Surgical De-Escalation for Re-Excision in Patients with a Margin Less Than 2 mm and a Diagnosis of DCIS.

The current surgical guidelines recommend an optimal margin width of 2 mm for the management of patients diagnosed with ductal carcinoma in situ (DCIS). However, there are still many controversies regarding re-excision when the optimal margin criteria are not met in the first resection. The purpose of this study is to understand the importance of surgical margin width, re-excision, and treatments to avoid additional surgery on locoregional recurrence (LRR). The study is retrospective and analyzed surgical margins, adjuvant treatments, re-excision, and LRR in patients with DCIS who underwent breast-conserving surgery (BCS). A total of 197 patients were enrolled. Re-operation for a close margin rate was 13.5%, and the 3-year recurrence was 7.6%. No difference in the LRR was reported among the patients subjected to BCS regardless of the margin width (p = 0.295). The recurrence rate according to margin status was not significant (p = 0.484). Approximately 36.9% (n: 79) patients had resection margins < 2 mm. A sub-analysis of patients with margins < 2 mm showed no difference in the recurrence between the patients treated with a second surgery and those treated with radiation (p = 0.091). The recurrence rate according to margin status in patients with margins < 2 mm was not significant (p = 0.161). The margin was not a predictive factor of LRR p = 0.999. Surgical re-excision should be avoided in patients with a focally positive margin and no evidence of the disease at post-surgical imaging.

Breast Volume Is a Predictor of Higher Heart Dose in Whole-Breast Supine Free-Breathing Volumetric-Modulated Arc Therapy Planning.

In breast cancer volumetric-modulated arc therapy (VMAT) planning, the rotation of the gantry around the target implies a greater dose spreading to the whole heart, compared to tangential-field standard treatment. A consecutive cohort of 121 breast cancer patients treated with the VMAT technique was investigated. The correlation of breast volume, heart volume and lung volume with mean heart dose (mHD) and mean and maximum LAD dose (mLAD dose, MLAD dose) was tested, and a subsequent a linear regression analysis was carried out. VMAT treatment plans from 56 left breast cancer and 65 right breast cancer patients were analyzed. For right-sided patients, breast volume was significantly correlated with mHD, mLAD and MLAD dose, while for left-sided patients, breast volume was significantly correlated with mHD and mLAD, while heart volume and lung volume were correlated with mHD, mLAD and MLAD dose. Breast volume was the only predictor of increased heart and LAD dose (p ≤ 0.001) for right-sided patients. In left-sided patients, heart and lung were also predictors of increased mHD (p = 0.005, p ≤ 0.001) and mean LAD dose (p = 0.009, p ≤ 0.001). In this study, we observed an increase in heart and LAD doses in larger-breasted patients treated with VMAT planning. In right-sided patients, breast volume was shown to be the only predictor of increased heart dose and LAD dose.

Preventing Cardiotoxicity in Personalized Breast Irradiation.

BACKGROUND: This study aims to assess the benefit of a deep inspiration breath hold (DIBH) over the standard irradiation technique, and eventually to identify anatomical and/or treatment preplanning characteristics correlated with the LAD dose. METHODS: Patients with left-sided breast cancer undergoing whole breast radiotherapy with DIBH were analyzed. All patients included in the analysis had plans in DIBH and free-breathing (FB). Receiving operating characteristics (ROC analysis) were used to identify the cut-off point of parameters to predict the LAD maximum dose > 10 Gy and LAD mean dose > 4 Gy, and the areas under the curve (AUCs) were computed. Post-test probability has been performed to evaluate the effect of parameters' combination. RESULTS: One hundred ninety-seven patients were analyzed. The LAD dose was significantly reduced in DIBH plans with the maximum and mean dose reduced by 31.7% (mean value 3.5 Gy vs. 4.8 Gy, p ≤ 0.001) and 28.1% (mean value 8.2 Gy vs. 12.8 Gy, p ≤ 0.001) in DIBH plans compared to FB plans. The strongest predictor of the LAD dose (maximum > 10 Gy and mean > 4 Gy) was the minimum distance of LAD from tangent open fields. Other parameters were lung volume and heart volume (LAD Dmax > 10 Gy) and lung volume, heart volume, and breast separation (LAD Dmean > 4 Gy). CONCLUSION: The dosimetric advantage of DIBH is clear in all patients and DIBH should always be preferred.

