New Insight into Intestinal Mast Cells Revealed by Single-Cell RNA Sequencing.

Mast cells (MCs) are tissue-resident immune cells distributed in all tissues and strategically located close to blood and lymphatic vessels and nerves. Thanks to the expression of a wide array of receptors, MCs act as tissue sentinels, able to detect the presence of bacteria and parasites and to respond to different environmental stimuli. MCs originate from bone marrow (BM) progenitors that enter the circulation and mature in peripheral organs under the influence of microenvironment factors, thus differentiating into heterogeneous tissue-specific subsets. Even though MC activation has been traditionally linked to IgE-mediated allergic reactions, a role for these cells in other pathological conditions including tumor progression has recently emerged. However, several aspects of MC biology remain to be clarified. The advent of single-cell RNA sequencing platforms has provided the opportunity to understand MCs' origin and differentiation as well as their phenotype and functions within different tissues, including the gut. This review recapitulates how single-cell transcriptomic studies provided insight into MC development as well as into the functional role of intestinal MC subsets in health and disease.

Breast Volume Is a Predictor of Higher Heart Dose in Whole-Breast Supine Free-Breathing Volumetric-Modulated Arc Therapy Planning.

In breast cancer volumetric-modulated arc therapy (VMAT) planning, the rotation of the gantry around the target implies a greater dose spreading to the whole heart, compared to tangential-field standard treatment. A consecutive cohort of 121 breast cancer patients treated with the VMAT technique was investigated. The correlation of breast volume, heart volume and lung volume with mean heart dose (mHD) and mean and maximum LAD dose (mLAD dose, MLAD dose) was tested, and a subsequent a linear regression analysis was carried out. VMAT treatment plans from 56 left breast cancer and 65 right breast cancer patients were analyzed. For right-sided patients, breast volume was significantly correlated with mHD, mLAD and MLAD dose, while for left-sided patients, breast volume was significantly correlated with mHD and mLAD, while heart volume and lung volume were correlated with mHD, mLAD and MLAD dose. Breast volume was the only predictor of increased heart and LAD dose (p ≤ 0.001) for right-sided patients. In left-sided patients, heart and lung were also predictors of increased mHD (p = 0.005, p ≤ 0.001) and mean LAD dose (p = 0.009, p ≤ 0.001). In this study, we observed an increase in heart and LAD doses in larger-breasted patients treated with VMAT planning. In right-sided patients, breast volume was shown to be the only predictor of increased heart dose and LAD dose.

18F-choline PET/CT driven salvage radiotherapy in prostate cancer patients: up-date analysis with 5-year median follow-up.

PURPOSE: Salvage radiotherapy is generally considered as the standard treatment for biochemical relapse after surgery. Best results have been obtained with a PSA value < 0.5 ng/ml at relapse, while 60-66 Gy is deemed as standard total dose. Modern imaging, as dynamic-18F-choline PET/CT may identify site of recurrence, allowing dose escalation to a biological target volume. METHODS: Hundred and fifty patients showed a local relapse at dynamic-18F-choline PET/CT at time of biochemical recurrence. High-dose salvage radiotherapy was delivered up to total dose of 80 Gy to 18F-choline PET/CT positive area. Toxicity and relapse-free survival were recorded. RESULTS: Median PSA value at the beginning of salvage radiotherapy was 0.47 ng/ml (range 0.2-17.5 ng/ml). One-hundred and thirty nine patients (93%) completed salvage radiotherapy without interruptions. Acute gastrointestinal grade ≥ 2 toxicity was recorded in 13 patients (9%), acute genitourinary grade ≥ 2 toxicity in 2 patients (1.4%). One patient (0.7%) experienced late gastrointestinal grade 4 toxicity and 2 patients (1.4%) late acute genitourinary grade 3 toxicity. With a median follow-up of 63.5 months, 5 and 7-years relapse-free survival were 70% and 60.7%, respectively. CONCLUSION: With a median follow-up of 5 years the present study confirms that high-dose salvage radiotherapy to a biological target volume is feasible, with low rate of late toxicity and promising activity.

Effects of ionizing radiation on bio-active plant extracts useful for preventing oxidative damages.

