Stereotactic Body Radiotherapy for Lymph-Nodal Oligometastatic Prostate Cancer: A Multicenter Retrospective Experience.

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.

Hypofractionated Radiotherapy in Localized, Low-Intermediate-Risk Prostate Cancer: Current and Future Prospectives.

At the time of diagnosis, the vast majority of prostate carcinoma patients have a clinically localized form of the disease, with most of them presenting with low- or intermediate-risk prostate cancer. In this setting, various curative-intent alternatives are available, including surgery, external beam radiotherapy and brachytherapy. Randomized clinical trials have demonstrated that moderate hypofractionated radiotherapy can be considered as a valid alternative strategy for localized prostate cancer. High-dose-rate brachytherapy can be administered according to different schedules. Proton beam radiotherapy represents a promising strategy, but further studies are needed to make it more affordable and accessible. At the moment, new technologies such as MRI-guided radiotherapy remain in early stages, but their potential abilities are very promising.

Effects of infections on the pathogenesis of cancer.

Several studies have shown an inverse relationship between acute infections and cancer development. On the other hand, there is a growing evidence that chronic infections may contribute significantly to the carcinogenesis. Factors responsible for increased susceptibility to infections may include modifications of normal defence mechanisms or impairment of host immunity due to altered immune function, genetic polymorphisms, ageing and malnourishment. Studies have demonstrated that children exposed to febrile infectious diseases show a subsequent reduced risk for ovarian cancer, melanoma and many other cancers, while common acute infections in adults are associated with reduced risks for melanoma, glioma, meningioma and multiple cancers. Chronic inflammation associated with certain infectious diseases has been suggested as a cause for the development of tumours. Mechanisms of carcinogenesis due to infections include cell proliferation and DNA replication by mitogen-activated protein kinase pathway, production of toxins that affect the cell cycle and lead to abnormal cell growth and inhibition of apoptosis. This review was aimed to summarize the available evidence on acute infections as a means of cancer prevention and on the role of chronic infections in the development and progression of cancer.

Spinal cord compression as tumor onset: an unusual case report of Hodgkin lymphoma in a teenager.

BACKGROUND: Spinal cord compression (SCC) is an uncommon, severe complication of Hodgkin lymphoma (HL), occurring in 0.2% of cases at the onset and in 6% during disease progression. We present a teenager with SCC with clinical onset of HL; her pre-existing neurological abnormalities covered the presence of an epidural mass, which could have misled us. CASE PRESENTATION: A 13-year-old girl presented with a three-month history of lower back pain and degrading ability to walk. She suffered from a chronic gait disorder due to her preterm birth. A magnetic resonance imaging of the spine revealed an epidural mass causing collapse of twelfth thoracic vertebra and thus compression and displacement of the spinal cord. Histological examination with immunohistochemical analysis of the epidural mass demonstrated a classic-type Hodgkin lymphoma. Early pathology-specific treatment allowed to avoid urgent surgery, achieve survival and restore of neurological function. CONCLUSIONS: Children and adolescents with back pain and neurological abnormalities should be prioritized to avoid diagnostic delay resulting in potential loss of neurological function. SCC requires a prompt radiological assessment and an expert multidisciplinary management.

Can Conventional and Diffusion-Weighted MR Enterography Biomarkers Differentiate Inflammatory from Fibrotic Strictures in Crohn's Disease?

Background and Objectives: To retrospectively assess the value of magnetic resonance enterography (MRE) parameters derived from conventional and diffusion weighted imaging (DWI) sequences to differentiate fibrotic strictures from inflammatory ones in adult patients with Crohn's disease (CD), using surgical specimens as the histopathological reference standard. Material and Methods: Twenty-three patients with CD who had undergone surgical resection of ileal strictures with full-thickness histopathologic analysis within 3 months from preoperative MRE were included. Two radiologists blinded to histopathology in consensus evaluated the following biomarkers on MRE images matched to resected pathological specimens: T1 ratio, T2 ratio, enhancement pattern, mural thickness, pre-stenotic luminal diameter, and apparent diffusion coefficient (ADC). A blinded pathologist graded stricture histological specimens with acute inflammation score (AIS) and fibrosis score (FS). MRE measurements were correlated with the reference standard. Results: Inflammation and fibrosis coexisted in 78.3% of patients. T2 ratio was reduced in patients with severe fibrosis (p = 0.01). Pre-stenotic bowel dilatation positively correlated with FS (p = 0.002). The ADC value negatively correlated with FS (p < 0.001) and was different between FS grades (p < 0.05). The area under the receiver operating characteristic curve for discriminating between none and mild/moderate-severe bowel wall fibrosis was 0.75 for pre-stenotic bowel dilatation (sensitivity 100%, specificity 44.4%) and 0.97 for ADC (sensitivity 80%, specificity 100%). Conclusions: Inflammation and fibrosis often coexist in CD bowel strictures needing surgery. The combination of parameters derived from conventional MR sequences (T2 ratio, pre-stenotic dilatation) and from DWI (ADC) may provide a contribution to detect and grade bowel fibrosis in adult CD patients.

