Search Results (18)

Background: Abdominoperineal resection (APR)—the standard surgical procedure for low-lying rectal cancer (LRC)—leads to significant perineal defects, posing considerable reconstruction challenges that, in selected cases, necessitate the use of plastic surgery techniques (flaps). Purpose: To develop valuable decision algorithms for choosing the appropriate surgical plan for the reconstruction of perineal defects. Methods: Our study included 245 LRC cases treated using APR. Guided by the few available publications in the field, we have designed several personalized decisional algorithms for managing perineal defects considering the following factors: preoperative radiotherapy, intraoperative position, surgical technique, perineal defect volume, and quality of tissues and perforators. The algorithms have been improved continuously during the entire period of our study based on the immediate and remote outcomes. Results: In 239 patients following APR, the direct closing procedure was performed versus 6 cases in which we used various types of flaps for perineal reconstruction. Perineal incisional hernia occurred in 12 patients (5.02%) with direct perineal wound closure versus in none of those reconstructed using flaps. Conclusion: The reduced rate of postoperative complications suggests the efficiency of the proposed decisional algorithms; however, more extended studies are required to categorize them as evidence-based management guide tools. Full article

Background: Modern treatment guidelines for women with advanced cervical cancer recommend staging using 2-deoxy-2-[¹⁸F]fluoro-D-glucose positron emission computed tomography ([¹⁸F]FDG-PET/CT). However, the risk of false-positive nodes and therapy-related adverse events requires caution in treatment planning. Using data from the Netherlands Cancer Registry (NCR), we estimated the impact of [¹⁸F]FDG-PET/CT on treatment management in women with locally advanced cervical cancer, i.e., on nodal boosting, field extension, and/or debulking in cases of suspected lymph nodes. Methods: Women diagnosed between 2009 and 2017, who received chemoradiotherapy for International Federation of Gynaecology and Obstetrics (2009) stage IB2, IIA2-IVB cervical cancer with an [¹⁸F]FDG-positive node, were retrospectively selected from the NCR database. Patients with pathological nodal examination before treatment were excluded. The frequency of nodal boosting, extended-field radiotherapy, and debulking procedures applied to patients with [¹⁸F]FDG-positive lymph nodes was evaluated. Results: Among the 434 eligible patients with [¹⁸F]FDG-positive nodes, 380 (88%) received interventions targeting these lymph nodes: 84% of these 380 patients received nodal boosting, 78% extended-field radiotherapy, and 12% debulking surgery. [¹⁸F]FDG-positive nodes in patients receiving these treatments were more likely to be classified as suspicious than inconclusive (p = 0.009), located in the para-aortic region (p < 0.001), and larger (p < 0.001) than in patients who did not receive these treatments. Conclusion: While existing guidelines advocate [¹⁸F]FDG-PET/CT-guided treatment planning for the management of advanced cervical cancer, this study highlights that not all cases of [¹⁸F]FDG-positive nodes received an intervention, possibly due to the risk of false-positive results. Improvement of nodal staging may reduce suboptimal treatment planning. Full article

