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Purpose: To evaluate the outcome of partial breast reirradiation (re-PBI) with intensity modulated radiation therapy using a hypofractionated scheme for breast cancer (BC) local relapse (LR) operated on with repeat breast-conservative surgery., Methods and Materials: Intensity modulated radiation therapy-based re-PBI was performed using either helical or step-and-shoot modality to deliver 37.05 Gy in 13 fractions in 2.5 weeks. Cumulative incidence of second LR, toxicity, disease-free survival (DFS), BC-specific survival, and overall survival were evaluated., Results: Between May 2012 and May 2021, 70 patients had re-PBI. The median follow-up (FU) was 6.3 years (quartiles 1-3, 4.0-8.1.). The median age at first LR was 62 years. The median primary BC first LR interval was 12.4 years (range, 1.6-26.7 years). Luminal A-like first LR accounted for 41% of the cases, and the median size was 0.8 cm. During FU, 18 (26%) patients showed a subsequent event: 3 second LRs (corresponding to an 8-year cumulative rate of 4%), 3 regional nodal recurrences, 7 distant metastases, and 5 other primary tumors. At 8 years, DFS, BC-specific survival, and overall survival were 76%, 90%, and 90%, respectively. At multivariate analysis, grade 3 and extensive intraductal components were independent predictors for DFS. For 51 and 46 patients, chronic toxicity and cosmesis were evaluated, respectively: 4% had grade 3 fibrosis, and cosmesis was deemed good/excellent in just >60% of the cases., Conclusions: Re-PBI after repeat breast-conservative surgery represents a feasible alternative to mastectomy with regard to local control, showing an acceptable toxicity profile. A long-term FU is crucial to better understand the pattern of relapse and consolidate the position of re-PBI in clinical practice., Competing Interests: Disclosures The Division of Radiation Oncology of IEO received research funding from the Italian Association for Cancer Research (AIRC), Fondazione Istituto Europeo di Oncologia-Centro Cardiologico Monzino (IEO-CCM), Accuray, and Ion Beam Applications (IBA), all outside the current project. Barbara Alicja Jereczek-Fossa received speaker fees from Bayer, Accuray, Astellas, IBA, Ipsen, AstraZeneca, Tecnologie Avanzate, Recordati, Novartis; Barbara Alicja Jereczek-Fossa participated in the Advisory Board of Accuray, Bayer, and Seagen, all outside the current project. Maria Cristina Leonardi received speaker fees from Accuray, and Samantha Dicuonzo received speaker fees from Accuray Asia (all outside the current project). The remaining authors declare no conflicts of interest that are relevant to the content of this article., (Copyright © 2024 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Background: The management of locally advanced rectal cancer (LARC) relies on a multimodal approach. Neither instrumental work-up nor molecular biomarkers are currently available to identify a risk-adapted strategy., Objectives: We aim to investigate the role of circulating tumor DNA (ctDNA) and its clearance at different timepoints during chemo-radiotherapy (CRT) and correlate them with clinical outcomes., Design: Between November 2014 and November 2019, we conducted a monocentric prospective observational study enrolling consecutive patients with LARC managed with neoadjuvant standard CRT (capecitabine and concomitant pelvic long-course radiotherapy), followed by consolidation capecitabine in selected cases and surgery., Methods: Blood samples for ctDNA were obtained at pre-planned timepoints. We evaluated the correlation of baseline variant allele frequency (VAF) with pathologic complete response (pCR) down-staging, node regression (pN0), event-free survival (EFS), and overall survival (OS)., Results: Among 112 screened patients, 61 were enrolled. In all, 38 (62%) had a positive ctDNA at baseline with VAF > 0 and 23 had negative ctDNA (VAF = 0). Among patients with negative ctDNA, 30% had a complete response, while only 13% of positive ctDNA patients had pCR [odds ratio (OR) 0.35 (95% confidence interval (CI): 0.10-1.26), p  = 0.11]. Similarly, 96% and 74% of pN0 were observed among negative and positive ctDNA patients, respectively [OR 0.13 (95% CI: 0.02-1.07), p  = 0.058]. The presence of a baseline VAF > 0 was associated with a trend toward a lower EFS compared with VAF = 0 patients [hazard ratio (HR) = 2.30, 95% CI: 0.63-8.36, p  = 0.21]. Within the limitations of small sample size, no difference in OS was observed according to the baseline ctDNA status (HR = 1.18, 95% CI: 0.35-4.06, p  = 0.79)., Conclusion: Within the limitations of a reduced number of patients, patients with baseline negative ctDNA seem to show a higher probability of pN0 status and a trend toward improved EFS. Prospective translational studies are required to define the role of ctDNA analysis in the multimodal treatment of LARC., Competing Interests: The authors declare that there is no conflict of interest., (© The Author(s), 2024.)

Similar to invasive breast cancer, ductal carcinoma in situ is also going through a phase of changes not only from a technical but also a conceptual standpoint. From prescribing radiotherapy to everyone to personalized approaches, including radiotherapy omission, there is still a lack of a comprehensive framework to guide radiation oncologists in decision making. Many pieces of the puzzle are finding their place as high-quality data mature and are disseminated, but very often, the interpretation of risk factors and the perception of risk remain very highly subjective. Sharing the therapeutic choice with patients requires effective communication for an understanding of risks and benefits, facilitating an informed decision that does not increase anxiety and concerns about prognosis. The purpose of this narrative review is to summarize the current state of knowledge to highlight the tools available to radiation oncologists for managing DCIS, with an outlook on future developments.

This study quantified the incidental dose to the first axillary level (L1) in locoregional treatment plan for breast cancer. Eighteen radiotherapy centres contoured L1-L4 on three different patients (P1,2,3), created the L2-L4 planning target volume (single centre planning target volume, SC-PTV) and elaborated a locoregional treatment plan. The L2-L4 gold standard clinical target volume (CTV) along with the gold standard L1 contour (GS-L1) were created by an expert consensus. The SC-PTV was then replaced by the GS-PTV and the incidental dose to GS-L1 was measured. Dosimetric data were analysed with Kruskal-Wallis test. Plans were intensity modulated radiotherapy (IMRT)-based. P3 with 90° arm setup had statistically significant higher L1 dose across the board than P1 and P2, with the mean dose (Dmean) reaching clinical significance. Dmean of P1 and P2 was consistent with the literature (77.4% and 74.7%, respectively). The incidental dose depended mostly on L1 proportion included in the breast fields, underlining the importance of the setup, even in case of IMRT., Competing Interests: Declaration of Conflicting InterestThe authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Division of Radiotherapy IEO received research funding from AIRC (Italian Association for Cancer Research) and Fondazione IEO-CCM (Istituto Europeo di Oncologia-Centro Cardiologico Monzino) (all outside the current project). BAJF received speakers fee from Roche, Bayer, Janssen, Carl Zeiss, Ipsen, Accuray, Astellas, Elekta, IBA Astra Zeneca (all outside the current project). MCL received a speaker fee from Accuray Inc (outside the current project). SD received speakers fee from Accuray Asia (outside the current project). MGV was supported by a research fellowship from AIRC entitled “Radioablation ± hormonotherapy for prostate cancer oligorecurrences (RADIOSA trial): potential of imaging and biology”, registered at ClinicalTrials.gov NCT03940235, approved by the Ethics Committee of IRCCS Istituto Europeo di Oncologia and Centro Cardiologico Monzino (IEO-997). IEO, the European Institute of Oncology IRCCS, was partially supported by the Italian Ministry of Health with Ricerca Corrente and 5x1000 funds and by institutional grants from Accuray Inc. The sponsors did not play any role in the study design, collection, analysis and interpretation of data, nor in the writing of the manuscript, nor in the decision to submit the manuscript for publication. The remaining authors declare no conflict of interest that are relevant to the content of this article.

The strategy to anticipate radiotherapy (RT) before surgery, for breast cancer (BC) treatment, has recently generated a renewed interest. Historically, preoperative RT has remained confined either to highly selected patients, in the context of personalized therapy, or to clinical research protocols. Nevertheless, in the recent years, thanks to technological advances and increased tumor biology understanding, RT has undergone great changes that have also impacted the preoperative settings, embracing the modern approach to breast cancer. In particular, the reappraisal of preoperative RT can be viewed within the broader view of personalized and tailored medicine. In fact, preoperative accelerated partial breast irradiation (APBI) allows a more precise target delineation, with less variability in contouring among radiation oncologists, and a smaller treatment volume, possibly leading to lower toxicity and to dose escalation programs. The aim of the present review, which represents a benchmark study for the AIRC IG-23118, is to report available data on different technical aspects of preoperative RT including dosimetric studies, patient's selection and set-up, constraints, target delineation and clinical results. These data, along with the ones that will become available from ongoing studies, may inform the design of the future trials and representing a step toward a tailored APBI approach with the potential to challenge the current treatment paradigm in early-stage BC.Trial registration: The study is registered at clinicaltrials.gov (NCT04679454)., (© 2023. Italian Society of Medical Radiology.)

