Total mesorectal excision after rectal-sparing approach in locally advanced rectal cancer patients after neoadjuvant treatment: a high volume center experience.

Background: In patient with a complete or near-complete clinical response after neoadjuvant treatment for locally advanced rectal cancer, the organ-sparing approach [watch & wait (W&W) or local excision (LE)] is a possible alternative to major rectal resection. Although, in case of local recurrence or regrowth, after these treatments, a total mesorectal excision (TME) can be operated. Method: In this retrospective study, we selected 120 patients with locally advanced rectal cancer (LARC) who had a complete or near-complete clinical response after neoadjuvant treatment, from June 2011 to June 2021. Among them, 41 patients were managed by W&W approach, whereas 79 patients were managed by LE. Twenty-three patients underwent salvage TME for an unfavorable histology after LE (11 patients) or a local recurrence/regrowth (seven patients in LE group - five patients in W&W group), with a median follow-up of 42 months. Results: Following salvage TME, no patients died within 30 days; serious adverse events occurred in four patients; 8 (34.8%) patients had a definitive stoma; 8 (34.8%) patients undergone to major surgery for unfavorable histology after LE - a complete response was confirmed. Conclusion: Notably active surveillance after rectal sparing allows prompt identifying signs of regrowth or relapse leading to a radical TME. Rectal sparing is a possible strategy for LARC patients although an active surveillance is necessary.

Oligo-metastatic neoPlasms from the gastro-intestinal tract: iDentIfiCaTIon of cliNical and molecular drivers: the PREDICTION study.

BACKGROUND: Metastatic disease in tumors originating from the gastrointestinal tract can exhibit varying degrees of tumor burden at presentation. Some patients follow a less aggressive disease course, characterized by a limited number of metastatic sites, referred to as "oligo-metastatic disease" (OMD). The precise biological characteristics that define the oligometastatic behavior remain uncertain. In this study, we present a protocol designed to prospectively identify OMD, with the aim of proposing novel therapeutic approaches and monitoring strategies. METHODS: The PREDICTION study is a monocentric, prospective, observational investigation. Enrolled patients will receive standard treatment, while translational activities will involve analysis of the tumor microenvironment and genomic profiling using immunohistochemistry and next-generation sequencing, respectively. The first primary objective (descriptive) is to determine the prevalence of biological characteristics in OMD derived from gastrointestinal tract neoplasms, including high genetic concordance between primary tumors and metastases, a significant infiltration of T lymphocytes, and the absence of clonal evolution favoring specific driver genes (KRAS and PIK3CA). The second co-primary objective (analytic) is to identify a prognostic score for true OMD, with a primary focus on metastatic colorectal cancer. The score will comprise genetic concordance (> 80%), high T-lymphocyte infiltration, and the absence of clonal evolution favoring driver genes. It is hypothesized that patients with true OMD (score 3+) will have a lower rate of progression/recurrence within one year (20%) compared to those with false OMD (80%). The endpoint of the co-primary objective is the rate of recurrence/progression at one year. Considering a reasonable probability (60%) of the three factors occurring simultaneously in true OMD (score 3+), using a significance level of α = 0.05 and a test power of 90%, the study requires a minimum enrollment of 32 patients. DISCUSSION: Few studies have explored the precise genetic and biological features of OMD thus far. In clinical settings, the diagnosis of OMD is typically made retrospectively, as some patients who undergo intensive treatment for oligometastases develop polymetastatic diseases within a year, while others do not experience disease progression (true OMD). In the coming years, the identification of true OMD will allow us to employ more personalized and comprehensive strategies in cancer treatment. TRIAL REGISTRATION: ClinicalTrials.gov ID NCT05806151.

Patterns of Care for Breast Radiotherapy in Italy: Breast IRRadiATA (Italian Repository of Radiotherapy dATA) Feasibility Study.

