Impact of inter-observer variability on first axillary level dosimetry in breast cancer radiotherapy: An AIRO multi-institutional study.

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.

AIRO Breast Cancer Group Best Clinical Practice 2022 Update.

INTRODUCTION: Breast cancer is the most common tumor in women and represents the leading cause of cancer death. Radiation therapy plays a key-role in the treatment of all breast cancer stages. Therefore, the adoption of evidence-based treatments is warranted, to ensure equity of access and standardization of care in clinical practice. METHOD: This national document on the highest evidence-based available data was developed and endorsed by the Italian Association of Radiation and Clinical Oncology (AIRO) Breast Cancer Group.We analyzed literature data regarding breast radiation therapy, using the SIGN (Scottish Intercollegiate Guidelines Network) methodology (www.sign.ac.uk). Updated findings from the literature were examined, including the highest levels of evidence (meta-analyses, randomized trials, and international guidelines) with a significant impact on clinical practice. The document deals with the role of radiation therapy in the treatment of primary breast cancer, local relapse, and metastatic disease, with focus on diagnosis, staging, local and systemic therapies, and follow up. Information is given on indications, techniques, total doses, and fractionations. RESULTS: An extensive literature review from 2013 to 2021 was performed. The work was organized according to a general index of different topics and most chapters included individual questions and, when possible, synoptic and summary tables. Indications for radiation therapy in breast cancer were examined and integrated with other oncological treatments. A total of 50 questions were analyzed and answered.Four large areas of interest were investigated: (1) general strategy (multidisciplinary approach, contraindications, preliminary assessments, staging and management of patients with electronic devices); (2) systemic therapy (primary, adjuvant, in metastatic setting); (3) clinical aspects (invasive, non-invasive and micro-invasive carcinoma; particular situations such as young and elderly patients, breast cancer in males and cancer during pregnancy; follow up with possible acute and late toxicities; loco-regional relapse and metastatic disease); (4) technical aspects (radiation after conservative surgery or mastectomy, indications for boost, lymph node radiotherapy and partial breast irradiation).Appendixes about tumor bed boost and breast and lymph nodes contouring were implemented, including a dedicated web application. The scientific work was reviewed and validated by an expert group of breast cancer key-opinion leaders. CONCLUSIONS: Optimal breast cancer management requires a multidisciplinary approach sharing therapeutic strategies with the other involved specialists and the patient, within a coordinated and dedicated clinical path. In recent years, the high-level quality radiation therapy has shown a significant impact on local control and survival of breast cancer patients. Therefore, it is necessary to offer and guarantee accurate treatments according to the best standards of evidence-based medicine.

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.

Omission of adjuvant radiotherapy for older adults with early-stage breast cancer particularly in the COVID era: A literature review (on the behalf of Italian Association of Radiotherapy and Clinical Oncology).

This review is aimed at evaluating whether radiation therapy (RT) can be omitted in older adult early-stage low-risk breast cancer (BC) patients. The published data are particularly relevant at present, during the COVID-19 pandemic emergency, to define a treatment strategy and to prioritize essential therapy. Cochrane Database of Systematic Reviews and PubMED were systematically researched from outset through April 2020 using Mesh terms. Only randomized controlled trials (RCT), with one arm without adjuvant whole-breast irradiation (WBI), were included in the analysis. Recent literature regarding the COVID pandemic and BC RT was assessed. The reported RCTs identified a group of BC patients (pT1-2N0M0 R0, grade 1-2, estrogen receptor (ER) positive, human epidermal growth factor receptor 2 (HER2) negative tumours) in which the absolute risk of local recurrence (LR) was considered low enough to omit RT. The most common risk factors were tumor diameter, nodal and receptor status. Adjuvant RT had a significant impact on LR but not on distant metastasis (DM) or death. During the COVID 19 pandemic, results from RTCs were re-considered to define treatment recommendations for BC patients. International scientific societies and radiation oncology experts suggested RT omission, whenever possible, in older adult early-stage BC patients. Adjuvant RT might be omitted in a highly selected group of older adult early-stage BC patients with favourable prognostic factors. Hypofractionated regimens should be the standard. RT omission, partial breast irradiation (PBI), and ultra- hypofractionated regimens could be considered in selected cases due to the pandemic.

