Osteoradionecrosis incidence in pre-radiation teeth extractions: A prospective study.

AIMS: To evaluate osteoradionecrosis (ORN) incidence in a cohort of patients undergoing tooth extraction (TE) before radiotherapy (RT) for head and neck cancers. METHODS: The study protocol was approved by the Ethics Committee of Università Cattolica del Sacro Cuore (ID-2132) and registered at clinicaltrials.gov (ID: NCT04009161). TE was performed in case of signs of pericoronitis, periapical lesions, restorative impossibility, severe periodontitis. ORN was defined as exposed bone at an unhealed post-extraction socket in the absence of oncological recurrence. The RT plans were reviewed, and each post-extractive socket was contoured to calculate the received radiation dose. RESULTS: In total, 156 patients with 610 TE were enrolled. The mean follow-up was 567 days. ORN was diagnosed in four patients (2.6% of patients and 0.7% of TE). Need for osteotomy and radiation dose at the extraction site were associated with ORN (OR for osteotomy: 21.9, 95% CI: 2.17-222.2, p = 0.009; OR for RT dose: 1.1, 95% CI: 1-1.15, p = 0.05). CONCLUSIONS: TE appears to be a significant risk factor for ORN, particularly when osteotomy is required, and post-extraction sockets receive a high RT dosage. This study proposes a decision-making algorithm for TE and outlines a straightforward surgical protocol.

Novel unconventional radiotherapy techniques: Current status and future perspectives - Report from the 2nd international radiation oncology online seminar.

•Improvement of therapeutic ratio by novel unconventional radiotherapy approaches.•Immunomodulation using high-dose spatially fractionated radiotherapy.•Boosting radiation anti-tumor effects by adding an immune-mediated cell killing.

Spatially fractionated radiotherapy (SFRT) targeting the hypoxic tumor segment for the intentional induction of non-targeted effects: An in silico study to exploit a new treatment paradigm.

INTRODUCTION: The possibility of intentionally triggering non targeted effects (NTEs) using spatially fractionated radiotherapy (SFRT) alone or combined with immunotherapy is an intriguing and fascinating area of research. Among different techniques for SFRT, stereotactic body radiotherapy targeting exclusively the central hypoxic segment of bulky tumors, (SBRT-PATHY) might trigger immunogenic cell death more efficiently. This in silico study aims to identify the best possible dosimetric trade-off for prescribing SFRT with volumetric modulated arc (VMAT) based stereotactic radiotherapy (SRT). MATERIAL AND METHODS: Eight spherical volumes defined "Gross Tumor Volumes" (GTVs) were generated with diameters of 3-10 cm (with incremental steps of 1 cm), simulating tumor lesions. The inner third part of each GTV (GTVcentral) was selected to simulate the central hypoxic area and a ring structure was derived around it to simulate the tumor periphery (GTVperipheral). Volumetric modulated arc radiation treatment (VMAT) plans were calculated to deliver a single fraction of 10 Gy to each GTVcentral with different dose prescription methods: target mean and isodose driven (40, 50, 60, 70, 80 and 90%).The volume of GTVperipheral receiving less than 2 Gy was recorded as dosimetric performance indicator. RESULTS: 56 possible dosimetric scenarios were analyzed. The largest percentage of GTVperipheral spared from the dose of 2 Gy was achieved with dose prescription methods to the 70% isodose line for lesions smaller than 6 cm (range 42.9-48.4%) and to the target mean for larger ones (range 52.9-64.5%). CONCLUSIONS: Optimizing the dose prescription method may reduce the dose to tumor periphery in VMAT-based SFRT, thus potentially sparing tumor infiltrating immune cells. The optimal method may vary according to the size of the lesion. This should be taken into account when designing prospective trials using SFRT.

Abscopal effect and interventional oncology: state of art and future perspectives.