Transperineal laser ablation (TPLA) with ultrasound/MRI fusion guidance in the treatment of localized radiotherapy-resistant prostate cancer.

Objective: The objective of this study was to assess the technical feasibility, safety, and efficacy of transperineal laser ablation (TPLA) guided by ultrasound/magnetic resonance (MR) fusion as a salvage treatment for refractory focal prostate cancer. Methods: A total of five patients who had undergone radiation therapy (RT) for prostate carcinoma and biochemical recurrence, confirmed by both prostate-specific antigen (PSA) levels and MRI (3T mpMRI), were enrolled in this study. Focal ablation was performed using a 1064 nm diode laser. Post-ablation follow-up was conducted for a duration of 18 months, which included regular PSA sampling, 3T mpMRI, and ultrasound/MR fusion-guided biopsies systematic and targeted at the site of the focal treatment. Results: The focal ablation procedure was carried out in an outpatient setting regimen with optimal clinical and biochemical outcomes. No recurrence was detected throughout the follow-up period. Conclusion: TPLA focal treatment effectively manages local recurrences of RT refractory prostate cancer without side-effects or complications. Preservation of quality of life and functional outcomes, along with a >70% reduction in PSA, were achieved. Advances in knowledge: Our study investigated TPLA as a salvage treatment for low-risk recurrent prostate cancer after RT, demonstrating its tolerability, feasibility, and effectiveness.

Untailored vs. Gender- and Body-Mass-Index-Tailored Skeletal Muscle Mass Index (SMI) to Assess Sarcopenia in Advanced Head and Neck Squamous Cell Carcinoma (HNSCC).

(1) Background: Sarcopenia lasting >1 year might be considered a chronic condition in many HNSCC patients. CT-scan-derived Skeletal Muscle Mass Index (SMI) is an established surrogate of sarcopenia; yet, the cut-off reported in the literature (literature-based, lb-SMI < 43.2) is mainly based on the risk of chemoradiotherapy-induced toxicity, and the optimal value to discriminate OS is under-investigated. (2) Methods: The effect on OS of the lb-SMI cutoff was compared with an untailored OS-oriented SMI cutoff obtained in a cohort of consecutive advanced HNSCC patients treated with primary chemoradiotherapy, bio-chemotherapy or chemo-immunotherapy (cohort-specific, cs-SMI cutoff). Gender- and BMI-tailored (gt-SMI and bt-SMI) cut-offs were also evaluated. Cutoff values were identified by using the maximally selected rank statistics for OS. (3) Results: In 115 HNSCC patients, the cs-SMI cutoff was 31.50, which was lower compared to the lb-SMI reported cut-off. The optimal cut-off separately determined in females, males, overweight and non-overweight patients were 46.02, 34.37, 27.32 and 34.73, respectively. gt-SMI categorization had the highest effect on survival (p < 0.0001); its prognostic value was independent of the treatment setting or the primary location and was retained in a multivariate cox-regression analysis for OS including other HNSCC-specific prognostic factors (p = 0.0004). (4) Conclusions: A tailored SMI assessment would improve clinical management of sarcopenia in chemoradiotherapy-, bio-chemotherapy- or chemo-immunotherapy-treated HNSCC patients. Gender-based SMI could be used for prognostication in HNSCC patients.

Stereotactic Body Radiation Therapy and Abiraterone Acetate for Patients Affected by Oligometastatic Castrate-Resistant Prostate Cancer: A Randomized Phase II Trial (ARTO).

PURPOSE: ARTO (ClinicalTrials.gov identifier: NCT03449719) is a multicenter, phase II randomized clinical trial testing the benefit of adding stereotactic body radiation therapy (SBRT) to abiraterone acetate and prednisone (AAP) in patients with oligometastatic castrate-resistant prostate cancer (CRPC). MATERIALS AND METHODS: All patients were affected by oligometastatic CRPC as defined as three or less nonvisceral metastatic lesions. Patients were randomly assigned 1:1 to receive either AAP alone (control arm) or AAP with concomitant SBRT to all the sites of disease (experimental arm). Primary end point was the rate of biochemical response (BR), defined as a prostate-specific antigen (PSA) decrease ≥50% from baseline measured at 6 months from treatment start. Complete BR (CBR), defined as PSA < 0.2 ng/mL at 6 months from treatment, and progression-free survival (PFS) were secondary end points. RESULTS: One hundred and fifty-seven patients were enrolled between January 2019 and September 2022. BR was detected in 79.6% of patients (92% v 68.3% in the experimental v control arm, respectively), with an odds ratio (OR) of 5.34 (95% CI, 2.05 to 13.88; P = .001) in favor of the experimental arm. CBR was detected in 38.8% of patients (56% v 23.2% in the experimental v control arm, respectively), with an OR of 4.22 (95% CI, 2.12 to 8.38; P < .001). SBRT yielded a significant PFS improvement, with a hazard ratio for progression of 0.35 (95% CI, 0.21 to 0.57; P < .001) in the experimental versus control arm. CONCLUSION: The trial reached its primary end point of biochemical control and PFS, suggesting a clinical advantage for SBRT in addition to first-line AAP treatment in patients with metastatic castration-resistant prostate cancer.

