Local Failure After Accelerated Partial Breast Irradiation with Intraoperative Radiotherapy with Electrons: An Insight into Management and Outcome from an Italian Multicentric Study.

BACKGROUND: The aim of this work is to evaluate pattern of care and clinical outcome in a large series of patients with in-breast recurrence (IBR), after quadrantectomy and intraoperative radiation therapy with electrons (IOERT) as partial breast irradiation. PATIENTS AND METHODS: Patients with IBR after IOERT, treated with salvage surgery ± adjuvant reirradiation (re-RT), were selected from a multiinstitution database. Disease-free survival (DFS), overall survival (OS), cumulative incidence of second IBR, and distant metastases (DM) were estimated. RESULTS: A total of 224/267 patients from seven institutions were included. Primary tumors received 21 Gy. Median time to first IBR was 4.3 years (range 2.6-6.1 years). Salvage mastectomy and repeat quadrantectomy were performed in 135 (60.3%) and 89 (39.7%) patients, followed by adjuvant re-RT in 21/135 (15.5%) and 63/89 (70.8%), respectively. Median follow-up after salvage treatment was 4.1 years. Overall, 5- and 8-year outcomes were as follows: cumulative incidence of second IBR: 8.4% and 14.8%; cumulative incidence of DM: 17.1% and 22.5%; DFS: 67.4% and 52.5%; OS: 89.3% and 74.7%. The risk of second IBR was similar in the salvage mastectomy and repeat quadrantectomy + RT groups [hazard ratio (HR) 1.41, p = 0.566], while salvage mastectomy patients had greater risk of DM (HR 3.15, p = 0.019), as well as poorer DFS (HR 2.13, p = 0.016) and a trend towards worse OS (HR 3.27, p = 0.059). Patients who underwent repeat quadrantectomy alone had worse outcomes (second IBR, HR 5.63, p = 0.006; DFS, HR 3.21, p = 0.003; OS, HR 4.38, p = 0.044) than those adding re-RT. CONCLUSIONS: Repeat quadrantectomy + RT represents an effective salvage approach and achieved local control comparable to that of salvage mastectomy.

Postoperative radiotherapy with volumetric modulated arc therapy of lacrimal gland carcinoma: two case reports and literature review.

AIMS: To evaluate technical issues and clinical outcomes after postoperative volumetric-modulated arc therapy (VMAT) in two cases of malignant lacrimal gland cancer. PATIENTS & METHODS: Patients were treated by postoperative VMAT and post-treatment clinical outcomes were followed-up to 18 months. RESULTS: Dosimetric results were acceptable and acute toxicity was manageable in both patients. No evidence of disease was found at latest follow-up. One patient underwent corneal transplant for central corneal ulceration, experiencing reduction of visual acuity. CONCLUSION: Postoperative VMAT for treatment of lacrimal gland tumors offers improved outcome, with manageable side effects. In the context of photon beam radiotherapy, VMAT emerged as a valuable treatment option for these malignant tumors.

A Customized 3D-Printed Bolus for High-Risk Breast Cancer with Skin Infiltration: A Pilot Study.

BACKGROUND: In high-risk breast cancer patients with skin infiltration, the administration of a uniform dose to superficial tissues is fundamental in order to reduce local skin relapse. A personalized bolus may prevent the potential inadequate dose distribution of a standard bolus due to air gaps between the bolus and the skin. In this pilot study, we introduced into clinical practice the use of a personalized 3D-printed bolus filled with ultrasound transmission gel. METHODS: Seven patients undergoing radiotherapy after mastectomy were selected. A 3D-printed bolus dosimetric assessment was performed with MOSFET dosimeters on an anthropomorphic phantom and, subsequently, on three selected cases with increasing bolus shape irregularity. Acute/late toxicity and local control were assessed. RESULTS: Overall, for the clinical cases, the percentage median difference between the measured and calculated doses was -2.7% (-7.0-4.9%). The median follow-up was 21 months. After two years, one patient showed G2 pain, one patient manifested G1 telangiectasia, one patient showed G1 hyperpigmentation, and two patients had no relevant toxicity. CONCLUSIONS: A personalized 3D-printed bolus filled with ultrasound gel may easily reproduce the standard bolus' consistency and provide accurate coverage of the target area with tolerable acute/late toxicity grades. This is a pilot study, and further investigations are needed.