OBJECTIVE: The concept of abscopal effect is currently gaining importance in modern oncology, as the link between localized irradiation and triggering of immuno-mediated systemic antitumor effects is getting clearer. An increasing number of reports documented abscopal effect mainly after external beam irradiation. Interventional radiotherapy (IR) may be used with sealed radioactive sources as brachytherapy (BT) or with unsealed radioactive sources as transarterial radioembolization (TARE). The aim of this paper is to review the existing clinical IR data and discuss the mechanisms of the abscopal effect. MATERIALS AND METHODS: A systematic research of the main bibliographic databases (PubMed, WOS, Scopus, and Google Scholar) from the earliest possible date through August 2019 was performed. The search strategy was based on the terms "abscopal effect", "interventional radiotherapy", "brachytherapy" and "TARE". RESULTS: Thirteen titles were identified. Three papers met inclusion criteria and were included in the review. All of them were case reports. CONCLUSIONS: Even though there are still scarce data in literature regarding the association of locoregional interventional treatments with the abscopal effect, this review demonstrates that the immunomodulatory theories, which have been widely used so far for external beam radiotherapy (EBRT), may be actually considered valid also in the contest of IR.

Organs at risk's tolerance and dose limits for head and neck cancer re-irradiation: A literature review.

Re-irradiation is becoming an established treatment option for recurrent or second primary head and neck cancer(HNC). However, acute and long-term RT-related toxicities could dramatically impact patients' quality of life. Due to the sparse literature regarding HNC re-irradiation, data on tolerance doses for various organs at risk (OARs) are scarce. Our aim was to systematically review the clinical literature regarding HNC re-irradiation, focusing on treatment toxicity, OARs tolerance, and dose limit recommendations. Thirty-nine studies (three randomized, five prospective, 31 retrospective) including 3766 patients were selected. The median interval time between the first course and re-irradiation was 28  months (range, 6-90). In 1043 (27.6%) patients, postoperative re-irradiation was performed. Re-irradiation doses ranged from 30 Gy in 3 fractions using stereotactic technique to 72 Gy in conventional fractionation using intensity-modulated radiotherapy. Pooled acute and late toxicityrates ≥G3 were 32% and 29.3%, respectively. The most common grade 3-4 toxic effects were radionecrosis, dysphagia requiring feeding tube placement and trismus. In 156 (4.1%) patients, carotid blowout was reported. Recommendations for limiting toxicity included the time interval between radiation treatments, the fractionation schedules, and the re-irradiation treatment volumes. Cumulative dose limit suggestions were found and discussed for the carotid arteries, temporal lobes, and mandible.

Isthmocele in a retroflexed uterus: a report of an unrecognized case.

The term "isthmocele" refers to a niche on the anterior wall of the uterine isthmus or of the cervical canal at the site of a previous cesarean delivery scar. Such anatomic defect can cause many gynecologic sequelae that only recently have being identified and described. Hysteroscopy is commonly considered the gold standard for the diagnosis and also for the treatment, at least in the case of defects of small size. The authors described the case of a 37-year-old woman who underwent a cesarean section (CS) seven years before, with a long lasting history of menstrual irregularities, and pelvic pain increasing during menstruation at the hypogastric level. Magnetic resonance imaging (MRI) showed an exceptionally large isthmocele on the anterior wall of a retroflexed uterus which was otherwise misinterpreted as the uterine cavity filled with menstrual blood during a previous hysteroscopy (HSC). Although exceptional, this case highlights the possibility that a large sized isthmocele in a retroflexed uterus could be misinterpreted as the uterine cavity filled by menstrual blood at HSC. In this case MRI definitely clarified the diagnosis.

Planning comparison between standard and conformal 3D techniques in post-operative radiotherapy of gastric cancer: a systematic review.

The objective of this study was to establish the impact of three-dimensional conformal radiotherapy (3D-CRT) technique in post-operative radiotherapy of gastric cancer. A bibliographical research was performed using the PubMed. On the database, Search was carried out using Medical Subject Heading (MeSH) database; the algorithm for search was ''Radiotherapy" (MeSH) AND ''Stomach Neoplasms" (MeSH). Only planning comparative studies on conformal techniques vs standard techniques in post-operative radiotherapy of gastric cancer were included in the review process. We identified 185 papers, five of them fulfilling the inclusion criteria. A great inhomogeneity was observed regarding the analysed dosimetric end points. Three of the five studies reported a benefit in favour of 3D-CRT for target irradiation despite a minimal advantage in most cases. The liver was better spared from irradiation by the traditional technique in all studies. No univocal result was obtained for the right kidney: the traditional technique performed better in two studies, 3D-CRT yielded better results in two others, whereas in the fifth study, each technique was either better or worse according to the different considered end point. 3D-CRT, however, allowed for better sparing of the left kidney in four studies. There is no absolute reason to prefer 3D-CRT with multiple beams in every patient. It may be preferable to choose the technique based on individual patient characteristics. Because there is no proof of superiority for 3D-CRT, there is no absolute reason to exclude patients who are treated in centres equipped with only the two-dimensional technique from the potential benefit of post-operative chemoradiation.