Background: Image-guided radiation therapy (IGRT) has changed clinical practice. We proposed a survey to radiotherapy centers in Lombardy to picture the current clinical practice of its use., Research Design and Methods: The survey consisted of 32 multiple-choice questions, divided into five topics: type of hospital, patients treated in 2019, number of LINACs; presence of protocols and staff involved in IGRT; IGRT in stereotaxis; IGRT in non-stereotactic treatments; availability of medical and technical staff., Results: Twenty-seven directors answered (77%). Most centers (74%) have produced protocols to ensure uniformity in the IGRT process. The most widely used IGRT modality (92%) is cone-beam CT. Daily IGRT control is favored for prostate (100%), head and neck (87%), and lung (78%) neoplasms. The resident doctors can always perform supervised IGRT matching in only six centers. Radiation therapists perform IGRT controls only for some sites in 12 cases (44%) and always in 9 cases (33%). Radiation oncologists are present in real time, in most cases., Conclusions: Today, IGRT can be considered standard practice but at the price of more time-consuming procedures. A balance between a fully physician-controlled process and an increased role for specifically trained RTTs is actively being sought.

Purpose: To evaluate oncological outcomes and late toxicities in a retrospective series of patients with locally-extended anal squamous cell carcinoma (ASCC), treated with curative Intensity Modulated Radiotherapy (IMRT) and chemotherapy., Methods: ASCC patients who underwent chemo-radiotherapy with IMRT from 2010 to 2020 were included. Oncological outcomes were assessed in terms of overall survival (OS), disease-free survival (DFS), colostomy-free survival (CFS) and event-free survival (EFS). Late toxicity was detected according to CTCAE v.5.0 and RTOG late radiation morbidity scoring system., Results: Ninety-five patients were included. Most patients (83%) received chemotherapy with oral Fluoropyrimidine plus Cisplatin. The median follow-up was 5.5 years. The OS was 85.2%, 82.1% and 79.3% at 3, 5 and 8 years, respectively. The DFS was 73.1%, 70%, and 65.3% at 3, 5 and 8 years, respectively; 3, 5 and 8 years CFS was 86.2%, 84.3% and 84.3%, respectively. The EFS was 71%, 67.9% and 63.1%, at 3, 5 and 8 years, respectively. On univariable analysis, a statistically significant lower OS was found for patients with T3-T4 stage (HR = 4.58, p = 0.005) and overall treatment time (OTT) ≥ 47 days (HR = 3.37, p = 0.038). A statistically significant lower DFS was reported for patients with T3-T4 stage (HR = 2.72, p = 0.008) and Serum Squamous Cell Carcinoma Antigen (SCC) value post-RT > 1.5 (HR = 2.90, p = 0.038.). Ten severe late toxicity (≥ G3) events were reported in 8 patients (8.6%)., Conclusions: Our data confirm IMRT concomitant with a Cisplatin-based chemotherapy as an effective treatment of ASCC, ensuring acceptable long-term toxicities and good oncological outcomes., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Aim: Stereotactic ablative radiotherapy (SABR) showed increasing survival in oligometastatic patients. Few studies actually depicted oligometastatic disease (OMD) evolution and which patient will remain disease-free and which will rapidly develop a polymetastatic disease (PMD) after SABR. Therefore, apart from the number of active metastases, there are no clues on which proven factor should be considered for prescribing local treatment in OMD. The study aims to identify predictive factors of polymetastatic evolution in lung oligometastatic colorectal cancer patients., Methods: This international Ethical Committee approved trial (Prot. Negrar 2019-ZT) involved 23 Centers and 450 lung oligometastatic patients. Primary end-point was time to the polymetastatic conversion (tPMC). Additionally, oligometastases number and cumulative gross tumor volume (cumGTV) were used as combined predictive factors of tPMC. Oligometastases number was stratified as 1, 2-3, and 4-5; cumGTV was dichotomized to the value of 10 cc., Results: The median tPMC in the overall population was 26 months. Population was classified in the following tPMC risk classes: low-risk (1-3 oligometastases and cumGTV ≤ 10 cc) with median tPMC of 35.1 months; intermediate-risk (1-3 oligometastases and cumGTV > 10 cc), with median tPMC of 13.9 months, and high-risk (4-5 oligometastases, any cumGTV) with median tPMC of 9.4 months (p = 0.000)., Conclusion: The present study identified predictive factors of polymetastatic evolution after SABR in lung oligometastatic colorectal cancer. The results demonstrated that the sole metastases number is not sufficient to define the OMD since patients defined oligometastatic from a numerical point of view might rapidly progress to PMD when the cumulative tumor volume is high. A tailored approach in SABR prescription should be pursued considering the expected disease evolution after SABR, with the aim to avoid unnecessary treatment and toxicity in those at high risk of polymetastatic spread, and maximize local treatment in those with a favorable disease evolution., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

Background and Purpose: A prognostic scoring system based on laboratory inflammation parameters, [Hemo-Eosinophils-Inflammation (HEI) index], including baseline hemoglobin level, the systemic inflammatory index and eosinophil count was recently proposed in patients with squamous cell carcinoma of the anus (ASCC). HEI was shown to discriminate disease-free (DFS) and overall (OS) survival in ASCC patients treated with concurrent chemoradiation (CRT). We tested the accuracy of the model on a multicentric cohort for external validation., Materials and Methods: Patients treated with CRT were enrolled. The Kaplan-Meier curves for DFS and OS based on HEI risk group were calculated and the log-rank test was used. Cox proportional hazards models were used to assess the prognostic factors for DFS and OS. The exponential of the regression coefficients provided an estimate of the hazard ratio (HR). For model discrimination, we determined Harrell's C-index, Gönen & Heller K Index and the explained variation on the log relative hazard scale., Results: A total of 877 patients was available. Proportional hazards were adjusted for age, gender, tumor-stage, and chemotherapy. Two-year DFS was 77 %(95 %CI:72.0-82.4) and 88.3 %(95 %CI:84.8-92.0 %) in the HEI high- and low- risk groups. Two-year OS was 87.8 %(95 %CI:83.7-92.0) and 94.2 %(95 %CI:91.5-97). Multivariate Cox proportional hazards model showed a HR = 2.02(95 %CI:1.25-3.26; p = 0.004) for the HEI high-risk group with respect to OS and a HR = 1.53(95 %CI:1.04-2.24; p = 0.029) for DFS. Harrel C-indexes were 0.68 and 0.66 in the validation dataset, for OS and DFS. Gonen-Heller K indexes were 0.67 and 0.71, respectively., Conclusion: The HEI index proved to be a prognosticator in ASCC patients treated with CRT. Model discrimination in the external validation cohort was acceptable., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Purpose: The purpose of the study was to evaluate the toxicity, local control, overall and disease-free survival of elderly breast cancer (BC) patients treated with adjuvant once-weekly ultra-hypofractionated radiotherapy (RT) either with intensity-modulated RT (IMRT) or 3D conformal RT (3DCRT)., Methods: From July 2011 to July 2018, BC patients receiving 5.7 Gy once a week for 5 weeks to the whole breast after breast-conserving surgery were considered for the study. Inclusion criteria were: T1-T3 invasive BC, no or limited axillary involvement, age ≥ 65 years or women with commuting difficulties or disabling diseases., Results: A total of 271 patients were included in the study. Median age was 76 (46-86) years. Most of BC were T1 (77%), while the remaining were T2 (22.2%) and T3 (0.4%). Axillary status was negative in 68.3% of the patients. The only severe acute toxicity (G3) at the end of RT was erythema (0.4%), registered in the 3DCRT group; no G3 edema or epitheliolysis was recorded. With 18 months of median follow-up, severe early-late toxicity (G3) was reported in terms of fibrosis and breast retraction, both with an incidence of 1.4%, mostly in the 3DCRT group. Oncological outcomes at a median follow-up of 2.9 years reported 249/271 (91.9%) patients alive and free from any event and 5 (1.8%) isolated locoregional recurrences. At 3 years, disease-free survival and overall survival were 94.9% and 97.8%, respectively. Breast volume > 500 cm 3 was reported as predictive for moderate-severe (≥ G2) acute toxicity., Conclusions: Weekly ultra-hypofractionated whole breast RT seems feasible and effective. Toxicity was mild, local control was acceptable, and overall survival was 97.8% at 3 years. Rates of severe toxicity were reduced with the IMRT technique., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: The aim of this study is to evaluate feasibility of salvage 4-week hypofractionated whole breast radiotherapy (WBRT) in patients with in-breast recurrence after receiving intraoperative radiotherapy with electrons (IOERT) for primary breast cancer (BC)., Methods: BC patients who had repeated quadrantectomy underwent modified WBRT with intensity-modulated radiotherapy using Helical Tomotherapy to underdose the IOERT region. This approach, called POLO (Partially Omitted Lobe), excluded the IOERT volume from receiving the full prescription dose., Results: Nine patients were treated with this approach, receiving 45 Gy in 20 fractions. A simultaneous integrated boost of 2.5 Gy in 20 fractions was delivered in 6/9 patients. Dose constraints and planning objectives were reported. No severe toxicity was reported while local control and overall survival were 100%., Conclusion: The POLO approach is technically feasible and capable to achieve a significant reduction of radiation dose delivered to the previous treated IOERT area., Advances in Knowledge: The study demonstrates the technical and dosimetric feasibility of conservative salvage whole breast radiotherapy, while sparing the area already treated with IORT, in patients with in-breast recurrence.

