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.

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.

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

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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.

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.

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.

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.

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.

[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.

Impact of the COVID-19 Pandemic on Radiotherapy Supply.

BACKGROUND: The impetuous entrance of the COVID-19 pandemic in Italy in March 2020, after the onset and diffusion in China, found the health system widely unfit to face the large amount of infected patients. The matter of this investigation was to evaluate how pandemic fear and guidelines for limiting the diffusion of SARS-CoV-2 virus could have impacted the regular supply of radiotherapy (RT) and the outcome of the treatments. MATERIALS AND METHODS: From March 9, 2020, to May 29, 2020, a register has been established to record patients that cancelled or postponed the RT appointment. The reasons were as follows: (1) patients whose appointments were postponed by the staff according to national guidelines; (2) patients who asked themselves to postpone the appointment; (3) patients who interrupted the treatment for causes directly or indirectly related to the pandemic; (4) patients who cancelled their care path. RESULTS: A total number of 277 patients started regular RT, and 384 respected their computed tomography (CT) simulation appointment, but 60 of them had alteration of their therapeutic pathway. Among these, 18 cancelled their appointment. 42 patients asked to postpone their procedure. Twenty-seven out of 42 adduced directly or indirectly SARS-CoV-2 infection-related reasons. CONCLUSIONS: The COVID-19 pandemic affected the regular RT delivery to oncologic patients, owing to the delay or cancellation of procedures with the likely effect to observe worsening of local disease control and reduced survival rates in the future.

Southern Italy: How the Availability of Radiation Therapy, Patient Outcomes, and Risk to Health Care Providers Have Changed During the Coronavirus Disease 2019 Pandemic.

The first actions and provisions in a Southern Italy Department of Radiation Oncology are described at the inception of the COVID-19 pandemic.

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.

B-type natriuretic peptide plasma level in 5-year breast cancer survivors after radiotherapy.

BACKGROUND: Left-sided breast cancer patients treated with radiotherapy (RT) are at risk for late radiation-induced cardiovascular complications. AIM: The aim of this study was to investigate the BNP plasma levels in long-term breast cancer survivors who received only RT as well to assess whether cardiac dose was associated with BNP values. METHODS: Plasma samples for BNP measurement were repeated in 29 patients (63 ± 11 years) who were alive at 5 years after radiotherapy, free of heart disease and available to provide new blood sample. All patients had BNP measurements at baseline. The ΔBNP was measured to analyze the role of marker variations. No patients received chemotherapy. RESULTS: The mean cardiac and ventricle dose were 2.1 ± 1.0 (range 0.02-4.5) Gy and 3.0 ± 1.7 (range 0.02-7.6), respectively. Median value of BNP was 47 pg/mL (interquartile ranges, 26-58.2 pg/mL) at baseline, and 34 pg/mL (interquartile ranges, 17.5-54 pg/mL) at 5 years after radiotherapy. There was no significantly different between two measurements (p = ns). Fifteen (52%) reported an improvement in BNP levels, 1 (3%) no changes and 13 (45%) reported a worsening. There was no correlation between ΔBNP and age (p = ns). When patients were stratified according to the median value of dose-volume data, ΔBNP was significantly higher in patients with increased cardiac Dmean (p = .02) and left ventricle Dmean (p = .009). CONCLUSION: At 5 years after radiotherapy, median plasma BNP levels remained within the normal range, but the delta-BNP levels are directly related to the heart and ventricular dose received.

Ultrasound B-lines for detection of late lung fibrosis in breast cancer patients after radiation therapy.

BACKGROUND AND PURPOSE: Radiation therapy (RT) for breast cancer after conservative surgery can be life-saving but remains associated with significant late side effects, including lung fibrosis, detected by chest CT. Aim of this study was to assess whether lung ultrasound (LUS) may detect late lung fibrosis through the biomarker of B-lines. MATERIALS AND METHODS: We evaluated 30 women (median age 67 years, range 46-80 years) about 3-8 years after RT (follow up 38-101 months, median 58 months) for left (n = 12) or right (n = 18) breast cancer (stage 1, n = 24; stage 2, n = 6), treated with total dose 40.5 - 50.00 Gy with/without boost dose). In all, both treated and contralateral hemithorax were evaluated. LUS was performed and B-lines evaluated with a 28-region antero-lateral scan, from second to fifth intercostal spaces, along the mid-axillary, anterior axillary, mid-clavicular, and parasternal lines. In each space, the B-lines were counted from 0 = black lung to 10 = white lung. The sum of B-lines in all spaces generated the B-line score of each hemithorax. RESULTS: Median B-line score was higher in the irradiated site than in the contralateral control hemithorax (9, 1st-3rd quartiles: 2-23 vs 3, 1st-3rd quartiles: 1-4; P < 0.05). In the treated hemithorax, higher mean lung doses ( > median value of 2.7 Gy) were associated with more B-lines when compared to lower doses (< 2.7 Gy): 9 vs 5, p <0.001. CONCLUSION: RT in female breast cancer survivors is associated with increase in B-lines in the targeted hemithorax, likely due to lung fibrosis, and related to the lung mean dose. LUS can provide a simple "echo-marker" of lung fibrosis.