The impact of intensified staging and combined therapies in locally advanced pancreatic cancer: a secondary analysis of prospective studies.

AIM: To investigate the use of comprehensive pre-treatment staging with multiple diagnostic modalities, including functional imaging and minimally invasive surgical procedures, in locally advanced pancreatic cancer (LAPC) patients. The primary objective was to detect occult metastatic disease using staging laparoscopy and 18FFDG-PET/CT scan. The study also evaluated treatment efficacy and outcomes in LAPC patients treated with combined therapies. MATERIALS AND METHODS: This study was a secondary analysis of three prospective studies of chemoradiotherapy (CRT) with or without induction chemotherapy (IC). The inclusion period was from December 2009 until February 2023. An intensified pretreatment staging was conducted for all LAPC patients. Patients without distant disease at initial staging, with borderline resectable or unresectable LAPC, were enrolled in chemoradiotherapy combination protocols (CRT with or without IC). IC regimens included GemOx or FOLFIRINOX for four cycles, followed by concurrent CRT with gemcitabine. The primary endpoint was the detection of occult metastatic disease, and secondary objectives included resection rate, treatment toxicity, overall survival (OS), progression-free survival (PFS), local control (LC), and metastasis-free survival (MFS). RESULTS: Out of the 134 LAPC patients, 33.5% were identified with metastatic disease. Of these, 23.1% had a positive exploratory laparoscopy. Additionally, 13.4% were identified as having distant metastases by 18-FDG PET/CT. The median PFS for all patients who completed CRT was 14.3 months, and the median OS was 17.2 months. Resected patients after the combined therapies demonstrated significantly improved outcomes compared to non-resected patients (median PFS, 22.5 mo vs. 9.5 mo, P<0.001; median OS, 38.2 mo vs. 13 mo, P<0.001). Moreover, patients treated with IC followed by CRT showed significantly better outcomes compared to upfront CRT group (median PFS, 19 mo vs. 9.9 mo, P<0.001; median OS, 19.3 mo vs. 14.6 mo, P<0.001). At univariate logistic regression analysis, the adding of IC was the only predictor for resection rate (95% CI 0.12-1.02, P=0.05), and this data was confirmed at multivariate analysis (95% CI 0.09-0.98, P=0.04). Haematological and gastrointestinal toxicities were observed during treatment, with manageable adverse events. CONCLUSIONS: The use of comprehensive pre-treatment staging, including laparoscopy and 18F-FDG-PET/CT scan, is an effective approach in identifying occult metastatic disease in LAPC patients. Our findings offer valuable insights into accurate staging and treatment efficacy, providing evidence-based support for optimal management strategies in LAPC patients.

Dynomics: A Novel and Promising Approach for Improved Breast Cancer Prognosis Prediction.

Traditional imaging techniques for breast cancer (BC) diagnosis and prediction, such as X-rays and magnetic resonance imaging (MRI), demonstrate varying sensitivity and specificity due to clinical and technological factors. Consequently, positron emission tomography (PET), capable of detecting abnormal metabolic activity, has emerged as a more effective tool, providing critical quantitative and qualitative tumor-related metabolic information. This study leverages a public clinical dataset of dynamic 18F-Fluorothymidine (FLT) PET scans from BC patients, extending conventional static radiomics methods to the time domain-termed as 'Dynomics'. Radiomic features were extracted from both static and dynamic PET images on lesion and reference tissue masks. The extracted features were used to train an XGBoost model for classifying tumor versus reference tissue and complete versus partial responders to neoadjuvant chemotherapy. The results underscored the superiority of dynamic and static radiomics over standard PET imaging, achieving accuracy of 94% in tumor tissue classification. Notably, in predicting BC prognosis, dynomics delivered the highest performance, achieving accuracy of 86%, thereby outperforming both static radiomics and standard PET data. This study illustrates the enhanced clinical utility of dynomics in yielding more precise and reliable information for BC diagnosis and prognosis, paving the way for improved treatment strategies.