Introduction: Stereotactic ablative radiotherapy (SABR) has been shown to increase survival in oligometastatic disease, but local control of colorectal metastases remains poor. We aimed to identify potential predictive factors of SBRT response through a multicenter large retrospective database and to investigate the progression to the polymetastatic disease (PMD)., Material and Methods: The study involved 23 centers, and was approved by the Ethical Committee (Prot. Negrar 2019-ZT). 1033 lung metastases were reported. Clinical and biological parameters were evaluated as predictive for freedom from local progression-free survival (FLP). Secondary end-point was the time to the polymetastatic conversion (tPMC)., Results: Two-year FLP was 75.4%. Two-year FLP for lesions treated with a BED < 00 Gy, 100-124 Gy, and ≥125 Gy was 76.1%, 70.6%, and 94% (p = 0.000). Two-year FLP for lesion measuring ≤10 mm, 10-20 mm, and >20 mm was 79.7%, 77.1%, and 66.6% (p = 0.027). At the multivariate analysis a BED ≥125 Gy significantly reduced the risk of local progression (HR 0.24, 95%CI 0.11-0.51; p = 0.000). Median tPMC was 26.8 months. Lesions treated with BED ≥125 Gy reported a significantly longer tPMC as compared to lower BED. The median tPMC for patients treated to 1, 2-3 or 4-5 simultaneous oligometastases was 28.5, 25.4, and 9.8 months (p = 0.035)., Conclusion: The present is the largest series of lung colorectal metastases treated with SABR. The results support the use of SBRT in lung oligometastatic colorectal cancer patients as it might delay the transition to PMD or offer relatively long disease-free period in selected cases. Predictive factors were identified for treatment personalization., Competing Interests: Conflicts of interest None declared., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Radio-chemotherapy with CDDP is the standard for H&N squamous cell cancer. CDDP 100 mg/m 2 /q3 is the standard; alternative schedules are used to reduce toxicity, mostly 40 mg/m 2 /q1., Methods: Patients were treated from 1/2010 to 1/2017 in two Radiation Oncology Centres. Propensity score analysis (PS) was retrospectively used to compare these two schedules., Results: Patients analyzed were 166. Most (114/166) had 1w-CDDP while 52 had 3w-CDDP. In the 3w-CDDP group, patients were younger, with better performance status, smaller disease extent and a more common nodal involvement than in the 1w-CDDP. Acute toxicity was similar in the groups. Treatment compliance was lower in the w-CCDP. Overall survival before PS was better for female, for oropharyngeal disease and for 3w-CDDP group. After PS, survival was not related to the CDDP schedule., Conclusions: 3w-CDDP remains the standard for fit patients, weekly schedule could be safely used in selected patients., (© 2021. The Author(s).)

The presence of a neobladder constitutes a limitation for the radiation oncologist, as there is no clear evidence about its tolerance to radiotherapy (RT). The limited literature only concerns the conventional postoperative treatment in patients with bladder cancer after cystectomy. Here we report a case of a patient with neobladder who underwent a stereotactic RT for a pelvic recurrence of disease, with response to treatment and no toxicity to the neobladder. This case represents a promising example of the chance to perform RT with ablative intent, using advanced techniques, even on lesions close to the neobladder.

Background: Postmastectomy radiotherapy (PMRT) with TomoHelical™ (TH) or TomoDirect™ (TD) allows a uniform target coverage. In this study, we compare treatment plans using TD and TH in the setting of hypofractionated PMRT and immediate breast reconstruction., Material and Methods: The TD-treatment plans of breast cancer patients treated between May 2016 and August 2019 were retrospectively selected. All the TD plans were re-planned on TH with the same prescription dose (40.05 Gy/15 fractions) and according to our dose/volume constraints. Data about the 2 treatment plans were compared with a focus on PTV coverage and all the organs at risk (OARs) constraints., Results: Fifty patients for a total number of 100 treatment plans (50 with TD and 50 re-planned with TH) were analyzed. All the median value in the TD PTV CHEST WALL plans fulfilled the predefined planning objectives, even though TH emerged as best for target coverage with statistically significant difference for V90%. TD provided the lowest V95% for the PTV SVC, but the median value was near to the recommended value of 90% (89.8 % vs 98.6% for TD and TH, respectively). Overall, TD reached the best OARs sparing. The main statistically significant differences with TH were for contralateral breast, ipsilateral and contralateral lung. All the other dose values for TH were higher than TD, but they fulfilled the recommended/acceptable predefined planning objectives., Conclusions: In the setting of PMRT, TD compared to TH reached an acceptable target volume coverage, with an optimal sparing of OARs., (Copyright © 2021 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.)

Aim: To evaluate reconstruction failure (RF) rate in patients receiving implant-based immediate breast reconstruction (IBR) and hypofractionated (HF) postmastectomy radiation therapy (PMRT)., Materials and Methods: Stage II-III breast cancer patients, treated with HF-PMRT using intensity modulated radiotherapy were stratified in two groups according to IBR: single-stage direct-to-implant (DTI-group) and two-stage expander and implant (TE/I-group). Irradiated patients were matched with non-irradiated ones who underwent the same IBR during the same period. Prescription dose was 40.05 Gy/15 fractions to chest wall and infra/supraclavicular nodal region. Primary endpoint was RF defined as the need of major revisional surgery (MaRS) for implant removal or conversion to autologous reconstruction. Secondary endpoint was the rate of minor revisional surgeries (MiRS) including implant repositioning or substitution with another implant., Results: One hundred and seven irradiated patients (62 in TE/I-group, 45 in DTI-group) were matched with 107 non-irradiated subjects. Median follow-up was 4.2 years (0.1-6.1) In the TE/I setting, MaRS was performed in 8/62 irradiated patients (12.9%) of the irradiated TE/I group compared to 1/62 (1.6%) non-irradiated subjects (p = 0.015). In the DTI setting, MaRs occurred in 3/45 irradiated patients (6.7%) compared to 1/45 non-irradiated ones (2.2%) (p = 0.35). Overall MaRS rate was 10.3% in the irradiated group. MiRS was performed in 35.6% and 31.1% of the irradiated and non-irradiated DTI-groups (p = 0.65), respectively, and in 12.9% and 8.1% of the irradiated and non-irradiated TE/I groups (p = 0.38), respectively., Conclusions: Compared to the non-irradiated counterparts, the TE/I group showed higher rate of RF, while no statistically significant difference was observed for the DTI group. The use of hypofractionation and IMRT to implant-based IBR did not seem to increase the risk of RF which appeared to be in line with the literature., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Aims: To report toxicity of a hypofractionated scheme of whole-breast (WB) intensity-modulated radiotherapy (IMRT) with simultaneous integrated boost (SIB) to the tumor bed (TB) using Tomotherapy ® with Direct modality., Methods: Patients with early breast cancer, undergoing radiotherapy (RT) in 15 daily fractions to WB (prescription dose 40.05 Gy) and SIB to the TB (48 Gy), between 2013 and 2017, was analyzed. Primary endpoint was acute and intermediate toxicity assessed at the end and within 6 months from RT, according to Radiation Therapy Oncology Group (RTOG) scale. Secondary endpoints included early chronic toxicity at 12-months follow-up, using the Late Effects Normal Tissue Task Subjective, Objective, Management, and Analytic (LENT-SOMA) scale, and cosmesis using Harvard criteria., Results: The study population was of 287 patients. Acute and intermediate toxicity was collected among 183 patients with data available at the end of RT and within 6 months, 85 (46%) experienced G2 toxicity and 84 (46%) G1 toxicity, while 14 (8%) did not report toxicity at any time. A significant reduction of any grade toxicity was observed between the two time points, with the majority of patients reporting no clinically relevant toxicity at 6 months. At univariate analysis, age < 40 years, breast volume > 1000 cm 3 and D max  ≤ 115% of prescription dose were predictive factors of clinically relevant acute toxicity (G ≥ 2) at any time. At multivariable analysis, only age and breast volume were confirmed as predictive factors, with Relative Risks (95% Confidence Intervals): 2.02 (1.13-3.63) and 1.84 (1.26-2.67), respectively. At 12-month follow-up, 113 patients had complete information on any toxicity with 53% of toxicity G < 2, while cosmetic evaluation, available for 102 patients, reported a good-excellent result for 86% of patients., Conclusions: Hypofractionated WB IMRT with a SIB to the TB, delivered with TomoDirect modality, is safe and well-tolerated. Most patients reported no toxicity after 6 months and good-excellent cosmesis. Predictive factors of clinically relevant toxicity might be considered during treatment planning in order to further reduce side effects.

