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Background: To identify optimal therapeutic strategies for managing fungating, large or ulcerating breast tumors and highlight existing gaps in the literature., Methods: We conducted a systematic search of Medline, Embase, APA, PsycInfo, CAB abstracts, Scopus, and Web of Science from inception to June 30, 2024, including studies on patients with fungating, large, or ulcerating breast cancers., Results: The search identified 7917 studies, with 79 meeting the inclusion criteria: 62 case reports, 7 case series, and 10 cohort studies. Owing to high heterogeneity, a narrative synthesis was performed, categorizing treatment by year, molecular subtype, histology, and staging. We found that treatment modalities increased, from an average of two in luminal-B cancers to three in HER2-positive cases, with over half achieving complete response. Triple-negative breast cancers averaged two modalities, with around half showing only partial response. Cohort analysis revealed a significant positive correlation between metastasis rate and radiotherapy use (Spearman's rho = 0.828, p = 0.042) and between chemotherapy and hormonal therapy use (rho = 0.69, p = 0.04). Median survival was positively correlated with surgical treatment (rho = 0.82, p = 0.046)., Conclusions: Local treatment is crucial for symptomatic palliation in fungating or ulcerating breast tumors, and histology should guide therapeutic choices. While local treatments remain primary, emerging systemic therapies show promise and may soon become first-line options. As the first systematic review on this topic, our study faced considerable source heterogeneity, precluding a meta-analysis. Instead, we analyzed treatment trends by demographics and tumor characteristics, providing a comprehensive overview and encouraging further research in this area., Competing Interests: Declaration of competing interest None declared., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Aims: To investigate whether the addition of radiotherapy could be an appropriate option to delay the time-to-next systemic treatment (TTNsT) in patients with oligoprogressive solid tumors who had acquired or innate resistance to immune checkpoint inhibitors (ICIs)., Material and Methods: Patients with oligoprogressive disease treated with ICIs and radiotherapy at our Institute from January 2019 to June 2023 were retrospectively identified. Patients were stratified as primary or secondary immunorefractory according to the time of onset of ICI resistance. TTNsT and Time-To-Resistance (TTR) were the primary outcomes. Secondary outcomes included: post-radiotherapy first progression-free survival (pR-PFS), Local Control (LC), Overall Survival (OS), and treatment-related toxicities. In addition, out-of-field effects (such as the abscopal effect) of radiotherapy have been hypothesized. The survival rates were analyzed using the Kaplan-Meier method and long-rank test., Results: 40 out of 105 screened patients with oligoprogressive disease met the inclusion criteria. Of these, 28 had an acquired drug resistance while 12 had an innate drug resistance. Radiotherapy was offered as a local treatment approach in all patients. RT techniques were classified into three regimens: standard palliative hypofractionated radiotherapy (hypo-RT), stereotactic radiotherapy (SRS/SBRT), and lattice radiotherapy (LRT). After a median follow-up of 22.5 months, the median TTR was 4 months (range 3-4) in patients with innate resistance vs 14 months (range 7-36) in patients with acquired resistance. Median TTNsT among patients with acquired and those with innate resistance was not reached (NR) vs 24 months (range 7-72). Overall, only six patients suffered from a local failure. Although out-of-field effects of radiotherapy were hypothesized, we were unable to record them as they did not occur during the observation period. Regardless of the radiation dose, there was no observable ≥ Grade 2 acute or late treatment-related toxicity., Conclusion: Our preliminary results seem to confirm that the integration of radiotherapy and ICIs may allow for the continuation of systemic therapy beyond progression, which can have a subsequent benefit in terms of survival outcomes even in patients with innate resistance., (© 2024. The Author(s).)

