A radiomic approach to predicting nodal relapse and disease-specific survival in patients treated with stereotactic body radiation therapy for early-stage non-small cell lung cancer.

PURPOSE: To describe the possibility of building a classifier for patients at risk of lymph node relapse and a predictive model for disease-specific survival in patients with early stage non-small cell lung cancer. METHODS: A cohort of 102 patients who received stereotactic body radiation treatment was retrospectively investigated. A set of 45 textural features was computed for the tumor volumes on the treatment planning CT images. Patients were split into two independent cohorts (70 patients, 68.9%, for training; and 32 patients, 31.4%, for validation). Three different models were built in the study. A stepwise backward linear discriminant analysis was applied to identify patients at risk of lymph node progression. The performance of the model was assessed by means of standard metrics derived from the confusion matrix. Furthermore, all textural features were correlated to survival data to build two separate predictive models for progression-free survival (PFS) and disease-specific survival (DS-OS). These models were built from the features/predictors found significant in univariate analysis and elastic net regularization by means of a multivarate Cox regression with backward selection. Low- and high-risk groups were identified by maximizing the separation by means of the Youden method. RESULTS: In the total cohort (77, 75.5%, males; and 25, 24.5%, females; median age 76.6 years), 15 patients presented nodal progression at the time of analysis; 19 patients (18.6%) died because of disease-specific causes, 25 (24.5%) died from other reasons, 28 (27.5%) were alive without disease, and 30 (29.4%) with either local or distant progression. The specificity, sensitivity, and accuracy of the classifier resulted 83.1 ± 24.5, 87.4 ± 1.2, and 85.4 ± 12.5 in the validation group (coherent with the findings in the training). The area under the curve for the classifier resulted in 0.84 ± 0.04 and 0.73 ± 0.05 for training and validation, respectively. The mean time for DS-OS and PFS for the low- and high-risk subgroups of patients (in the validation groups) were 88.2 month ± 9.0 month vs. 84.1 month ± 7.8 month (low risk) and 52.7 month ± 5.9 month vs. 44.6 month ± 9.2 month (high risk), respectively. CONCLUSION: Radiomics analysis based on planning CT images allowed a classifier and predictive models capable of identifying patients at risk of nodal relapse and high-risk of bad prognosis to be built. The radiomics signatures identified were mostly related to tumor heterogeneity.

Prognostic factors and outcome of HER2+ breast cancer with CNS metastases.

Aim: Trastuzumab prolongs progression-free and overall survival in HER2+ breast cancer (BC), but these are associated with increased distant recurrences and central nervous system metastases (CNSm). We retrospectively evaluated outcome and prognostic factors in CNSm and non-CNSm patients. Methods: Records of HER2+ BC treated in 2000-2017 were reviewed. Results: 283/1171 (24%) HER2+ BC patients developed metastatic disease. 109/283 patients (39%) have CNSm associated with worse prognosis and increased risk of death (hazard ratio: 4.7; 95% CI: 3.5-6.4). Prognostic factors were: number of CNSm (single vs multiple lesions; 3-year overall survival 39 vs 18%; p = 0.003); brain radiation (30 vs 14%; p < 0.001); new HER2-targeting therapies (30.6 vs 22.5%; p = 0.025). Conclusion: Prognosis of BC patients with CNSm has improved using HER2-targeting therapies but remains poor.

Stereotactic Body Radiation Therapy in Oligometastatic Ovarian Cancer: A Promising Therapeutic Approach.

OBJECTIVE: Stereotactic body radiation therapy (SBRT) has been successfully used to treat oligometastases of several primary tumors, but few experiences have been described in patients with gynecological oligometastatic cancer, particularly in ovarian neoplasm. The aim of this study was to evaluate the role of this new radiotherapy modality in a series of oligometastatic ovarian cancer patients. MATERIALS AND METHODS: Clinical records of patients affected by oligometastatic ovarian carcinoma treated with SBRT were reviewed. RESULTS: Twenty-six patients with 44 metastatic lesions (lymph nodes, 63.6%; liver, 31.8%; and lung, 4.5%) treated with SBRT between January 2011 and May 2017 were analyzed. After a median follow-up period of 28.5 months (range, 6-86 months), 17 patients (65.4%) were still alive at time of analysis: 6 are without evidence of disease, 11 experienced a disease progression. Eight patients died of disease, 1 died because of an heart attack while being disease free. The median local control (LC) was not reached. One-, 2-, and 5-year LCs were 92.9%. Median progression-free survival was 19 months, with 1-year progression-free survival of 69.3% and 38% at 2 years, 19% at 5 years. Median overall survival was 64.5 months, with all patients alive after 1 year, 92.7% at 2 years, and 61.7% at 5 years. Five (11.3%) cases experienced G2 toxicity; most common adverse effect was nausea and vomiting (3 cases [6.8%]) followed by abdominal pain (2 cases [4.5%]). None of the patients had grade 3 or grade 4 acute or late toxicity. CONCLUSIONS: In conclusion, SBRT is a feasible and safe approach for selected cases of oligometastatic ovarian cancer, with satisfactory results in terms of LC and disease free survival.