Purpose: To assess outcome of breast cancer (BC) stages pT1-2 N0-1 after mastectomy alone and to identify prognostic factors calling for the need of postmastectomy radiotherapy., Methods: Patients who were not eligible for breast conserving surgery (BCS) were operated on with mastectomy between 1998 and 2008. Locoregional (LRR), distant (DM) control and breast cancer specific survival (BCSS) were retrospectively evaluated. Cumulative incidence (CI) of events was estimated according to Kalbfleisch and Prentice while Gray's test tested difference. Kaplan-Meier method for survival and Cox proportional hazards model for univariable and multivariable analysis were used. A matched pair analysis between mastectomy alone and BCS plus whole breast irradiation (WBI), using the propensity score method, was performed., Results: 1281 pT1-2 N0 and 1081 pT1-2 N1 were identified. Median follow-up was 8.2 years (9.2 years for survival). Overall, LRR rate was low for both N0 and N1 subgroups (10-year CI, 8.8% and 10.9%, respectively). Young age, lymphovascular invasion and Ki-67 ≥ 20% were proved to be statistically significant prognostic factors at multivariable analysis. The combination of ≥ 2 risk factors increased LRR rate to ≥ 15%. Risk factors combination weighed on LRR rate more than nodal status itself. DM rate doubled moving from negative to positive nodal status (10-year CI 10.5% versus 20.3%, respectively). BCSS remained high in both N0 and N1 subgroups (10-year CI 92.4% versus 84.5%, respectively). Remarkably, all the molecular subtypes except Luminal A significantly affected DM and BCSS both in the N0 and N1 subgroups. Nodes number significantly impacted on DM and BCSS but not on locoregional control. In the matched pair analysis, WBI decreased nodal recurrence rate and improved distant control, without affecting survival., Conclusions: Selected patients, namely those with at least two additional risk factors, presented high enough LRR risk to support the use of postmastectomy radiotherapy in both N0 and N1 subgroups. Moreover, the observation that radiotherapy may provide benefits that go beyond local control deserves to be further investigated.

A multi-institutional retrospective study was conducted to evaluate the pattern of care and clinical outcomes of anal cancer patients treated with intensity-modulated radiotherapy (IMRT) techniques. In a cohort of 987 patients, the clinical complete response (CR) rate (beyond 6 months) was 90.6%. The 3-year local control (LC) rate was 85.8% (95% CI: 84.4-87.2), and the 3-year colostomy-free survival (CFS) rate was 77.9% (95% CI: 76.1-79.8). Three-year progression-free survival (PFS) and overall survival (OS) rates were 80.2% and 88.1% (95% CI: 78.8-89.4) (95% CI: 78.5-81.9), respectively. Histological grade 3 and nodal involvement were associated with lower CR ( p = 0.030 and p = 0.004, respectively). A statistically significant association was found between advanced stage and nodal involvement, and LC, CFS, PFS, OS and event-free survival (EFS). Overall treatment time (OTT) ≥45 days showed a trend for a lower PFS ( p = 0.050) and was significantly associated with lower EFS ( p = 0.030) and histological grade 3 with a lower LC ( p = 0.025). No statistically significant association was found between total dose, dose/fraction and/or boost modality and clinical outcomes. This analysis reports excellent clinical results and a mild toxicity profile, confirming IMRT techniques as standard of care for the curative treatment of anal cancer patients. Lymph node involvement and histological grade have been confirmed as the most important negative prognostic factors.

Anal squamous cell carcinoma (SCC) is a rare tumor, and bio-humoral predictors of response to chemo-radiation (CT-RT) are lacking. We developed a prognostic score system based on laboratory inflammation parameters. We investigated the correlation between baseline clinical and laboratory variables and disease-free (DFS) and overall (OS) survival in anal SCC patients treated with CT-RT in five institutions. The bio-humoral parameters of significance were included in a new scoring system, which was tested with other significant variables in a Cox's proportional hazard model. A total of 308 patients was included. We devised a prognostic model by combining baseline hemoglobin level, SII, and eosinophil count: the Hemo-Eosinophils Inflammation (HEI) Index. We stratified patients according to the HEI index into low- and high-risk groups. Median DFS for low-risk patients was not reached, and it was found to be 79.5 months for high-risk cases (Hazard Ratio 3.22; 95% CI: 2.04-5.10; p < 0.0001). Following adjustment for clinical covariates found significant at univariate analysis, multivariate analysis confirmed the HEI index as an independent prognostic factor for DFS and OS. The HEI index was shown to be a prognostic parameter for DFS and OS in anal cancer patients treated with CT-RT. An external validation of the HEI index is mandatory for its use in clinical practice.

Introduction: During the COVID-19 pandemic, Lombardy (Northern Italy) Regional Health Council created hubs for cancer care, meant to be SARS-CoV-2-free pathways for cancer patients. The workflow of breast cancer (BC) radiotherapy (RT) in one of the hubs is presented here., Methods: Candidates to adjuvant RT during the pandemic peak of March-April 2020 were compared to those treated in the same period of 2019, and patient volume, deferral rate, and type of RT were analyzed. Statistics were calculated with χ 2 or Fisher exact tests for categorical variables, and the Wilcoxon rank test for continuous variables., Results: In March-April 2020 the BC patient volume increased by 28% compared to the same period in 2019 (scheduled patients: 175 vs. 137) and amid travel restrictions it was kept high (treated patients: 136 vs. 133), mainly due to an influx from across Lombardy. RT schemes basically did not change, being already centered on hypofractionation. The increase of median time (67 vs. 74.5 days in 2019 and 2020, respectively) to the commencement of RT for low-risk patients was clinically negligible yet statistically significant ( p = 0.03), and in line with the pertinent recommendations. No significant difference was found in the time interval between treatments and RT for high-risk patients. Concomitant chemoradiotherapy was avoided throughout the pandemic peak. Twenty-one women (13.6%) delayed either computed tomography simulation or RT commencement mainly because of COVID-19-related concerns and mobility restrictions., Conclusion: The workload for BC was high during the pandemic peak. Hubs allowed the continuation of oncologic treatments, while mitigating the strain on frontline COVID-19 hospitals., Competing Interests: M.C.L., F.C., B.A.J.-F. received honorarium fees from Accuray Inc. outside the current work. The remaining authors declare no conflicts of interest., (Copyright © 2020 by S. Karger AG, Basel.)

Purpose: To retrospectively review our experience on 84 patients with squamous cell anal canal cancer (SCAC) within 12 months after combined treatment with intensity-modulated RT (IMRT), in terms of acute and early-late toxicity, overall treatment time and interruptions, colostomy-free survival (CFS), and tumor response., Methods: Acute gastrointestinal (GI), genitourinary (GU), and cutaneous (CU) toxicities were assessed according to Common Toxicity Criteria for Adverse Events (CTCAE) version 4.03. Early-late toxicity was scored using the Radiation Therapy Oncology Group (RTOG) late radiation morbidity scoring system. Tumor response was evaluated with response evaluation criteria in solid tumors (RECIST) v1.1., Results: Acute toxicity for 84 subjects (100%): severe (≥ G3) GI and skin toxicity was observed in 4 (5%) and 19 patients (23%), respectively. Early-late toxicity for 73 subjects (87%): severe (≥ G3) GI and vulvo-vaginal toxicity was observed in 2 (3%) and 2 (3%) patients, respectively. No acute or early-late severe GU toxicity was reported. A treatment interruption occurred in 65 patients (77%). CFS was 96% (95% CI 89-99) at 6 months and 92% (95% CI 83-96) at 12 months. At 6 months complete response (CR), partial response (PR) and progressive disease (PD) was observed in 70 (83%), 3 (4%), and 7 patients (8%), respectively. At 12 months, CR was observed in 60 patients (81%); eleven patients (15%) experienced PD., Conclusion: Our study showed an excellent clinical result and very low acute toxicity rates, confirming the IMRT as standard of care for curative treatment of anal cancer patients. The current trial was registered with the number IEO N87/11.

Objectives: stereotactic radiosurgery (SRS) and fractionated stereotactic radiotherapy (FSRT) are a therapeutic option for Oligometastatic/Oligoprogressive (OM/OP) NSCLC. This retrospective multicentre analysis aims to analyse clinical outcomes and treatment related toxicity of patients treated to all sites of know disease with SRS and/or FSRT for OM/OP NSCLC in 8 Italian radiation oncology centres., Materials and Methods: From January 2016 to January 2017 198 OM/OP NSCLC patients (pts) were treated in 8 Centres. Inclusion criteria were as follows: 1-5 lesions at onset or after previous systemic treatment; Pts must have all metastatic lesions treated. Endpoints analysed were local progression free survival (LPFS); out-of-field recurrence free survival (OFPS); progression free survival (PFS); overall survival (OS). Time to New systemic Therapy free survival (TNT) and toxicity were also analysed., Results: At the time of radiotherapy, 119 pts (60 %) were treated for a single lesion, 49 (25 %) for 2 lesions, 30 (15 %) for 3-5 metastases. Total number of lesions treated was 333: 204 brain, 68 lung, 24 bone, 16 nodal, 12 adrenal, 8 liver and 1 soft tissue. 83/198 pts (41.8 %) had the primary tumour controlled at the time of the SRT. After a median follow-up of 18 months, median OS and PFS were 29.6 months and 10.6 months, respectively. One year LPFS and OPFS were 90 % and 47 %, respectively. Median TNT was 10 months. At univariate analysis factors associated with better OS were PS 0-1; controlled primary tumour, 1-2 lesions; extracranial metastasis. Multivariate analysis confirmed number of lesions <3 and extracranial metastasis to be related with better survival (Relative Risk 0.4 and 0.41, respectively). Two cases of death possibly related to brain radionecrosis were observed., Conclusion: OM/OP NSCLC pts treated with an ablative SRT to all metastatic sites have fair outcomes with acceptable toxicity. Better results might be achieved in case of low disease burden and extracranial possibly when primary tumour is controlled., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: This study investigated the risk of reconstruction failure after mastectomy, immediate breast reconstruction, and radiotherapy to either a temporary tissue expander or permanent implant., Methods: Records of women treated at a single institution between June of 1997 and December of 2011 were reviewed. Two patient groups were identified based on type of immediate breast reconstruction: tissue expander followed by exchange with a permanent implant and permanent implant. The study endpoint was rate of reconstruction failure, defined as a replacement, loss of the implant, or conversion to flap., Results: The tissue expander/permanent implant and the permanent implant groups consisted of 63 and 75 patients, respectively. The groups were well balanced for clinical and treatment characteristics. With a median follow-up of 116 months, eight implant losses, 50 implant replacements, and four flap conversions were recorded. Reconstruction failure occurred in 22 of 63 patients in the expander/implant group and in 40 of 75 patients in the permanent implant group. A traditional proportional hazards model showed a higher risk of reconstruction failure for the expander/implant group (hazard ratio, 2.01) and a significantly shorter time to reconstruction failure compared with the permanent implant group (109.2 months versus 157.7 months; p = 0.03); however, according to a competing risk model, the between-groups cumulative incidences were not significantly different (hazard ratio, 1.09)., Conclusions: Radiotherapy to either a tissue expander or a permanent implant presented a fairly large risk of reconstruction failure over time. The expander/implant group was not more likely to develop reconstruction failure compared to permanent implant group, but the timing of onset was shorter. More complex techniques should be investigated to lower the risk of reconstruction failure., Clinical Question/level of Evidence: Therapeutic, III.

