Prospective study on stereotactic body radiotherapy for small pancreatic neuroendocrine tumors: tolerance and effectiveness analysis.

INTRODUCTION: Surgery is the standard treatment for pancreatic neuroendocrine tumors (pNETs), obtaining favorable results but associating high morbidity and mortality rates. This study assesses stereotactic body radiation therapy (SBRT) as a radical approach for small (< 2 cm) nonfunctioning pNETs. MATERIALS AND METHODS: From January 2017 to June 2023, 20 patients with small pNETs underwent SBRT in an IRB-approved study. Endpoints included local control, tolerance, progression-free survival, and overall survival (OS). Diagnostic assessments comprised endoscopy, CT scans, OctreScan or PET-Dotatoc, abdominal MRI, and histological confirmatory samples. RESULTS: In a 30-month follow-up of 20 patients (median age 55.5 years), SBRT was well-tolerated with no grade > 2 toxicity. 40% showed morphological response, 55% remained stable. Metabolically, 50% achieved significant improvement. With a median OS of 41.5 months, all patients were alive without local or distant progression or need for surgical resection. CONCLUSION: SBRT is a feasible and well-tolerated approach for small neuroendocrine pancreatic tumors, demonstrating effective local control. Further investigations are vital for validation and extension of these findings.

SBRT-SG-01: final results of a prospective multicenter study on stereotactic body radiotherapy for liver metastases.

OBJECTIVE: This study aimed to assess the efficacy and tolerability of stereotactic body radiation therapy (SBRT) for the treatment of liver metastases. METHODS: Patients with up to 5 liver metastases were enrolled in this prospective multicenter study and underwent SBRT. Efficacy outcomes included in-field local control (LC), progression-free survival (PFS), and overall survival (OS). Acute and late toxicities were evaluated using CTCAE v.4.0. RESULTS: A total of 52 patients with 105 liver metastases were treated between 2015 and 2018. The most common primary tumor was colorectal cancer (72% of cases). Liver metastases were synchronous with the primary tumor diagnosis in 24 patients (46.2%), and 21 patients (40.4%) presented with other extrahepatic oligometastases. All patients underwent intensity-modulated radiation therapy (IMRT)/volumetric-modulated arc therapy (VMAT) with image-guided radiation therapy (IGRT) and respiratory gating, and a minimum biologically effective dose (BED10Gy) of 100 Gy was delivered to all lesions. With a median follow-up of 23.1 months (range: 13.4-30.9 months) since liver SBRT, the median actuarial local progression-free survival (local-PFS) was not reached. The actuarial in-field LC rates were 84.9% and 78.4% at 24 and 48 months, respectively. The median actuarial liver-PFS and distant-PFS were 11 and 10.8 months, respectively. The actuarial median overall survival (OS) was 27.7 months from SBRT and 52.5 months from metastases diagnosis. Patients with lesion diameter ≤ 5 cm had significantly better median liver-PFS (p = 0.006) and OS (p = 0.018). No acute or late toxicities of grade ≥ 3 were observed. CONCLUSIONS: This prospective multicenter study confirms that liver SBRT is an effective alternative for the treatment of liver metastases, demonstrating high rates of local control and survival while maintaining a low toxicity profile.

Ultra-hypofractionated one-week locoregional radiotherapy for patients with early breast cancer: Acute toxicity results.

Purpose: Moderate hypofractionated radiotherapy is the standard of care for all patients with breast cancer, irrespective of stage or prior treatments. While extreme hypofractionation is accepted for early-stage tumours, its application in irradiating locoregional lymph nodes remains controversial. Materials and methods: A prospective registry analysis from July 2020 to September 2023 included 276 patients with early-stage breast cancer treated with one-week ultra-hypofractionation (UHF) at 26 Gy in 5 fractions on the whole breast (58.3 %) or thoracic wall (41.7 %) and ipsilateral regional lymph nodes and simultaneous integrated boost (58.3 %). Primary endpoint was assessment of acute adverse events (AEs). Secondarily, onset of early-delayed toxicity was assessed. A minimum 6-month follow-up was required for assessing potential treatment-related early-delayed complications. Acute or late complications attributable to treatment were assessed at inclusion using the Common Terminology Criteria for Adverse Events (CTCAE) v5.0 criteria. Results: With a median follow-up of 19 months (range 1-49 months), 159 (57.6 %) patients reported AEs, predominantly grade (G) 1 (n = 139, 50.4 %) and G2 (n = 20, 7.8 %). Skin acute toxicity was common (G1/2: 134, G3: 14), while breast oedema occurred in 10 patients (G1: 9, G2: 1), and 15.9 % reported breast pain (G1: 42, G2: 2). Ipsilateral arm oedema was observed in 1.8 % patients. For patients with a follow-up beyond 6 months (n = 213), 23.4 % patients reported G1/G2 skin AEs, 8.8 % had G1/G2 breast/chest wall oedema, and 8.9 % experienced arm lymphedema. There were no cases of brachial plexopathy or G3 toxicity in this group of patients. Conclusions: One-week UHF adjuvant locoregional radiation is well-tolerated, displaying low-toxicity profiles comparable to other studies using similar irradiation schedules.

