Elekta step and shoot IMRT.

PURPOSE: The aim of this work was to extend an in-vivo dosimetry (IVD) method, previously developed by the authors for 3D-conformal radiotherapy, to step and shoot IMRT treatments for pelvic tumors delivered by Elekta linacs. MATERIALS AND METHODS: The algorithm is based on correlation functions to convert EPID transit signals into in-vivo dose values at the isocenter point, Diso. The EPID images were obtained by the so-called "IMRT Dosimetric Weighting" mode as a superposition of many segment fields. This way each integral dosimetric image could be acquired in about 10 s after the end of beam delivery and could be processed while delivering the successive IMRT beams. A specific algorithm for Diso reconstruction especially featured for step and shoot IMRT was implemented using a fluence inhomogeneity index, FI, introduced to describe the degree of beam modulation with respect to open beams. A γ-analysis of 2D-EPID images obtained day to day, resulted rapid enough to verify the plan delivery reproducibility. RESULTS: Fifty clinical IMRT beams, planned for patients undergoing radiotherapy of pelvic tumors, were used to irradiate a homogeneous phantom. For each beam the agreement between the reconstructed dose, Diso, and the TPS computed dose, Diso,TPS, was well within 5%, while the mean ratio R = Diso/Diso,TPS resulted for 250 tests equal to 1.006 ± 0.036. The same beams were checked in vivo, i.e. during patient treatment delivery, obtaining 500 tests whose average R ratio resulted equal to 1.011 ± 0.042. The γ-analysis of the EPID images with 5% 3 mm criteria supplied 85% of the tests with pass rates γ(mean) ≤ 0.5 and P(γ<1) ≥ 90%.

Planning comparison between standard and conformal 3D techniques in post-operative radiotherapy of gastric cancer: a systematic review.

The objective of this study was to establish the impact of three-dimensional conformal radiotherapy (3D-CRT) technique in post-operative radiotherapy of gastric cancer. A bibliographical research was performed using the PubMed. On the database, Search was carried out using Medical Subject Heading (MeSH) database; the algorithm for search was ''Radiotherapy" (MeSH) AND ''Stomach Neoplasms" (MeSH). Only planning comparative studies on conformal techniques vs standard techniques in post-operative radiotherapy of gastric cancer were included in the review process. We identified 185 papers, five of them fulfilling the inclusion criteria. A great inhomogeneity was observed regarding the analysed dosimetric end points. Three of the five studies reported a benefit in favour of 3D-CRT for target irradiation despite a minimal advantage in most cases. The liver was better spared from irradiation by the traditional technique in all studies. No univocal result was obtained for the right kidney: the traditional technique performed better in two studies, 3D-CRT yielded better results in two others, whereas in the fifth study, each technique was either better or worse according to the different considered end point. 3D-CRT, however, allowed for better sparing of the left kidney in four studies. There is no absolute reason to prefer 3D-CRT with multiple beams in every patient. It may be preferable to choose the technique based on individual patient characteristics. Because there is no proof of superiority for 3D-CRT, there is no absolute reason to exclude patients who are treated in centres equipped with only the two-dimensional technique from the potential benefit of post-operative chemoradiation.

Mammography before post-operative radiotherapy in conservatively managed breast cancer patients: is it useful?