Aims: To compare the contouring of organs at risk (OAR) between a clinical specialist radiation therapist (CSRT) and radiation oncologists (ROs) with different levels of expertise (senior-SRO, junior-JRO, fellow-FRO)., Methods: On ten planning computed tomography (CT) image sets of patients undergoing breast radiotherapy (RT), the observers independently contoured the contralateral breast, heart, left anterior descending artery (LAD), oesophagus, kidney, liver, spinal cord, stomach and trachea. The CSRT was instructed by the JRO e SRO. The inter-observer variability of contoured volumes was measured using the Dice similarity coefficient (DSC) (threshold of ≥ 0.7 for good concordance) and the centre of mass distance (CMD). The analysis of variance (ANOVA) was performed and a p -value < 0.01 was considered statistically significant., Results: Good overlaps (DSC > 0.7) were obtained for all OARs, except for LAD (DSC = 0.34 ± 0.17, mean ± standard deviation) and oesophagus (DSC = 0.66 ± 0.06, mean ± SD). The mean CMD < 1 cm was achieved for all the OARs, but spinal cord (CMD = 1.22 cm). By pairing the observers, mean DSC > 0.7 and mean CMD < 1 cm were achieved in all cases. The best overlaps were seen for the pairs JRO-CSRT(DSC = 0.82; CMD = 0.49 cm) and SRO-JRO (DSC = 0.80; CMD = 0.51 cm)., Conclusions: Overall, good concordance was found for all the observers. Despite the short training in contouring, CSRT obtained good concordance with his tutor (JRO). Great variability was seen in contouring the LAD, due to its difficult visualization and identification of CT scans without contrast., Competing Interests: The authors declared that there is no conflict of interest., (© the authors; licensee ecancermedicalscience.)

Purpose: To report the dosimetric feasibility of the radiation technique HALFMOON (Helical ALtered Fractionation for iMplant partial OmissiON) for post-mastectomy radiation therapy (PMRT) in intermediate-high-risk breast cancer patients with implant-based immediate breast reconstruction, where the clinical target volume (CTV) does not include the whole implant (implant-sparing approach)., Methods: In the HALFMOON technique, the CTV consisted of skin, subcutaneous tissues, and pectoralis major muscle, excluding the implant, chest wall muscles, and rib plane. The HALFMOON plans were compared with conventionally contoured CTV plans, in which the whole implant, chest wall muscles, and ribs plane were included in the CTV, in a ratio 1:3. All patients underwent hypofractionated treatment of 40.05 Gy/15 fractions, using helical Tomotherapy ® ., Results: Eighteen patients undergoing HALFMOON technique were compared to 54 subjects treated with conventionally contoured CTV plans. No difference was found in the planning target volume coverage between the two groups. Conversely, a statistically relevant dose reduction in HALFMOON patients was observed for ipsilateral lung (D 15% , p < 0.0001; D 20% , p < 0.0001; D 35% , p = 0.003), contralateral lung (D 20% , p = 0.048), contralateral breast (D 15% , p = 0.031; D 20% , p = 0.047), and stomach (D mean , p = 0.011). Regarding the implant, V 90% and D 50% decreased by 46% and 8%, respectively, in the HALFMOON plans (p < 0.0001)., Conclusion: The HALFMOON approach is technically feasible and resulted in high-dose conformity of the target with a significant reduction of radiation dose delivered to implant and other organs. A clinical study is needed to assess the impact on reconstruction cosmetic outcome and local control.

The purpose of this study was to evaluate whether the visualization of surgical clips (SCs) on the same set of planning computed tomography (CT) of breast cancer (BC) patients influences agreement on tumour bed (TB) delineation. Planning CT (CT orig ) of 47 BC patients with SCs to visualize the TB was processed in order to blur SCs and create a virtual CT (CT mod ). Four radiation oncologists (ROs, 2 juniors and 2 seniors) contoured TB on both the CT sets. Centre of mass distance (CMD), percentage overlap as Dice similarity coefficient (DSC), surface distance as average Hausdorff distance (AHD) and TB volume size were analysed. The intra-observer variability when contouring TB with and without SCs was statistically significant (p-values = 0.016, 0.0002 and ≪ 0.001 for CMD, AHD and DSC, respectively). Junior ROs showed worse reproducibility compared to seniors. The median DSC was < 0.7. The inter-observer variability with and without SCs was statistically significant (p < 0.001) for all metrics, with an increase of 48.7% in DSC and decrease of 50.7% and 57.1% in CMD and AHD, respectively, as relative median values, when SCs were visible. Regarding TB volumes, when SCs were visible, the intra-observer analysis revealed that 3/4 ROs delineated larger volumes, especially juniors. The inter-observer analysis showed that, in presence of visible SCs, the difference in TB volume among all the ROs fell from statistically significant to borderline significance (p = 0.052). TB contouring is confirmed to be an observer-dependent task. SCs decreased the intra and inter-observer variability but the overall agreement between ROs remained low.

Aims: To report the long-term outcome of a single institution series of pure ductal carcinoma in situ (DCIS) treated with accelerated partial irradiation using intraoperative electrons (IOERT)., Methods: From 2000 to 2010, 180 DCIS patients, treated with quadrantectomy and 21 Gy IOERT, were analyzed in terms of ipsilateral breast recurrences (IBRs) and survival outcomes by stratification in two subgroups. The low-risk group included patients who fulfilled the suitable definition according to American Society of Radiation Oncology (ASTRO) Guidelines (size ≤2.5 cm, grade 1-2 and surgical margins ≥3 mm) (Suitable), while the remaining ones formed the high-risk group (Non-Suitable)., Results: Eighty-four and 96 patients formed the Suitable and Non-Suitable groups, respectively. In the whole population, the cumulative incidence of IBR at 5, 7 and 10 years was 19%, 21%, and 25%, respectively. In the Suitable group, the cumulative incidence of IBR remained constant at 11% throughout the years, while in the Non-Suitable group increased from 26% at 5 years to 36% at 10 years (p < 0.0001). When hormonal positivity and HER2 absence of expression were added to the selection of the Suitable group, the cumulative incidence of IBR dropped and stabilized at 4% at 10 years. None died of breast cancer. In the whole population, 5-year and 10-year overall survival rate was 98% and 96.5%, respectively, without any difference between the two groups., Conclusions: The overall and by group IBR rates were high and stricter criteria are required for acceptable local control for Suitable DCIS. Because of the concerns raised, IOERT should not be used in clinical practice., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Aims: To evaluate the use of radiotherapy (RT) for oligometastatic cancer (OMC) among radiation oncologists in Lombardy, Italy., Methods and Study Design: A survey with 12 items regarding data of 2016 was sent to all 34 Lombardy RT centers. The survey included six general items and six specific items regarding patient/disease/treatment characteristics., Results: Thirteen centers answered the survey (38%). All centers responded to general items and 12 centers submitted patient/disease/treatment data. General items The majority of centers (8/13) consider OMC if metastases number is less than 5. The most commonly prescribed dose/fraction is 5-10 Gy (8/13) using schedules of 3-5 fractions (11/13). Patient data items A total of 15.681 patients were treated in 2016 with external beam RT in 12 responding centers, and 1.087 patients were treated for OMC (7%). Primary tumor included lung, prostate, breast, colorectal and other malignancies in 33%, 21%, 12%, 9% and 25% of all OMC patients, respectively. Brain, lymph node, lung, bone, liver and others were the most common treated sites (24%, 24%, 22%, 17%, 8% and 5%, respectively). One and more than one metastasis were treated in 75 and 25% of patients, respectively. The vast majority of patients (95%) were treated with image-guided intensity-modulated RT or stereotactic RT., Conclusions: Seven percent of all RT patients in Lombardy are treated for OMC. Extreme hypofractionation and high-precision RT are commonly employed. The initiative of multicenter and multidisciplinary collaboration has been undertaken in order to prepare the platform for prospective and/or observational studies in OMC.