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.

Mood Disorder in Cancer Patients Undergoing Radiotherapy During the COVID-19 Outbreak.

Introduction: Novel coronavirus (COVID-19) is having a devastating psychological impact on patients, especially patients with cancer. This work aims to evaluate mood disorders of cancer patients undergoing radiation therapy during COVID-19 in comparison with cancer patients who underwent radiation therapy in 2019. Materials and Methods: We included all the patients undergoing radiation therapy at our department in two-time points (once a week for a month in May 2019) and during the COVID-19 outbreak (in April 2020). All the patients were asked to fulfill a validated questionnaire (STAI-Y1, State trait anxiety inventory scale), the Symptom Distress thermometer (SDT) (from 0 to 10 score), and the Beck Depression Inventory v.2 (BDI-2). We took into account the COVID-19 outbreak and also sex, age, week of radiation treatment, and disease. Results: We included 458 patients (220 males and 238 females), with a median age of 64 years. STAI-Y1 median score was 40 (mean 41,3, range 19-79), whereas the median score of SDT was five and BDI-2 median score was 11. STAI-Y1, SDT, and BDI-2 were significantly correlated with the COVID-19 outbreak (p < 0,001 for all the tests), sex (p: 0,016 for STAI-Y1, p < 0.001 for SDT, p:0.013 for BDI-2), week of treatment (p: 0.012 for STAI-Y1 and p: 0.031 for SDT), and disease (p:0.015 for STAI-Y1, p < 0.001 for SDT and p:0.020 for BDI-2). Conclusions: The prevalence of mood disorders in patients undergoing radiation therapy is higher than expected and even higher during the COVID-19 outbreak. These measurements could be useful as a baseline to start medical humanities programs to decrease these scores.

Ipilimumab and Stereotactic Radiosurgery with CyberKnife® System in Melanoma Brain Metastases: A Retrospective Monoinstitutional Experience.

The median overall survival (OS) and local control (LC) of patients with melanoma brain metastases (MBMs) are poor even with immune checkpoint inhibitors and/or radiotherapy (RT). The aims of the study were to evaluate the association and timing of stereotactic radiotherapy (SRT)/radiosurgery (SRS) performed with the CyberKnife® System and ipilimumab (IPI). A total of 63 MBMs patients were analyzed: 53 received RT+IPI and 10 RT alone. Therefore, the patients were divided into four groups: RT PRE-PI (>4 weeks before IPI) (18), RT CONC-IPI (4 weeks before/between first and last cycle/within 3 months of last cycle of IPI) (20), RT POST-IPI (>3 months after IPI) (15), and NO-IPI (10). A total of 127 lesions were treated: 75 with SRS (one fraction) and 24 with SRT (three to five fractions). The median follow-up was 10.6 months. The median OS was 10.6 months for all patients, 10.7 months for RT+IPI, and 3.3 months for NO-IPI (p = 0.96). One-year LC was 50% for all patients, 56% for RT+IPI, and 18% for NO-IPI (p = 0.08). The 1-year intracranial control was 45% for all patients, 44% for RT+IPI, and 51% for NO-IPI (p = 0.73). IPI with SRS/SRT in MBMs treatment could improve LC. However, the impact and timing of the two modalities on patients' outcomes are still unclear.

Present clinical practice of breast cancer radiotherapy in Italy: a nationwide survey by the Italian Society of Radiotherapy and Clinical Oncology (AIRO) Breast Group.