Mammography before post-operative radiotherapy in conservatively managed breast cancer patients: is it useful?

OBJECTIVE: The aim of this study was to evaluate the role of bilateral mammography undertaken before adjuvant radiotherapy in patients with conservatively managed invasive carcinoma of the breast. METHODS: Patients with invasive breast cancer referred to the Radiotherapy Unit of the Università Cattolica del Sacro Cuore, in Campobasso, Italy, between March 2002 and September 2006 were retrospectively reviewed. Patients were referred to our facility from other local and regional hospitals where they received breast-conserving surgery and adjuvant chemotherapy. They presented to our department for post-operative whole-breast radiotherapy. All patients underwent physical examination and bilateral mammography prior to adjuvant irradiation. RESULTS: 201 patients met the selection criteria as delineated. Of these 201 patients who underwent pre-radiotherapy mammography, 3 had suspicious findings on mammography. In two of those cases, the histopathological examination confirmed the presence of residual disease within the residual mammary gland. In one case, the pre-radiotherapy mammogram allowed for the detection of disease persistence which was not otherwise appreciated on physical exam. In the other case, the diagnostic imaging confirmed only the findings of the physical exam. In both cases of residual disease, the tumour was found elsewhere in the breast and not at the primary site. In one patient, the radiological re-assessment led to a false-positive result. No cases of contralateral synchronous breast cancer were observed. The overall adjunctive cost of this strategy including a routine mammography besides the clinical visit was €7012 for all patients. CONCLUSIONS: No clear recommendation exists regarding post-operative mammography before adjuvant radiotherapy. In our experience, this strategy allowed for the detection of gross disease persistence after surgery which was not appreciated at clinical examination in 1 case out of 201. In this patient, adjuvant radiotherapy up to a total dose of 50 Gy would have been inadequate. Given the low cost of mammography, further investigation about its role in pre-radiotherapy evaluation is warranted.

Volumetric modulated arc therapy with simultaneous integrated boost for locally advanced rectal cancer.

AIMS: To report the feasibility of volumetric modulated arc therapy (VMAT) for neoadjuvant radiotherapy in locally advanced rectal cancer in a dose-escalation protocol and simultaneous integrated boost (SIB) approach. Moreover, the VMAT technique was compared with three-dimensional conformal radiotherapy (3D-CRT) and fixed-field intensity modulated radiotherapy (IMRT), in terms of target coverage and irradiation of organs at risk. MATERIALS AND METHODS: Eight patients with locally advanced rectal cancer were treated with the SIB-VMAT technique. The VMAT plans were compared with 3D-CRT and IMRT techniques in terms of several clinically dosimetric parameters. The number of monitor units and the delivery time were analysed to score the treatment efficiency. All plans were verified in a dedicated solid water phantom using a two-dimensional array of ionisation chambers. RESULTS: All techniques meet the prescription goal for planning target volume coverage, with VMAT showing the highest level of conformality. VMAT is associated with 40, 53 and 58% reduction in the percentage of volume of small bowel irradiated to 30, 40 and 50Gy, compared with 3D-CRT. No significant differences were found with respect to SIB-IMRT. VMAT plans showed a significant reduction of monitor units by nearly 20% with respect to IMRT and reduced treatment time from 14 to 5min for a single fraction. CONCLUSIONS: SIB-VMAT plans can be planned and carried out with high quality and efficiency for rectal cancer, providing similar sparing of organs at risk to SIB-IMRT and resulting in the most efficient treatment option. SIB-VMAT is currently our standard approach for radiotherapy of locally advanced rectal cancer.

A novel route to the vinyl sulfide nine-membered macrocycle moiety of Griseoviridin.

The synthetic potentialities of cerium(III) chloride are demonstrated by the synthesis of a nine-membered ring heterocycle component of Griseoviridin (3) in optically active form. The key step involves the stereospecific formation of the alpha-carbalkoxy alkenyl sulfide moiety using a combination system of cerium(III) chloride heptahydrate and sodium iodide.