Purpose: To evaluate the incidence and predictors for late toxicity and tumor outcome after hypofractionated radiotherapy using three different image-guided radiotherapy (IGRT) systems (hypo-IGRT) compared with conventional fractionation without image guidance (non-IGRT)., Methods and Materials: We compared the late rectal and urinary toxicity and outcome in 179 prostate cancer patients treated with hypo-IGRT (70.2 Gy/26 fractions) and 174 non-IGRT patients (80 Gy/40 fractions). Multivariate analysis was performed to define predictors for late toxicity. 5- and 8-year recurrence-free survival (RFS) and overall survival (OS) were analyzed., Results: Mean follow-up was 81 months for hypo-IGRT and 90 months for non-IGRT group. Mainly mild late toxicity was observed: Hypo-IGRT group experienced 65 rectal (30.9% G1/G2; 6.3% G3/G4) and 105 urinary events (56% G1/G2; 4% G3/G4). 5- and 8-year RFS rates were 87.5% and 86.8% (hypo-IGRT) versus 80.4% and 66.8% (non-IGRT). 5- and 8-year OS rates were 91.3% and 82.7% in hypo-IGRT and 92.2% and 84% in non-IGRT group. Multivariate analysis showed that hypo-IGRT is a predictor for late genitourinary toxicity, whereas hypo-IGRT, acute urinary toxicity and androgen deprivation therapy are predictors for late rectal toxicity. Advanced T stage and higher Gleason score (GS) were correlated with worse RFS., Conclusions: A small increase in mild late toxicity, but not statistically significant increase in severe late toxicity in the hypo-IGRT group when compared with conventional non-IGRT group was observed. Our study confirmed that IGRT allows for safe moderate hypofractionation, offering a shorter overall treatment time, a good impact in terms of RFS and providing potentially more economic health care.

Purpose: Acute toxicity in head and neck (H&N) cancer patients treated with definitive radiotherapy (RT) has a crucial role in compliance to treatments. The aim of this study was to correlate doses to swallowing-associated structures and acute dysphagia., Methods: We prospectively analyzed 42 H&N cancer patients treated with RT. Dysphagia (grade ≥ 3) and indication for percutaneous endoscopic gastrostomy (PEG) insertion were classified as acute toxicity. Ten swallowing-related structures were considered for the dosimetric analysis. The correlation between clinical information and the dose absorbed by the contoured structures was analyzed. Multivariate logistic regression method using resampling methods (bootstrapping) was applied to select model order and parameters for normal tissue complication probability (NTCP) modelling., Results: A strong multiple correlation between dosimetric parameters was found. A two-variable model was suggested as the optimal order by bootstrap method. The optimal model (Rs = 0.452, p < 0.001) includes V 45 of the cervical esophagus (odds ratio [OR] = 1.016) and D mean of the cricopharyngeal muscle (OR = 1.057). The model area under the curve was 0.82 (95% confidence interval 0.69-0.95)., Conclusion: Our results suggested that the absorbed dose to the cricopharyngeal muscle and cervical esophagus might play a relevant role in the development of acute RT-related dysphagia.

Purpose: To investigate the local outcome of patients after accelerated partial breast irradiation with intraoperative electrons (IORT) for invasive lobular carcinoma (ILC) compared with invasive ductal carcinoma (IDC)., Methods and Materials: From 1999 to 2007, 2173 patients were treated with breast-conserving surgery and IORT (21 Gy/1 fraction) as the sole local treatment: 252 patients with ILC (11.6%) were compared with 1921 patients with IDC in terms of local control., Results: Compared with the IDC subgroup, patients with ILC had a low-risk profile and were more hormone responsive. The 5- and 10-year in-breast tumor reappearance (IBTR) rates were 5.5% and 14.4%, respectively, for the IDC group and 7.5% and 21.8%, respectively, for the ILC group (log-rank P=.03). The excess risk of IBTR associated with ILC was particularly high for small tumors (≤1 cm: hazard ratio [HR], 2.24; 95% confidence interval [CI], 1.03-4.85), elderly patients (60-69 years: HR, 2.27; 95% CI, 1.11-4.63; ≥70 years: HR, 3.28; 95% CI, 1.08-10.0), low-grade tumors (grade 1: HR, 3.50; 95% CI, 1.05-11.7), and luminal A molecular subtype (HR, 3.18; 95% CI, 1.49-6.77). Among the ILC histologic variants, no difference between classic and nonclassic subgroups was observed, although the signet ring cell and solid variants had the worst local control., Conclusions: Despite a favorable tumor profile, accelerated partial breast irradiation with IORT led to a higher incidence of IBTRs in patients with ILC compared with those with IDC. Our institutional experience emphasized the importance of the size of the irradiation field, pointing to the use of larger collimators, even when dealing with small tumors, to improve local control., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objectives: Atlas-based automatic segmentation (ABAS) addresses the challenges of accuracy and reliability in manual segmentation. We aim to evaluate the contribution of specific-purpose in ABAS of breast cancer (BC) patients with respect to generic-purpose libraries., Materials and Methods: One generic-purpose and 9 specific-purpose libraries, stratified according to type of surgery and size of thorax circumference, were obtained from the computed tomography of 200 BC patients. Keywords about contralateral breast volume and presence of breast expander/prostheses were recorded. ABAS was validated on 47 independent patients, considering manual segmentation from scratch as reference. Five ABAS datasets were obtained, testing single-ABAS and multi-ABAS with simultaneous truth and performance level estimation (STAPLE). Center of mass distance (CMD), average Hausdorff distance (AHD) and Dice similarity coefficient (DSC) between corresponding ABAS and manual structures were evaluated and statistically significant differences between different surgeries, structures and ABAS strategies were investigated., Results: Statistically significant differences between patients who underwent different surgery were found, with superior results for conservative-surgery group, and between different structures were observed: ABAS of heart, lungs, kidneys and liver was satisfactory (median values: CMD<2 mm, DSC≥0.80, AHD<1.5 mm), whereas chest wall, breast and spinal cord obtained moderate performance (median values: 2 mm ≤ CMD<5 mm, 0.60 ≤ DSC<0.80, 1.5 mm ≤ AHD<4 mm) and esophagus, stomach, brachial plexus and supraclavicular nodes obtained poor performance (median CMD≥5 mm, DSC<0.60, AHD≥4 mm). The application of STAPLE algorithm generally yields higher performance and the use of keywords improves results for breast ABAS., Conclusion: The homogeneity in the selection of atlases based on multiple anatomical and clinical features and the use of specific-purpose libraries can improve ABAS performance with respect to generic-purpose libraries., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Purpose: The aim of this retrospective study is to evaluate patient profile, feasibility, and acute toxicity of RadioTherapy (RT) delivered by VERO® in the first 20 months of clinical activity., Methods: Inclusion criteria: 1) adult patients; 2) limited volume cancer (M0 or oligometastatic); 3) small extracranial lesions; 4) treatment between April 2012 and December 2013 and 5) written informed consent. Two techniques were employed: intensity modulated radiotherapy (IMRT) and stereotactic body radiotherapy (SBRT). Toxicity was evaluated using Radiation Therapy Oncology Group/European Organisation for Research and Treatment of Cancer (RTOG/EORTC) criteria., Results: Between April 2012 and December 2013, 789 consecutive patients (957 lesions) were treated. In 84% of them one lesion was treated and in 16% more than one lesion were treated synchronously/metachronously; first radiotherapy course in 85%, re-irradiation in 13%, and boost in 2% of cases. The treated region included pelvis 46%, thorax 38%, upper abdomen 15%, and neck 1%. Radiotherapy schedules included <5 and >5 fractions in 75% and 25% respectively. All patients completed the planned treatment and an acceptable acute toxicity was observed., Conclusions: RT delivered by VERO® was administrated predominantly to thoracic and pelvic lesions (lung and urologic tumours) using hypofractionation. It is a feasible approach for limited burden cancer offering short and well accepted treatment with favourable acute toxicity profile. Further investigation including dose escalation and other available VERO® functionalities such as real-time dynamic tumour tracking is warranted in order to fully evaluate this innovative radiotherapy system.

The aim of this study is to access the feasibility, toxicity profile, and tumour outcome of an organ preservation curative approach in non-metastatic muscle-invasive bladder cancer. A retrospective analysis was conducted on patients affected by M0 bladder cancer, who refused cystectomy and were treated with a curative approach. The standard bladder preservation scheme included maximal transurethral resection of bladder tumour (TURBT) and combination of radiotherapy and platin-based chemotherapy, followed by endoscopic evaluation, urine cytology, and instrumental evaluation. Thirteen patients fulfilled the inclusion criteria. TNM stage was cT2cN0M0 and cT2cNxM0, in 12 and one patients, respectively. All patients had transitional cell cancer. Twelve patients completed the whole therapeutic programme (a bimodal treatment without chemotherapy for one patient). Median follow-up is 36 months. None of the patients developed severe urinary or intestinal acute toxicity. In 10 patients with a follow-up > 6 months, no cases of severe late toxicity were observed. Response evaluated in 12 patients included complete response and stable disease in 11 patients (92%), and one patient (8%), respectively. At the time of data analysis (March 2016), 10 patients (77%) are alive with no evidence of disease, two patients (15%) died for other reasons, and one patient has suspicious persistent local disease. The trimodality approach, including maximal TURBT, radiotherapy, and chemotherapy for muscle-invasive bladder cancer, is well-tolerated and might be considered a valid and feasible option in fit patients who refuse radical cystectomy.