We have read with great interest the recent paper by Grigsby-Rocca et al regarding recurrent pleomorphic xanthoastrocytoma (PXA) with leptomeningeal dissemination. While acknowledging the challenges in managing such cases, we wish to highlight the role of radiotherapy for symptom palliation and potential life extension. We report a case of a 27-year-old woman with recurrent anaplastic PXA and diffuse leptomeningeal spread, who was offered radiotherapy to the spinal axis. Initially presenting with headaches and seizures, she underwent surgical excision, postoperative radiotherapy, and temozolomide. Despite initial disease control, subsequent recurrences required additional surgeries and systemic therapies. With disease progression to leptomeningeal spread, radiotherapy was administered, resulting in clinical stability. This case underscores the importance of considering palliative radiotherapy to improve quality of life and potentially prolong survival in patients with recurrent PXA and leptomeningeal dissemination., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Background: This multicentric, retrospective study investigated the use of stereotactic body radiotherapy (SBRT) in patients (pts) with metastatic renal cell carcinoma (mRCC) who experienced oligoprogression during a combination therapy with an immune checkpoint inhibitor (ICI) and a tyrosine-kinase inhibitor (TKI)., Methods: We retrospectively evaluated 34 pts affected by oligoprogressive RCC treated with an ICI-TKI combination between January 2020 and December 2023. SBRT was delivered to each site of oligoprogressive metastatic disease. After SBRT, pts were given follow-up clinical evaluations. 6-12-18-month local control (LC) rates and median next-line treatment-free survival (NEST-FS) were the primary endpoints. The secondary endpoints were overall response rate (ORR), clinical benefits and safety., Results: After a median follow-up of 24 months, 6-12-18-month LC rates were 100%, 71% and 43%, respectively, and the median NEST-FS was 20 months. ORR was 90%, while clinical benefit was 100%. No > G2 adverse events related to SBRT were recorded., Conclusions: In our study, SBRT for oligoprogressive mRCC turned out to be a safe and useful treatment which was able to preserve current treatment. Further prospective studies are necessary to explore the effects of the ICIs-TKIs combination and SBRT upon oligoprogressive sites in mRCC.

Background/aim: To evaluate the safety and efficacy of lattice radiotherapy (LRT) for large, inoperable breast cancers., Patients and Methods: In this prospective study, patients who underwent LRT for breast tumors that were ulcerating/fungating/extensively eroding the chest wall, and were ineligible/unwilling for surgery, were enrolled from May 2021 to Nov 2023. Baseline Eastern Cooperative Oncology Group (ECOG) status, pre- and post-LRT numerical rating scale (NRS), and post-LRT changes in quality of life (QoL) were recorded. Survival outcomes were reported at 6 months and 1-year. Median rates of survival and dosimetric parameters were calculated. Kaplan-Meier curves for overall survival (OS), cancer-specific survival (CSS), and failure of local control (LC) were constructed., Results: Ten patients (8 females) underwent LRT. The median age was 76 years (range=57-99 years) and the median ECOG performance status was 2.5 (range=1-4). The planned schedule was completed by 9/10 patients, accounting for a 90% compliance rate. Among patients with pain (n=7), NRS rapidly reduced from 7 (range=5-10) to 3 (range=1-6). The median equivalent uniform dose was 0.71 Gy (0.09-1.59 Gy). The actuarial rates of 6-month LC, CSS, and OS were 75%, 89%, and 61%, respectively, with only LC rate changing to 50% at 1 year. Two patients had local relapse at the six-month and 1-year follow-up, respectively, after having achieved a complete response at three months, and two others died of COVID-19 infection and ischemic stroke., Conclusion: LRT was found to be effective and safe in palliating symptoms among patients with large inoperable breast tumors., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: The glioblastomas, aggressive brain tumors with a poor prognosis, have drawn interest in their interaction with the glymphatic system-an emerging brain drainage network. This review explores the relationship between glioblastomas and the glymphatic system, aiming to elucidate their impact on disease progression. The aim of the study was to address the alterations in the glymphatic system in the presence of glioblastoma, and their