Adenoid cystic carcinoma of trachea: long-term disease control after endoscopic surgery and radiotherapy.

Aim: Adenoid cystic carcinoma is a rare tumor of head and neck region and its development in the thoracic region is even less frequent. This implies the absence of guidelines for therapeutic management and a consequent case-by-case approach. The role of radiotherapy is not yet clearly defined, but intensity-modulated radiotherapy allows for improved organ-at-risk sparing. Materials & methods: We have collected the cases of four patients treated at our institutions by the means of intensity-modulated radiotherapy, after endoscopic resection. Results & conclusion: Patients treated achieved long-term disease control of about 5 years, with a minimal acute toxicity. Longer follow-up is needed to drain conclusion on the impact of this treatment on overall survival.

Intravitreal aflibercept for the treatment of radiation-induced macular edema after ruthenium 106 plaque radiotherapy for choroidal melanoma.

PURPOSE: To assess the efficacy of intravitreal aflibercept in patients suffering from post-radiation macular edema following plaque radiotherapy for choroidal melanoma. METHODS: This prospective, interventional case series included patients affected by radiation maculopathy (RM) with macular edema secondary to ruthenium-106 plaque brachytherapy for choroidal melanoma. The effect of intravitreal aflibercept on best-corrected visual acuity (BCVA), central foveal thickness (CFT) detected by spectral domain optical coherence tomography (sd-OCT), and Horgan's grading scale of RM was evaluated throughout the 24-month follow-up. Intraocular pressure (IOP) and possible complications were also recorded. RESULTS: Nine eyes of 9 patients were included. A mean of 4.4 ± 1.2 injections were given over the 24 months. At the end of follow-up, mean BCVA was significantly improved, from 0.9 ± 0.19 logMAR at baseline to 0.56 ± 0.3 logMAR (P = 0.028), and mean CFT was significantly decreased, from 546 ± 123 µm at baseline to 223 ± 34 µm (P < 0.001). Intravitreal aflibercept lowered baseline maculopathy stage as well. No significant change in IOP values and no complications, such as endophthalmitis, was recorded. CONCLUSION: Intravitreal aflibercept is an effective treatment for patients with radiation-induced macular edema, allowing functional and anatomical improvements to be achieved with a relatively low number of injections.

Rare breast and subcutaneous metastases from pancreatic neuroendocrine tumor: a case report.

BACKGROUND: Neuroendocrine tumors are a group of rare neoplasms, and the pancreatic neuroendocrine tumors (PNETs) represent only 1-2% of all pancreatic malignant tumors. The most common sites of these tumors include the gastrointestinal tract, lung, adrenal gland, and thyroid gland. Moreover, the most common sites of PNET metastases are the lymph nodes, liver, spleen, and bone. A 40-year-old woman with pT3N1 PNET underwent surgical excision of the lesion (12 cm, at the level of the pancreatic body and tail). Postsurgical treatment included chemotherapy and radiation, both of which the patient showed a good tolerance for. After a 12-month disease-free interval, however, the patient reported the development of a lesion in her left breast and a small lesion in the left posterior region of her neck. The lesions were surgically excised, and the histological findings characterized both as pancreatic neuroendocrine metastatic poorly differentiated neoplasms (G3). A re-staging CT scan showed multiple metastases in the left axillary, clavicular, and latero-cervical lymph nodes, as well as diffuse osteolytic-osteoblastic bone metastases, almost mimicking the behavior of a primitive breast tumor. CONCLUSION: This case of breast and subcutaneous metastases from PNET should prompt awareness of potential metastatic lesions in unusual locations.

Trends in combined radio-chemotherapy for locally advanced rectal cancer: a survey among radiation oncology centers of Sicily region on behalf of AIRO.

