Stereotactic MR-guided adaptive radiotherapy (SMART) for primary rectal cancer: evaluation of early toxicity and pathological response.

Background: The purpose of this study is to measure the effects of stereotactic MR-guided adaptive radiotherapy (SMART) for rectal cancer patients in terms of early toxicity and pathological response. Materials and methods: For this prospective pilot study, patients diagnosed with locally advanced rectal cancer (LARC) with positive lymph node clinical staging underwent SMART on rectal lesion and mesorectum using hybrid MR-Linac (MRIdian ViewRay). Dose prescription at 80% isodose for the rectal lesion and mesorectum was 40 Gy (8 Gy/fr) and 25 Gy (5 Gy/fr), respectively, delivered on 5 days (3 fr/week). Response assessment by MRI was performed 3 weeks after SMART, then patients fit for surgery underwent total mesorectal excision. Primary endpoint was evaluation of adverse effect of radiotherapy. Secondary endpoint was pathological complete response rate. Early toxicity was graded according to the Common Terminology Criteria for Adverse Events (CTCAE v5.0). Results: From October 2020 to January 2022, twenty patients underwent rectal SMART. No grade 3-5 toxicity was recorded. Twelve patients were eligible for total mesorectal excision (TME). Mean interval between the completion of SMART and surgery was 4 weeks. Pathological downstaging occurred in all patients; rate of pathological complete response (pCR) was 17%. pCR occurred with a prolonged time to surgery (> 7 weeks). Conclusion: To our knowledge, this is the first study to use stereotactic radiotherapy for primary rectal cancer. SMART for rectal cancer is well tolerated and effective in terms of tumor regression, especially if followed by delayed surgery.

[Participation and facilitation in environment and health contexts. The case study of San Donaci (Apu-lia Region, Southern Italy)]. / Partecipazione e facilitazione nei contesti ambientali e sanitari. L'esperienza di San Donaci (Brindisi).

On behalf of the municipal administration of San Donaci (Brindisi Province, Apulia Region, Southern Italy), the Italian National Research Council counducted a participatory epidemiology experience. The activity of participation and discussion between the research group, the public administration, and citizens involved an association with expertise in facilitation. The participation methodology, adapted to the context, was articulated in focus groups and circle time. In addition to expanding the environmental and health analyses by enriching the final report, facilitation supported the expression of the different points of view, restoring greater complexity to the discussion by rebuilding a partial climate of trust among the participants.

Safety culture to improve accidental event reporting in radiotherapy.

BACKGROUND AND PURPOSE: The potential for unintended and adverse radiation exposure in radiotherapy (RT) is real and should be studied because RT is a highly complex, multistep process, which requires input from numerous individuals from different areas and steps of the RT workflow. The 'Incident' (I) is an event the consequence of which is not negligible from the point of view of protection or safety. A 'near miss' (NM) is defined as an event that is highly likely to happen but did not occur. The purpose of this work is to show that through systematic reporting and analysis of these adverse events, their occurrence can be reduced. MATERIALS AND METHODS: Staff were trained to report every type of unintended and adverse radiation exposure and to provide a full description of it. RESULTS: By 2018, 110 worksheets had been collected, with an average of 6.1 adverse events per year (with 780 patients treated per year, meaning an average incident rate of 0.78%). In 2001-2009, 37 events were registered (13 I and 24 NM), the majority of them were in the decision phase (12/37), while in 2010-2013, there were 42 (1 I and 41 NM) in both the dose-calculation and transfer phase (19/42). In 2014-2018, 31 events (1 I and 30 NM) were equally distributed across the phases of the RT process. In 9/15 cases of I, some checkpoint was introduced. CONCLUSION: The complexity of the RT workflow is prone to errors, and this must be taken into account by encouraging a safety culture. The aim of this paper is to present the collected incidents and near misses and to show how organization and practice were modified by the acquired knowledge.

Long-term effect of arsenic exposure: Results from an occupational cohort study.

BACKGROUND: In 1976 in Manfredonia (Italy), arsenic was released into the atmosphere due to an accident in a petrochemical plant. We aimed to analyze the mortality of workers involved in the factory for the site cleaning activities. METHODS: The cohort consisted of 1467 workers grouped into contract, fertilizer, and plastic workers. The outcome of interest was mortality for specific causes. Standardized mortality ratios (SMR) and 95% confidence intervals (95%CI) were computed. RESULTS: For all workers and all causes of death combined, the SMR was less than 1.0. Mortality ratios were increased for malignant neoplasms of the pleura, bone and melanoma of the skin. Contract workers, the group mostly exposed to arsenic, showed statistically significant SMRs for several malignancies, in particular for lung cancer (SMR = 1.26; 95%CI: 1.05-1.54). CONCLUSIONS: Overall, the results reported here on mortality among persons occupationally exposed to arsenic are consistent with the literature and biologically plausible.