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.

The role of SBRT in oligometastatic patients with liver metastases from breast cancer.

Liver metastases from breast cancer are a common occurrence. Local ablative therapies are a promising therapeutic option for these patients, with the potential for a long term disease control in the setting of "oligometastatic patients". Identification of the perfect candidate for local approaches is still challenging and unclear. Stereotactic body radiation therapy (SBRT) is one of the most valuable local therapy, because of great efficiency, low morbidity and minimal invasiveness. In this paper, we reviewed the state of the art in the care of breast cancer patients with liver metastases, with a focus on SBRT.

Role of Stereotactic Body Radiation Therapy with Volumetric-Modulated Arcs and High-Intensity Photon Beams for the Treatment of Abdomino-Pelvic Lymph-Node Metastases.

AIM: To study clinical outcome for oligometastatic patients (abdominal lymph-node metastases) treated with stereotactic body radiation therapy. MATERIALS AND METHODS: Seventy-one patients were studied retrospectively. Dose prescription was 45 Gy in six fractions. Clinical outcome was assessed with actuarial analysis. RESULTS: The median follow-up was 1.5 years; 45 patients (63.3%) had solitary metastasis, and 26 (36.6%) had multiple lesions. Local control was achieved in 97.5% with a 1-year actuarial rate of 83%. Two-year progression-free survival was 63.1%, and the overall survival was 76.9%. Two patients (3%) developed grade 2 gastro-enteric toxicity. CONCLUSIONS: The treatment provided adequate clinical response in the management of oligometastatic cases.

Multimodality therapy approaches, local and systemic treatment, compared with chemotherapy alone in recurrent glioblastoma.

BACKGROUND: Long-term local control in Glioblastoma is rarely achieved and nearly all patients relapse. In this study we evaluated the clinical effect of different treatment approaches in recurrent patients. METHODS: Forty-three patients, with median age of 51 years were evaluated for salvage treatment: re-resection and/or re-irradiation plus chemotherapy or chemotherapy alone. Response was recorded using the Response Assessment in Neuro-Oncology criteria. Hematologic and non-hematologic toxicities were graded according to Common Terminology Criteria for Adverse Events 4.0. Twenty-one patients underwent chemotherapy combined with local treatment, surgery and/or radiation therapy, and 22 underwent chemotherapy only. RESULTS: The median follow up was 7 months (range 3-28 months). The 1 and 2-years Progression Free Survival was 65 and 10 % for combined treatment and 22 and 0 % for chemotherapy alone (p < 0.01). The 1 and 2-years overall survival was 69 and 29 % for combined and 26 and 0 % for chemotherapy alone (p < 0.01). No toxicity greater than grade 2 was recorded. CONCLUSION: These data showed that in glioblastoma recurrence the combination of several approaches in a limited group of patients is more effective than a single treatment alone. This stress the importance of multimodality treatment whenever clinically feasible.

Hypofractionated stereotactic radiation therapy in skull base meningiomas.

