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.

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.

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.

Predictive and Prognostic Value of Early Disease Progression by PET Evaluation in Advanced Non-Small Cell Lung Cancer.

OBJECTIVE: To assess the predictive and prognostic value of progressive metabolic disease (PMD) by the use of early 18Fluorodeoxyglucose positron emission tomography (18FDG-PET) in patients with clinical stage IV non-small cell lung cancer (NSCLC) treated with first-line chemotherapy. METHODS: An 18FDG-PET performed following the first cycle of chemotherapy (PET-1) was compared with a pretreatment 18FDG-PET (PET-0) and a computed tomography (CT) scan after the third cycle (CT-3). The primary endpoint was the positive predictive value (PPV) of PMD. Secondary endpoints included the prognostic value of PMD. RESULTS: Eleven of 38 patients (29%) had a PMD by PET-1, and 15 (39%), including all patients with a PMD, experienced a progressive disease by CT-3. The PPV of PMD was 100% according to both the European Organization for Research and Treatment of Cancer (EORTC) criteria and the PET Response Criteria In Solid Tumors (PERCIST) (p value for both, <0.0001). Patients with a PMD by PET-1 had a median overall survival of 7.0 months versus 14.0 months for those without a PMD (p = 0.04, according to the EORTC criteria). CONCLUSIONS: Early 18FDG-PET assessment deserves further investigation for the identification of NSCLC patients who do not benefit from first-line chemotherapy.

Salvage Radiotherapy PSMA PET/CT-guided in Men With PSA Recurrence.

BACKGROUND/AIM: To evaluate the clinical outcome in men with recurrent prostate cancer (PCa) treated by salvage radiotherapy (sRT) prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT)-guided. PATIENTS AND METHODS: From January 2021 to January 2023, 33 patients who previously underwent definitive/systemic therapy were submitted to sRT PSMA PET/CT-guided for PCa recurrence: 16 (48.5%) on the prostate bed (PB), 12 (36.4%) on the lymph node (LN) and five (15.1%) on the bone. The median PSA value was 3.3 ng/ml (range=0.3-15.5 ng/ml): 0.2-0.5 ng/ml (18.2% cases), 0.51-1 ng/ml (39.4% cases) and >1 ng/ml (42.4% cases). Median 18F PSMA PET/CT standardized uptake value (SUVmax) was evaluated on PB, vs. LN vs. bones PCa recurrences and was equal to 12.5 vs. 19.0 vs. 30.1, respectively. RESULTS: Overall, at a median follow up of 12 months, 23/33 patients (69.7%) had local control without distant progression (PSA and SUVmax evaluation): 14/16 (87.5%) vs. 7/12 (58.3%) vs. 2/5 (40%) underwent sRT on the PB vs. LN vs. bone metastases, respectively. CONCLUSION: PSMA PET/CT allows to perform sRT early in men with PCa recurrence and low PSA values obtaining a complete clinical response in approximately 70% of the cases one year from treatment.

Erectile dysfunction following hydrogel injection and hypofractionated radiotherapy for prostate cancer: Our experience in 56 cases.

INTRODUCTION: The incidence of erectile dysfunction (ED) in men with organ-confined prostate cancer (PCa) submitted to hypofractionated radiotherapy (HRT) has been prospectively evaluated. MATERIALS AND METHODS: From April 2018 to September 2020, 56 patients (median age 70 years) with cT1c PCa were treated by HRT directed to the prostate and seminal vesicle. Median PSA was 8.3 ng/ml; 20 patients (35.7%) vs. 28 (50%) vs. 8 (22.3%) had a PCa Grade Group 1 vs. 2 vs. 3, respectively. All patients underwent hydrogel injection of Space OAR and intraprostatic fiducials before HRT. The prescription dose was 60 Gy in 20 fractions 5 days/week over 4 weeks. During the follow up, PSA, genitourinary (GU) and gastrointestinal (GI) toxicities were evaluated. The sexual function was evaluated by International Index of Erectile Function - 5 (IIEF-5) before, 6 and 18 months from HRT; 32/56 (57.1%) men referred a normal sexual activity before HRT (median IIEF-5 score: 22). RESULTS: Median PSA level at median follow up of 18 months was 0.92 ng/ml and none used adjuvant therapy. One man (1.8%) referred a tardive grade 1 GU complication. At a median follow up of 6 and 18 months, 20/32 (62.5%) kept pretreatment sexual potency (median IIEF-5 score: 21). The 12/32 men who worsened the sexual function following HRT had a median age higher than patients without ED (78 vs. 67 years). CONCLUSIONS: The use of hydrogel injection and intraprostatic fiducials followed by HRT allowed to kept pretreatment sexual potency in 62.5% of the cases.