Cancer mortality in the West Bank, Occupied Palestinian Territory.

BACKGROUND: The burden of cancer is difficult to study in the context of the occupied Palestinian territory because of the limited data available. This study aims to evaluate the quality of mortality data and to investigate cancer mortality patterns in the occupied Palestinian territory's West Bank governorates from 1999 to 2009. METHODS: Death certificates collected by the Palestinian Ministry of Health for Palestinians living in the West Bank were used. Direct and indirect age-standardised mortality rates were computed and used to compare different governorates according to total and specific cancer mortality. Furthermore, standardised proportional mortality ratios were calculated to compare mortality by urban, rural and camp locales. RESULTS: The most common cause of death out of all cancer types was lung cancer among males (22.8 %) and breast cancer among females (21.5 %) followed by prostate cancer for males (9.5 %) and by colon cancer for females (11.4 %). Regional variations in cancer-specific causes of death were observed. The central- West Bank governorates had the lowest mortality for most cancer types among men and women. Mortality for lung cancer was highest in the north among men (SMR 109.6; 95%CI 99.5-120.4). For prostate cancer, mortality was highest in the north (SMR 103.6; 95%CI 88.5-120.5) and in the south (SMR 118.6; 95%CI 98.9-141.0). Breast cancer mortality was highest in the south (SMR 119.3; 95%CI 103.9-136.2). Similar mortality rate patterns were found in urban, rural and camp locales. CONCLUSION: The quality of the Palestinian mortality registry has improved over time. Results in the West Bank governorates present different mortality patterns. The differences might be explained by personal, contextual and environmental factors that need future in-depth investigations.

The Potential Role of Lung Ultrasound B-Lines for Detection of Lung Radio-Induced Toxicity in Breast Cancer Patients after Radiation Therapy.

BACKGROUND AND PURPOSE: Breast cancer patients exposed to doses of radiation after radiotherapy could develop toxicity to lung. Lung ultrasound (LUS) is able to detect interstitial lung disease by the evaluation of B-lines. The aim of our study was to assess the number of B-lines to diagnose lung involvement after chest radiotherapy. MATERIALS AND METHODS: We measured LUS B-lines in the treated and contralateral lung of 20 breast cancer patients, 1-3 months after the end of radiotherapy and 1 year after previous LUS. The sum of the B-lines number in the 72 sites on anterior and posterior chest yielded a global B-lines score. RESULTS: B-lines were more numerous in treated (median: 21; 1st-3rd quartiles: 11-31) versus untreated hemithorax (median: 3; 1st-3rd quartiles: 1-5) in both examination at T1-3 months (Kolmogorov-Smirnov test P < 0.001) and T1 year (median: 21; 1st-3rd quartiles: 12-28 vs. median: 4; 1st-3rd quartiles: 1-10; Kolmogorov-Smirnov test P < 0.01). Within the treated hemithorax, B-lines were more frequent in the anterior than in the posterior chest in both examination at T1-3 months (Kolmogorov-Smirnov test: P < 0.0001) and T1 year (Kolmogorov-Smirnov test: P < 0.01). Abnormal scores (B-lines>5) were present in 17/20 treated versus 7/20 untreated hemithoraxes (85.0 vs. 35.0%, P < 0.01) in the first LUS and likewise in 16/17 treated versus 7/17 in untreated hemithorax (94.1% vs. 41.2%, P < 0.01) after 1-year follow-up. CONCLUSION: Among women receiving radiotherapy after breast cancer, B-lines are present predominantly in the irradiated lung. These data suggest that B-lines by LUS could provide, at a subclinical stage, a radiation-free biomarker of radiotherapy-induced lung damage.

Durable complete response to PET-CT driven stereotactic radiation therapy plus pembrolizumab for pleomorphic Pancoast cancer: Case report and literature review.

PET-driven SBRT plus pembrolizumab as first-line therapy against pleomorphic Pancoast cancer appears beneficial, probably due to high equivalent doses of SBRT on photopenic necrotic core and synergic immune system stimulation of immunoradiotherapy.

10-yr Results of Moderately Hypofractionated Postoperative Radiotherapy for Prostate Cancer Focused on Treatment Related Toxicity.