Aim. Breast IRRADIATA (Italian Repository of RADIotherapy dATA) is a collaborative nationwide project supported by the Italian Society of Radiotherapy and Clinical Oncology (AIRO) and the Italian League Against Cancer (LILT). It focuses on breast cancer (BC) patients treated with radiotherapy (RT) and was developed to create a national registry and define the patterns of care in Italy. A dedicated tool for data collection was created and pilot tested. The results of this feasibility study are reported here. Methods. To validate the applicability of a user-friendly data collection tool, a feasibility study involving 17 Italian Radiation Oncology Centers was conducted from July to October 2021, generating a data repository of 335 BC patients treated between January and March 2020, with a minimum follow-up time of 6 months. A snapshot of the clinical presentation, treatment modalities and radiotherapy toxicity in these patients was obtained. A Data Entry Survey and a Satisfaction Questionnaire were also sent to all participants. Results. All institutions completed the pilot study. Regarding the Data Entry survey, all questions achieved 100% of responses and no participant reported spending more than 10 min time for either the first data entry or for the updating of follow-up. Results from the Satisfaction Questionnaire revealed that the project was described as excellent by 14 centers (82.3%) and good by 3 (17.7%). Conclusion. Current knowledge for the treatment of high-prevalence diseases, such as BC, has evolved toward patient-centered medicine, evidence-based care and real-world evidence (RWE), which means evidence obtained from real-world data (RWD). To this aim, Breast IRRADIATA was developed as a simple tool to probe the current pattern of RT care in Italy. The pilot feasibility of IRRADIATA encourages a larger application of this tool nationwide and opens the way to the assessment of the pattern of care radiotherapy directed to other cancers.

Electrochemotherapy of Primary Colon Rectum Cancer and Local Recurrence: Case Report and Prospective Analysis.

PURPOSE: Surgery, radiotherapy, and oncological treatment (chemotherapy and antineoplastic antibodies) are standard treatments of rectal cancer. ECT has shown its effectiveness and suitability in deep solid tumors conducted in both preclinical and clinical studies. We show here an update and preliminary results with locally advanced rectum cancer (LARC) treated with ECT. METHODS: Two patients with major clinical response to restaging after neoadjuvant treatment for LARC were subjected to ECT 12 weeks after completing chemo-radiation therapy. One patient was subjected to ECT on a colorectal local recurrence formed after neoadjuvant treatment for LARC and surgery. Computed Tomography and Magnetic Resonance Imaging were used to assess ECT response. RESULTS: The results showed stable disease in two of the three patients treated, while one patient achieved a complete response. The local control of disease is maintained in the patient follow-up. For each patient, a reduction in pain was observed and for the patient with local recurrence, a reduction in bleeding present before ECT was also achieved. CONCLUSION: Preliminary results showed that ECT is a safe and effective treatment in patients with a major clinical response or local recurrence after neoadjuvant therapy for LARC and allows a reduction in pain and bleeding with a consequent improvement to quality of life.

Management of Metastatic Disease in Campania (MAMETIC): An Observational Multicenter Retrospective and Prospective Trial on Palliative Radiotherapy in an Italian Region. Study Protocol.

Background: In the Italian Campania Region, 30.517 new cases of solid cancer have been diagnosed, in 2019. Of those, patients with metastatic disease are up to 20%. This class of patients is extremely diversified and copious, and the offer of radiotherapy may vary in different geographical areas within the same region. The aim of this observational multicenter retrospective and prospective trial is to evaluate the occurrence of metastatic metastatic cancer patients candidates for palliative radiotherapy in several areas of a great Italian region, the management of the disease through RT approaches, and its impact on cancer-related pain and overall HRQoL. Methods: This is a multicenter, retrospective and prospective observational investigation. The retrospective part of the study concerns all patients enrolled with a diagnosis of metastatic disease and treated in RT centers within the Campania Region between January 2019 and July 2020. The prospective phase is going to involve all the metastatic patients with an indication of palliative RT. Considering regional epidemiological data, we expect an enrollment of 12.500-21.000 patients in 5 years. Conclusion: The MAMETIC Trial in an observational study designed for investigating on the use of radiotherapy in patients with advanced disease within a regional area, and for evaluating the local response to the patient's request. It can be a unique opportunity, not only to highlight possible geographic differences but also to regularly collect and share data to standardize the therapeutic offer within the regional area. ClinicalTrials.gov ID NCT04595032, retrospectively registered.