implications for disease pathogenesis and prognosis., Materials and Methods: Following PRISMA guidelines, we conducted a systematic literature review, identifying studies on the glymphatic system in glioblastomas. Four high-quality studies were selected based on stringent criteria. Data extraction involved categorizing key findings, and thematic analysis uncovered recurring patterns in glymphatic alterations associated with glioblastomas., Results: Out of 356 studies, four meeting the high-quality criteria were included. These studies revealed modifications in lymphatic outflow, factors contributing to glymphatic dysfunction, impediments to cerebrospinal fluid drainage, and emerging roles in glioma management. The findings allow a comprehensive understanding of alterations within the glymphatic system in the presence of glioblastoma., Conclusion: The glymphatic system in glioblastomas exhibits changes, including diminished lymphatic outflow, disruptions and obstacles to fluid drainage, which represent new dimensions in glioma management. These alterations affect drug delivery, immunotherapy, and imaging interpretation. Future research should prioritize elucidating molecular mechanisms, developing therapeutic strategies, optimizing drug delivery, exploring immunotherapy, and translating findings into clinical practice., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Purpose: This systematic review aims to investigate the role of nuclear imaging techniques in detecting incidentalomas and their impact on patient management., Methods: Following PRISMA guidelines, a comprehensive literature search was conducted from February to May 2022. Studies in English involving patients undergoing nuclear medicine studies with incidental tumor findings were included. Data on imaging modalities, incidentaloma characteristics, management changes, and follow-up were extracted and analyzed., Results: Ninety-two studies involving 64.884 patients were included. Incidentalomas were detected in 611 cases (0.9%), with thyroid being the most common site. PET/CT with FDG and choline tracers showed the highest incidentaloma detection rates. Detection of incidentalomas led to a change in therapeutic strategy in 59% of cases. Various radiotracers demonstrated high sensitivity for incidentaloma detection, particularly in neuroendocrine tumors and prostate cancer., Conclusion: Nuclear imaging techniques play a crucial role in detecting incidentalomas, leading to significant changes in patient management. The high sensitivity of these modalities highlights their potential in routine oncology follow-up protocols. Future directions may include enhancing spatial resolution and promoting theranostic approaches for improved patient care., (© 2024. The Author(s).)

Purpose: Glioblastoma (GBM) recurrence poses challenges in radiation therapy treatment planning because reirradiation has limited leeway needed for precise target delineation. Although effective radiotracers are emerging for treatment planning, comparisons of 11 C-methionine positron emission tomography (MET-PET), 68 Ga-prostate-specific membrane antigen PET (PSMA-PET), and magnetic resonance imaging (MRI) for contouring recurrent GBMs are lacking in the literature. This case study aimed to highlight the differences and similarities in target contours delineated from 3 examinations, aiming to raise doubts about the adequacy of current radiation therapy planning practices., Methods and Materials: A 37-year-old female patient with recurrent Isocitrate dehydrogenase (IDH)1/2 wild-type GBM underwent MRI, MET-PET, and PSMA-PET scans. Target delineations were performed, and volumes were compared using the Dice similarity coefficient, conformity index, and overlap volume, considering different planning target volume margins., Results: We found that MET-PET and MRI volumes showed superior agreement compared with PSMA-PET across all similarity parameters, indicating a more marked discrepancy between PSMA-PET and other modalities. Increasing planning target volume margins demonstrated progressive convergence in intervolume discrepancies. Notably, PSMA-PET delineated larger volumes extending beyond MRI-based volumes., Conclusions: MRI alone may not suffice for target delineation in recurrent GBMs. PET imaging modalities offer complementary insights. Combined PET-MRI guidance could improve tumor boundary detection in target delineation for reirradiation. Prospective trials are necessary to ascertain its impact on patient outcomes., Competing Interests: None., (© 2024 The Author(s).)