AIM: To conduct a survey among Sicilian centers of radiation oncology belonging to Associazione Italiana di Radioterapia ed Oncologia Clinica (AIRO), to record the different methods of integration of radio-chemotherapy both in neoadjuvant and adjuvant settings, to evaluate surgical procedures in relation to the sphincter preservation and to report the different toxicity profiles of the treatment strategies. METHODS: A questionnaire was sent at the end of 2017 to all the radiation oncology centers of Sicily region in order to collect the data from individual centers and the treatment characteristics retrospectively over the previous 5 years, from 2012 to 2016. The required data were collected from 13 centers out of 17 which, in relation to the single catchment areas, correspond to approximately 85% of the Sicilian population. The requested data concerned the type of integrated treatment (neoadjuvant vs adjuvant vs radical), combination with chemotherapy (induction, concomitant, adjuvant), type of surgical intervention (sphincter-saving vs abdomino-perineal resection), disease stage, schedule and radiotherapy technique adopted, as well as toxicity detected over the treatment period. RESULTS: A total of 784 pts (M/F: 509/275) were treated between 2012 and 2016, with a median age of 67 years (range 25-92). The majority of patients was treated in the neoadjuvant phase (62% of the total) compared to the adjuvant phase (31%) and to those treated radically (7%). Twenty-five percent of patients did not receive combination chemotherapy mainly for cardiovascular problems. Chemotherapy used concomitantly to radiotherapy was single-agent capecitabine (73% of patients) or 5-fluorouracil (27%). The use of chemotherapy alone before concomitant treatment is more common for patients treated in the adjuvant phase (64% of this subgroup), while 14% of patients treated in the neoadjuvant phase received induction chemotherapy before the concomitant phase; in both cases of chemotherapy alone, the majority of patients (91%) received oxaliplatin-based protocols (FOLFOX/XELOX/CAPOX). Few patients (3%) received chemotherapy alone after the concomitant phase. Information on the surgical treatment received is available for 88% of the sample. Of these, 93% received a surgical treatment. The overall rate of sphincter-saving surgery (anterior resection) was 72%, but the contribution of neoadjuvant treatment allowed to reach a rate of 83% in this subgroup (against 65% found in the subgroup of patients treated in adjuvant phase). Traditional radiotherapy schedule (45-50 Gy in 25-28 fractions) was used in 90% of patients, of which an intensified treatment in neoadjuvant phase (45 Gy + boost of 9-10 Gy) was used in 11% of patients. A short-course regimen (25 Gy in 5 fraction) in neoadjuvant setting was opted rarely (7%). Three-dimensional conformal technique was preferred over intensity-modulated ones (73% vs 27%). Toxicity was mainly of grade I-II CTCAE (skin 23%, gastrointestinal 39%, genitourinary 14%) compared to grade III (gastrointestinal 4%, genitourinary and hematological < 1%). Interestingly, the toxicity rates were significantly higher in the adjuvant group compared to the neoadjuvant (GI: 58% vs 31%, GU: 21% vs 10%). CONCLUSION: The present survey shows that in the Sicily region integrated therapies for rectal cancer have allowed a neoadjuvant approach in the majority of patients, thus resulting in a greater use of sphincter conservative surgery. The toxicity has also been reported to be significantly less in this treatment setting.

Single-institution experience of intensity-modulated radiotherapy for malignant pleural mesothelioma at University of Catania.

AIM: The multimodal approach to malignant pleural mesothelioma is gradually becoming the standard of care for this disease in patients with good performance status. Materials & methods: We report our experience concerning eight cases treated with the use of static step-and-shoot intensity-modulated radiotherapy to the whole pleural cavity, in patients already undergoing surgical and/or antiblastic therapy. Results & conclusion: Results at a median follow-up of 16 months showed a median survival from the initial treatment of 29 months, with lung toxicity of grade II reported only in two patients.

Combined taxane-based chemotherapy and intensity-modulated radiotherapy with simultaneous integrated boost for gastroesophageal junction adenocarcinoma.

We describe our experience, gained over the past 3 years, in the treatment of gastroesophageal junction adenocarcinoma, whose incidence has been increasing in recent years. In our series, we present the results to a follow-up of about 2 years for a total of 18 patients, treated with a particularly intensive combination treatment. It consists of neoadjuvant induction chemotherapy with the protocol docetaxel-cisplatin-5-fluorouracil for four cycles, before a concomitant chemoradiotherapy treatment. During combined phase, patients received an intensity-modulated radiotherapy and a weekly cisplatin. We will present the data to a long follow-up time and we will discuss the literature, the integration with thoracoabdominal surgery and other specific issues of this pathology.

DEXAMETHASONE INTRAVITREAL IMPLANT VS RANIBIZUMAB IN THE TREATMENT OF MACULAR EDEMA SECONDARY TO BRACHYTHERAPY FOR CHOROIDAL MELANOMA.