INTRODUCTION: To retrospectively report long term outcomes following postoperative hypofractionated radiotherapy (RT) for prostate cancer, emphasizing treatment related toxicity. MATERIAL AND METHODS: Patients for whom adjuvant or salvage RT was indicated after prostatectomy were treated with a course of moderate hypofractionation consisting in the delivery of 62.5 Gy in 25 fractions (2.5 Gy per fraction) on the prostate bed in 5 consecutive weeks (EQD21.5 = 70 Gy) by means of 3D-CRT in most of them. Androgen deprivation therapy (ADT) was allowed at physician's discretion. Patients were evaluated for urinary and rectal complications according to the Common Terminology Criteria for Adverse Events v4 (CTCAE v.4). Overall survival (OS), biochemical recurrence free survival (bRFS), and metastasis-free survival (MFS) were estimated using the Kaplan-Meier method. RESULTS: One hundred and ten patients with a median age of 67 years (range 51-78) were enrolled. The majority of them (82%) had adverse pathologic features only, while 31 (28%) had early biochemical relapse. Median PSA level before RT was 0.12 ng/mL (range 0-9 ng/mL). Median time from surgery was 4 months (range 1-136 months). Twenty-eight patients (25.4%) also received ADT. At a median follow up of 103 months (range 19-138 months), late Grade 3 and Grade 4 rectal toxicity were 0.9% (1 case of hematochezia) and 0.9% (1 case of fistula), respectively, while late Grade 3 GU side effects (urethral stenosis) occurred in 9 cases (8%). No late Grade 4 events were observed, respectively. Ten-year OS, b-RFS and MFS were 77.3% (95%CI: 82.1%-72.5%), 53.3% (95%CI: 59.9%-47.6%), and 76.7% (95%CI: 81.2%-72.2%), respectively. CONCLUSION: Our study provides long term data that a shortened course of postoperative RT is as safe and effective as a long course of conventionally fractionated RT and would improve patients' convenience and significantly reduce RT department workloads.

Explainable prediction model for the human papillomavirus status in patients with oropharyngeal squamous cell carcinoma using CNN on CT images.

Several studies have emphasised how positive and negative human papillomavirus (HPV+ and HPV-, respectively) oropharyngeal squamous cell carcinoma (OPSCC) has distinct molecular profiles, tumor characteristics, and disease outcomes. Different radiomics-based prediction models have been proposed, by also using innovative techniques such as Convolutional Neural Networks (CNNs). Although some of these models reached encouraging predictive performances, there evidence explaining the role of radiomic features in achieving a specific outcome is scarce. In this paper, we propose some preliminary results related to an explainable CNN-based model to predict HPV status in OPSCC patients. We extracted the Gross Tumor Volume (GTV) of pre-treatment CT images related to 499 patients (356 HPV+ and 143 HPV-) included into the OPC-Radiomics public dataset to train an end-to-end Inception-V3 CNN architecture. We also collected a multicentric dataset consisting of 92 patients (43 HPV+ , 49 HPV-), which was employed as an independent test set. Finally, we applied Gradient-weighted Class Activation Mapping (Grad-CAM) technique to highlight the most informative areas with respect to the predicted outcome. The proposed model reached an AUC value of 73.50% on the independent test. As a result of the Grad-CAM algorithm, the most informative areas related to the correctly classified HPV+ patients were located into the intratumoral area. Conversely, the most important areas referred to the tumor edges. Finally, since the proposed model provided additional information with respect to the accuracy of the classification given by the visualization of the areas of greatest interest for predictive purposes for each case examined, it could contribute to increase confidence in using computer-based predictive models in the actual clinical practice.

Further Clarification of Pain Management Complexity in Radiotherapy: Insights from Modern Statistical Approaches.

BACKGROUND: The primary objective of this study was to assess the adequacy of analgesic care in radiotherapy (RT) patients, with a secondary objective to identify predictive variables associated with pain management adequacy using a modern statistical approach, integrating the Least Absolute Shrinkage and Selection Operator (LASSO) algorithm and the Classification and Regression Tree (CART) analysis. METHODS: This observational, multicenter cohort study involved 1387 patients reporting pain or taking analgesic drugs from 13 RT departments in Italy. The Pain Management Index (PMI) served as the measure for pain control adequacy, with a PMI score < 0 indicating suboptimal management. Patient demographics, clinical status, and treatment-related factors were examined to discern the predictors of pain management adequacy. RESULTS: Among the analyzed cohort, 46.1% reported inadequately managed pain. Non-cancer pain origin, breast cancer diagnosis, higher ECOG Performance Status scores, younger patient age, early assessment phase, and curative treatment intent emerged as significant determinants of negative PMI from the LASSO analysis. Notably, pain management was observed to improve as RT progressed, with a greater discrepancy between cancer (33.2% with PMI < 0) and non-cancer pain (73.1% with PMI < 0). Breast cancer patients under 70 years of age with non-cancer pain had the highest rate of negative PMI at 86.5%, highlighting a potential deficiency in managing benign pain in younger patients. CONCLUSIONS: The study underscores the dynamic nature of pain management during RT, suggesting improvements over the treatment course yet revealing specific challenges in non-cancer pain management, particularly among younger breast cancer patients. The use of advanced statistical techniques for analysis stresses the importance of a multifaceted approach to pain management, one that incorporates both cancer and non-cancer pain considerations to ensure a holistic and improved quality of oncological care.