DNA Damage Response in Early Breast Cancer: A Phase III Cohort in the Phobos Study.

We assessed the impact of DNA damage response and repair (DDR) biomarker expressions in 222 node-positive early breast cancer (BC) patients from a previous Phase III GOIM 9902 trial of adjuvant taxanes. At a median follow-up of 64 months, the original study showed no disease-free survival (DFS) or overall survival (OS) differences with the addition of docetaxel (D) to epirubicine-cyclophosphamide (EC). Immunohistochemistry was employed to assess the expression of DDR phosphoproteins (pATM, pATR, pCHK1, γH2AX, pRPA32, and pWEE1) in tumor tissue, and their association with clinical outcomes was evaluated through the Cox elastic net model. Over an extended follow-up of 234 months, we confirmed no significant differences in DFS or OS between patients treated with EC and those receiving D → EC. A DDR risk score, inversely driven by ATM and ATR expression, emerged as an independent prognostic factor for both DFS (HR = 0.41, p < 0.0001) and OS (HR = 0.61, p = 0.046). Further validation in a public adjuvant BC cohort was possible only for ATM, confirming its protective role. Overall, our findings confirm the potential role of the DDR pathway in BC prognostication and in shaping treatment strategies advocating for an integrated approach, combining molecular markers with clinical-pathological factors.

A Systematic Review on the Impact of Hypofractionated and Stereotactic Radiotherapy on Immune Cell Subpopulations in Cancer Patients.

We investigated how hypofractionated radiotherapy (HFRT) and stereotactic body radiotherapy (SBRT) may impact immune cells in different type of tumors. A systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The PubMed, Embase and Cochrane databases were searched. Overall, 11 studies met the inclusion criteria and were eligible for the present analysis. Both HFRT and SBRT have different impact on lymphocyte subpopulations, confirming their immunomodulatory effect which may have a crucial role in future combined treatment with new emergent therapies such as immunotherapy. Further studies are needed to shed more light on this emerging topic to ultimately improve patient care, treatment and clinical benefits for cancer patients.

Stereotactic partial breast irradiation in primary breast cancer: A comprehensive review of the current status and future directions.

In selected low-risk breast cancer patients, accelerated partial breast irradiation (APBI) may represent an alternative option to the whole breast irradiation to reduce the volume of irradiated breast and total treatment duration. In the last few years, preliminary data from clinical trials showed that stereotactic partial breast radiotherapy may have the advantage to be less invasive compared to other APBI techniques, with preliminary good results in terms of local toxicity and cosmesis: the use of magnetic resonance, fiducial markers in the tumor bed, and new breast devices support both a precise definition of the target and radiation planning. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021257856, identifier CRD42021257856.

Subclinical synovitis in primary Sjögren's syndrome: an ultrasonographic study.

OBJECTIVES: To evaluate, by musculoskeletal ultrasound (MSUS), articular involvement in primary SS (pSS) patients by analysing hand and wrist changes, and to correlate them with clinical evaluation and laboratory tests. METHODS: Thirty-two pSS patients underwent clinical and laboratory examinations, including the SS Disease Damage Index (SSDDI) and the SS Disease Activity Index (SSDAI). MSUS was performed in all patients in both hands and wrists, evaluating the presence of inflammation within joints and periarticular tissues, and the existence of permanent joint damage. For synovial hypertrophy, joint effusion and Doppler signal findings, a semi-quantitative score (0-3) was used indicating the degree of involvement (0 = normal; 1 = mild change; 2 = moderate change; and 3 = severe change). For tenosynovitis and bone erosions, a dichotomous score (0 = absent and 1 = present) was applied. RESULTS: Sonographic signs of synovitis of the radio-ulno-carpal joint were found in 17 (26.5%) out of 64 wrists. Wrist synovitis was found in 12 (37.5%) out of 32 patients. Ultrasonographic examination of the hand did not show significant changes. A statistically significant correlation was found between SSDDI score and the degree of sonographic signs of synovial proliferation in the wrist (P = 0.04). The correlation between the incidence of clinical involvement and the presence of pathological ultrasonographic findings was not significant. Patients with synovitis had a higher median age and higher median SSDDI (P = 0.004). CONCLUSIONS: In pSS patients, MSUS may be considered a useful tool for detecting synovitis since articular involvement can often be silent but correlated with SSDDI.