The dosimetric impact of axillary nodes contouring variability in breast cancer radiotherapy: An AIRO multi-institutional study.

AIM: To quantify the dosimetric impact of contouring variability of axillary lymph nodes (L2, L3, L4) in breast cancer (BC) locoregional radiotherapy (RT). MATERIALS AND METHODS: 18 RT centres were asked to plan a locoregional treatment on their own planning target volume (single centre, SC-PTV) which was created by applying their institutional margins to the clinical target volume of the axillary nodes of three BC patients (P1, P2, P3) previously delineated (SC-CTV). The gold standard CTVs (GS-CTVs) of P1, P2 and P3 were developed by BC experts' consensus and validated with STAPLE algorithm. For each participating centre, the GS-PTV of each patient was created by applying the same margins as those used for the SC-CTV to SC-PTV expansion and replaced the SC-PTV in the treatment plan. Datasets were imported into MIM v6.1.7 [MIM Software Inc.], where dose-volume histograms (DVHs) were extracted and differences were analysed. RESULTS: 17/18 centres used intensity-modulated RT (IMRT). The CTV to PTV margins ranged from 0 to 10 mm (median 5 mm). No correlation was observed between GS-CTV coverage by 95% isodose and GS-PTV margins width. Doses delivered to 98% (D98) and 95% (D95) of GS-CTVs were significantly lower than those delivered to the SC-CTVs. No significant difference between SC-CTV and GS-CTV was observed in maximum dose (D2), always under 110%. Mean dose ≥99% of the SC-CTVs and GS-CTVs was satisfied in 84% and 50%, respectively. In less than one half of plans, GS-CTV V95% was above 90%. Breaking down the GS-CTV into the three nodal levels (L2, L3 and L4), L4 had the lowest probability to be covered by the 95% isodose. CONCLUSIONS: Overall, GS-CTV resulted worse coverage, especially for L4. IMRT was largely used and CTV-to-PTV margins did not compensate for contouring issues. The results highlighted the need for delineation training and standardization.

Watch and Wait Approach for Rectal Cancer Following Neoadjuvant Treatment: The Experience of a High Volume Cancer Center.

Multimodal treatments for rectal cancer, along with significant research on predictors to response to therapy, have led to more conservative surgical strategies. We describe our experience of the rectal sparing approach in rectal cancer patients with clinical complete response (cCR) after neoadjuvant treatment. We also specifically highlight our clinical and imaging criteria to select patients for the watch and wait strategy (w&w). Data came from 39 out of 670 patients treated for locally advanced rectal cancer between January 2016 until February 2020. The selection criteria were a clinical complete response after neoadjuvant chemotherapy managed with a watch and wait (w&w) strategy. A strict follow-up period was adopted in these selected patients and follow-ups were performed every three months during the first two years and every six months after that. The median follow-up time was 28 months. Six patients had a local recurrence (15.3%); all were salvageable by total mesorectal excision (TME). Five patients had a distant metastasis (12.8%). There was no local unsalvageable disease after w&w strategy. The rectal sparing approach in patients with clinical complete response after neoadjuvant treatment is the best possible treatment and is appropriate to analyze from this perspective. The watch and wait approach after neoadjuvant treatment for rectal cancer can be successfully explored after inflexible and strict patient selection.

Prospective Evaluation of Radiotherapy-Induced Immunologic and Genetic Effects in Colorectal Cancer Oligo-Metastatic Patients with Lung-Limited Disease: The PRELUDE-1 Study.