Humans are exposed to ionizing radiations in medical radiodiagnosis and radiotherapy that cause oxidative damages and degenerative diseases. Airplane pilots, and even more astronauts, are exposed to a variety of potentially harmful factors, including cosmic radiations. Among the phytochemicals, phenols are particularly efficient in countering the oxidative stress. In the present study, different extracts obtained from plant food, plant by-products and dietary supplements, have been compared for their antioxidant properties before and after irradiation of 140 cGy, a dose absorbed during a hypothetical stay of three years in the space. All the dry extracts, characterized in terms of vitamin C and phenolic content, remained chemically unaltered and maintained their antioxidant capability after irradiation. Our results suggest the potential use of these extracts as nutraceuticals to protect humans from oxidative damages, even when these extracts must be stored in an environment exposed to cosmic radiations as in a space station.

Multifraction radiotherapy for palliation of painful bone metastases: 20 Gy versus 30 Gy.

AIMS AND BACKGROUND: To compare 2 multifraction radiotherapy schedules in the palliation of painful bone metastases. METHODS AND STUDY DESIGN: We retrospectively analyzed clinical data of 105 patients with a total of 140 painful bone metastases who were treated with 20 Gy in 5 fractions or 30 Gy in 10 fractions. The primary tumors were breast (30%), lung (28%), and prostate (14%). The main sites of irradiation were spine (n = 79) and sacrum or pelvis (n = 39). Pain was graded by patients according to the pain numeric rating scale just before and 1 month after radiotherapy. Pain progression was defined as an increase ≥2 on pain scale after an initial response. RESULTS: The overall response rate at 1 month was 88.6%. Overall response rate was 89.6% in the 20-Gy arm and 87.3% in the 30-Gy arm (p = 0.669). The rate of complete response was statistically better in patients treated with 30 Gy (p = 0.019). The mean reduction in pain was 3.2 in the 20-Gy group and 3.6 in the 30-Gy group. Pain progression was 6.5% and 1.6%, respectively. The incidence of acute toxicity was statistically significantly higher in the 30-Gy arm (23.8%) than in the 20-Gy arm (2.6%) (p = 0.001). One pathologic fracture of the irradiated bone was observed in the 30-Gy arm. Two lesions, one in each group, were re-irradiated for pain recurrence. Pain progression was found in 6.5% of the irradiated lesions in the 20-Gy arm and in 1.6% in the 30-Gy arm. CONCLUSIONS: In our series, both regimens achieved high rate of pain relief, although the group treated with higher total dose reported better complete response rate. The 30-Gy arm had a significantly higher rate of acute toxicity.

Role of salvage stereotactic body radiation therapy in post-surgical loco-regional recurrence in a selected population of non-small cell lung cancer patients.

AIM: This is a retrospective analysis of a selected series of high-risk non-small cell lung cancer (NSCLC) patients with post-surgical loco-regional relapse treated with salvage stereotactic body radiotherapy (SBRT). Outcome and toxicity profiles were assessed. PATIENTS AND METHODS: Twenty-eight patients (unfit for surgery or systemic therapy) with 30 lesions underwent salvage SBRT as an alternative therapy because of advanced age, co-morbid conditions or no response obtained from other treatments. RESULTS: Complete and partial responses were 16% and 70%, respectively. Local progression was observed in 3 patients. Regional relapse occurred in 5 patients. Distant progression occurred in 10 patients. The 2-year overall survival (OS) and disease-free survival (DFS) were 57.5% and 36.6%, respectively. Radiation acute pneumonitis occurred as follows: three patients developed grade 1, two patients experienced grade 2 and one patient experienced grade 3 toxicity. CONCLUSION: Stereotactic body radiotherapy could have an alternative role in isolated loco-regional relapse in patients unfit or resistant to other therapies.

Image guided intensity modulated hypofractionated radiotherapy in high-risk prostate cancer patients treated four or five times per week: analysis of toxicity and preliminary results.