AIMS: To investigate the present attitude of the Italian Radiation Oncologists in the management of breast cancer (BC) concerning hypofractionated radiotherapy (hRT), partial-breast irradiation (PBI), re-irradiation (rRT) and radiotherapy after neoadjuvant chemotherapy (post-NAC RT). METHODS: A nationwide, 21-point questionnaire was distributed online via SurveyMonkey. RESULTS: Seventy-four Italian Radiotherapy Centers answered to the survey. In most cases, the responding centers treated more than 100 BC patients/year between January 2016 and December 2017. Almost half of responding centers (49%) treated patients with hRT, out of these, 95% as routine practice for early-stage BC. Dose prescriptions ranged between 39 and 45 Gy indicating a high use of moderate hRT. The chest wall and regional lymph nodes were irradiated with hRT by 13% and 15% of the responding centers, respectively. PBI was used by 60% of responders, with different techniques. Only 0.6% of participants perform rRT after BC recurrence. Finally, only 11% of the interviewed centers responded to their attitude toward post-NAC RT, which, however, was indicated in 97% of patients after breast-conserving surgery. CONCLUSIONS: This survey shows a fairly good use of hRT and a moderate practice of PBI in Italy. Some practices like hRT to the chest wall and regional lymph nodes as well as rRT need further verification. Likewise, the management of post-NAC RT is very heterogeneous. Future national clinical collaborative studies are advocated in order to investigate these controversial topics about breast cancer radiotherapy.

The role of radiation therapy and systemic therapies in elderly with breast cancer.

The focus of this review deals with the management of elderly patients with early stage breast cancer, discussing the role of systemic therapies [endocrine therapy (ET), chemotherapy, novel agents] and radiation therapy (RT). Several studies have evaluated in elderly low risk patients the possibility of omitting the RT but, at the same time, higher locoregional relapse (LR) rates without significant impact on overall survival (OS) were observed in all studies when RT was excluded. Technological improvements [intensity-modulated RT (IMRT), volumetric modulated arc therapy (VMAT), high dose brachy therapy (HDBT)] are very useful in order to reduce cosmetic outcome and improve quality of life of frail patients. The optimal sequence of ET, concomitant or sequential to RT, is currently under investigation, and specifically in the elderly it is questioned the possible choice of prolonged therapy after standard 5 years. Data regarding chemotherapy suggesting no benefit of OS in endocrine responsive diseases, whereas endocrine non-responsive breast cancer still showed a better outcome. Cyclophosphamide, methotrexate and 5-fluorouracil (CMF) regimen is recognized as the standard protocol, although age-dependent increase in therapy related mortality was reported. Neoadjuvant chemotherapy in elderly showed a lower ratio of pathological complete response in comparison to younger patients, but triple negative breast cancer patients showed a good prognosis regarding OS, comparable to younger patients. The risk of cardiotoxicity seems to increase with age, so the use trastuzumab in this setting is much debated. Currently, other anti-HER2 agents (pertuzumab, lapatinib) are used in neoadjuvant setting, but the data on elderly are still premature. Novel molecules are rapidly changing the clinical management of breast cancer patients but are tested especially in locally advanced and metastatic setting. Among these, particularly interesting are inhibitors of CDK4 and 6, alpelisib (PI3K enzymes mutations), immune checkpoint (PD1, PDL1, CTLA4) inhibitors, atezolizumab. Elderly patients are under-represented in clinical trials, although ageing can be frequently correlated with a decrease in the effectiveness of the immune system. For elderly women, treatment decisions should be individually decided, taking into account the geriatric assessment and limited life expectancy and tumor characteristics.

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.

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.

External radiotherapy for breast cancer in the elderly.