Moderate hypofractionated radiation therapy and pathologic response for soft tissue sarcomas (STS) of limbs and trunk: experience from a tertiary cancer center.

BACKGROUND: Preoperative radiation therapy following by limb-sparing or conservative surgery is a standard approach for limb and trunk STS. Data supporting hypofractionated radiotherapy schedules are scarce albeit biological sensitivity of STS to radiation would justify it. We sought to evaluate the impact of moderate hypofractionation on pathologic response and its influence on oncologic outcomes. MATERIAL AND METHODS: From October 2018 to January 2023, 18 patients with limb or trunk STS underwent preoperative radiotherapy at a median dose of 52.5 Gy (range 49.5-60 Gy) in 15 fractions of 3.5 Gy (3.3-4 Gy) with or without neoadjuvant chemotherapy. A favorable pathologic response (fPR) was considered as ≥ 90% tumor necrosis on specimen examination. RESULTS: All patients completed planned preoperative radiotherapy. Eleven patients (61.1%) achieved a fPR, and 7 patients (36.8%) a complete pathologic response with total disappearance of tumor cells. Nine patients (47%) developed grade 1-2 acute skin toxicity, and 7 patients (38.8%) had wound complications on follow-up. With a median follow-up of 14 months (range 1-40), no cases of local relapse were observed, and actuarial 3-year overall survival (OS) and distant metastases-free survival (DMFS) are 87% and 76.4%, respectively. In the univariate analysis, the presence of a favorable pathologic response (fPR) was associated with improved 3-year OS (100% vs. 56.03%, p = 0.058) and 3-year DMFS (86.91% vs. 31.46%, p = 0.002). Moreover, both complete or partial RECIST response and radiological stabilization of the tumor lesion showed a significant association with higher rates of 3-year distant metastasis-free survival (DMFS) (83% vs. 83% vs. 56%, p < 0.001) and 3-year overall survival (OS) (100% vs. 80% vs. 0, p = 0.002). CONCLUSIONS: Preoperative moderate hypofractionated radiation treatment for STS is feasible and well tolerated and associates encouraging rates of pathologic response that could have a favorable impact on final outcomes.

Acute skin toxicity of ultra-hypofractionated whole breast radiotherapy with simultaneous integrated boost for early breast cancer.

Background: Whole-breast irradiation (WBI) after breast conserving surgery (BCS) is indicated to improve loco-regional control and survival. Former studies showed that addition of tumor bed boost in all age groups significantly improved local control although no apparent impact on overall survival but with an increased risk of worse cosmetic outcome. Even though shortened regimens in 3 weeks are considered the standard, recent studies have shown the non-inferiority of a treatment regimen of 5 fractions in one-week in both locoregional control and toxicity profile, although simultaneous integrated boost (SIB) in this setting has been scarcely studied. Materials and Methods: From March-2020 to March-2022, 383 patients with early breast cancer diagnosis and a median age of 56 years-old (range 30-99)were included in a prospective registry of ultra-hypofractionated WBI up to a total dose of 26 Gy in 5.2 Gy/fraction with a SIB of 29 Gy in 5.8 Gy/fraction in 272 patients (71%), 30-31 Gy in 6-6.2 Gy/fraction in 111 patients (29%) with close/focally affected margins. Radiation treatment was delivered by conformal 3-D technique in 366 patients (95%), VMAT in 16patients (4%) and conformal 3-D with deep inspiration breath hold (DIBH) in 4patients (1%). Ninety-three per cent of patients received endocrine therapy and 43% systemic or targeted chemotherapy. Development of acute skin complications was retrospectively reviewed. Results: With a median follow-up of 18 months (range 7-31), all patients are alive without evidence of local, regional or distant relapse. Acute tolerance was acceptable, with null o mild toxicity: 182 (48%) and 15 (4%) patients developed skin toxicity grade 1 and 2 respectively; 9 (2%) and 2 (0.5%) patients breast edema grade 1and 2 respectively. No other acute toxicities were observed. We also evaluated development of early delayed complications and observed grade 1 breast edema in 6 patients (2%); grade 1 hyperpigmentation in 20 patients (5%); and grade 1 and 2 breast induration underneath boost region in 10(3%) and 2 patients (0.5%) respectively. We found a statistically significant correlation between the median PTVWBI and presence of skin toxicity (p = 0.028) as well as a significant correlation between late hyperpigmentation with the median PTVBOOST (p = 0.007) and the ratio PTVBOOST/PTVWBI (p = 0.042). Conclusion: Ultra-hypofractionated WBI + SIB in 5 fractions over one-week is feasible and well tolerated, although longer follow-up is necessary to confirm these results.