PURPOSE: To evaluate the efficacy of an intravitreal dexamethasone (Dex) implant 0.7 mg compared with intravitreal ranibizumab (Ra) for the treatment of radiation maculopathy with macular edema secondary to plaque brachytherapy in choroidal melanoma. METHODS: Eight patients were treated with intravitreal Ra, and eight patients received the Dex intravitreal implant. Visual acuity and foveal thickness were evaluated using spectral domain optical coherence tomography. RESULTS: The mean calculated irradiation to the fovea and mean times from brachytherapy to maculopathy development did not differ significantly between groups. In the Ra group, a mean 7.8 ± 3.9 injections were given and the mean follow-up was 33 ± 15 months (range, 7-52 months). In the Dex group, a mean 2.1 ± 0.8 injections were given and the mean follow-up was 22 ± 7 months (range, 11-31 months). The mean visual acuity improved significantly from the baseline to the last follow-up visit in both groups. Foveal thickness decreased significantly in both groups from 459 ± 81 µm to 243 ± 58 µm and from 437 ± 71 µm to 254 ± 44 µm from the baseline to the last follow-up visit in the Ra and Dex groups, respectively. No patients developed significant cataract or ocular hypertension in both groups. CONCLUSION: Both Ra and Dex are effective treatments for macular edema secondary to plaque brachytherapy for uveal melanoma. Dex-treated patients required fewer injections to achieve anatomical and functional improvement.

Uveal melanoma: quantitative evaluation of diffusion-weighted MR imaging in the response assessment after proton-beam therapy, long-term follow-up.

PURPOSE: The purpose of this prospective study was to investigate the proton-beam-induced changes in apparent diffusion coefficient (ADC) values of ocular melanoma treated with proton-beam therapy (PBT) in patients undergoing long-term magnetic resonance imaging (MRI) follow-up and to assess whether variations in ADC constitute a reliable biomarker for predicting and detecting the response of ocular melanoma to PBT. METHODS: Seventeen patients with ocular melanoma treated with PBT were enrolled. All patients underwent conventional MRI and diffusion-weighted imaging (DWI) at baseline and 1, 3, 6, and 18 months after the beginning of therapy. Tumor volumes and ADC values of ocular lesions were measured at each examination. Tumor volumes and mean ADC measurements of the five examination series were compared; correlation of ADC values and tumor regression was estimated. RESULTS: Mean ADC values of ocular melanomas significantly increased already 1 month after therapy whereas tumor volume significantly decreased only 6 months after therapy. Pretreatment ADC value of ocular melanomas and early change in ADC value 1 month after therapy significantly correlated with tumor regression. CONCLUSIONS: In ocular melanoma treated with PBT, ADC variations precede volume changes. Both pretreatment ADC and early change in ADC value may predict treatment response, thus expanding the role of DWI from diagnostic to prognostic.

Intensity-modulated radiotherapy for relapsed malignant pleural mesothelioma.

The use of novel radiotherapy techniques is widely increasing, allowing clinicians to treat diseases that were previously difficult to treat with radiation therapy. Malignant pleural mesothelioma is a clear example of this clinical challenge. We describe our first experience with intensity-modulated radiotherapy technique which was used to treat a 73-year-old patient with multiple relapsing malignant pleural mesothelioma. Intensity-modulated radiation therapy has allowed to respect the QUANTEC (quantitative analyses of normal tissue effects in the clinic) dose constraints, patient has experienced a 14 months progression-free time, without relevant subacute or late lung toxicity.

Role, timing and technique of radiotherapy in pediatric pleuropulmonary synovial sarcoma.

The management of pediatric thoracic synovial sarcoma remains a matter of debate in clinical oncology, especially as regard to the local control of the disease. Surgery remains the gold standard, while the role and timing of radiotherapy is still controversial. We report a 14-year-old male, who has not received proper treatment at the time of diagnosis and initial management. Intensity-modulated irradiation was performed only at relapse, as a salvage treatment and, at 10-month follow-up, the young patient was free from relapse, without significant acute and subacute toxicity. We discuss the role and timing of radiotherapy in thoracic synovial sarcoma, a disease in which the need to increase local control should be placed in the foreground.

Follicular dendritic cell sarcoma of mediastinum: a key role of radiotherapy in a multidisciplinary approach.