Clinical Outcomes of Hydrogel Spacer Injection Space OAR in Men Submitted to Hypofractionated Radiotherapy for Prostate Cancer.

BACKGROUND/AIM: To evaluate the clinical outcomes of men with prostate cancer (PCa) submitted to hydrogel spacer injection before hypofractionated radiotherapy (HRT). PATIENTS AND METHODS: From April 2018 to April 2020, 32 patients with clinically localized PCa underwent hydrogel injection Space OAR before HRT to the prostate and seminal vesicle; the prescription dose was 60 Gy in 20 fractions, 5 days/week over 4 weeks. PSA levels, genitourinary (GU) and gastrointestinal (GI) toxicities, and sexual function were prospectively evaluated. RESULTS: PSA levels at the median follow up of 15 months was 0.52 ng/ml; 28.1% vs. 78.1% patients had GI vs. GU Grade 0 acute toxicity and 93.7% vs. 0% had GI vs. GU Grade 0 late toxicity. Furthermore, 88.1% of patients kept pretreatment sexual potency. CONCLUSION: The use of the hydrogel Spacer OAR before HRT is useful for reducing acute and late GU and GI toxicities.

Histology-based Combination Induction Chemotherapy for Elderly Patients with Clinical Stage III Non-small Cell Lung Cancer.

AIM: To explore the feasibility and activity of a histology-based induction combination chemotherapy for elderly patients with clinical stage III non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients aged ≥70 years with stage IIIA and IIIB lung squamous cell carcinoma (SCC) or adenocarcinoma were treated with three cycles of carboplatin and gemcitabine or pemetrexed, respectively, followed by definitive radiotherapy or surgery. The primary endpoint was the overall response rate (ORR) following induction. RESULTS: Twenty-seven patients, with a median age of 74 years (range=70-80 years) were treated for adenocarcinoma in 14 (52%) and SCC in 13 (48%), clinical stage IIIA in eight (30%) and IIIB in 19 (70%). Grade 3 or 4 toxicity was reported for five patients (18.5%). The ORR was 46% in 12 (partial responses) out of 26 assessable patients. CONCLUSION: Histology-based induction combination chemotherapy is active and feasible in elderly patients with stage III NSCLC.

A fully automatic approach for multimodal PET and MR image segmentation in gamma knife treatment planning.