[SENTIERI Project on Italian polluted sites: health in Brindisi]. / Il progetto SENTIERI sui siti di interesse nazionale per le bonifiche (SIN): Brindisi alla salute?

Epidemiological data should support policy makers in their decisions. Misjudgments in data interpretation can justify the preservation of the existing situation and the lack of decision about health and environment safeguard. In the SENTIERI study on Italian polluted sites, women mortality results significantly lower than the regional mean in 11 sites in 44. The authors of this paper think that these data depend on the different impact of pollution on the population of a site, as witnessed by the cases of Brindisi and Manfredonia (Southern Italy). It is now necessary to conduct studies at suburban level integrating mortality data with other available health data.

Prescriptive appropriateness in early breast cancer staging exams: preliminary investigation about adherence to the guidelines in the clinical practice.

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Adequacy of Pain Management in Patients Referred for Radiation Therapy: A Subanalysis of the Multicenter ARISE-1 Study.

BACKGROUND: Pain is a prevalent symptom among cancer patients, and its management is crucial for improving their quality of life. However, pain management in cancer patients referred to radiotherapy (RT) departments is often inadequate, and limited research has been conducted on this specific population. This study aimed to assess the adequacy and effectiveness of pain management when patients are referred for RT. Moreover, we explored potential predictors of adequate pain management. METHODS: This observational, prospective, multicenter cohort study included cancer patients aged 18 years or older who were referred to RT departments. A pain management assessment was conducted using the Pain Management Index (PMI), calculated by subtracting the pain score from the analgesic score (PMI < 0 indicated inadequate pain management). Univariate and multivariate analyses were performed to identify predictors of adequate pain management. RESULTS: A total of 1042 cancer outpatients were included in the study. The analysis revealed that 42.9% of patients with pain did not receive adequate pain management based on PMI values. Among patients with pain or taking analgesics and referred to palliative or curative RT, 72% and 75% had inadequate or ineffective analgesic therapy, respectively. The odds of receiving adequate pain management (PMI ≥ 0) were higher in patients undergoing palliative RT (OR 2.52; p < 0.001), with worse ECOG-PS scores of 2, 3 and 4 (OR 1.63, 2.23, 5.31, respectively; p: 0.017, 0.002, 0.009, respectively) compared to a score of 1 for those with cancer-related pain (OR 0.38; p < 0.001), and treated in northern Italy compared to central and southern of Italy (OR 0.25, 0.42, respectively; p < 0.001). CONCLUSIONS: In this study, a substantial proportion of cancer patients referred to RT departments did not receive adequate pain management. Educational and organizational strategies are necessary to address the inadequate pain management observed in this population. Moreover, increasing the attention paid to non-cancer pain and an earlier referral of patients for palliative RT in the course of the disease may improve pain response and treatment outcomes.

Outcomes and toxicity following post-operative hypofractionated radiotherapy to the regional nodes and the breast or the chest wall in locally advanced breast cancer.