V5 and High Sensitivity Cardiac Troponin T for Early Detection of Cardiac Toxicity During Left Breast Cancer Irradiation.

BACKGROUND/AIM: The high sensitivity cardiac troponin T (Hs-cTnT) is a myocardial damage biomarker that could have a predictive value in patients who undergo radiotherapy for left sided breast cancer. The aim of this study was to evaluate the early effect of left whole breast radiotherapy (WB-RT) on serum Hs-cTnT levels and its correlation with pre-existing factors. PATIENTS AND METHODS: The study was conducted from December 2017 to May 2018. Forty-five patients with early stage left-sided breast cancer who received adjuvant breast hypofractionated RT without prior chemotherapy were included. Serum levels of Hs-cTnT were obtained before, weekly during RT, and within one week after the end of treatment. Considering the physiological variations of serum levels, an increase in Hs-cTnT (∆Hs-cTnT) of more than 30% from the baseline value was chosen as a threshold. The main cardiovascular risk factors were recorded. Dose volume histograms (DVHs) were used to provide a quantitative analysis for the whole heart, left ventricle, and left anterior descending artery (LAD). RESULTS: Twelve of 45 patients (26.6%) showed a ∆Hs-cTnT ≥30%. The maximum Hs-cTnT level was recorded in the last week of treatment. ∆Hs-cTnT was strongly associated with heart V5 (p=0.05) and hypertension (p=0.05). Multivariate analysis confirmed the importance of the heart V5 and correlated with ∆Hs-cTnT. CONCLUSION: The increase in Hs-cTnT serum levels during adjuvant WB-RT suggested a correlation with the cardiac radiation dose in chemotherapy-naive breast cancer patients. A longer follow-up is needed to correlate Hs-cTnT values with cardiac events.

BOMB trial: First results of stereotactic radiotherapy to primary breast tumor in metastatic breast cancer patients.

Aim: A prospective dose escalation trial was developed to evaluate the maximum tolerated dose of stereotactic body radiotherapy (SABRT) to primary breast cancer in stage IV disease. The aim of the present report was to describe safety and outcome of the first dose level cohort of patients. Material and methods: Patients with histologically confirmed diagnosis of invasive breast carcinoma (biological immuno-histochemical profile: luminal and/or HER2 positive) and distant metastatic disease not progressing after 6 months of systemic therapy with a tumor CT or 5FDG-PET detectable were deemed eligible. The starting dose was 40 Gy in 5 fractions (level 1) because this dose proved to be safe in previous dose-escalation trial on adjuvant stereotactic body radiotherapy. The maximum dose level was chosen as 45 Gy in 5 fractions. Dose limiting toxicity was any grade 3 or worse toxicity according to CTCAE v.4. Time-to-event Keyboard (TITE-Keyboard) design (Lin and Yuan, Biostatistics 2019) was used to find the maximum tolerated dose (MTD). MTD was the dose of radiotherapy associated with a ≤ 20% rate pre-specified treatment-related dose-limiting toxicity (DLT). Results: To date 10 patients have been treated at the starting dose level. Median age was 80 years (range 50-89). 7 patients had a luminal disease, while 3 patients had an HER2 positive disease. No patient suspended ongoing systemic treatment. No protocol defined DLTs were observed. Grade 2 skin toxicity occurred in 4 patients with diseases located close to or involving the skin. Median follow-up was 13 months and all 10 patients were evaluable for response: 5 achieved a complete response, 3 achieved a partial response and 2 showed a stable disease, all with a clinical benefit (resolution of skin retraction, bleeding and pain). The mean reduction in the sum of the largest diameters of target lesions was of 61.4% (DS=17.0%). Conclusions: SABR to primary breast cancer seems feasible and is associated with symptoms reduction. Continued accrual to this study is needed to confirm the safety and assess the MTD. Clinical trial registration: ClinicalTrials.gov, identifier NCT05229575.