BACKGROUND: Breast cancer is the most common malignancy amongst elderly women and the main cause of mortality. A specific management for elderly woman is not clear because clinical trials are usually not customized for this subset of patients. AIMS: The aim of this paper is to provide an overview of the available information on the main issues in the field of breast cancer radiotherapy in the elderly population. MATERIALS AND METHODS: Authors discuss on different radiation treatments for breast cancer in the elderly, based on the data of the literature with a focus on new strategy: hypo-fractionation, accelerated partial breast irradiation, and the utility of a dose boost. DISCUSSION: The treatment of breast cancer is not standardized in the elderly. The optimal management in this population often requires complex multidisciplinary supportive care due to multiple comorbidities to optimize their cancer care. CONCLUSIONS: New options such as APBI or HyRT regimens should be taken into consideration and offered as a breach of duty to the elderly population. Furthermore, they should be extensively investigated through randomized clinical trials.

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.

Long-Term Toxicity and Quality of Life in Patients Treated for Locally Advanced Cervical Cancer.

OBJECTIVE: The aim of this study was to analyze the long-term toxicity and quality of life (QOL) in patients with locally advanced cervical cancer (LACC) treated with chemoradiation [chemotherapy/radiotherapy (CT/RT)] or neoadjuvant CT (NACT) followed by radical surgery (RS). METHODS: Fifty-nine patients with LACC in remission after treatment with NACT + RS (n = 34) or CT/RT (n = 25) were interviewed with an Incontinence Impact Questionnaire (IIQ-7), a Quality of Life Questionnaire (EORTC QLQ-C30), and a Quality of Life Questionnaire for Cervical Cancer (EORTC QLQ-CX24) to compare long-term toxicity and QOL. RESULTS: The mean age was 53 ± 9.8 and 59 ± 11.5 years in the NACT + RS and CT/RT groups, respectively. Overall, diarrhea and constipation were reported in 15 and 68%, respectively, while bladder complaints and a low level of sexual enjoyment were reported in 36 and 47%, respectively. The NACT + RS patients showed a worse sexual activity (74.71 ± 33.57 vs. 92.06 ± 17.96; p = 0.019) and sexual enjoyment (71.21 ± 23.67 vs. 88.88 ± 21.71; p = 0.040) and more frequently complained of constipation (49.01 ± 34.06 vs. 26.66 ± 31.66; p = 0.013), while CT/RT patients more frequently suffered from diarrhea (1.96 ± 7.96 vs. 14.66 ± 28.40; p = 0.017). CONCLUSIONS: Many patients treated for LACC have long-term complaints regarding sexual activity and bladder and bowel function. The majority of QOL aspects were similar in the two groups at long-term follow-up. However, diarrhea was more frequent and severe in CT/RT patients, while constipation was more frequent and severe in NACT + RS patients, and they showed a worse sexual life perception. Larger randomized trials addressing these issues are 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.

Tomotherapy concomitant with cetuximab, followed by cetuximab as single-agent therapy for unresectable squamous cell carcinoma of the skin: a case report.

BACKGROUND: Cutaneous squamous cell carcinoma (SCC) is the second most frequency of all skin tumors. Incidence of SCC has risen significantly due to an increased sun exposure and the number of immunodeficient patients. Cutaneous SCC is characterized by high Epidermal growth factor receptor (EGFR) expression with low frequency of RAS mutations. Generally, locoregional surgery is curative and systemic therapy is not indicated. We evaluated the activity and toxicity profile of tomotherapy concomitant with Cetuximab, followed by Cetuximab as single agent therapy in a patient affected by unresectable, locally advanced cutaneous SCC. CASE PRESENTATION: At our institution, on March 2012 we treated a 45 years-old patient affected by locally advanced, unresectable G1 SCC of the lumbar region. At our first observation, the patient was asthenic, with severe pain and functional limitations. There was also a superinfection due to Pseudomonas Aeruginosa resistant to antibiotics, and a G3 anemia secondary to the bleeding lesion. ECOG Performance Status was 2. Tomotherapy has been performed concomitant with the Cetuximab (400 mg/m2, followed by weekly doses of 250 mg/m2) at the total dose of 60 Gy (2 Gy/fx), followed by Cetuximab monotherapy.The lesion reduced progressively until disappear even after the suspension of the treatment and the patient achieved complete response. Toxicity resulted in G1 cutaneous rash and G2 toxicity to the nails, appeared after 5 months of treatment, typical toxicity profile of the anti-EGFR therapies. After one month of therapy the Pseudomonas Aeruginosa superinfection totally disappeared. Quality of life resulted significantly improved with reduction until discontinuation of the anti-pain drugs, and progressive increase of the hemoglobin levels. At follow up of 15 months there was no evidence of active disease and the ECOG Performance Status was 0 (zero). CONCLUSION: The treatment was effective and feasible. Considering these excellent results, further studies about concomitant tomotherapy with Cetuximab for advanced/inoperable SCC of the skin are needed.