Stereotactic body radiation therapy (SBRT) for spinal metastases: 12 years of a single center experience.

OBJECTIVE: To assess the clinical outcomes of patients with spine metastases treated with SBRT at our institution. MATERIALS AND METHODS: Patients with spine metastases treated with SBRT (1 fraction/18 Gy or 5 fractions/7 Gy) during the last 12 years have been analyzed. All patients were simulated supine in a vacuum cushion or with a shoulder mask. CT scans and MRI image registration were performed. Contouring was based on International Spine-Radiosurgery-Consortium-Consensus-Guidelines. Highly conformal-techniques (IMRT/VMAT) were used for treatment planning. Intra and interfraction (CBCT or X-Ray-ExacTrac) verification were mandatory. RESULTS: From February 2010 to January 2022, 129 patients with spinal metastases were treated with SBRT [1 fraction/18 Gy (75%) or 5 fractions/7 Gy] (25%). For patients with painful metastases (74/129:57%), 100% experienced an improvement in pain after SBRT. With a median follow-up of 14.2 months (average 22.9; range 0.5-140) 6 patients (4.6%) experienced local relapse. Local progression-free survival was different, considering metastases's location (p < 0.04). The 1, 2 and 3 years overall survival (OS) were 91.2%, 85.1% and 83.2%, respectively. Overall survival was significantly better for patients with spine metastases of breast and prostate cancers compared to other tumors (p < 0.05) and significantly worse when visceral metastases were present (p < 0.05), when patients were metastatic de novo (p < 0.05), and in those patients receiving single fraction SBRT (p: 0.01). CONCLUSIONS: According to our experience, SBRT for patients with spinal metastases was effective in terms of local control and useful to reach pain relief. Regarding the intent of the treatment, an adequate selection of patients is essential to propose this ablative approach.

Real-world efficacy of postoperative radiotherapy with a moderate dose-escalation for phyllodes tumors of the breast.

Background: Phyllodes tumors are rare breast tumors comprising less than 1% of cases, categorized as benign, borderline, or malignant. Treatment typically involves complete surgical excision with wide margins. Adjuvant radiotherapy may be recommended for borderline or malignant tumors, or when clear margins cannot be achieved through surgery alone. Methods: We conducted a retrospective review of 14 women diagnosed with phyllodes tumors between 2015 and 2023. Among them, 36% had benign tumors and 64% had borderline/malignant tumors. The majority (86%) underwent breast-conserving surgery. Postoperative radiation therapy was delivered to the whole breast/chest wall, with a median biologically effective dose (BED) of 92.7 Gy (90.0-102.6 Gy), representing a moderate dose-escalation over conventional breast cancer schedules. Results: After a median follow-up of 48.5 months, no local or distant recurrence were observed. Mild to moderate skin toxicity occurred in all patients: 36% reported grade 1, 43% grade 2, and 21% grade 3 toxicity. One patient developed grade 2 fibrosis during follow-up. No significant correlations were found between the severity of acute/late toxicity and tumor size, surgical approach, or the radiation field's planning target volume (PTV). Conclusions: Adjuvant radiation therapy appears to be well tolerated and feasible for high-risk phyllodes tumors. However, the decision to utilize radiotherapy should be personalized, considering tumor characteristics and the risks and benefits associated with treatment.

Suppression of Berberine and Probiotics (in vitro and in vivo) on the Growth of Colon Cancer With Modulation of Gut Microbiota and Butyrate Production.