Matching BRCA and prostate cancer in a public health system: Report of the Italian Society for Uro-Oncology (SIUrO) consensus project.

The recent approval of PARP inhibitors for the treatment of metastatic -castration-resistant prostate cancer (mCRPC) patients with BRCA mutations firstly introduced the possibility of proposing a targeted treatment in this disease. However, the availability of this therapeutic option raises a number of questions concerning the management of prostate cancer in everyday clinical practice: the timing and method of detecting BRCA mutations, the therapeutic implications of the detection, and the screening of the members of the family of a prostate cancer patient with a BRCA alteration. These challenging issues led the Italian Society for Uro-Oncology (SIUrO) to organise a Consensus Conference aimed to develop suggestions capable of supporting clinicians managing prostate cancer patients. The present paper described the development of the statements discussed during the consensus, which involved all of the most important Italian scientific societies engaged in the multi-disciplinary and multi-professional management of the disease.

nmCRPC, a look in the continuous care of prostate cancer patients: state of art and future perspectives.

Non-metastatic castration resistant prostate cancer (nmCRPC) is a clinical setting defined as confirmed rising levels of PSA in patients treated with ADT but without detectable metastases on conventional imaging with computerized tomography (CT) and technetium-99 m scintigraphy. Men with nmCRPC and a PSA doubling time (PSADT) ≤ 10 months are considered at high risk of rapidly developing metastases with a consequent possible impact on survival. Three recent phase III trials have demonstrated, in this setting, the efficacy of adding a next-generation androgen receptor targeted agent (ARTA) to ADT in respect to ADT only, in delaying the development of metastases (metastasis-free survival, MFS) and prolong overall survival. The magnitude of clinical benefit of these agents was even more meaningful if considering the low incidence of drug related adverse events. Our review described the latest advances in the management of nmCRPC, deriving from the pivotal clinical trials, SPARTAN, PROSPER and ARAMIS, in order to support clinicians to optimally manage these patients. Of note, the emergence of novel, more accurate, next-generation imaging techniques (including Ga PSMA-PET/CT), as well as eventual future tumor biomarkers, is modifying the entity and definition of the nmCRPC setting, with a consequent impact on patient's diagnosis and management.

External validation of a composite bio-humoral index in anal cancer patients undergoing concurrent chemoradiation.

BACKGROUND AND PURPOSE: A prognostic scoring system based on laboratory inflammation parameters, [Hemo-Eosinophils-Inflammation (HEI) index], including baseline hemoglobin level, the systemic inflammatory index and eosinophil count was recently proposed in patients with squamous cell carcinoma of the anus (ASCC). HEI was shown to discriminate disease-free (DFS) and overall (OS) survival in ASCC patients treated with concurrent chemoradiation (CRT). We tested the accuracy of the model on a multicentric cohort for external validation. MATERIALS AND METHODS: Patients treated with CRT were enrolled. The Kaplan-Meier curves for DFS and OS based on HEI risk group were calculated and the log-rank test was used. Cox proportional hazards models were used to assess the prognostic factors for DFS and OS. The exponential of the regression coefficients provided an estimate of the hazard ratio (HR). For model discrimination, we determined Harrell's C-index, Gönen & Heller K Index and the explained variation on the log relative hazard scale. RESULTS: A total of 877 patients was available. Proportional hazards were adjusted for age, gender, tumor-stage, and chemotherapy. Two-year DFS was 77 %(95 %CI:72.0-82.4) and 88.3 %(95 %CI:84.8-92.0 %) in the HEI high- and low- risk groups. Two-year OS was 87.8 %(95 %CI:83.7-92.0) and 94.2 %(95 %CI:91.5-97). Multivariate Cox proportional hazards model showed a HR = 2.02(95 %CI:1.25-3.26; p = 0.004) for the HEI high-risk group with respect to OS and a HR = 1.53(95 %CI:1.04-2.24; p = 0.029) for DFS. Harrel C-indexes were 0.68 and 0.66 in the validation dataset, for OS and DFS. Gonen-Heller K indexes were 0.67 and 0.71, respectively. CONCLUSION: The HEI index proved to be a prognosticator in ASCC patients treated with CRT. Model discrimination in the external validation cohort was acceptable.

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.

Achieving Consensus for Management of Hormone-Sensitive, Low-Volume Metastatic Prostate Cancer in Italy.