BACKGROUND: To evaluate efficacy and toxicity of hypofractionated intensity-modulated simultaneous integrated boost (IMRT-SIB) and image-guided (IGRT) radiotherapy in the treatment of high-risk prostate cancer patients. METHODS: Eighty-two patients with high-risk prostate cancer were analysed. An IMRT treatment was planned delivering 68.75 Gy to the prostate, 55 Gy to the seminal vesicles and positive nodes and 45 Gy to the pelvis in 25 fractions. The first 59 patients received 4 weekly fractions whereas the last 23 patients received 5 weekly fractions. All patients were submitted to hormonal therapy. RESULTS: The median follow-up was 31 months. Acute grade 1-2 gastrointestinal (GI) toxicity rates were 13.4%. Grade 1-2 and grade 3 genitourinary (GU) toxicity rates were 22% and 1.2%, respectively.Grade 1 and 2 GI late toxicity rates were 1.2%. No grade ≥3 toxicity was recorded. Grade 1 GU late toxicity rate was 2.4%. No grade ≥2 toxicity was recorded.No significant difference was calculated in terms of acute and late toxicity between the group treated 4 or 5 times weekly.The actuarial 3-years Overall survival and Freedom from biochemical failure were 98.6% and 91.3%, respectively. CONCLUSIONS: The present study demonstrated that hypofractionated IGRT-IMRT-SIB in patients with high-risk prostate cancer is efficient with acceptable toxicity profile. Outcome in terms of survival are promising, but longer follow-up is needed.

Image-guided hypofractionated radiotherapy in low-risk prostate cancer patients.

AIM: To evaluate efficacy and toxicity of image-guided hypofractionated radiotherapy (HFRT) in the treatment of low-risk prostate cancer. Outcomes and toxicities of this series of patients were compared to another group of 32 low-risk patients treated with conventional fractionation (CFRT). METHODS: Fifty-nine patients with low-risk prostate cancer were analysed. Total dose for the prostate and proximal seminal vesicles was 60 Gy delivered in 20 fractions. RESULTS: The median follow-up was 30 months. The actuarial 4-year overall survival, biochemical free survival, and disease specific survival were 100%, 97.4%, and 97.4%, respectively. Acute grade 1-2 gastrointestinal (GI) and genitourinary (GU) toxicity rates were 11.9% and 40.7%, respectively. Grade 1 GI and GU late toxicity rates were 8.5% and 13.6%, respectively. No grade ≥ 2 late toxicities were recorded. Acute grade 2-3 GU toxicity resulted significantly lower (P = 0.04) in HFRT group compared to the CFRT group. The cumulative 4-year incidence of grade 1-2 GU toxicity was significantly higher (P < 0.001) for HFRT patients. CONCLUSIONS: Our study demonstrated that hypofractionated regimen provided excellent biochemical control in favorable risk prostate cancer patients. The incidence of GI and GU toxicity was low. However, HFRT presented higher cumulative incidence of low-grade late GU toxicity than CFRT.

Hypofractionated intensity-modulated simultaneous integrated boost and image-guided radiotherapy in the treatment of high-risk prostate cancer patients: a preliminary report on acute toxicity.

AIMS AND BACKGROUND: To evaluate acute toxicity of hypofractionated intensity-modulated radiotherapy with simultaneous integrated boost and image-guided radiotherapy in the treatment of high-risk prostate cancer patients. METHODS: Between November 2009 and March 2012, 59 patients with high-risk prostate cancer were enrolled. The eclipse inverse planning system (Varian) was used to calculate an IMRT plan with simultaneous integrated boost, delivering 68.75 Gy (2.75 Gy per fraction) to the prostate, 55 Gy (2.2 Gy per fraction) to the seminal vesicles and positive nodes, and 45 Gy (1.8 Gy per fraction) to the pelvis, 4 fractions per week, 25 fractions. Prior to each treatment, patients underwent a kilo-voltage cone-beam CT performing an image-guided radiation therapy (IGRT). All patients were submitted to neoadjuvant, concomitant and adjuvant hormone therapy. RESULTS: The median follow-up for all patients was 13 months (range, 3-28). At the last follow-up, no grade 3 or 4 side effect was observed. Toxicity occurred as follows during the treatment: grade 1 and 2 gastrointestinal toxicity 5.2% and 6.9%, respectively; grade 1 and 2 genitourinary toxicity 24.1% and 1.7%, respectively. Only 1.7% of the patients developed grade 3 genitourinary toxicity. No grade 3 gastrointestinal toxicity was observed. CONCLUSIONS: The present study demonstrated that 4/w hypofractionated intensity-modulated radiotherapy with simultaneous integrated boost and image-guided radiotherapy in patients with high-risk prostate cancer is feasible and safe. Low acute toxicity rates were verified. Longer follow-up is needed to evaluate the outcomes in terms of late toxicity and survival.