BACKGROUND: in recent years, the management of advanced colorectal cancer (CRC) has been greatly improved with integrated strategies including stereotactic radiation therapy (SRT). The administration of SRT has been demonstrated, particularly in oligo-metastatic (om) CRC, to be a safe and effective option. Interestingly, it has been demonstrated that SRT can induce regression of tumors in non-irradiated regions ("abscopal effect") through stimulation of anti-tumor immune effects ("radiation-induced immunity"). We have recently shown that lung-limited omCRC is characterized by regression of tumor clones bearing specific key driver gene mutations. AIMS: to assess the genetic evolution on tumor cancer cells induced by SRT in lung-limited omCRC. Secondary objectives included descriptions of the abscopal effect, responses' duration, toxicity, and progression-free survival. A translational research will be performed to evaluate tumor genetic evolution (through liquid biopsies and Next Generation Sequencing), HLA class I repertoire, peripheral immune cells, and cytokine dynamics. METHODS: PRELUDE-1 is a prospective translational study. SRT will be administered only to the largest nodule (with a maximum diameter ≤ 25 mm) in omCRC with two or three radiologically evident lesions. The sample size is based on the innovative hypothesis that radiation-induced immunity could induce regression of tumor clones bearing KRAS oncogene mutations. According to the binomial test, considering the frequency of KRAS mutations and assuming a probability of mutant KRAS→wild type KRAS of p0 = 0.0077, with α = 0.05 and 1-ß = 0.60, the final sample size is 25 patients.

Validation of the standardized index of shape tool to analyze DCE-MRI data in the assessment of neo-adjuvant therapy in locally advanced rectal cancer.

PURPOSE: Standardized index of shape (SIS) tool validation to examine dynamic contrast enhanced-magnetic resonance imaging (DCE-MRI) in preoperative chemo-radiation therapy (pCRT) assessment of locally advanced rectal cancer (LARC) in order to guide the surgeon versus more or less conservative treatment. MATERIALS AND METHODS: A total of 194 patients (January 2008-November 2020), with III-IV locally advanced rectal cancer and subjected to pCRT were included. Three expert radiologists performed DCE-MRI analysis using SIS tool. Degree of absolute agreement among measurements, degree of consistency among measurements, degree of reliability and level of variability were calculated. Patients with a pathological tumour regression grade (TRG) 1 or 2 were classified as major responders (complete responders have TRG 1). RESULTS: Good significant correlation was obtained between SIS measurements (range 0.97-0.99). The degree of absolute agreement ranges from 0.93 to 0.99, the degree of consistency from 0.81 to 0.9 and the reliability from 0.98 to 1.00 (p value < < 0.001). The variability coefficient ranges from 3.5% to 26%. SIS value obtained to discriminate responders by non-responders a sensitivity of 95.9%, a specificity of 84.7% and an accuracy of 91.8% while to detect complete responders, a sensitivity of 99.2%, a specificity of 63.9% and an accuracy of 86.1%. CONCLUSION: SIS tool is suitable to assess pCRT response both to identify major responders and complete responders in order to guide the surgeon versus more or less conservative treatment.

Geometric contour variation in clinical target volume of axillary lymph nodes in breast cancer radiotherapy: an AIRO multi-institutional study.