Winter is over: The use of Artificial Intelligence to individualise radiation therapy for breast cancer.

Artificial intelligence demonstrated its value for automated contouring of organs at risk and target volumes as well as for auto-planning of radiation dose distributions in terms of saving time, increasing consistency, and improving dose-volumes parameters. Future developments include incorporating dose/outcome data to optimise dose distributions with optimal coverage of the high-risk areas, while at the same time limiting doses to low-risk areas. An infinite gradient of volumes and doses to deliver spatially-adjusted radiation can be generated, allowing to avoid unnecessary radiation to organs at risk. Therefore, data about patient-, tumour-, and treatment-related factors have to be combined with dose distributions and outcome-containing databases.

Number of mediastinal lymph nodes as a prognostic factor in PN2 non small cell lung cancer: a single centre experience and review of the literature.

Currently the most important prognostic factor in lung cancer is the stage. In the current lung TNM classification system, N category is defined exclusively by anatomic nodal location though, in other type of tumours, number of lymph nodes is confirmed to be a fundamental prognostic factor. Therefore we evaluated the number of mediastinal lymph nodes as a prognostic factor in locally advanced NSCLC after multimodality treatment, observing a significant effect of the number of lymph nodes in terms of OS (p<0.01) and DFS (p<0.001): patients with a low number of positive mediastinal nodes have a better prognosis.

Multiple bone metastases from glioblastoma multiforme without local brain relapse: a case report and review of the literature.

Extracranial metastases from glioblastoma multiforme (GBM) are a very rare event, even if an increasing incidence has been documented. We report the case of a young woman with primary GBM who developed bone metastases without local brain relapse. Because of persistent headache and visual disturbances, in March 2011 the patient underwent magnetic resonance imaging (MRI) evidencing a temporoparietal mass, which was surgically resected. Histology revealed GBM. She was given concomitant chemoradiotherapy according to the Stupp regimen. After a 4-week break, the patient received 6 cycles of adjuvant temozolomide according to the standard 5-day schedule every 28 days. In December 2011 she complained of progressive low back pain, and MRI showed multiple bone metastases from primary GBM, confirmed by histology. Cases of metastatic GBM in concurrence with a primary brain tumor or local relapse are more common in the literature; only a few cases have been reported where extracranial metastases from GBM occurred without any relapse in the brain. Here we report our experience.

Complete response and long-term survival in malignant pleural mesothelioma: case report.

UNLABELLED: Malignant pleural mesothelioma is a rare tumour. A three-modal strategy, comprising of surgery, radiotherapy and chemotherapy has been shown to be essential for appropriate management. Current literature evidences the importance of radiation therapy in the adjuvant setting for local control of the disease, as part of a multidisciplinary treatment, with increment of progression-free survival rate, but also of disease-free survival. CASE REPORT: At the beginning of 2007, a 26-year-old Peruvian woman was admitted to the hospital referring breathlessness and other non-specific symptoms such as fever and weight loss. After the diagnosis of pleural mesothelioma by thoracoscopic talc insufflation, combined with pleural biopsy, and total body computed tomographic scan, the patient underwent two cycles of neoadjuvant chemotherapy with pemetrexed (500 mg/m(2)) and cisplatin (75 mg/m(2)), followed by an extra-pleural pneumonectomy. After 6 months, the patient was treated with three-dimensional external beam radiation therapy to the left hemithorax. Computed tomographic scans, performed after the ending of the radiotherapy, integrated with positron-emission tomography, were all negative for neoplastic pathology. The patient remains in good health and free from recurrence at four years. CONCLUSION: This clinical case shows a disease-free survival interval of 4 years for malignant pleural mesothelioma. A good staging system and a combined treatment, involving surgery, neoadjuvant chemotherapy and adjuvant radiation therapy, represent a useful strategy not only to contain local disease progression, but even to increase disease-free survival in pleural mesothelioma.