Background/aim: This study aimed to assess whether the patient's abdominal adiposity affects the performance of the Exactrac imaging system compared to the cone beam computed tomography (CBCT)-based setup, which was used as the reference positioning for the image-guided radiotherapy (IGRT) delivery to patients with localized prostate cancer., Patients and Methods: The daily positionings of patients with localized prostate cancer undergoing definitive or adjuvant/salvage radiotherapy (RT) were analyzed. The abdominal fat areas and pelvic incidence angle were determined on the CT simulation for each patient. A couple of ExacTrac images and a CBCT were acquired daily to verify the patient setup. We recorded every daily set of the three residual translational errors detected on the CBCT after the ExacTrac-based setup. These sets were clustered within three different thresholds (0.1 mm, 0.2 mm, and 0.3 mm), for each of which the influence of adipose tissues on Exactrac accuracy was assessed as the percentage of sub-threshold displacements as the fat parameters varied. A full bladder and empty rectum preparation protocol was adopted as much as possible., Results: From the assessment of 1,770 daily positionings in 55 patients (38 definitive RT, 17 adjuvant/salvage RT), a good agreement between ExacTrac and CBCT could be inferred, which was quite robust against slight variations in the bladder and rectal filling, and the presence or not of the prostate. The percentages of above-threshold corrections increased with increasing abdominal fat, which therefore seemed to reduce the ExacTrac accuracy. This might be influenced by any intrafraction prostate displacement, likely induced by abdominal respiratory movements, and are more pronounced among overweight men., Conclusion: Our results promote the CBCT use over ExacTrac for IGRT of overweight patients with localized prostate cancer, while calling for attention to the probable need for personalization of planning target volume margins depending on the patient's body habitus., (Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: The favorable role of SBRT for lymph-nodal oligometastases from prostate cancer has been reported by several retrospective and prospective experiences, suggesting a more indolent natural history of disease when compared to patients with bone oligometastases. This retrospective multicenter study evaluates the outcomes of a cohort of patients treated with stereotactic body radiotherapy for lymph-nodal oligometastases. Methods: Inclusion criteria were up to five lymph-nodal oligometastases detected either with Choline-PET or PSMA-PET in patients naïve for ADT or already ongoing with systemic therapy and at least 6 Gy per fraction for SBRT. Only patients with exclusive lymph-nodal disease were included. The primary endpoint of the study was LC; a toxicity assessment was retrospectively performed following CTCAE v4.0. Results: A total of 100 lymph-nodal oligometastases in 69 patients have been treated with SBRT between April 2015 and November 2022. The median age was 73 years (range, 60-85). Oligometastatic disease was mainly detected with Choline-PET in 47 cases, while the remaining were diagnosed using PSMA-PET, with most of the patients treated to a single lymph-nodal metastasis (48/69 cases), two in 14 cases, and three in the remaining cases. The median PSA prior to SBRT was 1.35 ng/mL (range, 0.3-23.7 ng/mL). Patients received SBRT with a median total dose of 35 Gy (range, 30-40 Gy) in a median number of 5 (range, 3-6) fractions. With a median follow-up of 16 months (range, 7-59 months), our LC rates were 95.8% and 86.3% at 1 and 2 years. DPFS rates were 90.4% and 53.4%, respectively, at 1 and 2 years, with nine patients developing a sequential oligometastatic disease treated with a second course of SBRT. Polymetastatic disease-free survival (PMFS) at 1 and 2 years was 98% and 96%. Six patients needed ADT after SBRT for a median time of ADT-free survival of 15 months (range, 6-22 months). The median OS was 16 months (range, 7-59) with 1- and 2-year rates of both 98%. In multivariate analysis, higher LC rates and the use of PSMA-PET were related to improved DPFS rates, and OS was significantly related to a lower incidence of distant progression. No G3 or higher adverse events were reported. Conclusions: In our experience, lymph-nodal SBRT for oligometastatic prostate cancer is a safe and effective option for ADT delay with no severe toxicity.

Background: The rarity of hand acrometastases hampers the consensus-building for their optimal management among the involved oncology professionals. In the current literature, demolitive surgery overcomes the use of palliative radiotherapy, which proved to be ineffective in more than 30% of cases treated with classic palliative dose schemes, carrying also a not negligible radiation-related adverse event rate. Against this background, stereotactic body radiation therapy (SBRT) could emerge as a well-balanced therapeutic option., Case Summary: Here we describe the methods and outcomes of a SBRT treatment of a painful and function-limiting hand acrometastasis in a patient with a history of stage IIIB lung adenocarcinoma. We delivered a total dose of 30 Gy in five daily fractions to a soft-tissue metastasis abutting the fifth metacarpal bone through the SBRT protocol generally used for intracranial treatments. A few weeks later, the patient reported a clinical complete response with acrometastasis and pain disappearance, function recovery, and no significant toxicity. The acrometastasis was the first sign of an atypical cancer progression., Conclusions: SBRT for hand acrometastases is feasible and might have the best therapeutic profile among the currently available treatment options for this rare clinical scenario. Larger investigations are needed to confirm the present single-case experience., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ferini, Zagardo, Viola, Aiello, Harikar, Venkataram, Palmisciano, Illari, Valenti and Umana.)