Objective: To compare the toxicity of image-guided intensity-modulated radiotherapy (IG-IMRT) to the pelvis or prostate bed (PB) only. To test the hypothesis that the potentially injurious effect of pelvic irradiation can be counterbalanced by reduced irradiated normal tissue volume using IG-IMRT., Methods: Between February 2010 and February 2012, 208 patients with prostate cancer were treated with adjuvant or salvage IG-IMRT to the PB (102 patients, Group PB) or the pelvis and prostate bed (P) (106 patients, Group P). The Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer criteria were used to evaluate toxicity., Results: Median follow-up was 27 months. Toxicity G ≥ 2 in Group PB: in the bowel acute and late toxicities were 11.8% and 10%, respectively; urinary acute and late toxicities were 10.8% and 15%, respectively. Toxicity G ≥ 2 in Group P: in the bowel acute and late toxicities were both 13.2%; urinary acute and late toxicities were 13.2% and 15.1%, respectively. No statistical difference in acute or late toxicity between the groups was found (bowel: p = 0.23 and p = 0.89 for acute and late toxicity, respectively; urinary: p = 0.39 and p = 0.66 for acute and late toxicity, respectively). Of the clinical variables, only previous abdominal surgery was correlated with acute bowel toxicity. Dosimetric parameters that correlated with bowel toxicity were identified., Conclusion: The toxicity rates were low and similar in both groups, suggesting that IG-IMRT allows for a safe post-operative irradiation of larger volumes. Further investigation is warranted to exclude bias owing to non-randomized character of the study., Advances in Knowledge: Our report shows that modern radiotherapy technology and careful planning allow maintaining the toxicity of pelvic lymph node treatment at the acceptable level, as it is in the case of PB radiotherapy.

Objective: To retrospectively evaluate external beam reirradiation (re-EBRT) delivered to the prostate/prostatic bed for local recurrence, after radical or adjuvant/salvage radiotherapy (RT)., Methods: 32 patients received re-EBRT between February 2008 and October 2013. All patients had clinical/radiological local relapse in the prostate or prostatic bed and no distant metastasis. re-EBRT was delivered with selective RT technologies [stereotactic RT including CyberKnife(TM) (Accuray, Sunnyvale, CA); image-guidance and intensity-modulated RT etc.]. Toxicity was evaluated using the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer criteria. Biochemical control was assessed according to the Phoenix definition (NADIR + 2 ng ml(-1))., Results: Acute urinary toxicity: G0, 24 patients; G1, 6 patients; G2, 2 patients. Acute rectal toxicity: G0, 28 patients; G1, 2 patients; and G2, 1 patient. Late urinary toxicity (evaluated in 30 cases): G0, 23 patients; G1, 6 patients; G2, 1 patient. Late renal toxicity: G0, 25 patients; G1, 5 patients. A mean follow-up of 21.3 months after re-EBRT showed that 13 patients were free of cancer, 3 were alive with biochemical relapse and 12 patients were alive with clinically evident disease. Four patients had died: two of disease progression and two of other causes., Conclusion: re-EBRT using modern technology is a feasible approach for local prostate cancer recurrence offering 2-year tumour control in about half of the patients. Toxicity of re-EBRT is low. Future studies are needed to identify the patients who would benefit most from this treatment., Advances in Knowledge: Our series, based on experience in one hospital alone, shows that re-EBRT for local relapse of prostate cancer is feasible and offers a 2-year cure in about half of the patients.

Aims and Background: Bladder preservation is a treatment option in muscle-invasive bladder carcinoma. The most investigated approach is a trimodality schedule including maximum transurethral resection of bladder tumor (TURBT) followed by chemoradiotherapy. Our aim was to evaluate the use of bladder preservation by radiation oncologists of the Lombardy region in Italy., Methods and Study Design: A survey with 13 items regarding data of 2012 was sent to all 32 radiotherapy centers within the collaboration between the Lombardy Oncological Network and the Lombardy Section of the Italian Society of Oncological Radiotherapy., Results: Thirteen centers (41%) answered the survey; the presented data come from 11 active centers. In these centers, 11,748 patients were treated with external-beam radiotherapy in 2012, 100 of whom having bladder cancer (0.9%). 74/100 patients received radiotherapy as palliative treatment for T, N or M lesions. A further 9 and 5 patients received radiotherapy for oligometastatic disease (ablative doses to small volumes) and postoperatively, respectively. Bladder preservation was performed in 12 cases and included trimodality and other strategies (mainly TURBT followed by radiotherapy). A multidisciplinary urology tumor board met regularly in 5 of 11 centers. All responders declared their interest in the Lombardy multicenter collaboration on bladder preservation., Conclusions: Our survey showed that bladder preservation is rarely used in Lombardy despite the availability of the latest radiotherapy technologies and the presence of an urology tumor board in half of the centers. The initiative of multicenter and multidisciplinary collaboration was undertaken to prepare the platform for bladder preservation as a treatment option in selected patients.

Objective: To report the image-guided hypofractionated radiotherapy (hypo-IGRT) outcome for patients with localised prostate cancer according to the new outcome models Trifecta (cancer control, urinary continence, and sexual potency) and SCP (failure-free survival, continence and potency)., Patients and Methods: Between August 2006 and January 2011, 337 patients with cT1-T2N0M0 prostate cancer (median age 73 years) were eligible for a prospective longitudinal study on hypo-IGRT (70.2 Gy/26 fractions) in our Department. Patients completed four questionnaires before treatment, and during follow-up: the International Index of Erectile Function-5 (IIEF-5), the International Prostate Symptom Score (IPSS), and the European Organization for Research and Treatment of Cancer prostate-cancer-specific Quality of Life Questionnaires (QLQ) QLQ-PR25 and QLQ-C30. Baseline and follow-up patient data were analysed according to the Trifecta and SCP outcome models. Cancer control, continence and potency were defined respectively as no evidence of disease, score 1 or 2 for item 36 of the QLQ-PR25 questionnaire, and total score of >16 on the IIEF-5 questionnaire. Patients receiving androgen-deprivation therapy (ADT) at any time were excluded., Results: Trifecta criteria at baseline were met in 72 patients (42% of all ADT-free patients with completed questionnaires). Both at 12 and 24 months after hypo-IGRT, 57% of the Trifecta patients at baseline were still meeting the Trifecta criteria (both oncological and functional success according to the SCP model). The main reason for failing the Trifecta criteria during follow-up was erectile dysfunction: in 18 patients after 6 months follow-up, in 12 patients after 12 months follow-up, and in eight patients after 24 months. Actuarial 2-year Trifecta failure-free survival rate was 44% (95% confidence interval 27-60%). In multivariate analysis no predictors of Trifecta failure were identified. Missing questionnaires was the main limitation of the study., Conclusion: The Trifecta and SCP classifications can be used as tools to report RT outcome., (© 2013 The Authors. BJU International © 2013 BJU International.)

Objectives: Uterine leiomyosarcoma (LMS) was traditionally staged by modified 1988 International Federation of Gynecology and Obstetrics (FIGO) staging criteria for endometrial adenocarcinoma. Contemporary methods of staging include the 2009 FIGO system for uterine LMS and the 2010 American Joint Committee on Cancer (AJCC) soft tissue sarcoma system. The aim of this study was to compare the accuracy of these 3 staging systems and a novel system in predicting disease-specific survival for patients with uterine LMS., Methods: Patients, evaluated at our institution with uterine LMS from 1976 to 2009, were identified. Stage was assigned retrospectively based on operative and pathology reports. Staging systems performance was compared using confidence indices., Results: We identified 244 patients with uterine LMS with sufficient information to be staged by all 3 systems. For each staging method, lower stage was associated with significantly improved disease-specific survival, P < 0.001. Patients with 2010 AJCC stage IA disease (low-grade, ≤5 cm) experienced no disease-specific deaths. We created a novel staging system, which used size and grade to stratify patients with disease confined to the uterus and/or cervix and combined the remaining patients with extrauterine disease as stage IV. Based on confidence index, the 2010 AJCC system and our novel system provided more accurate prognostic information than either of the 2 FIGO systems., Conclusions: Uterine LMS remains a clinically aggressive malignancy. Size and grade provided accurate prognostic information for patients with disease confined to the uterus and/or cervix. Patients with small, low-grade uterine LMS do not benefit from adjuvant therapy.

Objectives: To evaluate the impact of the introduction of checklists at the daily progress note to improve patient care among gynecologic oncology patients., Methods: A progress note incorporating checklists that were pertinent for our patient population was developed with input obtained from all staff involved on patients care. The form was approved by the hospital. The average length of stay, compliance with prophylactic guidelines (anticoagulation, peptic ulcer disease), reason for admission, and readmission rate were compared among the preimplementation and postimplementation periods., Results: A total of 492 discharge summaries were evaluated through the study period (267 for the preimplementation period and 225 for the postimplementation period). The mean length of stay was of 4.46 days for the preimplementation and 3.46 days for the postimplementation period (P = 0.007). TEDs/SCDs were not used in 9.3% of the patients in the pre group versus 0.6% in the post group (P < 0.001). DVT prophylaxis was given to 30.1% of the pre group versus 34.8% of the post group (P = 0.0013). The administration of PUD prophylaxis also increased from 28.3% in the pre group to 40.2% of the post group (P < 0.001). There was a decrease in the nonsurgical admissions from 22.2% in the pre group versus 14.6% in the post group (P = 0.049)., Conclusions: The use of checklists in daily progress notes enhances patient care by improving the delivery of routine care that is often overlooked in the light of major medical issues.