OBJECTIVES: To determine interobserver variability in axillary nodal contouring in breast cancer (BC) radiotherapy (RT) by comparing the clinical target volume of participating single centres (SC-CTV) with a gold-standard CTV (GS-CTV). METHODS: The GS-CTV of three patients (P1, P2, P3) with increasing complexity was created in DICOM format from the median contour of axillary CTVs drawn by BC experts, validated using the simultaneous truth and performance-level estimation and peer-reviewed. GS-CTVs were compared with the correspondent SC-CTVs drawn by radiation oncologists, using validated metrics and a total score (TS) integrating all of them. RESULTS: Eighteen RT centres participated in the study. Comparative analyses revealed that, on average, the SC-CTVs were smaller than GS-CTV for P1 and P2 (by -29.25% and -27.83%, respectively) and larger for P3 (by +12.53%). The mean Jaccard index was greater for P1 and P2 compared to P3, but the overlap extent value was around 0.50 or less. Regarding nodal levels, L4 showed the highest concordance with the GS. In the intra-patient comparison, L2 and L3 achieved lower TS than L4. Nodal levels showed discrepancy with GS, which was not statistically significant for P1, and negligible for P2, while P3 had the worst agreement. DICE similarity coefficient did not exceed the minimum threshold for agreement of 0.70 in all the measurements. CONCLUSIONS: Substantial differences were observed between SC- and GS-CTV, especially for P3 with altered arm setup. L2 and L3 were the most critical levels. The study highlighted these key points to address. ADVANCES IN KNOWLEDGE: The present study compares, by means of validated geometric indexes, manual segmentations of axillary lymph nodes in breast cancer from different observers and different institutions made on radiotherapy planning CT images. Assessing such variability is of paramount importance, as geometric uncertainties might lead to incorrect dosimetry and compromise oncological outcome.

Consensus statements on ablative radiotherapy for oligometastatic prostate cancer: A position paper of Italian Association of Radiotherapy and Clinical Oncology (AIRO).

Oligometastatic prostate cancer comprises a wide spectrum of conditions, ranging from de novo oligometastatic cancer at diagnosis to oligometastatic castration-resistant disease, which are distinct entities in terms of biology and prognosis. In order to clarify and standardize the clinical role of ablative radiotherapy in oligometastatic prostate cancer, the Italian Association of Radiotherapy and Clinical Oncology (AIRO) formed an expert panel to review the current literature and develop a formal consensus. Oligometastatic prostate cancer was defined as the presence of up to three metastatic lesions involving bones or nodes outside pelvis. Thereafter, four clinical scenarios were explored: metastatic castration-sensitive disease at diagnosis and after primary treatment, and metastatic castration-resistant disease at diagnosis and during treatment, where the role of ablative radiotherapy was defined either in conjunction with systemic therapy or as the only treatment in selected cases. This paper summarizes the current literature about these issues and the proposed recommendations.

Clinical management of localized undifferentiated sinonasal carcinoma: our experience and review of the literature.

Undifferentiated sinonasal carcinoma (SNUC) is defined as a small round blue cell tumor that is immunohistochemically distinct from other sinonasal malignancies, such as lymphoma, mucosal melanoma, nasopharyngeal carcinoma, neuroendocrine carcinoma, and olfactory neuroblastoma. SNUCs are very aggressive malignancies, provoking quick destruction of the splanchnocranium structures. Being a very rare neoplasm, there are no prospective clinical trials assessing their treatment strategies, so lots of data are derived by small retrospective trials. Tri-modality treatments (namely those treatments which use together surgery, radiation therapy and chemotherapy) are now considered the best of care for this category of poor prognosis tumors, and whenever possible they should be employed. Despite the tri-modality treatments and the multidisciplinary management, SNUCs are characterized by poor prognosis with a median overall survival reaching 14 months. Ameliorating radiotherapy techniques and performing therapies adapted to the genetics of the disease could represent a promising strategy of therapy in the near future. In this report, we have presented our experience, describing the treatment and the prognosis of four patients seen at our Institution. Moreover, we have performed a review of the literature analyzing the now available therapy options and the possible future strategies.

Radiosurgery and stereotactic radiotherapy with cyberknife system for meningioma treatment.