The landscape of cranial base surgery has undergone monumental transformations over the past several decades. This article serves as a comprehensive survey, detailing both the historical and current techniques and technologies that have propelled this field into an era of unprecedented capabilities and sophistication. In the prologue, we traverse the historical evolution from rudimentary interventions to the state-of-the-art neurosurgical methodologies that define today’s practice. Subsequent sections delve into the anatomical complexities of the anterior, middle, and posterior cranial fossa, shedding light on the intricacies that dictate surgical approaches. In a section dedicated to advanced techniques and modalities, we explore cutting-edge evolutions in minimally invasive procedures, pituitary surgery, and cranial base reconstruction. Here, we highlight the seamless integration of endocrinology, biomaterial science, and engineering into neurosurgical craftsmanship. The article emphasizes the paradigm shift towards “Functionally” Guided Surgery facilitated by intraoperative neuromonitoring. We explore its historical origins, current technologies, and its invaluable role in tailoring surgical interventions across diverse pathologies. Additionally, the digital era’s contributions to cranial base surgery are examined. This includes breakthroughs in endoscopic technology, robotics, augmented reality, and the potential of machine learning and AI-assisted diagnostic and surgical planning. The discussion extends to radiosurgery and radiotherapy, focusing on the harmonization of precision and efficacy through advanced modalities such as Gamma Knife and CyberKnife. The article also evaluates newer protocols that optimize tumor control while preserving neural structures. In acknowledging the holistic nature of cranial base surgery, we advocate for an interdisciplinary approach. The ecosystem of this surgical field is presented as an amalgamation of various medical disciplines, including neurology, radiology, oncology, and rehabilitation, and is further enriched by insights from patient narratives and quality-of-life metrics. The epilogue contemplates future challenges and opportunities, pinpointing potential breakthroughs in stem cell research, regenerative medicine, and genomic tailoring. Ultimately, the article reaffirms the ethos of continuous learning, global collaboration, and patient-first principles, projecting an optimistic trajectory for the field of cranial base surgery in the coming decade. Full article

Antioxidants in cancer therapy have been a hot topic in the medical field for 20 years. Antioxidants are able to reduce the risk of cancer formation by neutralizing free radicals. Protons (H+) and molecular hydrogen (H2) interact in the cell and are essential in a wide variety of processes. The antioxidant, anti-inflammatory, and antiapoptotic effects of H2 have been studied in numerous experimental and clinical studies. Experimental data indicate that H2 is an antitumor agent in the treatment of glioblastoma (GBM). In vivo H2 inhalation could suppress the growth of GBM tumors, thereby extending the survival of mice with GBM. The sphere-forming ability of glioma cells was suppressed by hydrogen treatment. In addition, H2 treatment also suppressed the migration, invasion, and colony-forming ability of glioma cells. Proton therapy and proton beam radiotherapy offer some advantages over other modern conformal photon-based therapies when used in the treatment of central nervous system malignancies. Full article

The interest in fiber Bragg gratings dosimeters for radiotherapy dosimetry lies in their (i) submillimeter size, (ii) multi-points dose measurements, and (iii) customizable spatial resolution. However, since the radiation measurement relies on the thermal expansion of the surrounding polymer coating, such sensors are strongly temperature dependent, which needs to be accounted for; otherwise, the errors on measurements can be higher than the measurements themselves. In this paper, we test and compare four techniques for temperature compensation: two types of dual grating techniques using different coatings, a pre-irradiation and post-irradiation temperature drift technique, which is used for calorimetry, and finally, we developed a real-time interpolated temperature gradient for the multi-points dosimetry technique. We show that, over these four tested techniques, the last one outperforms the others and allows for real-time temperature correction when an array of 13 fiber Bragg gratings spatially extending over the irradiation zone is used. For a 20 Gy irradiation, this technique reduces the measurement errors from 200% to about 10%, making it suitable for a radiotherapy dose range. Temperature correction for medical low-dose range dosimetry is a first in our field and is essential for clinical FBG dosimetry applications. Full article

Tumor regression throughout treatment would induce organ movement, but little is known of this in the esophagus. To achieve successful tumor regression, radiation therapy requires several weeks of radiation to be delivered accurately to the tumor. Usually, a 5–10 mm margin is allowed for set-up error and internal organ motion. Our case exhibited an unexpectedly large movement of the esophagus across the aorta with tumor regression that extended outside the margin and thus outside the radiotherapy field. These movements may affect subsequent invasive procedures or treatment during cancer therapy. After the unexpected large movement of the esophagus due to tumor regression, we revised the radiotherapy plan to reflect the new esophageal position. This implied that regular imaging and close monitoring are required during treatment of esophageal cancer. Full article