OBJECTIVES: We aimed to analyze the impact of a 3-week schedule of HypoFractionated (HF) radiotherapy (RT) after axillary dissection and breast surgery, in terms of safety and efficacy in patients with locally advanced breast cancer (BC). METHODS: Eligible patients were females with Stage IIA - IIIC BC who underwent axillary dissection and breast surgery, either quadrantectomy or mastectomy. HF RT was delivered in 15 or 16 fractions for a total dose of 40.05 Gy or 42.56 Gy, respectively, to the clavicular nodal region along with the whole breast (HF WBRT) or the chest wall (HF PMRT), according to the type of surgery. Locoregional recurrence (LRR), distant metastases-free survival (DMFS), overall survival (OS) and acute and late treatment-related toxicities were estimated. RESULTS: 57 patients with a median age of 60 years (32-85) were retrospectively analyzed. 34 (60%) of patients underwent breast conservative surgery in the form of quadrantectomy and 23 (40%) were offered radical mastectomy. All patients underwent hypofractionated regional nodal irradiation (HF RNI). 34 (60%) of them underwent HF WBRT, while 23 (40%) received HF PMRT.At a median follow-up of 80 months (30-113), the 7-year LRR-free survival was 93% (95% CI, 74%-95%). The same features for DMFS and OS were 76% (95% CI, 52%-78%) and 67% (95% CI, 50%-80%), respectively. Only one (2%) patient experienced G3 acute skin toxicity. No grade ≥2 late toxicity was observed. CONCLUSION: Our study shows that HF RNI with HF RT to the whole breast or the chest wall after breast surgery is safe and effective in patients with locally advanced BC. Longer follow-up is needed to strengthen further analyses on late toxicity and clinical outcomes. ADVANCES IN KNOWLEDGE: This paper adds to the evidence that post-operative RNI with WBRT or PMRT can be safely and effectively delivered with 3-week HF regimen. Locally advanced BC patients can be offered HF RT to the regional nodes and the breast or the chest wall regardless the type of surgery.

Economic Evaluations of Magnetic Resonance Image-Guided Radiotherapy (MRIgRT): A Systematic Review.

OBJECTIVES: This review systematically summarizes the evidence on the economic impact of magnetic resonance image-guided RT (MRIgRT). METHODS: We systematically searched INAHTA, MEDLINE, and Scopus up to March 2022 to retrieve health economic studies. Relevant data were extracted on study type, model inputs, modeling methods and economic results. RESULTS: Five studies were included. Two studies performed a full economic assessment to compare the cost-effectiveness of MRIgRT with other forms of image-guided radiation therapy. One study performed a cost minimization analysis and two studies performed an activity-based costing, all comparing MRIgRT with X-ray computed tomography image-guided radiation therapy (CTIgRT). Prostate cancer was the target condition in four studies and hepatocellular carcinoma in one. Considering the studies with a full economic assessment, MR-guided stereotactic body radiation therapy was found to be cost effective with respect to CTIgRT or conventional or moderate hypofractionated RT, even with a low reduction in toxicity. Conversely, a greater reduction in toxicity is required to compete with extreme hypofractionated RT without MR guidance. CONCLUSIONS: This review highlights the great potential of MRIgRT but also the need for further evidence, especially for late toxicity, whose reduction is expected to be the real added value of this technology.

Adequacy of Pain Treatment in Radiotherapy Departments: Results of a Multicenter Study on 2104 Patients (Arise).

Aim: The frequent inadequacy of pain management in cancer patients is well known. Moreover, the quality of analgesic treatment in patients treated with radiotherapy (RT) has only been rarely assessed. In order to study the latter topic, we conducted a multicenter, observational and prospective study based on the Pain Management Index (PMI) in RT Italian departments. Methods: We collected data on age, gender, tumor site and stage, performance status, treatment aim, and pain (type: CP­cancer pain, NCP­non-cancer pain, MP­mixed pain; intensity: NRS: Numeric Rating Scale). Furthermore, we analyzed the impact on PMI on these parameters, and we defined a pain score with values from 0 (NRS: 0, no pain) to 3 (NRS: 7−10: intense pain) and an analgesic score from 0 (pain medication not taken) to 3 (strong opioids). By subtracting the pain score from the analgesic score, we obtained the PMI value, considering cases with values < 0 as inadequate analgesic prescriptions. The Ethics Committees of the participating centers approved the study (ARISE-1 study). Results: Two thousand one hundred four non-selected outpatients with cancer and aged 18 years or older were enrolled in 13 RT departments. RT had curative and palliative intent in 62.4% and 37.6% patients, respectively. Tumor stage was non-metastatic in 57.3% and metastatic in 42.7% of subjects, respectively. Pain affected 1417 patients (CP: 49.5%, NCP: 32.0%; MP: 18.5%). PMI was < 0 in 45.0% of patients with pain. At multivariable analysis, inadequate pain management was significantly correlated with curative RT aim, ECOG performance status = 1 (versus both ECOG-PS3 and ECOG- PS4), breast cancer, non-cancer pain, and Central and South Italy RT Departments (versus Northern Italy).Conclusions: Pain management was less adequate in patients with more favorable clinical condition and stage. Educational and organizational strategies are needed in RT departments to reduce the non-negligible percentage of patients with inadequate analgesic therapy.