Objective The aim of this work was to evaluate the impact of stereotactic radiosurgery/fractionated stereotactic radiotherapy with the Cyberknife system on local disease control, clinical outcome and toxicity in patients with meningioma, according to the site and histological grade of lesion. From January 2013 to April 2017, 52 patients with intracranial meningiomas were treated with the Cyberknife system. Twenty-four patients had undergone previous surgery: 38% gross total resection, 10% subtotal resection; 27 patients underwent no surgery; 22 patients had a recurrence of meningioma. Methods Radiosurgery was used for lesions smaller than 2 cm, stereotactic radiotherapy for lesions larger than 2 cm, or smaller but close to a critical site such as the optical chiasm, optic pathway or brainstem. Results Local control and clinical outcomes were analysed. Median follow-up was 20 months: six patients died, one after re-surgery died from post-surgical sepsis, three from heart disease. Progression-free survival had a mean value of 38.3 months and overall survival of 41.6 months. We evaluated at 12 months 28 patients (100% local control); at 24 months 19 patients (89% local control); at 36 months nine patients (89% local control). At baseline, 44/52 patients (85%) were symptomatic: 19 visual disorders, 17 motor disorders, six hearing disorders, 10 headache and six epilepsy. Visual symptoms remained unchanged in 52%, improved in 32%, resolved in 16%. Headache was improved in 40%, resolved in 10%, unchanged in 50%. Epilepsy was resolved in 17%, unchanged in 33%, worsened in 33%. Conclusions Stereotactic radiosurgery/fractionated stereotactic radiotherapy with Cyberknife provides a good local disease control, improving visual, hearing and motor symptoms.

Variability in axillary lymph node delineation for breast cancer radiotherapy in presence of guidelines on a multi-institutional platform.

AIM: To quantify the variability between radiation oncologists (ROs) when outlining axillary nodes in breast cancer. MATERIAL AND METHODS: For each participating center, three ROs with different levels of expertise, i.e., junior (J), senior (S) and expert (E), contoured axillary nodal levels (L1, L2, L3 and L4) on the CT images of three different patients (P) of an increasing degree of anatomical complexity (from P1 to P2 to P3), according to contouring guidelines. Consensus contours were generated using the simultaneous truth and performance level estimation (STAPLE) method. RESULTS: Fifteen centers and 42 ROs participated. Overall, the median Dice similarity coefficient was 0.66. Statistically significant differences were observed according to the level of expertise (better agreement for J and E, worse for S); the axillary level (better agreement for L1 and L4, worse for L3); the patient (better agreement for P1, worse for P3). Statistically significant differences in contouring were found in 18% of the inter-center comparison. Less than a half of the centers could claim to have a good agreement between the internal ROs. CONCLUSIONS: The overall intra-institute and inter-institute agreement was moderate. Central lymph-node levels were the most critical and variability increased as the complexity of the patient's anatomy increased. These findings might have an effect on the interpretation of results from multicenter and even mono-institute studies.

Locally advanced paranasal sinus carcinoma: A study of 30 patients.

Sinonasal carcinomas (SNcs) are rare neoplasms arising from the paranasal sinuses and nasal cavity. Although these tumours have a heterogeneous histology, they are commonly diagnosed as a locally advanced disease and are associated with a poor prognosis. The present retrospective study reviewed 30 patients with locally advanced SNc, who were treated with surgery followed by chemoradiotherapy or radiotherapy, or radiotherapy with or without concomitant chemotherapy between January 1999 and January 2013 at the Department of Radiation Therapy, University of Naples 'Federico II' (Naples, Italy). A total of 19 patients were treated with upfront surgery followed by adjuvant radio- or chemoradiotherapy (group A), while the remaining 11 patients received exclusive radiotherapy with or without concomitant chemotherapy (group B). Concurrent cisplatin-based chemotherapy (100 mg/m2, days 1, 22 and 43 for 3 cycles) was administered to 34% of patients in group A and 55% of patients in group B. At a median follow-up of 31 months, 33.3% of patients were alive. Cause-specific survival (CSS) and progression-free survival (PFS) times were 32 and 12 months, respectively. No difference in CSS rate was observed between the two treatment groups. Univariate analysis determined that disease stage was the only factor that significantly affected CSS (P=0.002) and PFS (P=0.0001) rates. Acute and chronic toxicities were mild, with only 23.3% of patients reporting G1-2 side effects and no treatment-related blindness. The present study reported moderate activity and efficacy of surgery followed by adjuvant radio- or chemoradiotherapy, and exclusive radiotherapy with or without chemotherapy in this poor prognosis category of patients.