To investigate the role of hypo-fractionated stereotactic radiation treatment (HSRT) in the management of skull base meningioma. Twenty-six patients were included in the study and treated with a dose of 30 Gy in 5 fractions with volumetric modulated arc therapy (RapidArc). Eighteen patients were symptomatic before treatment. Endpoints were local toxicity and relief from symptoms. Tumors were located in anterior skull base in 4/27 cases, in middle skull base in 12/27 and in posterior skull base in 11/27. HSRT was performed as first treatment in 17 (65 %) patients, in 9 (35 %) patients it followed a previous partial resection. Median follow up was 24.5 months (range 5-57 months). clinical remission of symptoms, complete or partial, was obtained in the vast majority of patients after treatment. Out of the 18 symptomatic patients, partial remission occurred in 9 (50 %) patients and complete remission in 9 (50 %). All asymptomatic patients retained their status after treatment. No severe neurologic toxicity grade III-IV was recorded. No increase of meningioma in the same site of treatment occurred; 16 (62 %) patients had stable disease and 9 (38 %) patients had tumor reduction. The mean tumor volume after treatment was 10.8 ± 17.8 cm(3) compared with 13.0 ± 19.1 cm(3) before treatment (p = 0.02). The mean actuarial OS was 54.4 ± 2.8 months. The 1- and 2-years OS was 92.9 ± 0.7 %. HSRT proved to be feasible for these patients not eligible to full surgery or to ablative radiation therapy. Local control and durability of results suggest for a routine application of this approach in properly selected cases.

SBRT for lung oligometastases: Who is the perfect candidate?

AIM: To analyze the literature data about lung oligometastatic patients who underwent SBRT with regard to doses, fractionation, outcomes, response assessment and prognostic factors, trying to define "the right patient" for the local treatment. BACKGROUND: "Oligometastatic disease" is defined as a state in which metastases are limited in number and site and characterized by unusual cancer biology and behavior. In this setting local therapy could have a potential curative role. Recently, technological advances in Radiation Oncology permitted the introduction of Stereotactic Body Radiation Therapy (SBRT), a novel treatment modality that delivers ablative dose of radiation to the extra-cranial sites with high precision using single or a small number of fractions. MATERIALS AND METHODS: We performed a literature search using Medical Subject Heading terms "stereotactic body radiation therapy" and "lung metastases", considering a period of 10 years. RESULTS: Many non-randomized studies have shown that SBRT for lung oligometastases is safe and effective, with local control rates of about 80%. To date SBRT represents an alternative and competitive option in patients with lung oligometastatic disease who refuse surgical treatment or unsuitable for surgery. Based on published studies, SBRT might have major benefit for a patient with breast histology, disease-free interval ≥12 months, control of the primary tumor, small lesions, limited number of lesions and higher radiation dose delivered. CONCLUSIONS: Well-designed collaborative trials are necessary to draw final conclusions. To date, the discussion within a multidisciplinary team becomes crucial to perform a careful patients' selection in the setting of oligometastatic disease.

Radiation therapy of anal canal cancer: from conformal therapy to volumetric modulated arc therapy.

BACKGROUND: To appraise the role of volumetric modulated arc (RapidArc, RA) in the treatment of anal canal carcinoma (ACC). METHODS: A retrospective analysis has been conducted on 36 patients treated with RA since 2009 comparing outcome against a group of 28 patients treated with conformal therapy (CRT). RA treatments were prescribed with SIB technique with 59.4 Gy to the primary tumor and nodes and 49.5 Gy to the elective nodes. CRT was sequentially delivered with 45 Gy to the pelvic target and a boost of 14.4 Gy to the primary tumor. RESULTS: Median age of patients was 65 yrs for RA (59 yrs for CRT); 90% had Stage II-III (93% in the CRT group). No statistically significant differences were observed concerning survival or control. 5 yrs disease specific survival was 85.7% and 81.2%, loco-regional control was of 78.1% and 82.1% for RA and CRT respectively. RA treatments lead to lower incidence of higher grade of toxicity events (all retrospectively retrieved from charts as worse events). Grade 2-3 toxicity, compared to CRT, reduced from 89% to 68% for GI, from 39% to 33% for GU and from 82% to 75% for the skin. Late toxicity was as follows: 5/36 (14%) and 3/36 (8%) patients had G1 or G2 GI toxicity in the RA group (1/28 (4%) and 4/28 (14%) in the CRT group). GU late toxicity was observed only in 4/28 (14%) patients of the CRT group: 3/28 (11%) had G2 and 1/28 (4%) had G1. CONCLUSIONS: RA treatments of ACC patients proved to be equally effective than CRT but it was associated to a reduction of toxicity.

Stereotactic Ablative Radiotherapy (SABR) in inoperable oligometastatic disease from colorectal cancer: a safe and effective approach.