BACKGROUND AND OBJECTIVES: Nowadays, clinical practice in Gamma Knife treatments is generally based on MRI anatomical information alone. However, the joint use of MRI and PET images can be useful for considering both anatomical and metabolic information about the lesion to be treated. In this paper we present a co-segmentation method to integrate the segmented Biological Target Volume (BTV), using [11C]-Methionine-PET (MET-PET) images, and the segmented Gross Target Volume (GTV), on the respective co-registered MR images. The resulting volume gives enhanced brain tumor information to be used in stereotactic neuro-radiosurgery treatment planning. GTV often does not match entirely with BTV, which provides metabolic information about brain lesions. For this reason, PET imaging is valuable and it could be used to provide complementary information useful for treatment planning. In this way, BTV can be used to modify GTV, enhancing Clinical Target Volume (CTV) delineation. METHODS: A novel fully automatic multimodal PET/MRI segmentation method for Leksell Gamma Knife® treatments is proposed. This approach improves and combines two computer-assisted and operator-independent single modality methods, previously developed and validated, to segment BTV and GTV from PET and MR images, respectively. In addition, the GTV is utilized to combine the superior contrast of PET images with the higher spatial resolution of MRI, obtaining a new BTV, called BTVMRI. A total of 19 brain metastatic tumors, undergone stereotactic neuro-radiosurgery, were retrospectively analyzed. A framework for the evaluation of multimodal PET/MRI segmentation is also presented. Overlap-based and spatial distance-based metrics were considered to quantify similarity concerning PET and MRI segmentation approaches. Statistics was also included to measure correlation among the different segmentation processes. Since it is not possible to define a gold-standard CTV according to both MRI and PET images without treatment response assessment, the feasibility and the clinical value of BTV integration in Gamma Knife treatment planning were considered. Therefore, a qualitative evaluation was carried out by three experienced clinicians. RESULTS: The achieved experimental results showed that GTV and BTV segmentations are statistically correlated (Spearman's rank correlation coefficient: 0.898) but they have low similarity degree (average Dice Similarity Coefficient: 61.87 ± 14.64). Therefore, volume measurements as well as evaluation metrics values demonstrated that MRI and PET convey different but complementary imaging information. GTV and BTV could be combined to enhance treatment planning. In more than 50% of cases the CTV was strongly or moderately conditioned by metabolic imaging. Especially, BTVMRI enhanced the CTV more accurately than BTV in 25% of cases. CONCLUSIONS: The proposed fully automatic multimodal PET/MRI segmentation method is a valid operator-independent methodology helping the clinicians to define a CTV that includes both metabolic and morphologic information. BTVMRI and GTV should be considered for a comprehensive treatment planning.

Lactobacillus rhamnosus GG: An Overview to Explore the Rationale of Its Use in Cancer.

Cancer is the second leading cause of death in the western world. In the era of precision medicine, a significant number of cancer patients can be cured with several anti-cancer therapeutic regimens. However, therapy failure may be caused by treatment side effects, such as diarrhea, especially occurring in patients with gastrointestinal or pelvic malignancies. In particular, diarrhea is one of the most frequent gastrointestinal toxicity during cancer treatment and it can result from nearly bot chemo- and radio-therapeutic strategies currently used. Diarrhea has a serious impact on patients' quality of life and treatment dosing and schedule modification due to its severity can negatively influence treatment outcomes. In this context, probiotics may play an interesting role in several human diseases with an inflammatory bowel involvement and, among these, Lactobacillus rhamnosus GG (LGG) is one of the most characterized and utilized. In particular, LGG is able to reverse intestinal dysbiosis and moderate diarrhea. Moreover, preclinical studies have documented its effects in reducing chronic inflammation associated with cancer development. This review summarizes the preclinical results of LGG on cancer cells proliferation and tumor invasion as well as the potential role of LGG use in cancer patients for the prevention and management of diarrhea associated with cancer treatment. Overall, these encouraging data support further investigation on the use of LGG in stratified patients undergoing specific therapeutic protocols, including chemotherapy and pelvic radiotherapy, in order to reduce the development of severe diarrhea and thus improve the adherence to the therapy and patients' quality of life.

Fludarabine, mitoxantrone and dexamethasone as front-line therapy in elderly patients affected by newly-diagnosed, low-grade non-Hodgkin's lymphomas with unfavorable prognostic factors: results of a phase II study.