Purpose: To investigate the ability of radiotherapy (RT) to prolong progression-free survival (PFS) and to report treatment-related toxicities among oligoprogressive metastatic Merkel cell carcinoma (mMCC) patients on avelumab., Methods: We retrospectively collected clinical data on mMCC patients who underwent radiotherapy for limited progression on avelumab. Patients were categorized as primary or secondary immune refractory depending on the time of onset of resistance to immunotherapy (at the first or subsequent follow-up visits after avelumab initiation). Pre- and post-RT PFS were calculated. Overall survival (OS) from the first progression treated with RT was also reported. Radiological responses and toxicities were evaluated according to the irRECIST criteria and RTOG scoring system, respectively., Results: Eight patients, including five females, with a median age of 75 years, met our inclusion criteria. The median gross tumor and clinical target volumes at first progression on avelumab were 29.85 cc and 236.7 cc, respectively. The treatment sites included lymph node, skin, brain, and spine metastases. Four patients received more than one course of RT. Most patients were treated with palliative radiation doses (mainly 30 Gy in 3 Gy/day fractions). Two patients were treated with stereotactic RT. Five/eight patients were primary immune refractory. The objective response rate at the first post-RT assessment was 75%, whereas no local failure was reported. The median pre-RT PFS was 3 months. The pre-RT PFS was 37.5% at 6 months and 12.5% at 1 year. The median post-RT PFS was not reached. The post-RT PFS was 60% at 6 months and 1 year. The post-RT OS was 85.7% at 1 year and 64.3% at 2 years. No relevant treatment-related toxicity was observed. After a median follow-up of 18.5 months, 6/8 patients are still alive and continuing on avelumab therapy., Conclusions: Adding radiotherapy to mMCC patients with limited progression on avelumab seems to be safe and effective in prolonging the successful use of immunotherapy, regardless of the type of immune refractoriness.

Objective: The aim of this work is to define a methodological strategy for the minimally invasive tubular retractor (MITR) parafascicular transulcal approach (PTA) for the management of brain tumors sited in eloquent areas., Methods: An observational prospective study was designed to evaluate the benefits of PTA associated with MITRs, tractography and intraoperative cortical stimulation. They study was conducted from June 2018 to June 2021. Information regarding white matter tracts was processed, preventing a potential damage during the approach and/or resection. All patients older than 18 years who had a single brain tumor lesion were included in the study. Patients with a preoperative Karnofsky Performance Scale (KPS) score greater than 70% and a Glasgow Coma Scale (GCS) score > 14 points were included., Results: 72 patients were included in the study, the mean age was 49.6, the most affected gender was male, 12.5% presented aphasia, 11.1% presented paraphasia, 41.6% had motor deficit, 9.7% had an affection in the optic pathway, the most frequently affected region was the frontal lobe (26.3%), the most frequent lesions were high-grade gliomas (34.7%) and the measurement of the incisions was on average 5.58 cm. Of the patients, 94.4% underwent a total macroscopic resection and 90.2% did not present new postoperative neurological deficits. In all cases, a PTA was used., Conclusion: Tubular minimally invasive approaches (MIAs) allow one to perform maximal safe resection of brain tumors in eloquent areas, through small surgical corridors. Future comparative studies between traditional and minimally invasive techniques are required to further investigate the potential of these surgical nuances.