Follicular dendritic cell sarcoma is a rare and aggressive tumor and its management is a major clinical challenge. Surgery is considered the mainstay of treatment and no adjuvant approach has demonstrated the ability to reduce the rate of relapses. We report on a case of a man with a 26-year clinical history of mediastinal follicular dendritic cell sarcoma, with several relapses after multiple surgical interventions. The impact of chemotherapy was very small, unlike the radiation therapy that was performed twice, with an interval time of 8 years, through an intensity-modulated technique and an altered fractionation schedule.

Wider implications of video-assisted thoracic surgery versus open approach for lung metastasectomy.

Lung metastasectomy is considered a safe and potentially curative procedure despite there is not a strong evidence that metastasectomy prolongs long-term survival in patients with lung metastases. Moreover, the debate is open regarding the best approach for lung metastasectomy, video-assisted thoracic surgery versus open approach. A systematic review of literature to clarify what is the best approach to prolong survival in patients with lung metastases was performed. Our study confirms that overall survival is equivalent for video-assisted thoracic surgery and thoracotomy, therefore the 'gold standard' surgical treatment for lung metastases remains a point of debate. The choice of the surgical approach still depends more on the single center or surgeon practice than on strong scientific evidence. A prospective randomized trial could clarify the question.

Cytoreductive surgery and hyperthermic intrapleural chemotherapy for malignant pleural diseases: preliminary experience.

Cytoreductive surgery and hyperthermic-intraoperative-intrapleural-chemotherapy (HITHOC) is a known approach for malignant pleural diseases (MPD). This study was started to clarify the role of cytoreductive surgery and HITHOC in MPD. Criteria of inclusion were early-stage disease in malignant pleural mesothelioma (MPM), young age, good condition and selected stage-M1a lung cancer. Six patients with MPM and two patients with lung cancer were enrolled. After surgical debulking, intrapleural cisplatin was administered for 60 min at 42.5°C. Wedge, rib resection and repaired diaphragm were added in three, one and one patient, respectively. Morbidity, toxicity and mortality was nil. Hospital stay was 8 days. Mean survival is 13.6 months. This experience confirms that cytoreductive surgery and HITHOC is a good option in the treatment of MPD. A randomized controlled trial is necessary.

Pleurectomy/decortication and hyperthermic intrapleural chemotherapy for malignant pleural mesothelioma: initial experience.

Cytoreductive surgery and hyperthermic intraoperative intrapleural chemotherapy (HITHOC) are a known option for malignant pleural mesothelioma (MPM). This prospective study was started to prove that pleurectomy/decortication and HITHOC could be successfully performed in a low volume center. Criteria of inclusion were a proven diagnosis of MPM, early-stage disease and good performance status. Six consecutive patients were enrolled. After pleurectomy/decortication, intrapleural cisplatin was administered for 60 min at 42.5 °C. Wedge resections and diaphragmatic reconstruction were added in two and one patient, respectively. Morbidity was 16.6%. Mortality was nil. Hospital stay was 7.8 days. Mean survival was 21.5 months (range: 6-30). This small experience confirms that pleurectomy/decortication and HITHOC are a good therapeutic option in the multimodality treatment of MPM. A randomized controlled trial is necessary.

The Immunomodulatory Potential of Concurrent High-Dose Radiotherapy and Immune Checkpoint Inhibitor Cemiplimab in Advanced Cutaneous Squamous Cell Carcinoma: Initial Results.

In this retrospective case series, we investigate the synergistic effect and the immunomodulatory potential of combination radiotherapy and immunotherapy on 11 patients affected by locally advanced or metastatic cutaneous squamous cell carcinoma (CSCC), treated at our institution between 2020 and 2023. The primary endpoints of this study are objective tumor response, assessed by Immunotherapy Response Evaluation Criteria in Solid Tumors (iRECIST), and time to treatment failure (disease progression). In all patients, surgery was deemed not amenable, due to its potential functional and aesthetic impact. Therefore, upon multidisciplinary agreement, radiotherapy and immunotherapy with cemiplimab were alternatively administered. After 6 months, an early objective tumor response was observed in 9/11 patients, with 17/20 cutaneous lesions (85%) presenting either a complete or partial response. Only 2/11 patients, with a total of 3/20 cutaneous lesions (15%), had stable disease. These benefits persisted at a longer follow-up (21.4 ± 9.7 months), with no patients presenting disease progression. Despite the retrospective nature of this study and small sample size, our experience highlights the ability of concomitant radiotherapy and cemiplimab to promote an early objective response in patients with advanced CSCC. Moreover, in our population, the clinical benefits were also related to a longer progression-free survival, without any safety alert reported.