BACKGROUND: To assess the safety and efficacy of Stereotactic Ablative Radiotherapy (SABR) in oligometastatic patients from colorectal cancer. METHODS: 82 patients with 1-3 inoperable metastases confined to one organ (liver or lung), were treated with SABR for a total of 112 lesions in an observational study. Prescription dose ranged between 48 and 75 Gy in 3 or 4 consecutive fractions. Primary end-points were local control (LC), overall survival (OS) and progression-free survival (PFS). Secondary end-point was toxicity. RESULTS: Median follow-up was 24 months (range 3-47). One, two and three years LC rate was 90%,80% and 75% (85%,75% and 70% for lung and 95%, 90% and 85% for liver metastases; no statistically significance was found). The difference in LC between the subgroup of lesions treated with ≥ 60 Gy (n = 58) and those irradiated with <60 Gy (n = 52) was statistically significant, with a 1, 2 and 3 yrs LC of 97%,92% and 83% for the higher dose, compared to 85%,70% and 70% for the lower dose (p < 0.04). Median OS was 32 months. Actuarial OS rate at 1, 2 and 3 yrs was 85%,65% and 43%. Univariate analysis showed a correlation only between OS and cumulative GTV > 3 cm (p < 0.02). Median PFS was 14 months, with a PFS rate of 56% at 1 yr and 40% at 2-3 yrs, without correlation with the site and prescription dose (p < 0.48 and p < 0.56). No patients experienced radiation-induced liver disease or grade >3 toxicity. CONCLUSIONS: SABR is a safe and feasible alternative treatment of oligometastatic colorectal liver and lung metastases in patients not amenable to surgery or other ablative treatments.

Salvage breast conserving surgery and re-irradiation with intraoperative electrons for recurrent breast cancer: a multicentric study on behalf of AIRO (Italian Association of Radiotherapy and clinical Oncology).

AIM: Intraoperative radiotherapy with electrons (IOERT) may represent a viable choice for partial breast re-irradiation (rePBI) after repeat quadrantectomy for local recurrence (LR) for primary breast cancer (BC) in lieu of mastectomy. MATERIALS AND METHODS: A database collecting data on rePBI with IOERT from 8 Italian centres was set up in 2016- 2018, providing data on cumulative incidence (CumI) of 2nd LR nd survival with a long follow-up (FU) RESULTS: From 2002 to 2015, 109 patients underwent the conservative retreatment. The median primary BC -1stLR interval was 11.1 years (range: 2.4-27.7). The median 1stLR size was 0.9 cm (range: 0.3-3.0) and 43.6% were Luminal A. Median IOERT dose was 18 Gy (range: 12-21) and median collimator was 4 cm (range: 3-6). Median FU was 11.7 years (interquartile range: 7.7-14.6). The 2ndLR CumI was 12.2% (95% CI: 6.8-19.2) at 5 years and 32.3% at 10 years (95% CI: 22.8-42.2), occurring in the same site as the 1stLR in about half of the cases. HER2 status and collimator size were independent LR predictors. The 5- and 10-year overall survival were 95.2% and 88.3%, respectively, while 5- and 10-year BC specific survival were 98% and 94.5%. The development of a 2ndLR significantly reduced BCSS (HR=9.40, P<0.001). Grade ≥3 fibrosis was 18.9%. Patient-reported cosmesis was good/excellent in 59.7% of the cases. CONCLUSION: 2ndLR CumI was within the range of the literature, but higher than expected, opening questions on radiation field extension and fractionation schedule. Since a 2ndLR worsened the outcome, salvage modality must be carefully planned.

Automatic delineation for replanning in nasopharynx radiotherapy: what is the agreement among experts to be considered as benchmark?