Rectal/urinary toxicity after hypofractionated vs conventional radiotherapy in low/intermediate risk localized prostate cancer: systematic review and meta analysis.

PURPOSE: The aim of this review was to compare radiation toxicity in Localized Prostate Cancer (LPC) patients who underwent conventional fractionation (CV), hypofractionated (HYPO) or extreme hypofractionated (eHYPO) radiotherapy. We analyzed the impact of technological innovation on the management of prostate cancer, attempting to make a meta-analysis of randomized trials. METHODS: PubMed database has been explored for studies concerning acute and late urinary/gastrointestinal toxicity in low/intermediate risk LPC patients after receiving radiotherapy. Studies were then gathered into 5 groups: detected acute and chronic toxicity data from phase II non randomized trials were analyzed and Odds Ratio (OR) was calculated by comparing the number of patients with G0-1 toxicity and those with toxicity > G2 in the studied groups. A meta-analysis of prospective randomized trials was also carried out. RESULTS: The initial search yielded 575 results, but only 32 manuscripts met all eligibility requirements: in terms of radiation-induced side effects, such as gastrointestinal and genitourinary acute and late toxicity, hypofractionated 3DCRT seemed to be more advantageous than 3DCRT with conventional fractionation as well as IMRT with conventional fractionation compared to 3DCRT with conventional fractionation; furthermore, IMRT hypofractionated technique appeared more advantageous than IMRT with conventional fractionation in late toxicities. Randomized trials meta-analysis disclosed an advantage in terms of acute gastrointestinal and late genitourinary toxicity for Hypofractionated schemes. CONCLUSIONS: Although our analysis pointed out a more favorable toxicity profile in terms of gastrointestinal acute side effects of conventional radiotherapy schemes compared to hypofractionated ones, prospective randomized trials are needed to better understand the real incidence of rectal and urinary toxicity in patients receiving radiotherapy for localized prostate cancer.

Intraoperative radiotherapy in elderly patients with breast cancer: Is there a clinical applicability? Review of the current evidence.

INTRODUCTION: Screening and adjuvant postoperative therapies have increased survival amongst women with breast cancer, but these tools are seldom applied in elderly patients. Higher rates of local recurrence occur in those elderly patients who avoid radiotherapy. TARGIT-A and ELIOT trials has been reported to not to be inferior to external beam RT in suitable subgroups of patients. The TARGIT-Elderly trial has been launched in order to confirm the efficacy of intraoperative radiotherapy (IORT) in a well selected group of elderly patients who are more likely to decline radiation treatment. OBJECTIVES: Current evidence of the medical literature on the clinical reliability and applicability of intraoperative radiotherapy amongst older women diagnosed with early breast cancer is after summarized. MATERIALS AND METHODS: Literature databases were searched up to June 2015. Terms used to retrieve articles were 'breast cancer', 'elderly', 'intraoperative radiotherapy', 'IORT' and 'IOERT'. RESULTS: Elderly patients with pT1N0 tumours are regarded to be suitable for IORT according to ASTRO and GEC-ESTRO recommendations, respectively. DISCUSSION: In the light of the medical literature we can assume that patients benefit from postoperative radiation therapy, but we still do not know who can be spared from it. These issues emphasize the urgent need to develop and support clinical trials for this older population of breast cancer patients. CONCLUSIONS: Whether radiotherapy is beneficial in elderly still remains a matter of debate. IORT along with BCS in a selected subgroup of patients (>70years, pT1N0 tumours) could represent a valid option for a better local control.

Short-course radiotherapy in elderly women with breast cancer: Comparison by age, comorbidity index and toxicity.