Metastatic hormone-sensitive prostate cancer (mHSPC) is usually categorized as high- or low-volume disease. This is relevant because low- and high-volume metastatic disease are associated with different outcomes, and thus management of the two forms should differ. Although some definitions have been reported, the concept of oligometastatic disease is not so clearly defined, giving rise to further variability in the choice of treatment, mainly between systemic agents and radiotherapy, especially in the era of metastasis-directed therapy. With the aim of providing clinicians with guidance on best practice, a group of medical and radiation oncologists, experts in prostate cancer, used the round robin method to generate a series of consensus statements on management of low-volume mHSPC. Consensus was obtained on three major areas of controversy: (1) with regard to clinical definitions of mHSPC, it was held that oligometastatic and low-volume disease refer to different concepts and should not be used interchangeably; (2) regarding therapy of de novo low-volume metastatic disease, androgen deprivation therapy alone can be considered undertreatment, and all patients should be evaluated for systemic treatment combinations; local therapy should not be denied in patients with mHSPC, regardless of the intensity of systemic therapy, and metastasis-directed therapy can be proposed in selected cases; (3) with regard to treatment of metachronous metastatic disease, patients should be evaluated for systemic treatment combinations. Metastasis-directed therapy can be proposed to delay systemic treatment in selected cases, especially if prostate-specific membrane antigen positron emission tomography staging has been performed and when indolent disease occurs. It is hoped that clinicians treating patients with mHSPC in daily practice will find this expert opinion of value.

Total neoadjuvant therapy for the treatment of locally advanced rectal cancer: a systematic minireview.

Colorectal carcinoma is the second leading cause of cancer-related deaths, and indeed, rectal cancer accounting for approximately one third of newly diagnosed patients. Gold standard in the treatment of rectal cancer is a multimodality approach, aiming at a good control of the local disease. Distant recurrences are the major cause of mortality. Currently, Locally Advanced Rectal Cancer (LARC) patients undergo a combined treatment of chemotherapy and radiotherapy, followed by surgery. Eventually, more chemotherapy, namely adjuvant chemotherapy (aCT), may be necessary. Total Neoadjuvant Therapy (TNT) is an emerging approach aimed to reduce distant metastases and improve local control. Several ongoing studies are analyzing whether this new approach could improve oncological outcomes. Published results were encouraging, but the heterogeneity of protocols in use, makes the comparison and interpretation of data rather complex. One of the major concerns regarding TNT administration is related to its effect on larger and more advanced cancers that might not undergo similar down-staging as smaller, early-stage tumors. This minireview, based on a systematic literature search of randomized clinical trials and meta-analysis, summarizes current knowledge on TNT. The aim was to confirm or refute whether or not current practice of TNT is based on relevant evidence, to establish the quality of that evidence, and to address any uncertainty or variation in practice that may be occurring. A tentative grouping of general study characteristics, clinical features and treatments characteristics has been undertaken to evaluate if the reported studies are sufficiently homogeneous in terms of subjects involved, interventions, and outcomes to provide a meaningful idea of which patients are more likely to gain from this treatment.

Stereotactic or conventional radiotherapy for macroscopic prostate bed recurrence: a propensity score analysis.

PURPOSE: To assess outcomes between salvage radiation therapy (SRT) with curative intent and stereotactic radiotherapy for macroscopic prostate recurrence (SSRT) after radical prostatectomy (RP). In order to compare these two different options, we compared their outcomes with a propensity score-based matched analysis. METHODS: Data from 185 patients in seven Italian centres treated for macroscopic prostate bed recurrence after RP were retrospectively collected. To make a comparison between the two treatment groups, propensity matching was applied to create comparable cohorts. RESULTS: After matching, 90 patients in the SRT and SSRT groups were selected (45 in each arm). Kaplan-Meier analysis did not show any significant differences in terms of BRFS and PFS between matched populations (p = 0.08 and p = 0.8, respectively). Multivariate models show that treatment was not associated with BRFS, neither in the whole or matched cohort, with HR of 2.15 (95%CI 0.63-7.25, p = 0.21) and 2.65 (95%CI 0.59-11.97, p = 0.21), respectively. In the matched cohort, lower rate of toxicity was confirmed for patients undergoing SSRT, with acute GI and GU adverse events reported in 4.4 versus 44.4% (p < 0.001) and 28.9 versus 46.7% (p = 0.08) of patients, and late GI and GU adverse events reported in 0 versus 13.3% (p = 0.04) and 6.7 versus 22.2% (p = 0.03) of patients, respectively. CONCLUSION: Considering the favourable therapeutic ratio of this approach and the lower number of fractions needed, SSRT should be considered as an attractive alternative to conventional SRT in this setting.