BACKGROUND AND PURPOSE: Anatomic changes during head and neck radiotherapy require replanning. The primary aim of this study is the definition of the agreement among experts in the head and neck automatic delineation frame to use as benchmark. The secondary goal is to assess the reliability of automatic delineation for nasopharynx radiotherapy and time saving. MATERIAL AND METHODS: A computed tomography (CT) scan was acquired in 10 nasopharynx patients along intensity-modulated radiotherapy (IMRT) treatment for replanning. Deformable registration with replanning autocontouring of the structures was performed using VelocityAI 2.3© software defining Structure Set A. The optimization of these contours was obtained through revision by a skilled operator, drawing Structure Set B. An ex novo Structure Set C was segmented on the replanning CT-scan by an expert delineation team. The mean Dice's Similarity Index (mDSI) was calculated between Structure Set A and B, A and C, and between B and C for each volume. All segmentation times for organs at risk (OARs) and clinical target volume (CTV) were recorded and compared. RESULTS: We validated the replanning autocontoured Structure Sets for 10 patients. For volumetric analysis we observed mDSI values of 0.87 for the OARs, 0.70 for nodes, 0.90 for CTV in the Structure Set A-B comparison and respectively of 0.74, 0.63 and 0.78 for the Structure Set A-C one, and 0.78, 0.78 and 0.85 for Structure Set B-C, which represents the existing expert based benchmark. We calculated a mean saved time in Structure Set B of 30 minutes. CONCLUSIONS: Autocontouring procedures offer considerable segmentation time saving with acceptable reliability of the contours, even if an independent check procedure for their optimization is still required to increase their adherence to referential benchmark gold standard among experts, which stands at a 0.80 DSI value.

Technological advancements and future perspectives in breast cancer radiation therapy.

INTRODUCTION: Breast cancer is still one of the most common tumors worldwide and radiation therapy has a central role in the oncological pathway. Several technological options are now available with the aim to improve therapeutic index, target definition, and patient selection. AREAS COVERED: In this review, we summarize current available technologies in the management of breast cancer. These advances can support the prescription of postoperative partial breast cancer treatment and preoperative stereotactic partial breast irradiation. Moreover, image-guided radiotherapy is crucial for high-quality radiation treatments. Additionally, the recent development of hybrid magnetic resonance linear accelerator can impact target volume outline procedure, adaptive planning and radiomics. Finally, artificial intelligence represents the new frontier in medicine, supporting clinicians in target definition, patient selection, and treatment planning. EXPERT OPINION: In patients with breast cancer the overall level of evidence about new technologies is still low even if some advances are potentially very interesting to further development.

Axillary Management in Breast Cancer Patients Undergoing Upfront Surgery: Results from a Nationwide Survey on Behalf of the Clinical Oncology Breast Cancer Group (COBCG) and the Breast Cancer Study Group of the Italian Association of Radiotherapy and Clinical Oncology (AIRO).

BACKGROUND: We assessed the current practice concerning the axillary management of breast cancer (BC) patients undergoing upfront surgery among radiation oncologists (ROs) practising in Italy. METHODS: An online survey via SurveyMonkey (including 21 questions) was distributed amongst ROs in Italy through personal contacts and the Italian Association for Radiotherapy and Clinical Oncology (AIRO) network from August to September 2022. We particularly focused on the emerging omission of axillary lymph node dissection (ALND) in the presence of 1-2 sentinel node-positive patients and the consequent change in the role of regional nodal irradiation (RNI). RESULTS: A total of 101/195 (51% response rate) Italian Radiotherapy Cancer Care Centres answered the survey. With respect to patients with 1-2 sentinel node-positive, the relative proportion of respondents that offer patients ALND a) always, b) only in selected cases, and c) never was 37.6%, 60.4%, and 2.0%, respectively, with no significant geographical (North vs. Centre-South Italy; p = 0.92) or institutional (Academic vs. non-Academic; p = 0.49) differences. Radiation therapy indications varied widely in patients who did not undergo ALND. Among these, about a third of the respondents (17/56, 30.4%) stated that RNI was constantly performed. On the other hand, half of the respondents offered RNI in selected cases, stating that an unfavourable biologic tumour profile and extracapsular nodal extension were considered drivers of their decision. CONCLUSIONS: Results of the present survey show the variability of axillary management offered in clinical practice for BC patients undergoing conserving surgery upfront in Italy. Analysis of these attitudes may trigger the modification of some clinical approaches through multidisciplinary collaboration and create the background for future clinical investigations.

Whole Breast Irradiation Versus Intraoperative Electron Radiation Therapy for Breast Conserving Therapy: A Large Mature Single Institution Matched-Pair Evaluation of True Local Relapse, Progression Free Survival, and Overall Survival.