High-precision image-guided radiation therapy (RT) for tumors abutting the appendicular skeleton may mean technical difficulties and concerns among practitioners. This technical note addresses the specific challenge for normofractionated image-guided RT of a tumor target in a forearm through an unconventional use of a treatment verification system usually devoted to stereotactic RT., (Copyright © 2022 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Background: Infratemporal fossa (ITF) tumors represent various pathologies and are seldom described in the literature, reflecting their rarity. Here we review the literature on tumors invading ITF and describe patient characteristics, treatment strategies, and clinical outcomes., Methods: Relevant articles were retrieved from PubMed, Scopus, and Cochrane. A systematic review and meta-analysis were conducted on the clinical presentation, treatment protocols, and clinical outcomes., Result: A total of 27 articles containing 106 patients with ITF tumors (median tumor size: 24.3 cm 3 [interquartile range, 15.2-42 cm 3 ]) were included (median age: 46 years [interquartile range, 32-55 years]; 59.4% were males]). Of the confirmed tumor pathology data, schwannomas ( n = 24; 26.1%) and meningiomas ( n = 13; 14.1%) were the most common tumors. Facial hypoesthesia ( n = 22; 18.5%), auricular/preauricular pain ( n = 20; 16.8%), and headaches ( n = 11; 9.2%) were the most common presenting symptoms. Of patients who had surgical resection ( n = 97; 95.1%), 70 (73.7%) had transcranial surgery (TCS) and 25 (26.3%) had endoscopic endonasal surgery (EES). Among available details on the extent of resection ( n = 84), gross-total resection (GTR) was achieved in 62 (73.8%), and 5 (6.0%) had biopsy only. Thirty-five (33.0%) patients had postoperative complications. Among cases with available data on reconstruction techniques ( n = 8), four (50%) had adipofascial antero-lateral thigh flap, three (37.5%) had latissimus dorsi free flap, and one (12.5%) had antero-lateral thigh flap. Fourteen (13.2%) patients had adjuvant chemotherapy, and sixteen (15.1%) had adjuvant radiotherapy. During a median follow-up time of 28 months (IQR, 12.25-45.75 months), 15 (14.2%) patients had recurrences, and 18 (17.0%) patients died. The median overall survival (OS) time was 36 months (95% confidence interval: 29-41 months), and the 5-year progression-free survival (PFS) rate was 61%., Conclusion: Various tumor types with different biological characteristics invade the ITF. The present study describes patient demographics, clinical presentation, management, and outcomes. Depending on the tumor type and patient condition, patient-tailored management is recommended to optimize treatment outcomes.

Purpose: To evaluate feasibility, toxicities, and clinical response in Stage IV patients treated with palliative “metabolism-guided” lattice technique. Patients and Methods: From June 2020 to December 2021, 30 consecutive clinical stage IV patients with 31 bulky lesions were included in this study. All patients received palliative irradiation consisting of a spatially fractionated high radiation dose delivered in spherical deposits (vertices, Vs) within the bulky disease. The Vs were placed at the edges of tumor areas with different metabolisms at the PET exam following a non-geometric arrangement. Precisely, the Vs overlapped the interfaces between the tumor areas of higher 18F-FDG uptake (>75% SUV max) and areas with lower 18F-FDG uptake. A median dose of 15 Gy/1 fraction (range 10−27 Gy in 1/3 fractions) was delivered to the Vs. Within 7 days after the Vs boost, all the gross tumor volume (GTV) was homogeneously treated with hypo-fractionated radiation therapy (RT). Results: The rate of symptomatic response was 100%, and it was observed immediately after lattice RT delivery in 3/30 patients, while 27/30 patients had a symptomatic response within 8 days from the end of GTV irradiation. Radiation-related acute grade ≥1 toxicities were observed in 6/30 (20%) patients. The rate of overall clinical response was 89%, including 23% of complete remission. The 1-year overall survival rate was 86.4%. Conclusions: “Metabolism-guided” lattice radiotherapy is feasible and well-tolerated, being able to yield very impressive results both in terms of symptom relief and overall clinical response rate in stage IV bulky disease patients. These preliminary results seem to indicate that this kind of therapy could emerge as the best therapeutic option for this patient setting.