Abscopal effects of radiotherapy on advanced melanoma patients who progressed after ipilimumab immunotherapy.

Cancer radiotherapy (RT) may induce what is referred to as the "abscopal effect," a regression of non-irradiated metastatic lesions distant from the primary tumor site directly subject to irradiation. This clinical response is rare, but has been surmised to be an immune-mediated phenomenon, suggesting that immunotherapy and RT could potentially synergize. Here, we report the outcome of patients with advanced melanoma treated with the immune checkpoint blockade monoclonal antibody antagonist, ipilimumab followed by RT. Patients were selected for enrollment at the National Cancer Institute "Fondazione G.Pascale" through the expanded access program in Italy. Those who experienced disease progression after ipilimumab thus received subsequent RT and were selected for analysis. Among 21 patients, 13 patients (62%) received RT to treat metastases in the brain and 8 received RT directed at extracranial sites. An abscopal response was observed in 11 patients (52%), 9 of whom had partial responses (43%) and 2 had stable disease (10%). The median time from RT to an abscopal response was 1 month (range 1-4). Median overall survival (OS) for all 21 patients was 13 months (range 6-26). Median OS for patients with abscopal responses was extended to 22.4 months (range 2.5-50.3) vs. 8.3 months (range 7.6-9.0) without. A local response to RT was detected in 13 patients (62%) and, of these, 11 patients (85%) had an abscopal response and abscopal effects were only observed among patients exhibiting a local response. These results suggest RT after ipilimumab may lead to abscopal responses in some patients with advanced melanoma correlating with prolonged OS. Our data also suggest that local responses to RT may be predictive of abscopal responses. Further research in larger randomized trials is needed to validate these results.

Contouring of the Pharyngeal Superior Constrictor Muscle (PSCM). A cooperative study of the Italian Association of Radiation Oncology (AIRO) Head and Neck Group.

BACKGROUND AND PURPOSE: Irradiation of the Pharyngeal Superior Constrictor Muscle (PSCM) seems to play a crucial role in radiation-related swallowing dysfunctions. Purpose of our study was to quantify operator-related variability in the contouring of PSCM on Computed Tomography (CT) scans and adherence with contours derived from MR images. MATERIALS AND METHODS: Three sets of treatment planning CT and their corresponding MR images were selected. Contouring of the PSCM was performed using both a literature-based method, derived from literature review, and an optimized method, derived from Magnetic Resonance (MR) images thus obtaining "literature-based" and "optimized" contours. Each operator contoured the PSCM on CT scans according to both methods for three times in three different days. Inter- and intra-operator variability and adherence to a contour obtained from MR images (named "MR-derived" contour) were analyzed. RESULTS: Thirty-four operators participated and 612 contours were obtained. Both intra- and inter-operator variability and adherence to the "MR-derived" contour were significantly different between the two methods (p⩽0.05). The "optimized" method showed a lower intra- and inter-operator variability and a higher adherence to the "MR-derived" contour. CONCLUSIONS: The "optimized" method ameliorates both operator-related variability and adherence with MR images.