Objective: The aim of this study was to determine if comprehensive surgical staging is a better predictor of outcome than incomplete staging for women with stage I noninvasive or minimally invasive (≤3 mm) uterine serous carcinoma (USC)., Methods: Retrospective chart review was used to identify patients undergoing hysterectomy at the Johns Hopkins Hospital from 1989 to 2010. Relevant clinical and pathologic data were extracted. Patients with noninvasive and minimally invasive (≤3-mm myometrial invasion) USC were identified. Stage was assigned based on the 2009 International Federation of Gynecology and Obstetrics endometrial cancer criteria. Survival curves were generated using the Kaplan-Meier method., Results: We identified 63 patients with noninvasive or minimally invasive (≤3 mm) USC. Stages I, II, III, and IV disease were noted in 65% (41/63), 6% (4/63), 14% (9/63), and 14% (9/63) of the patients, respectively. Lower stage was associated with a significantly improved disease-specific survival (P = 0.001). Comprehensive staging, including total hysterectomy, bilateral salpingo-oophorectomy, pelvic and para-aortic lymphadenectomy, omentectomy, and peritoneal biopsies, was completed in 29% (12/41) of the patients with stage I disease. There were no disease-specific deaths in the comprehensive staging group. Compared with incomplete staging, comprehensive staging was associated with a significantly improved disease-specific survival (P = 0.039)., Conclusions: Patients with stage I noninvasive and minimally invasive USC on comprehensive staging have an excellent prognosis. Adjuvant therapy may not benefit this patient population.

Robotic surgery has been used increasingly for the management of benign or malignant gynecologic conditions. Vaginal hemorrhage after hysterectomy is fairly uncommon. Uterine artery pseudoaneurysm is a rare phenomenon causing late onset hemorrhage that could be potentially life-threatening. This case describes the management of vaginal bleeding due to ruptured uterine artery pseudoaneurysm after robotic-assisted total hysterectomy. This is the first known reported case of a ruptured uterine artery pseudoaneurysm after a robotic-assisted hysterectomy.

Objective: To examine disparities in delivery of care and survival according to racial classification among White and African-American women with Stage IIIC epithelial ovarian cancer undergoing initial treatment in a tertiary referral center setting., Methods: All consecutive patients diagnosed with Stage IIIC epithelial ovarian cancer between 1/1/95 and 12/31/08 were identified and clinic-pathologic variables retrospectively collected. Differences in initial treatment paradigm, surgical and adjuvant therapy, and overall survival according to racial classification were assessed by univariate and multivariate analyses., Results: A total of 405 patients (White, n=366; African-American, n=39) were identified. There were no significant differences according to racial classification in age, CA125, ASA class, histology, tumor grade, the frequency of initial surgery (90.4% vs 82.1%, p=0.06), optimal residual disease (73.0% vs 69.2%, p=0.28), no gross residual disease (51.4% vs 53.8%, p=0.49), and platinum-taxane chemotherapy (88.3% vs 87.2%, p=0.55). The median overall survival for White patients was 50.5 months (95%CI=43.2-57.9 months), compared to 47.0 (95%CI=36.2-57.8) months for African-Americans (p=0.57). On multivariate analysis, age, tumor grade 3, serum albumin <3.0 g/dl, platinum-based chemotherapy, and no gross residual disease were independently associated with overall survival, while African-American race was not (HR=1.06, 95%CI=0.61-1.79)., Conclusions: Among women undergoing initial treatment for ovarian cancer at a tertiary referral center, African-American patients were as likely as White patients to undergo cytoreductive surgery, be left with minimal post-surgical residual disease, and receive appropriate chemotherapy. With equal access to gynecologic oncology care and multidisciplinary cancer resources, the survival disparities according to race observed in population-based studies are largely mitigated., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Objective: To describe the technique and short-term post-operative outcomes associated with diaphragm full-thickness resection (FTR) and intraoperative trans-diaphragmatic decompression of the resultant pneumothorax (TDDP)., Methods: All patients undergoing cytoreductive surgery for primary or recurrent ovarian cancer between 8/1/98 and 7/30/09 were retrospectively identified from the tumor registry database. Patients undergoing diaphragm FTR were selected for detailed review of the operative technique and post-operative outcomes. The operative technique of TDDP using a fenestrated Robinson catheter is described., Results: A total of 45 patients met study inclusion criteria. Diaphragm FTR surgery was performed exclusively by gynecologic oncologists in 73.3% of cases. The median patient age was 60 years, and the majority (75.6%) of cases were performed for primary cytoreduction of Stage IIIC (n=27) or Stage IV (n=18) disease. The two-dimensional surface area of tumor involvement ranged from 9 cm(2) to 192 cm(2). The right hemi-diaphragm alone was involved in 71.1% of cases, while both the right and left hemi-diaphragms were involved in 24.4%. TDDP was performed in 41 of the 45 patients undergoing diaphragm FTR, while 4 patients had intraoperative thoracostomy tubes placed. Among the 41 TDDP patients, post-operative days 3-4 radiographic imaging revealed that 56% had a small residual pleural effusion and 9.8% had a residual pneumothorax; however, only 2 patients (4.9%) required post-operative thoracostomy tube placement or thoracentesis., Conclusion: The technique of TDDP eliminates the need of intraoperative and post-operative thoracostomy tube/thoracentesis in 95.1% of patients undergoing diaphragm FTR as a component of ovarian cancer cytoreductive surgery., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Objectives: To evaluate the safety, feasibility, and economic impact of a clinical pathway, including rapid diet advancement, for patients undergoing rectosigmoid colectomy as part of cytoreductive surgery for advanced ovarian and primary peritoneal cancers., Methods: Between 8/1/98 and 6/30/06, 64 consecutive patients met study inclusion criteria. Using case-control methodology, post-operative management was dictated by a prescribed clinical pathway in 19 patients (Group A) and directed by individual surgeon preference in 45 patients (Group B). Critical elements of the clinical pathway included: rapid diet advancement, early discontinuance of nasogastric suction, criteria-based utilization of parenteral nutrition, selective laboratory testing, and deferring initiation of chemotherapy until after discharge., Results: Stage IIIC/IV disease was present in 94% of all patients. The median time to flatus was 6 days for both groups (p=0.95); however, the median time to tolerance of diet was 3 days for Group A and 6 days for Group B (p=0.013). Compared to Group B, patients in Group A had a significantly shorter median length of hospital stay (7 days vs 10 days, p=0.014) and lower median 30-day post-operative hospital cost ($19,700 vs $25,110, p=0.028), with no significant difference in 30-day readmission rate (21% vs 33%, p=0.379). Clinical pathway-directed management was associated with a median reduction in hospital cost of $5410 per patient., Conclusions: A critical pathway incorporating rapid diet advancement for patients undergoing primary cytoreductive surgery with rectosigmoid colectomy for ovarian and primary peritoneal cancers is feasible, safe, and associated with a significant reduction in length of hospital stay and hospital-related costs.

We report two controlled comparisons of a previously validated multicomponent (relaxation, thermal biofeedback, and cognitive therapy) treatment for irritable bowel syndrome (IBS) to an ostensible attention-placebo control (pseudo-meditation and EEG alpha suppression biofeedback) and to a symptom-monitoring control. In Study 1 (n = 10 per condition) there were nonsignificant trends for the multicomponent treatment to be superior to the attention-placebo condition. In Study 2 (n = 30 per condition), we found no advantage for the multicomponent treatment over the attention-placebo condition. Subjects in both treatment conditions showed significant reductions in GI symptoms, as measured by daily symptom diaries, and significant reductions in trait anxiety and depression. The GI symptom reductions held up over a 6 month follow-up. Possible explanations for the results are explored.

Comparisons were made among patients with IBS (n = 55), tension headache (n = 69), or migraine headache (n = 68) and nonpatient controls (n = 64) on the MMPI and several other psychological tests, including BDI, STAI, Life Events, and Psychosomatic Symptom Checklist. With two nonsignificant exceptions (MMPI scale F and Life Events) the groups were consistently ordered, in terms of increasing psychological distress: Normals less than Migraine Headache less than Tension Headache less than IBS. The IBS patients were more like the tension headache patients than any other group. Subgroups of IBS patients, on the basis of presence or absence of diarrhea or constipation in addition to abdominal pain, were generally not significantly different on the psychological tests.

We compared a clinic-based regimen of 16 individual sessions (2 per week) of thermal biofeedback with a largely home-based regimen of 5 sessions (spread over 8 weeks) for the treatment of essential hypertension in patients who required at least two drugs to maintain control of blood pressure (BP). On the basis of the clinical end point of being successfully withdrawn from the second stage medication while BP remained under control, the clinic-based regimen (5 of 9) was superior (chi less than (1) = 4.0, p less than .05) to the home-based regimen (1 of 9). Internal analyses point to more frequently obtaining a hand temperature of at least 95 degrees F by the office-based patients as possibly the reason for the difference.