Clinical outcomes of single dose stereotactic radiotherapy for lung metastases.

INTRODUCTION: Stereotactic body radiation therapy is an emerging noninvasive technique for the treatment of oligometastatic cancer. The use of small numbers of large doses achieve a high percentage of local control. The aim of this study was to evaluate the efficacy and tolerability of SBRT for the treatment of lung metastases in a cohort of patients treated between 2008 and 2012 at our institution. PATIENTS AND METHODS: A total of 66 patients with oligometastatic lung tumors (single pulmonary nodules in 40 patients; 61%) were included in the study. SBRT was performed with a stereotactic body frame and a 3-D conformal technique. Forty-nine central tumors received 23 Gy in a single fraction and 54 peripheral tumors received a dose of 30 Gy in a single fraction. The primary end point was local control; secondary end points were survival and toxicity. RESULTS: Median follow-up was 15 months (range, 3-45 months). Local control rates at 1 and 2 years were 89.1% and 82.1%, overall survival rates were 76.4% and 31.2%, cancer-specific survival rates were 78.5% and 35.4%, and progression-free survival rates were 53.9% and 22%, respectively. Median survival time was 12 months, and median progression-free survival time was 10 months. Toxicity profiles were good, with 2 cases of Grade 3 toxicity (pneumonitis). CONCLUSION: SBRT is an effective and safe local treatment option for patients with lung metastases, although it remains investigational; longer follow-up to confirm results is required.

Radiation therapy after breast reconstruction: outcomes, complications, and patient satisfaction.

PURPOSE: The aim of this study was to evaluate treatment-related complications, outcomes, and patient satisfaction in women with locally advanced breast cancer who received post-mastectomy radiation therapy (PMRT) after breast reconstruction (BR). MATERIALS AND METHODS: Between October 2007 and November 2010, 46 patients with locally advanced breast cancer who underwent mastectomy followed by BR received PMRT at our Department. Radiotherapy was delivered to the chest wall with a dose of 50 Gy in 25 fractions over 5 weeks. RESULTS: The median follow-up was 19 months. Skin erythema grade 1 and 2 was seen in 44 (96%) and two (4%) patients, respectively. Major complications, requiring additional corrective surgical procedure, occurred in three (7%) patients (one patient with prosthesis, one patient with tissue expander and one patient with deep inferior epigastric perforator flap). At univariate analysis, smoking, chemotherapy, hormone therapy with tamoxifen and reconstruction with implant were associated with overall complications (capsular contracture and reconstruction failure). Forty (86%) patients were very satisfied or satisfied with the cosmetic outcome of reconstruction. CONCLUSIONS: Radiotherapy can be safely delivered after BR, with a low complication rate and good patient satisfaction. Further randomised studies are needed to better define the optimal timing of breast reconstruction and post-mastectomy radiation therapy.

Exclusive electron intraoperative radiotherapy in early-stage breast cancer: a monoinstitutional experience.

AIM: To evaluate the effectiveness of intra-operative radiotherapy (IORT) in breast cancer in terms of local control, esthetic results and disease-free survival. PATIENTS AND METHODS: From June 2007 to October 2011, 110 patients with early-stage breast cancer were submitted to quadrantectomy and IORT. A total dose of 21 Gy prescribed at 90-100% isodose was delivered in all cases. Patients were evaluated after surgery for early and late complications. RESULTS: Median follow-up was 27 (range: 2-54) months. In 10 patients (9.1%), breast ultrasound showed liponecrosis. Six patients (5.5%) developed grade 2 fibrosis. Disease-free survival rates at 2 and 3 years were 96.8% and 92.9 %. Three patients (2.7%) developed local recurrence, two patients (1.8%) distant metastasis. Two patients died. The 2- and 3-year overall survival rates were 100% and 97.3%, respectively. CONCLUSION: IORT could be an appropriate therapeutic alternative in selected patients although it remains investigational; longer follow-up to confirm these results is required.