About one-third of the cases of non-Hodgkin's lymphomas occur in patients aged 60 years or more. Nevertheless, there are very few data in the literature regarding the optimal therapeutic approach for both aggressive and indolent histologies. Fludarabine-based combination regimens are an effective choice for younger patients affected by low-grade non-Hodgkin's lymphomas, but there is a lack of information about their tolerability and efficacy in older patients. We performed a phase II study to test the efficacy and safety of the combination of Fludarabine, Mitoxantrone and Dexamethasone (FND) in newly-diagnosed, chemo-naive elderly patients affected by low-grade non-Hodgkin's lymphomas with unfavorable prognostic factors. From March 1999 to March 2002, 18 patients were enrolled into the study. All the patients were evaluated for toxicity and response. Neutropenia and thrombocytopenia have been registered as the main toxicities. Thirteen (72%) patients experienced a complete response and 4 (22%) a partial response: the overall response rate was 94%. At a median follow-up of 19 months, the median time for progression-free-survival and the median survival time were not reached yet. The 2-years projected progression-free-survival and overall-survival are 52% and 67% respectively. When administered as first-line treatment to a population of elderly patients affected by high-risk, low-grade non-Hodgkin's lymphomas, FND showed a high efficacy and a good toxicity profile. Our data compare favorably to those reported for the same schedule administered both as first- or second-line therapy in younger patients.

Breast cancer bone metastases: an epidemiologic study in selected radiation departments.

AIMS: To quantify radiation treatments for bone metastases from breast cancer in three Sicilian provinces (Messina, Catania, Ragusa) with respect to the general population and the incidence and prevalence of breast cancer in this macro-area in a 8-year period. METHODS: All bone metastasis patients treated using radiotherapy in 8 radiation departments operating in the provinces of Messina, Catania and Ragusa were collected. Among these, metastases from breast carcinoma were analyzed according to year of irradiation. An analysis of breast cancer incidence and prevalence with respect to inhabitants in this macro-area was conducted using literature and census data. RESULTS: From January 2004 to December 2011, irradiation was delivered in 4419 bone metastasis patients. Among these, 1617 had a primary breast cancer with a median treatment per year of 206.5 (range, 164-251); 211 patients were treated in 2004 and 206 in 2011. In 2004, there were 1,048,957 female residents in the three provinces and 1,065,422 in 2011. The reported breast cancer incidence and prevalence in Sicily was respectively 100.79/100,000 and 908.54/100,000 in 2004 and 108.41/100,000 and 1091.29/100,000 in 2010. CONCLUSIONS: There has been an increase in both incidence and prevalence of breast cancer in Sicily. Nevertheless, it seems that there was no increment in skeletal-related events requiring irradiation in such patients in eastern Sicily radiation departments.

A three-drug induction chemotherapy with gemcitabine, carboplatin, and paclitaxel for stage III non-small cell lung cancer.

The aim of the study is to evaluate the efficacy and safety of a three-drug chemotherapy regimen including gemcitabine, carboplatin, and paclitaxel as induction therapy in clinical stage III non-small cell lung cancer (NSCLC). Patients aged 18-75 years, ECOG PS 0-1, with unresectable clinical stage IIIA or IIIB NSCLC suitable for definitive radiation treatment, were treated in a phase II study with i.v. carboplatin AUC 5 and i.v., paclitaxel 175 mg/m(2) on day 1, and i.v. gemcitabine 800 mg/m(2) on days 1 and 8, every 3 weeks for 3 cycles, as previously assessed in a dose-finding study. Primary end point was overall response rate (ORR). Secondary end points included: toxicity, progression-free survival (PFS), resection rate, and overall survival (OS). Out of the 60 enrolled patients, 49 were males and 11 females, 31 patients had stage IIIA and 29 stage IIIB NSCLC. Forty-four partial responses and one complete response were observed, for an ORR of 75 %. The most frequent G3-G4 toxicity included: neutropenia (in 23 % of cases), hypertransaminasemia (12 %), and diarrhea (5 %). With a median follow-up of 15 months (range 2-72), median PFS was 10.5 months (95 % CI 9.9-11.4) and median OS was 21.1 months (95 % CI 19.7-22.8). Fourteen stage IIIA patients underwent surgery, for a resection rate of 45 %. A median PFS of 17.8 months (95 % CI 16.2-19.7) and a median OS of 25.5 months (95 % CI 23.0-28.4) were observed in stage IIIA patients. The three-drug chemotherapy regimen, at the employed dose, demonstrated a considerable disease response and resection rate, with acceptable toxicity.