Background: Concepts improving local tumor control in high-grade glioma (HGG) are desperately needed. The aim of this study is to report an extended series of cases treated with a combination of 5-ALA-fluorescence-guided resection (FGR) and intracavitary thermotherapy with superparamagnetic iron oxide nanoparticles (SPION). Methods: We conducted a single-center retrospective review of all recurrent HGG treated with FGR and intracavitary thermotherapy (n = 18). Patients underwent six hyperthermia sessions in an alternating magnetic field and received additional adjuvant therapies on a case-by-case basis. Results: Nine patients were treated for first tumor recurrence; all other patients had suffered at least two recurrences. Nine patients received combined radiotherapy and thermotherapy. The median progression-free survival was 5.5 (95% CI: 4.67–6.13) months and median overall survival was 9.5 (95% CI: 7.12–11.79) months. No major side effects were observed during active treatment. Thirteen patients (72%) developed cerebral edema and more clinical symptoms during follow-up and were initially treated with dexamethasone. Six (33%) of these patients underwent surgical removal of nanoparticles due to refractory edema. Conclusions: The combination of FGR and intracavitary thermotherapy with SPION provides a new treatment option for improving local tumor control in recurrent HGG. The development of cerebral edema is a major issue requiring further refinements of the treatment protocol. Full article

Background: The increase of lymphoma patient survival led to a modification of the incidence of long-term sequelae, including second malignancies (SM). Several groups have dealt with the incidence of SM, according to the primary treatment; however, a standardized approach for the early detection and screening of SM in the population of lymphoma survivors should be implemented. Methods: A systematic review was conducted by Fondazione Italiana Linfomi (FIL), in order to define the incidence of SM, the impact of modern radiotherapy on SM risk, and the usefulness of tailored follow-up and screening strategies for early diagnosis of SM. Classical Hodgkin lymphoma (cHL) and diffuse large B-cell lymphoma (DLBCL) survivors were investigated. The MEDLINE, Embase, and Cochrane Library databases were checked for relevant reports published up to January 2020. The selection process was reported according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. Results: A total of 27 full-text manuscripts resulted as eligible for the analysis. The incidence of SM in cHL patients treated with ABVD was higher compared to the general population and was even higher in patients treated with intensified regimens. The risk increased over time, as well as after 10–15 years from therapy, and was augmented by radiotherapy exposure. In DLBCL, more intensive regimens (i.e., R-CHOEP or R-MegaCHOEP) vs. R-CHOP were associated with a higher SM incidence. Salvage chemotherapy and autologous stem cell transplants increased the risk of SM in both cHL and DLBCL cohorts. A lower incidence of SM, particularly of breast cancer (BC), was shown in cohorts of cHL survivors treated with reduced radiation volumes and doses (involved fields vs. extended fields), but robust trials are still lacking. Considering the advantage of a structured screening for early detection of SM, all the included studies regarded cHL survivors and screening strategy for early BC detection. Moreover, the authors discuss additional papers, to guide the early diagnosis of lung, colorectal, skin, and thyroid cancer in patients at risk due to family history, drug or RT exposure, or unhealthy lifestyles. These screening strategies all passed through patient awareness. Conclusion: A modern approach to chemotherapy and radiotherapy led to a lower risk of SM, which should be confirmed over time. Early detection of secondary cancers could be achieved through a tailored screening program, according to the individual risk profile. Full article

The peculiar and rare clinical condition below clearly requires a customized care approach in the context of personalized medicine. An 80-year-old female patient who was subjected in 2018 to surgical removal of a cutaneous Merkel cell carcinoma (MCC) nodule located on the posterior surface of the left thigh and to three subsequent palliative radiotherapy treatments developed a fourth relapse in October 2020, with fifteen nodular metastases located in the left thigh and leg. Since the overall macroscopic disease was still exclusively regionally located and microscopic spread was likely extended also to clinically negative skin of the thigh and leg, we performed an irradiation of the whole left lower extremity. For this purpose the total target (65.5 cm) was divided into three sub-volumes. Dose prescription was 30 Gy in 15 daily fractions. A sequential boost of 10 Gy in 5 daily fractions was planned for macroscopic nodules. Plans were calculated by means of volumetric modulated arc therapy (VMAT) with the field overlap technique. Thanks to this, we obtained a homogeneous dose distribution in the field junction region; avoidance structures were delineated in the central part of the thigh and leg with the aim of achieving an optimal superficial dose painting and to reduce bone exposure to radiation. This case study demonstrates that VMAT allows for a good dose coverage for circumferential cutaneous targets while sparing deeper organs at risk. A reproducible image-guided set-up is fundamental for an accurate and safe dose delivery. However, local treatments such as radiotherapy for very advanced MCC of the lower extremities might have limited impact due to the high probability of systemic progression, as illustrated in this case. Radiation is confirmed as being effective in preventing MCC nodule progression toward skin wounding. Full article