BACKGROUND: Breast cancer is the most common malignancy amongst elderly women. It represents the main cause of mortality for those women and it is steadily increasing. The primary therapeutic approach remains surgery, as in other age groups. The role of radiotherapy following surgery is still debated. The use of hypofractionated schedules is challenging the standard fractionation and has now been considered an advantageous option within this subgroup of patients. Results from randomized controlled trials have not been shown to be inferior to standard fractionation in terms of local recurrence, disease-free survival and overall survival. Acute and late side effects were not increased by hypofractionated regimens. PATIENTS AND METHODS: 60 elderly women treated by hypofractionated radiotherapy after breast conserving surgery were stratified by age. Comorbidities associated compliance and toxicity correlation to age were the first endpoints of the study. Comorbidity associated compliance was calculated by Cumulative Illness Rating Scale Geriatric. RESULTS: At a median follow-up of 15 months overall survival was 100%, without severe late toxicity. No statistical significant differences were found between Cumulative Illness Rating Scale-Geriatric, systemic therapy and toxicity. CONCLUSION: In our experience hypofractioned regimens seem to be safe and reliable in the elderly setting, although longer follow up is needed.

Adjuvant treatment in patients at high risk of recurrence of thymoma: efficacy and safety of a three-dimensional conformal radiation therapy regimen.

BACKGROUND: The clinical benefits of postoperative radiation therapy (PORT) for patients with thymoma are still controversial. In the absence of defined guidelines, prognostic factors such as stage, status of surgical margins, and histology are often considered to guide the choice of adjuvant treatment (radiotherapy and/or chemotherapy). In this study, we describe our single-institution experience of three-dimensional conformal PORT administered as adjuvant treatment to patients with thymoma. METHODS: Twenty-two consecutive thymoma patients (eleven male and eleven female) with a median age of 52 years and treated at our institution by PORT were analyzed. The patients were considered at high risk of recurrence, having at least one of the following features: stage IIB or III, involved resection margins, or thymic carcinoma histology. Three-dimensional conformal PORT with a median total dose on clinical target volume of 50 (range 44-60) Gy was delivered to the tumor bed by 6-20 MV X-ray of the linear accelerator. Follow-up after radiotherapy was done by computed tomography scan every 6 months for 2 years and yearly thereafter. RESULTS: Two of the 22 patients developed local recurrence and four developed distant metastases. Median overall survival was 100 months, and the 3-year and 5-year survival rates were 83% and 74%, respectively. Median disease-free survival was 90 months, and the 5-year recurrence rate was 32%. On univariate analysis, pathologic stage III and presence of positive surgical margins had a significant impact on patient prognosis. Radiation toxicity was mild in most patients and no severe toxicity was registered. CONCLUSION: Adjuvant radiotherapy achieved good local control and showed an acceptable toxicity profile in patients with high-risk thymoma.

Management of breast cancer in elderly patients.

Even if there is not a general consensus, we consider elderly patients of 65 years old or more. The degree of aging is extremely variable so that we can individuate different groups of patients that are different one from the other in relation with Performance Status, the presence of other pathology, and of eventual social discomfort. Breast Cancer is the most common Tumor in elderly woman and it represent the first death cause The 45% of Breast Cancer arise in women more than 65 years old and the 33% arise in women of more than 70 years old. Despite these data elderly women are often excluded from screening schedules, moreover despite there is no evidence that breast cancer is less aggressive in elderly patient they are generally non considered in trial studies so that they are under treated if compared to young patients that's why we cannot observe a decrease of mortality such as in younger patients Relative survival between 5 and 10 years in patients more than 75 years old it's lesser than the one observed in younger patients (between 45 and 70 years old) maybe that's because of the incongruity in the access to sanitary structures and because of the social and economic discomfort. When we speak about Breast Cancer we cannot be able to leave a multidisciplinary approach out of consideration. Patient's evaluation must be done by a group of dedicated specialists that are: Radiologist, Pathologist, Surgeon, Radiotherapist and Oncologist. The team need to analyze all data to improve treatment and obtain a better cosmetic result [4]. Complex cases must be discussed collectively before surgery to obtain the best therapeutic strategy. Moreover it's strictly important patient's involvement in treatment selection. Consensus is mandatory and it can be obtained only if the patient is well informed about treatment phases, adverse effects, and results.