Radiotherapy for HER 2 Positive Brain Metastases: Urgent Need for a Paradigm Shift.

Brain metastases (BMs) are common among patients affected by HER2+ metastatic breast cancer (>30%). The management of BMs is usually multimodal, including surgery, radiotherapy, systemic therapy and palliative care. Standard brain radiotherapy (RT) includes the use of stereotactic radiotherapy (SRT) for limited disease and whole brain radiotherapy (WBRT) for extensive disease. The latter is an effective palliative treatment but has a reduced effect on brain local control and BM overall survival, as it is also associated with severe neurocognitive sequelae. Recent advances both in radiation therapy and systemic treatment may change the paradigm in this subset of patients who can experience long survival notwithstanding BMs. In fact, in recent studies, SRT for multiple BM sites (>4) has shown similar efficacy when compared to irradiation of a limited number of lesions (one to three) without increasing toxicity. These findings, in addition to the introduction of new drugs with recognized intracranial activity, may further limit the use of WBRT in favor of SRT, which should be employed for treatment of both multiple-site BMs and for oligo-progressive brain disease. This review summarizes the supporting literature and highlights the need for optimizing combinations of the available treatments in this setting, with a particular focus on radiation therapy.

Factors Predicting Pathological Response to Neoadjuvant Chemoradiotherapy in Rectal Cancer: The Experience of a Single Institution with 269 Patients (STONE-01).

AIMS: The aim of this study was to define a potential benefit of pathological complete response rate (pCR) and downstaging rate after neoadjuvant chemoradiotherapy (CRT) in relation to treatment and patient factors in locally advanced rectal cancer. METHODS: We performed a retrospective cohort study. Patients were divided according to chemotherapy regimens concurrent to radiotherapy (1-drug vs. 2-drug) and according to the time interval between the end of CRT and surgery (≤8 weeks vs. >8 weeks), as well as in relation to specific relevant clinical factors. Logistic regression was used to estimate the independent factors for pCR and downstaging. RESULTS: 269 patients were eligible for this study. Overall, pCR and downstaging rates were 26% and 75.4%, respectively. Univariate analysis showed that female gender (p = 0.01) and time to surgery >8 weeks (p = 0.04) were associated with pCR; age > 70 years (p = 0.05) and time to surgery >8 weeks (p = 0.002) were correlated to downstaging. At multivariate analysis, interval time to surgery of >8 weeks was the only independent factor for both pCR and downstaging (p = 0.02; OR: 0.5, CI: 0.27-0.93 and p = 0.003; OR: 0.42, CI: 0.24-0.75, respectively). CONCLUSIONS: This study indicates that, in our population, an interval time to surgery of >8 weeks is an independent significant factor for pCR and downstaging. Further prospective studies are needed to define the best interval time.

Resilience in Radiotherapy Services During the COVID-19 Emergency: Collaboration Between the Regional Radiation Oncology Departments of Lazio, Abruzzo and Molise.

AIM: Radiation therapy is a cornerstone of oncological treatment and oncological patients show greater risk of developing complications related to COVID-19 infection. Stringent social restrictions have ensured a significant reduction in the spread of the virus, but also gave rise to a number of critical issues for radiation oncology wards. For this reason, the Directors of the Radiation Oncology Departments (RODs) of Lazio, Abruzzo and Molise regions shared their experience and ideas in order to create a common document that may assist in facing the negative impacts of the pandemic on radiation oncology wards and patients. PATIENTS AND METHODS: The study was conducted according to the Estimate-Talk-Estimate method. Five issues were proposed and rated. Among approved issues, statements were proposed anonymously, then harmonized and finally voted on according to a Likert scale from 1 to 9. Those for which an agreement of 7-9 was observed were finally approved. RESULTS: The document was developed with 42 statements dealing about safety measures for patients and staff, organization of clinical and work activities, usage of Information Technology systems for meetings/smart working. An agreement was recorded for 34 statements. CONCLUSION: This document sets out some recommendations for RODs and can provide valuable management information for Oncological Radiotherapy wards.