FLASH radiotherapy is a rapidly developing field which promises improved normal tissue protection compared to conventional irradiation and no compromise on tumour control. The transient hypoxic state induced by the depletion of oxygen at high dose rates provides one possible explanation. However, studies have mostly focused on uniform fields of dose and there is a lack of investigation into the spatial and temporal variation of dose from proton pencil-beam scanning (PBS). A model of oxygen reaction and diffusion in tissue has been extended to simulate proton PBS delivery and its impact on oxygen levels. This provides a tool to predict oxygen effects from various PBS treatments, and explore potential delivery strategies. Here we present a number of case applications to demonstrate the use of this tool for FLASH-related investigations. We show that levels of oxygen depletion could vary significantly across a large parameter space for PBS treatments, and highlight the need for in silico models such as this to aid in the development and optimisation of FLASH radiotherapy. Full article

Radiation-induced emesis (RIE) is usually noted during abdominal-pelvic radiotherapy. In gynecological malignancies, it is usually noted in para-aortic but not whole-pelvic irradiation. Irradiated small bowel (SB) may be associated with RIE. The significance of SB dosimetry remains unclear. Dosimetric and non-dosimetric factors were evaluated and correlated with RIE in 45 patients with gynecological malignancies undergoing extended-field radiotherapy (EFRT) (median 45 Gy) from 2006 to 2021. Early-onset RIE (within 72 h after the first fraction of EFRT) was noted in 10 of 12 RIE patients. RIE was significantly associated with the SB mean dose. The RIE rates were 58.3% and 15.2% (p = 0.007) in patients with a low (<63%) and high (≥63%) SB mean dose. Logistic regression revealed that the SB mean dose remained the independent factor of overall RIE (p = 0.049) and early-onset RIE (p = 0.014). Therefore, constraint of the SB mean dose limited to less than 63% of the prescribed dose is suggested to decrease RIE. Full article

Glioblastoma multiforme (GBM) is a highly malignant primary brain tumor. The current standard of care for GBM is the Stupp protocol which includes surgical resection, followed by radiotherapy concomitant with the DNA alkylator temozolomide; however, survival under this treatment regimen is an abysmal 12–18 months. New and emerging treatments include the application of a physical device, non-invasive ‘tumor treating fields’ (TTFs), including its concomitant use with standard of care; and varied vaccines and immunotherapeutics being trialed. Some of these approaches have extended life by a few months over standard of care, but in some cases are only available for a minority of GBM patients. Extensive activity is also underway to repurpose and reposition therapeutics for GBM, either alone or in combination with the standard of care. In this review, we present select molecules that target different pathways and are at various stages of clinical translation as case studies to illustrate the rationale for their repurposing-repositioning and potential clinical use. Full article