PURPOSE: Comparative outcome data after intraoperative radiation therapy and whole breast irradiation (WBI) for breast cancer at >10 years median follow-up are rare. We present a mature, single-institution, matched-pair comparison reporting survival and relapse rates in patients treated with either modality. METHODS AND MATERIALS: Complete data sets for 258 intraoperative electron radiation therapy (IOERT) patients treated between 2000 and 2010 were matched with 258 patients postoperatively treated with WBI by age/histology/tumor size, grading/lymph-node-status/hormone receptors/type of adjuvant therapy/surgical margins, and treatment date. Relapse at surgical intervention site was classified as true local recurrence (LR). All recurrences in the treated breast (any quadrant) were classified as ipsilateral recurrence (IR). RESULTS: Median follow-up was 157 months (12-251) for the IOERT group and 154 months (31-246) for the WBI group. Cumulative incidence of IR at 5, 10, and 15 years was 2.4%, 7.9%, and 12.7% for IOERT and 1.2%, 4.1%, and 5.0% for WBI (P = .02). Cumulative incidence of LR at 5, 10, and 15 years was 1.6%, 5.1%, and 8.3% for IOERT and 0.4%, 2.1%, and 2.5% for WBI (P = .02). No differences in overall survival, disease-free survival, second cancer incidence, or cardiac events were recorded in either treatment group. Outcome was better in the accelerated partial breast irradiation (APBI)-suitable group than in the APBI-unsuitable group (2009 criteria) (cumulative incidence of IR at 5, 10, and 15 years was 0% vs 7.3%, 6.1% vs 13.3%, and 7.3% vs 19.9% for IOERT and 0% vs 1.8%, 2.0% vs 3.9%, and 3.1% vs 3.9% for WBI) and in the revised APBI-suitable group than in the APBI-cautionary group (2017 criteria) (cumulative incidence of IR at 5, 10, and 15 years was 1.1% vs 6.4%, 6.2% vs 13.3%, and 7.8% vs 27.5% for IOERT and 1.7% vs 0%, 4.1% vs 4.4%, and 5.4% vs 4.4% for WBI). CONCLUSIONS: The IR and LR rate were higher after IOERT than after WBI for the American Society for Radiation Oncology suitable patient group, although without reaching statistical significance. Thus, IOERT could be an alternative to WBI upon stringent patient selection, but patients should be counseled carefully about the potential for increased IR rate with IOERT. Second cancer incidence and cardiac events did not differ between IOERT and WBI.

Rethinking breast cancer follow-up based on individual risk and recurrence management.

Current follow-up policies for early breast cancer aim to detect loco-regional recurrences and manage treatment-related adverse effects. Their "one size fits all" approach does not take into account differences in subtypes at initial diagnosis, individual prognosis and treatments received. They are derived from clinical trials conducted when early detection means - other than mammography - and treatment options were limited. Herein, we address the arguments for re-evaluating current breast cancer follow-up strategies starting from recent advances in breast cancer local and systemic treatments and discussing individual risk of recurrence prediction models, time-adapted imaging and biomarker assessment for disease diagnostic anticipation. This change in perspective would transform breast cancer follow-up into an integrated, multidisciplinary team medical practice. Hence we discuss the important role of patient-centered approaches, but also of general practitioners and other health professionals, in the final promotion of personalized surveillance programs and patient education.

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.

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.

Lymph nodal radiotherapy in breast cancer: what are the unresolved issues?

Introduction: Sentinel lymph node biopsy (SLNB) is the gold standard in invasive breast cancer. Axillary dissection (ALND) is controversial in some presentations.Areas covered: Key questions were formulated and explored focused on four different scenarios in adjuvant axillary radiation management in early and locally advanced breast cancer. Answers to these questions were searched in MEDLINE, PubMed from June 1946 to August 2020. Clinical trials, retrospective studies, international guidelines, meta-analysis, and reviews were explored.Expert opinion: Analysis according to biological disease characteristics is necessary to establish the impact of ALND avoidance in unexpectedly positive SLNB (pN1) in cN0 patients. A low-risk probability of axillary recurrence was observed if axillary radiotherapy (ART) or ALND were offered without impact on outcomes. Adjuvant RNI in pT1-3 pN1 treated with mastectomy or BCS should be proposed in unfavorable disease and risk factors. In ycN0 after NACT, SLNB can be offered in selected cases or ALND should be performed. After SLNB post-NACT (ypN1), ALND and adjuvant radiotherapy are mandatory.