OBJECTIVE: The aim of this study was to evaluate the role of bilateral mammography undertaken before adjuvant radiotherapy in patients with conservatively managed invasive carcinoma of the breast. METHODS: Patients with invasive breast cancer referred to the Radiotherapy Unit of the Università Cattolica del Sacro Cuore, in Campobasso, Italy, between March 2002 and September 2006 were retrospectively reviewed. Patients were referred to our facility from other local and regional hospitals where they received breast-conserving surgery and adjuvant chemotherapy. They presented to our department for post-operative whole-breast radiotherapy. All patients underwent physical examination and bilateral mammography prior to adjuvant irradiation. RESULTS: 201 patients met the selection criteria as delineated. Of these 201 patients who underwent pre-radiotherapy mammography, 3 had suspicious findings on mammography. In two of those cases, the histopathological examination confirmed the presence of residual disease within the residual mammary gland. In one case, the pre-radiotherapy mammogram allowed for the detection of disease persistence which was not otherwise appreciated on physical exam. In the other case, the diagnostic imaging confirmed only the findings of the physical exam. In both cases of residual disease, the tumour was found elsewhere in the breast and not at the primary site. In one patient, the radiological re-assessment led to a false-positive result. No cases of contralateral synchronous breast cancer were observed. The overall adjunctive cost of this strategy including a routine mammography besides the clinical visit was €7012 for all patients. CONCLUSIONS: No clear recommendation exists regarding post-operative mammography before adjuvant radiotherapy. In our experience, this strategy allowed for the detection of gross disease persistence after surgery which was not appreciated at clinical examination in 1 case out of 201. In this patient, adjuvant radiotherapy up to a total dose of 50 Gy would have been inadequate. Given the low cost of mammography, further investigation about its role in pre-radiotherapy evaluation is warranted.

Volumetric modulated arc therapy with simultaneous integrated boost for locally advanced rectal cancer.

AIMS: To report the feasibility of volumetric modulated arc therapy (VMAT) for neoadjuvant radiotherapy in locally advanced rectal cancer in a dose-escalation protocol and simultaneous integrated boost (SIB) approach. Moreover, the VMAT technique was compared with three-dimensional conformal radiotherapy (3D-CRT) and fixed-field intensity modulated radiotherapy (IMRT), in terms of target coverage and irradiation of organs at risk. MATERIALS AND METHODS: Eight patients with locally advanced rectal cancer were treated with the SIB-VMAT technique. The VMAT plans were compared with 3D-CRT and IMRT techniques in terms of several clinically dosimetric parameters. The number of monitor units and the delivery time were analysed to score the treatment efficiency. All plans were verified in a dedicated solid water phantom using a two-dimensional array of ionisation chambers. RESULTS: All techniques meet the prescription goal for planning target volume coverage, with VMAT showing the highest level of conformality. VMAT is associated with 40, 53 and 58% reduction in the percentage of volume of small bowel irradiated to 30, 40 and 50Gy, compared with 3D-CRT. No significant differences were found with respect to SIB-IMRT. VMAT plans showed a significant reduction of monitor units by nearly 20% with respect to IMRT and reduced treatment time from 14 to 5min for a single fraction. CONCLUSIONS: SIB-VMAT plans can be planned and carried out with high quality and efficiency for rectal cancer, providing similar sparing of organs at risk to SIB-IMRT and resulting in the most efficient treatment option. SIB-VMAT is currently our standard approach for radiotherapy of locally advanced rectal cancer.

Role of comorbidities in locally advanced cervical cancer patients administered preoperative chemoradiation: impact on outcome and treatment-related complications.

AIMS: The study aimed at describing the prevalence, and pattern of comorbidities, as well as their clinical role in a large series of locally advanced cervical cancer (LACC) patients triaged to preoperative chemoradiation. METHODS: The Charlson index (CCI), and the ACE27 index were used to retrospectively evaluate comorbidities in 258 LACC patients: life tables were computed by the Kaplan-Meier method; multivariate analysis was performed by Cox's regression model. RESULTS: A CCI score = 0 was documented in 225 patients (87.2%), while 24 patients (9.3%) had a CCI score = 1, and only 9 patients (3.5%) had a CCI score ≥ 2. An ACE27 score = 0 was documented in 170 patients (65.9%), and was 1 in 59 patients (22.8%), 2 in 24 patients (9.3%) and 3 in 5 patients (2%). There was no association between the presence of comorbidities and clinico-pathological variables with the exception of a direct association with older age. There was no difference in the distribution of comorbid cases according to the extent of hysterectomy and lymphadenectomy. DFS or OS curves did not differ in patients with or without comorbidities according to both indexes. No difference in the distribution of patients with comorbidities according to presence of complications was documented. CONCLUSIONS: The role of comorbidities in the decision-making process relative to the enrollment of LACC patients into this trimodal therapeutic strategy needs to be established in specifically designed prospective trials.