(1) Background: To assess the role of postoperative external beam radiotherapy (pEBRT) on locoregional failure (LRF) for patients with locally advanced high-risk non-anaplastic thyroid carcinoma (naTC) at primary event or relapse. (2) Methods: Between 1995 and 2015, postoperative naTC patients with a theoretical indication for EBRT were included based on criteria that were common to American-British-French current guidelines, i.e., pT3-4, pN+, gross or microscopic residual disease. Inverse probability of treatment weighting (IPTW) after multiple imputation was used to reduce selection biases. (3) Results: Of 254 naTC patients, 216 patients underwent pEBRT (106 de novo, 110 at relapse, median dose 60 Gy) and 38 underwent surgery only. pEBRT patients had more gross residual disease, a major prognostic factor (p = 0.027) but less perineural invasion (p = 0.008) or lymphovascular emboli (p = 0.009). pEBRT patients more frequently underwent radioiodine therapy (p = 0.026). The 10-year cumulative incidence of LRF was 56% (95% CI, 32–74%) in operated patients, and 23% (95% CI, 17–30%) in pEBRT patients. After IPTW method, pEBRT reduced the risk of LRF (hazard ratio 0.30; 95% CI [0.18–0.49], p < 0.001), but had no impact on OS. In the pEBRT group, non-Intensity Modulated RadioTherapy (IMRT) plans and interruption of the radiotherapy were associated with poorer survival, while extended versus limited field strategy and dose were not. (4) Conclusions: In naTC patients who have pT3-4, pN+ disease or R1-2 resection, pEBRT improved LRF. Limited-field IMRT is preferred. Full article

Background: Pre-operative radiosurgery (SRS) preceding the resection of brain metastases promises to circumvent limitations of post-operative cavity SRS. It minimizes uncertainties regarding delineation and safety margins and could reduce dose exposure of the healthy brain (HB). Methods: We performed a systematic treatment plan comparison on 24 patients who received post-operative radiosurgery of the resection cavity at our institution. Comparative treatment plans were calculated for hypofractionated stereotactic radiotherapy (7 × 5 Gray (Gy)) in a hypothetical pre-operative (pre-op) and two post-operative scenarios, either with (extended field, post-op-E) or without the surgical tract (involved field, post-op-I). Detailed volumetric comparison of the resulting target volumes was performed, as well as dosimetric comparison focusing on targets and the HB. Results: The resection cavity was significantly smaller and different in morphology from the pre-operative lesion, yielding a low Dice Similarity Coefficient (DSC) of 53% (p = 0.019). Post-op-I and post-op-E targets showed high similarity (DSC = 93%), and including the surgical tract moderately enlarged resulting median target size (18.58 ccm vs. 22.89 ccm, p < 0.001). Dosimetric analysis favored the pre-operative treatment setting since it significantly decreased relevant dose exposure of the HB (Median volume receiving 28 Gy: 6.79 vs. 10.79 for pre-op vs. post-op-E, p < 0.001). Dosimetrically, pre-operative SRS is a promising alternative to post-operative cavity irradiation that could furthermore offer practical benefits regarding delineation and treatment planning. Comparative trials are required to evaluate potential clinical advantages of this approach. Full article

Background: In patients with advanced-stage endometrial carcinoma (eca), extended-field radiotherapy (efrt) is traditionally delivered by the 3-dimensional conformal (3d-crt) 4-field box technique. In recent years, the use of intensity-modulated radiotherapy (imrt) in gynecologic cancers has increased. We compared the delivery of efrt by the 3d-crt and contemporary imrt techniques. Methods: After surgical staging and adjuvant chemotherapy in 38 eca patients, efrt was delivered by either imrt or 3d-crt. Doses to the organs at risk, side effects, and outcomes were compared between the techniques. Results: Of the 38 eca patients, 33 were stage iiic, and 5 were stage ivb. In the imrt group, maximal doses to rectum, small intestine, and bladder were significantly higher, and mean dose to bladder was lower (p < 0.0001). Most acute gastrointestinal, genitourinary, and hematologic side effects were grade i or ii and were comparable between the groups. In long-term follow-up, only grade 1 cystitis at 3 months was statistically higher in the imrt patients. No grade iii or iv gastrointestinal or genitourinary toxicities were observed. No statistically significant differences in overall and disease-free survival or recurrence rates were observed between the techniques. Conclusions: In advanced eca patients, imrt is a safe and effective technique for delivering efrt to the pelvis and para-aortic region, and it is comparable to the 3d-crt 4-field box technique in both side effects and efficacy. For centres in which imrt is not readily available, 3d-crt is a valid alternative. Full article