Background and Objective: An increasing number of evidence has revealed that the gut microbiome functions in immunity, inflammation, metabolism, and homeostasis and is considered to be crucial due to its balance between human health and diseases such as cancer, leading to the emergence of treatments that target intestinal microbiota. Probiotics are one of them. However, many challenges remain regarding the effects of probiotics in cancer treatment. Berberine (BBR), a natural extract of Rhizoma Coptidis and extensively used in the treatment of gastrointestinal diseases, has been found to have antitumor effects in vivo and in vitro by many recent studies, but its definite mechanisms are still unclear. This study aimed to explore the inhibitory effect of BBR and probiotics on the growth of colon cancer cells in vitro and in vivo, and the regulatory influence on the gut microbiome and butyrate production. Methods: Colon cancer cell line HT29 was used to establish a xenograft model of nude mice and an in vitro model. A total of 44 nude mice and HT29 cells were divided into control, model, model + BBR, model + probiotics, and model + combination of BBR with probiotics (CBPs). Live combined Bifidobacterium, Lactobacillus, and Enterococcus powder (LCBLEP) was used as a probiotic preparation. LCBLEP was cultured in the liquid medium under anaerobic conditions (the number of viable bacteria should reach 1 × 108CFU), and the supernatant was collected, and it is called probiotic supernatant (PS). Model + BBR and model + probiotics groups were treated with BBR and LCBLEP or PS for 4 weeks in vivo or 48, 72, and 96 h in vitro, respectively. Tumor volume or cell proliferation was measured. Gut microbiota was pyrosequenced using a 16S rDNA amplicon. HDAC1 mRNA level in HT29 cells and sodium butyrate (SB) expression in the serum of mice was detected by QPCR and ELISA. Results: The treatment of BBR and CBP reduced the growth of neoplasms in mice to a different extent (p > 0.05), especially at 14 days. The inhibitory effect of LCBLEP on tumor growth was more significant, especially at 11-21 days (p < 0.05). Inhibition of BBR on in vitro proliferation was concentration-dependent. The suppression of 75% probiotic supernatant (PS) on the proliferation was the most significant. The supplement of LCBLEP significantly increased the richness and evenness of the gut microbe. BBR dramatically increased the abundance of Bacteroidetes and Proteobacteria, with reduced Ruminococcus, followed by the LCBLEP. The LCBLEP reduced the relative abundance of Verrucomicrobia and Akkermansia, and the CBP also promoted the relative level of Bacteroidetes but reduced the level of Verrucomicrobia and Akkermansia. BBR and LCBLEP or CBP improved the alpha and beta diversity and significantly affected the biomarker and metabolic function of the gut microbe in nude mice with colon cancer. The level of HDAC1 mRNA was reduced in HT29 cells treated with BBR or PS (p < 0.05), the mice treated with BBR revealed a significantly increased concentration of SB in serum (p < 0.05), and the inhibitory effect of SB on the proliferation of HT29 cells was stronger than panobinostat and TSA. Conclusion: Although the combination of BBR and probiotics has no advantage in inhibiting tumor growth compared with the drug alone, BBR can be used as a regulator of the intestinal microbiome similar to the probiotics by mediating the production of SB during reducing the growth of colon cancer.

Radiation therapy with curative intention in men with de novo metastatic prostate carcinoma: shoot'em all!

BACKGROUND: About 5% of prostate cancer cases are metastatic at diagnoses. Radiotherapy of both primary tumor and secondary lesions can be, in addition to systemic treatments, a radical alternative for selected patients. MATERIALS AND METHODS: Patients with de novo prostate carcinoma with bone or lymph node metastases were retrospectively reviewed. All patients received moderate hypofractionated IMRT/VMAT up to 63 Gy in 21 daily fractions of 3 Gy to prostate and metastases with neoadjuvant and concurrent androgen deprivation therapy (ADT). According to known advances some patients also received abiraterone, enzalutamide, or docetaxel. RESULTS: Between 2015-2020, we attended 26 prostate cancer patients (median age 69.5 years, range 52-84) with simultaneous oligometastases [mean 2.1 metastases, median 1.5 metastases (range 1-6)]. Eighteen patients (69%) presented lymph node metastases, 4 (15.5%) bone metastases and 4 (15.5%) both lymph node and bone metastases. With a median follow-up of 15.5 months (range 3-65 months), 16 patients (62%) are alive and tumor free while 10 (38%) are alive with tumor. Four patients (17%) developed tumor progression, out of irradiated area in all cases, with a median time to progression of 43.5 months (range 27-56 months). Actuarial progression-free survival (PFS) rates at 12 and 24 months were 94.1% and 84.7%, respectively. No grade > 2 acute or late complications were recorded. CONCLUSIONS: Simultaneous directed radical hypofractionated radiation therapy for prostate and metastases is feasible, well tolerated and achieves an acceptable PFS rate. However, further studies with longer follow-up are necessary to definitively address these observations.

Diagnosis and management of spinal metastasis of primary brain tumours.

The prognosis for patients with high-grade glioma is poor despite aggressive multimodal treatment. About 90% of these lesions recur intracranially. The frequency of spinal cord disease is less than 2%. We report two cases of high-grade glioma with spinal drop metastases. One of the learning points we want to share is to think in the possibility of spinal cord metastases from brain gliomas. When symptoms are suggestive of spinal cord compromise, spine MRI should be done.